• Incidence and severity of CAD increases as GFR decreases
• Nakano T, Ninomiya T, Sumiyoshi S et al. Association of kidney function with coronary atherosclerosis and
calcification in autopsy samples from Japanese elders: the Hisayama study. Am J Kidney Dis 2010; 55: 21–30
• Chonchol M, Whittle J, Desbien A et al. Chronic kidney disease is associated with angiographic coronary
artery disease. Am J Nephrol 2008; 28: 354–360.
• Diffuse multivessel involvement with calcification
• Ix JH, Shlipak MG, Liu HH et al. Association between renal insufficiency and inducible ischemia in patients
with coronary artery disease: the heart and soul study. J Am Soc Nephrol 2003; 14: 3233–3238.
• Among pts with CAD, presence of CKD portends a worse CV
• Joki N, Hase H, Nakamura R et al. Onset of coronary artery disease prior to initiation of haemodialysis in
patients with end-stage renal disease. Nephrol Dial Transplant 1997; 12: 718–723.
• Ohtake T, Kobayashi S, Moriya H et al. High prevalence of occult coronary artery stenosis in patients with
chronic kidney disease at the initiation of renal replacement therapy: an angiographic examination. J Am Soc
Nephrol 2005; 16: 1141–1148.
CKD and CAD – a tempestuous relationship
Ohtake T, Kobayashi S, Moriya H et al. High prevalence of occult coronary artery stenosis in patients with chronic
kidney disease at the initiation of renal replacement therapy: an angiographic examination. J Am Soc Nephrol 2005
CKD and CAD – a tempestuous relationship
• Standard CVRFs are common in CKD + CAD setting
• Longenecker JC, Coresh J, Powe NR et al. Traditional cardiovascular disease risk factors in dialysis patients
compared with the general population: the CHOICE Study. J Am Soc Nephrol 2002; 13: 1918–1927.
• Weiner DE, Tighiouart H, Elsayed EF et al. The Framingham predictive instrument in chronic kidney disease.
J Am Coll Cardiol 2007; 50:217–224.
• Oxidative stress & inflammation linked to pathogenesis of
plaque formation and rupture, as is mineralocorticoid excess
• deFilippi C, Wasserman S, Rosanio S et al. Cardiac troponin T and C-reactive protein for predicting prognosis,
coronary atherosclerosis, and cardiomyopathy in patients undergoing long-term hemodialysis. JAMA 2003;
• Weiner DE, Tighiouart H, Elsayed EF et al. Inflammation and cardiovascular events in individuals with and
without chronic kidney disease. Kidney Int 2008; 73: 1406–1412
• Menon V, Greene T, Wang X et al. C-reactive protein and albumin as predictors of all-cause and
cardiovascular mortality in chronic kidney disease. Kidney Int 2005; 68: 766–772
• Bayes B, Pastor MC, Bonal J et al. Homocysteine, C-reactive protein, lipid peroxidation and mortality in
haemodialysis patients. Nephrol Dial Transplant 2003; 18: 106–112.
Longenecker JC, Coresh J, Powe NR et al. Traditional cardiovascular disease risk factors in dialysis patients compared
with the general population: the CHOICE Study. J Am Soc Nephrol 2002; 13: 1918–1927.
deFilippi C, Wasserman S, Rosanio S et al. Cardiac troponin T and C-reactive protein for predicting prognosis, coronary
atherosclerosis, and cardiomyopathy in patients undergoing long-term hemodialysis. JAMA 2003; 290: 353–359
CKD and CAD – a tempestuous relationship
• Disordered mineral and bone metabolism accelerates CAD
• Giovannucci E, Liu Y, Hollis BW et al. 25-Hydroxyvitamin D and risk of myocardial infarction in men: a
prospective study. Arch Intern Med 2008; 168: 1174–1180.
• Kovesdy CP, Ahmadzadeh S, Anderson JE et al. Association of activated vitamin D treatment and mortality in
chronic kidney disease. Arch Intern Med 2008; 168: 397–403.
• Gutierrez OM, Mannstadt M, Isakova T et al. Fibroblast growth factor 23 and mortality among patients
undergoing hemodialysis. N Engl J Med 2008; 359: 584–592.
• CKD pts with clinical IHD symptoms may not have significant
• Rostand SG, Kirk KA, Rutsky EA. Dialysis-associated ischemic heart disease: insights from coronary
angiography. Kidney Int. 1984;25: 653–659.
Gutierrez OM, Mannstadt M, Isakova T et al. Fibroblast growth factor 23 and mortality among patients undergoing
hemodialysis. N Engl J Med 2008; 359: 584–592.
• CKD vs ESRD – is there a difference for those already on
• PCI vs CABG; DES vs BMS
• Multivessel / LM CAD; CTO management
• New PCI devices (rotablation, 3rd/4th Gen DES) and
antithrombotics (ticagrelor, prasugrel)
• Peri-PCI interim HD for CKD pts – does “prophylaxis” help
• STE ACS vs NSTE ACS vs Stable CAD
• The anemia conundrum – strategies (bivalirudin vs heparin,
DAPT duration, transfusion / Hb target, femoral vs radial)
Association of kidney function with coronary atherosclerosis and calcification in autopsy samples from Japanese elders: the Hisayama study. Nakano T1, Ninomiya T, Sumiyoshi S, Fujii H, Doi Y, Hirakata H, Tsuruya K, Iida M, Kiyohara Y, Sueishi K. Author information 1Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. firstname.lastname@example.org Abstract BACKGROUND: Chronic kidney disease (CKD) is associated with increased risk of coronary heart disease. However, information regarding the histopathologic characteristics of coronary atherosclerosis in individuals with CKD is scarce. This study investigated the relationship between CKD and severity of coronary atherosclerosis in population-based autopsy samples. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 126 individuals randomly selected from 844 consecutive population-based autopsy samples. PREDICTOR: Estimated glomerular filtration rate (eGFR) calculated using the 6-variable Modification of Diet in Renal Disease (MDRD) Study equation. OUTCOMES: Severity of atherosclerosis in 3 main coronary arteries, including atherosclerotic lesion types defined using the American Heart Association classification; stenosis rates; and coronary calcified lesions. MEASUREMENTS: The relationship between CKD and severity of coronary atherosclerosis was evaluated using generalized estimating equation methods. RESULTS: Frequencies of advanced atherosclerotic lesions increased gradually as eGFR decreased (33.6%, 41.7%, 52.3%, and 52.8% for eGFRs > or = 60, 45-59, 30-44, and <30 mL/min/1.73 m(2), respectively; P for trend = 0.006). This relationship was substantially unchanged even after adjustment for potential confounding factors (ORs, 1.40 [95% CI, 0.76-2.55], 2.02 [95% CI, 0.99-4.15], and 3.02 [95% CI, 1.22-7.49] for eGFRs of 45-59, 30-44, and <30 mL/min/1.73 m(2), respectively). Frequencies of calcified lesions of coronary arteries also increased gradually with lower eGFRs (P for trend = 0.02). Hypertension and diabetes were associated with increased risk of advanced coronary atherosclerosis and calcification of coronary arteries in individuals with decreased eGFR. LIMITATIONS: Cross-sectional study, absence of data for proteinuria, and extremely high proportion of aged people. CONCLUSIONS: The autopsy findings presented here suggest that CKD is associated significantly with severity of coronary atherosclerosis. Patients with CKD should be considered a high-risk population for advanced coronary atherosclerosis.
Chronic Kidney Disease Is Associated with Angiographic Coronary Artery Disease Background/Aims: Patients with chronic kidney disease (CKD) have a dramatically increased risk for cardiovascular mortality. Few prior studies have examined the independent association of CKD with coronary anatomy. Methods: We evaluated the relationship between CKD and severe coronary artery disease (CAD) in 261 male veterans with nuclear perfusion imaging tests suggesting coronary ischemia. We used chart review and patient and provider interviews to collect demographics, clinical characteristics, and coronary anatomy results. We defined CKD as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2, based on the creatinine obtained prior to angiography. We defined significant coronary obstruction as at least one 70% or greater stenosis. We used logistic regression to determine whether CKD was independently associated with significant coronary obstruction. Results: The likelihood of CAD increased monotonically with decreasing eGFR, from 51% among patients with eGFR ≧90 ml/min/1.73 m2 to 84% in those with eGFR <30 ml/min/1.73 m2 (p = 0.0046). Patients with CKD were more likely than those without CKD to have at least one significant coronary obstruction (75.9 vs. 60.7%, p = 0.016). Patients with CKD also had more significant CAD, that is, were more likely to have three-vessel and/or left main disease than those without CKD (34.9 vs. 16.9%, p = 0.0035). In logistic regression analysis, controlling for demographics and comorbidity, CKD continued to be independently associated with the presence of significant CAD (p = 0.0071). Conclusion: CKD patients have a high prevalence of obstructive coronary disease, which may contribute to their high cardiovascular mortality.
Association between renal insufficiency and inducible ischemia in patients with coronary artery disease: the heart and soul study. Chronic renal insufficiency (CRI) is a predictor of stroke, cardiovascular, and all-cause mortality, but the mechanisms responsible for these associations are unclear. Whether CRI was associated with severity of coronary artery disease (CAD) as measured by exercise stress echocardiography among outpatients with stable CAD was evaluated. This study is a cross-sectional analysis of the Heart and Soul study, a prospective cohort of patients with known CAD. Renal function was assessed by 24-h urine collection, and CRI was defined as measured creatinine clearance < or =60 ml/min. Exercise stress echocardiography was used to identify inducible ischemia, defined as any wall motion abnormality seen at stress but not at rest. Logistic regression was used to evaluate the association of CRI with exercise-induced ischemia after adjustment for cardiovascular risk factors. Participants with CRI composed 97 (23%) of the 431 participants and were characterized by older age, worse CAD, lower ejection fraction, greater left ventricular mass and higher C-reactive protein values. The prevalence of exercise-induced ischemia was also substantially greater in the participants with CRI (42% versus 23%; odds ratio [OR], 2.3; 95% confidence interval [CI], 1.4 to 3.8; P < 0.001). This association was minimally changed by adjustment for traditional cardiovascular risk factors and coronary disease history (OR, 2.0; 95% CI, 1.3 to 3.3; P < 0.01) and remained strong even after adjustment for C-reactive protein (OR, 2.3; 95% CI, 1.0 to 5.1; P = 0.04). CRI is strongly associated with exercise-induced ischemia in patients with CAD. The greater severity of atherosclerotic disease observed in patients with CRI may in part explain the association of CRI with increased cardiovascular risk among individuals with CAD.
Onset of coronary artery disease prior to initiation of haemodialysis in patients with end-stage renal disease. To determine whether the onset of coronary artery disease may precede the initiation of dialysis in patients with end-stage renal disease, we performed coronary angiography within 1 month of initiation of maintenance haemodialysis in 24 patients (age range 42-78 years; mean 63.7 +/- 11). Coronary angiography was performed regardless of the absence or presence of angina. Fifteen patients had diabetic nephropathy, and nine had non-diabetic nephropathy. Significant coronary stenosis was defined as at least 75% narrowing of the reference segment. Fifteen patients (62.5%) with a total of 49 lesions were classified as the coronary artery disease present group. Eleven of those 15 (73.3%) had multivessel disease. The average number of stenotic lesions was 3.3 per patient. The most common patterns of stenosis were complex (23 lesions; 47%), and diffuse lesions over 20 mm long (14 lesions; 29%). None of the clinical or haematological factors evaluated differed significantly between the groups with and without coronary artery disease. The prevalence of coronary artery disease was 72.7% in the symptomatic patients and 53.8% in the asymptomatic patients. The diagnosis of coronary artery disease at the start of maintenance haemodialysis based only on chest symptoms and clinical factors proved to be difficult. Coronary angiography is thus essential for evaluating coronary artery disease in uraemic patients. Many patients with end-stage renal disease had coronary artery disease prior to the start of haemodialysis.
High prevalence of occult coronary artery stenosis in patients with chronic kidney disease at the initiation of renal replacement therapy: an angiographic examination.
The prevalence of coronary artery stenosis (CAS) at the initiation of renal replacement therapy (RRT) in patients with chronic kidney disease (CKD) and no previous history of angina and/or myocardial infarction (MI) has not been fully elucidated. The prevalence of significant CAS was evaluated in 30 asymptomatic stage 5 CKD patients without a history of angina and/or MI by coronary angiography at the initiation of RRT. The correlations of various parameters with the prevalence of CAS were also examined. Atherosclerotic surrogate markers, including intima-media thickness of carotid artery and ankle-brachial BP index (ABI), were also evaluated. Significant CAS (>50% stenosis) was seen in 16 (53.3%) of 30 asymptomatic CKD patients on coronary angiography at the start of RRT. Stress cardiac scintigraphy was not effective for detecting hidden cardiac ischemia among the CKD patients. Univariate analysis showed that diabetes (P = 0.01), left ventricular mass index (P = 0.04), hyperlipidemia (P = 0.04), total cholesterol (P = 0.02), LDL cholesterol (P < 0.01), intima-media thickness (P = 0.04), and fibrinogen (P = 0.01) were positively correlated with the presence of CAS, whereas ABI (P < 0.01) showed a negative correlation with CAS. Stepwise logistic regression analysis revealed that diabetes and fibrinogen were significant and independent risk factors for CAS in asymptomatic CKD patients who started RRT. The results clearly demonstrated that despite the absence of cardiac events, stage 5 CKD patients are already in a very high risk group for CAS at the initiation of RRT, which was also closely associated with a significant decrease in ABI.
Traditional Cardiovascular Disease Risk Factors in Dialysis Patients Compared with the General Population: The CHOICE Study
Although atherosclerotic cardiovascular disease (AS- CVD) risk in end-stage renal disease (ESRD) is 5 to 30 times that of the general population, few data exist comparing AS- CVD risk factors among new dialysis patients to the general population. This cross-sectional study of 1041 dialysis patients describes the prevalence of ASCVD risk factors at the begin- ning of ESRD compared with estimates of ASCVD risk factors in the adult US population derived from the Third National Health and Nutrition Examination (NHANES III). CHOICE Study participants had a high prevalence of diabetes (54%), hypertension (96%), left ventricular hypertrophy by electrocar- diogram (EKG) criteria (22%), low physical activity (80%), hypertriglyceridemia (36%), and low HDL cholesterol (33%). CHOICE participants were more likely to be older, black, and male than NHANES III participants. After adjustment for age, race, gender, and ASCVD (defined as myocardial infarction, revascularization procedure, stroke, carotid endarterectomy, and amputation in CHOICE; and as myocardial infarction and stroke in NHANES III), the prevalence of diabetes, hyperten- sion, left ventricular hypertrophy by EKG, low physical activ- ity, low HDL cholesterol, and hypertriglyceridemia were still more common in CHOICE participants. Smoking, obesity, hypercholesterolemia, and high LDL cholesterol, however, were less common in CHOICE than NHANES III participants. The projected 5-yr ASCVD risk based on the Framingham Risk Equation among those older than 40 yr without ASCVD was higher in CHOICE Study participants (13%) than in the NHANES III participants (6%). In summary, many ASCVD risk factors are more prevalent in ESRD than in the general population and may explain some, but probably not all, of the increased ASCVD risk in ESRD.
===================================================================== The Framingham predictive instrument in chronic kidney disease. J Am Coll Cardiol 2007; 50:217–224. The Framingham Risk Score (FRS) was developed to predict coronary heart disease in various populations, and it tended to under-estimate the risk in chronic kidney disease (CKD) patients. Our objectives were to determine whether FRS was associated with cardiovascular events, and to evaluate the role of new risk markers and echocardiographic parameters when they were added to a FRS model. This study enrolled 439 CKD patients. The FRS is used to identify individuals categorically as “low” (<10% of 10-year risk), “intermediate” (10–20% risk) or “high” risk (≧ 20% risk). A significant improvement in model prediction was based on the −2 log likelihood ratio statistic and c-statistic. “High” risk (v.s. “low” risk) predicts cardiovascular events either without (hazard ratios [HR] 2.090, 95% confidence interval [CI] 1.144 to 3.818) or with adjustment for clinical, biochemical and echocardiographic parameters (HR 1.924, 95% CI 1.008 to 3.673). Besides, the addition of albumin, hemoglobin, estimated glomerular filtration rate, proteinuria, left atrial diameter >4.7 cm, left ventricular hypertrophy or left ventricular ejection fraction<50% to the FRS model significantly improves the predictive values for cardiovascular events. In CKD patients, “high” risk categorized by FRS predicts cardiovascular events. Novel biomarkers and echocardiographic parameters provide additional predictive values for cardiovascular events. Future study is needed to assess whether risk assessment enhanced by using these biomarkers and echocardiographic parameters might contribute to more effective prediction and better care for patients.
===================================================================== Cardiac troponin T and C-reactive protein for predicting prognosis, coronary atherosclerosis, and cardiomyopathy in patients undergoing long-term hemodialysis Cardiac troponin T (cTnT) and C-reactive protein (CRP) are prognostic markers in acute coronary syndromes. However, for patients with end-stage renal disease (ESRD) the ability of combinations of these markers to predict outcomes, and their association with cardiac pathology, are unclear. OBJECTIVE: To investigate the association between levels of cTnT and CRP and long-term risk of cardiac pathology and death in patients with ESRD.DESIGN, SETTING, AND PARTICIPANTS:A prospective cohort study initiated February through June 1998 and enrolling 224 patients with ESRD from 5 hemodialysis centers in the Houston-Galveston region of Texas. Levels of cTnT and CRP were analyzed at study entry in patients without ischemic symptoms.MAIN OUTCOME MEASURES:All-cause mortality during a mean follow-up of 827 (range, 29-1327) days. Secondary outcomes in predefined substudies were coronary artery disease (CAD), decreased (< or =40%) left ventricular ejection fraction (LVEF), and presence of left ventricular hypertrophy (LVH).RESULTS:One hundred seventeen (52%) patients died during follow-up. For levels of cTnT and CRP, progressively higher levels predicted increased risk of death compared with the lowest quartile (for cTnT quartile 2: unadjusted hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.2-4.1; quartile 3: HR, 2.7; 95% CI, 1.5-4.9; quartile 4: HR, 3.0; 95% CI, 1.6-5.3. For CRP quartile 2: HR, 0.9; 95% CI, 0.5-1.6; quartile 3: HR, 1.8; 95% CI, 1.1-3.1; quartile 4: HR, 1.8; 95% CI, 1.1-3.2). Both cTnT and CRP remained independent predictors of death after adjusting for a number of potential confounders. The combination of cTnT and CRP results provided prognostic information when patients were divided into groups at or above and below the biomarker medians (high cTnT/high CRP levels vs low cTnT/low CRP levels for risk of death: HR, 2.5; 95% CI, 1.5-4.0). Elevated levels of cTnT, but not CRP, were strongly associated with diffuse CAD (n = 67; 0%, 25%, 50%, and 62% prevalence of multivessel CAD across progressive cTnT quartiles, P<.001). An LVEF of 40% or less was identified in 4 (9%), 3 (8%), 10 (27%), and 7 (19%) of patients across cTnT quartiles (P =.07). No trend for cTnT levels was found among patients with LVH (P =.45); similarly, no trend for CRP was found among patients with LVH (P =.65) or an LVEF of 40% or less (P =.75).CONCLUSIONS: Among stable patients with ESRD, increasing levels of cTnT and CRP are associated with increased risk of death. Furthermore, higher levels of cTnT may identify patients with severe angiographic coronary disease.
===================================================================== Inflammation and cardiovascular events in individuals with and without chronic kidney disease Inflammation and chronic kidney disease predict cardiovascular events. Here we evaluated markers of inflammation including fibrinogen, albumin and white blood cell count in individuals with and without stages 3-4 chronic kidney disease to assess inflammation as a risk factor for adverse events, the synergy between inflammation and chronic kidney disease, and the prognostic ability of these inflammatory markers relative to that of C-reactive protein. Using Atherosclerosis Risk in Communities and Cardiovascular Health Study data, inflammation was defined by worst quartile of at least 2 of these 3 markers. In Cox regression models, inflammation was assessed as a risk factor for a composite of cardiac events, stroke and mortality as well as components of this composite. Among 20 413 patients, inflammation was identified in 3594 and chronic kidney disease in 1649. In multivariable analyses, both inflammation and chronic kidney disease predicted all outcomes, but their interaction was non-significant. In 5597 patients with C-reactive protein levels, inflammation and elevated C-reactive protein had similar hazard ratios. When focusing only on individuals with the worst quartile of white cell count and albumin, results remained consistent.
===================================================================== C-reactive protein and albumin as predictors of all-cause and cardiovascular mortality in chronic kidney disease. Kidney Int 2005; 68: 766–772 C-reactive protein and albumin as predictors of all-cause and cardiovascular mortality in chronic kidney disease.Background High C-reactive protein (CRP) and hypoalbuminemia are associated with increased risk of mortality in patients with kidney failure. There are limited data evaluating the relationships between CRP, albumin, and outcomes in chronic kidney disease (CKD) stages 3 and 4..Methods The Modification of Diet in Renal Disease (MDRD) Study was a randomized controlled trial conducted between 1989 and 1993. CRP was measured in frozen samples taken at baseline. Survival status and cause of death, up to December 31, 2000, were obtained from the National Death Index. Multivariable Cox models were used to examine the relationship of CRP [stratified into high CRP 3.0 mg/L (N = 414) versus low CRP<3.0 mg/L (N = 283)], and serum albumin, with all-cause and cardiovascular mortality..Results Median follow-up time was 125 months, all-cause mortality was 20% (N = 138) and cardiovascular mortality was 10% (N = 71). In multivariable analyses adjusting for demographic, cardiovascular and kidney disease factors, both high CRP (HR, 95% CI = 1.56, 1.07–2.29) and serum albumin (HR = 0.94 per 0.1 g/dL increase, 95% CI = 0.89-0.99) were independent predictors of all-cause mortality. High CRP (HR 1.94, 95% CI 1.13–3.31), but not serum albumin (HR 0.94, 95% CI 0.87–1.02), was an independent predictor of cardiovascular mortality..Conclusion Both high CRP and low albumin, measured in CKD stages 3 and 4, are independent risk factors for all-cause mortality. High CRP, but not serum albumin, is a risk factor for cardiovascular mortality. These results suggest that high CRP and hypoalbuminemia provide prognostic information independent of each other in CKD.
===================================================================== Homocysteine, C-reactive protein, lipid peroxidation and mortality in haemodialysis patients. Nephrol Dial Transplant 2003; 18: 106–112 Background. Cardiovascular disease (CVD) is common in haemodialysis patients with chronic renal insufficiency and is the leading cause of death. The accelerated state of atherosclerosis found in these patients is due to a combination of different mechanisms. Recent studies confirm that inflammation plays an important role in the development of atherosclerosis. However, the role of hyperhomocysteinaemia and the immune response to oxidation of low‐density lipoproteins (LDL) remains unclear and studies show contradictory results. The objective of this study was to determine whether there is a relationship between inflammation, hyperhomocysteinaemia and oxidative stress and whether these CVD risk factors are predictors of mortality in haemodialysis patients.Methods. A prospective follow‐up study was carried out in 94 stable, chronic haemodialysis patients for 24 months (July 1999–July 2001). All the patients were given folic acid and vitamin B complex supplements. Homocysteine was determined by fluorescence polarization immunoassay. C‐reactive protein (CRP) levels were determined by chemiluminescent enzyme‐labelled immunometric assay. Plasma copper oxidized anti‐LDL (oxLDL) antibodies were measured by ELISA using native LDL and oxLDL as antigens.Results. Thirty‐two patients died during the study and 59.3% of the deaths could be attributed to CVD (eight to acute myocardial infarction and 11 to non‐coronary vascular disease). The patients had slight hyperhomocysteinaemia (25.8±7.82 µmol/l), evidence of inflammation (CRP 5.16 mg/l (0.35–88.7)) and oxidative stress (oxLDL antibodies=162±77 optical density at 495 nm ×1000). Age (P<0.01), CRP (P=0.03) and the oxLDL antibody titre (P<0.01) were predictive of mortality. The patients who died from heart disease showed higher oxLDL antibody titres (P=0.03). No correlation was found between homocysteine, CRP and the oxLDL antibody titre, or between serum homocysteine levels and the different causes of mortality.Conclusions. These results suggest that lipid peroxidation and inflammation, but not hyperhomocysteinaemia, are the main risk factors for mortality in haemodialysis patients receiving vitamin supplements. As the study was carried out in a relatively limited number of patients, our findings need to be confirmed in a larger patient population.
25-Hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med 2008 BACKGROUND:Vitamin D deficiency may be involved in the development of atherosclerosis and coronary heart disease in humans.METHODS:We assessed prospectively whether plasma 25-hydroxyvitamin D (25[OH]D) concentrations are associated with risk of coronary heart disease. A nested case-control study was conducted in 18,225 men in the Health Professionals Follow-up Study; the men were aged 40 to 75 years and were free of diagnosed cardiovascular disease at blood collection. The blood samples were returned between April 1, 1993, and November 30, 1999; 99% were received between April 1, 1993, and November 30, 1995. During 10 years of follow-up, 454 men developed nonfatal myocardial infarction or fatal coronary heart disease. Using risk set sampling, controls (n = 900) were selected in a 2:1 ratio and matched for age, date of blood collection, and smoking status.RESULTS:After adjustment for matched variables, men deficient in 25(OH)D (<or=15 ng/mL [to convert to nanomoles per liter, multiply by 2.496]) were at increased risk for MI compared with those considered to be sufficient in 25(OH)D (>or=30 ng/mL) (relative risk [RR], 2.42; 95% confidence interval [CI], 1.53-3.84; P < .001 for trend). After additional adjustment for family history of myocardial infarction, body mass index, alcohol consumption, physical activity, history of diabetes mellitus and hypertension, ethnicity, region, marine omega-3 intake, low- and high-density lipoprotein cholesterol levels, and triglyceride levels, this relationship remained significant (RR, 2.09; 95% CI, 1.24-3.54; P = .02 for trend). Even men with intermediate 25(OH)D levels were at elevated risk relative to those with sufficient 25(OH)D levels (22.6-29.9 ng/mL: RR, 1.60 [95% CI, 1.10-2.32]; and 15.0-22.5 ng/mL: RR, 1.43 [95% CI, 0.96-2.13], respectively).CONCLUSION:Low levels of 25(OH)D are associated with higher risk of myocardial infarction in a graded manner, even after controlling for factors known to be associated with coronary artery disease.
=========================================== Association of activated vitamin D treatment and mortality in chronic kidney disease. Arch Intern Med 2008
Treatment of secondary hyperparathyroidism (SHPT) with activated vitamin D analogues is associated with better survival in patients receiving dialysis. It is unclear whether such a benefit is present in patients with predialysis chronic kidney disease (CKD).METHODS:We examined the association of oral calcitriol treatment with mortality and the incidence of dialysis in 520 male US veterans (mean [SD] age, 69.8 [10.3] years; 23.5% black) with CKD stages 3 to 5 and not yet receiving dialysis (mean [SD] estimated glomerular filtration rate, 30.8 [11.3]). Associations were examined by the Kaplan-Meier method and in Poisson regression models with adjustment for age, race, comorbidities, smoking, blood pressure, body mass index, use of phosphate binders, estimated glomerular filtration rate, proteinuria, white blood cell count, percentage of lymphocytes, and levels of parathyroid hormone, calcium, phosphorus, albumin, bicarbonate, and hemoglobin.RESULTS:Two hundred fifty-eight of 520 subjects received treatment with calcitriol, 0.25 to 0.5 microg/d, for a median duration of 2.1 years (range, 0.06-6.0 years). The incidence rate ratios for mortality and combined death and dialysis initiation were significantly lower in treated vs untreated patients (P < .001 for both in the fully adjusted models). Treatment with calcitriol was associated with a trend toward a lower incidence of dialysis. These results were consistent across different subgroups. CONCLUSIONS:Treatment with the activated vitamin D analogue calcitriol appears to be associated with significantly greater survival in patients with CKD not yet receiving dialysis. Randomized clinical trials are required to verify the causality of these associations and to examine whether similar associations are seen with different activated vitamin D analogues. =========================================== Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 2008; 359: 584–592. Fibroblast growth factor 23 (FGF-23) is a hormone that increases the rate of urinary excretion of phosphate and inhibits renal production of 1,25-dihydroxyvitamin D, thus helping to mitigate hyperphosphatemia in patients with kidney disease. Hyperphosphatemia and low 1,25-dihydroxyvitamin D levels are associated with mortality among patients with chronic kidney disease, but the effect of the level of FGF-23 on mortality is unknown.METHODS:We examined mortality according to serum phosphate levels in a prospective cohort of 10,044 patients who were beginning hemodialysis treatment and then analyzed FGF-23 levels and mortality in a nested case-control sample of 200 subjects who died and 200 who survived during the first year of hemodialysis treatment. We hypothesized that increased FGF-23 levels at the initiation of hemodialysis would be associated with increased mortality.RESULTS:Serum phosphate levels in the highest quartile (>5.5 mg per deciliter [1.8 mmol per liter]) were associated with a 20% increase in the multivariable adjusted risk of death, as compared with normal levels (3.5 to 4.5 mg per deciliter [1.1 to 1.4 mmol per liter]) (hazard ratio, 1.2; 95% confidence interval [CI], 1.1 to 1.4). Median C-terminal FGF-23 (cFGF-23) levels were significantly higher in case subjects than in controls (2260 vs. 1406 reference units per milliliter, P<0.001). Multivariable adjusted analyses showed that increasing FGF-23 levels were associated with a monotonically increasing risk of death when examined either on a continuous scale (odds ratio per unit increase in log-transformed cFGF-23 values, 1.8; 95% CI, 1.4 to 2.4) or in quartiles, with quartile 1 as the reference category (odds ratio for quartile 2, 1.6 [95% CI, 0.8 to 3.3]; for quartile 3, 4.5 [95% CI, 2.2 to 9.4]; and for quartile 4, 5.7 [95% CI, 2.6 to 12.6]). CONCLUSIONS: Increased FGF-23 levels appear to be independently associated with mortality among patients who are beginning hemodialysis treatment. Future studies might investigate whether FGF-23 is a potential biomarker that can be used to guide strategies for the management of phosphorus balance in patients with chronic kidney disease.
=========================================== Dialysis-associated ischemic heart disease: insights from coronary angiography. Kidney Int. 1984;25: 653–659. Dialysis-associated ischemic heart disease: Insights from coronary angiography. We reviewed the records of 44 dialysis patients who had undergone one or more coronary angiograms to determine the frequency with which symptomatic ischemic heart disease (IHD) and significant coronary artery narrowing coincided and to determine those factors which were associated with the coronary atherosclerotic process. Thirty-four patients were catheterized for angina pectoris or myocardial infarction. Of this group, 53% were found to have significant narrowing of coronary arteries. This group was older than the group with trivial or no coronary artery occlusion and their duration of dialysis was shorter. All the patients with significant coronary occlusion were white and the majority were adult males. Discriminant function analysis revealed that the presence of significant coronary artery occlusion could be predicted with high sensitivity and specificity by the following variables: older age, white race, male sex, the presence of symptomatic IHD prior to the onset of dialysis, increased total serum cholesterol, abnormal left ventricular wall motion, and reduced alkaline phosphatase. We also found that the occurrence of symptomatic IHD far exceeded the presence of significant atherosclerotic coronary artery narrowing. We suggest that this may result from several dialysis-associated alterations in oxygen delivery and myocardial oxygen consumption.
Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 2008; 359: 584–592. Fibroblast growth factor 23 (FGF-23) is a hormone that increases the rate of urinary excretion of phosphate and inhibits renal production of 1,25-dihydroxyvitamin D, thus helping to mitigate hyperphosphatemia in patients with kidney disease. Hyperphosphatemia and low 1,25-dihydroxyvitamin D levels are associated with mortality among patients with chronic kidney disease, but the effect of the level of FGF-23 on mortality is unknown.METHODS:We examined mortality according to serum phosphate levels in a prospective cohort of 10,044 patients who were beginning hemodialysis treatment and then analyzed FGF-23 levels and mortality in a nested case-control sample of 200 subjects who died and 200 who survived during the first year of hemodialysis treatment. We hypothesized that increased FGF-23 levels at the initiation of hemodialysis would be associated with increased mortality.RESULTS:Serum phosphate levels in the highest quartile (>5.5 mg per deciliter [1.8 mmol per liter]) were associated with a 20% increase in the multivariable adjusted risk of death, as compared with normal levels (3.5 to 4.5 mg per deciliter [1.1 to 1.4 mmol per liter]) (hazard ratio, 1.2; 95% confidence interval [CI], 1.1 to 1.4). Median C-terminal FGF-23 (cFGF-23) levels were significantly higher in case subjects than in controls (2260 vs. 1406 reference units per milliliter, P<0.001). Multivariable adjusted analyses showed that increasing FGF-23 levels were associated with a monotonically increasing risk of death when examined either on a continuous scale (odds ratio per unit increase in log-transformed cFGF-23 values, 1.8; 95% CI, 1.4 to 2.4) or in quartiles, with quartile 1 as the reference category (odds ratio for quartile 2, 1.6 [95% CI, 0.8 to 3.3]; for quartile 3, 4.5 [95% CI, 2.2 to 9.4]; and for quartile 4, 5.7 [95% CI, 2.6 to 12.6]). CONCLUSIONS: Increased FGF-23 levels appear to be independently associated with mortality among patients who are beginning hemodialysis treatment. Future studies might investigate whether FGF-23 is a potential biomarker that can be used to guide strategies for the management of phosphorus balance in patients with chronic kidney disease.
Cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD) is high, and the presence of CKD worsens outcomes of cardiovascular disease (CVD). CKD is associated with specific risk factors. Emerging evidence indicates that the pathology and manifestation of CVD differ in the presence of CKD. During a clinical update conference convened by the Kidney Disease: Improving Global Outcomes (KDIGO), an international group of experts defined the current state of knowledge and the implications for patient care in important topic areas, including coronary artery disease and myocardial infarction, congestive heart failure, cerebrovascular disease, atrial fibrillation, peripheral arterial disease, and sudden cardiac death. Although optimal strategies for prevention, diagnosis, and management of these complications likely should be modified in the presence of CKD, the evidence base for decision making is limited. Trials targeting CVD in patients with CKD have a large potential to improve outcomes.
Chronic kidney disease1 (CKD) is a worldwide public health problem. In the United States, there is a rising incidence and prevalence of kidney failure, with poor outcomes and high cost. The number of individuals with kidney failure treated by dialysis and transplantation exceeded 320 000 in 1998 and is expected to surpass 650 000 by 2010.1,2 There is an even higher prevalence of earlier stages of CKD (Table 1).1,3 Kidney failure requiring treatment with dialysis or transplantation is the most visible outcome of CKD. However, cardiovascular disease (CVD) is also frequently associated with CKD, which is impor- tant because individuals with CKD are more likely to die of CVD than to develop kidney failure,4 CVD in CKD is treatable and potentially preventable, and CKD appears to be a risk factor for CVD. In 1998, the National Kidney Foundation (NKF) Task Force on Cardiovascular Disease in Chronic Renal Disease issued a report emphasizing the high risk of CVD in CKD.5 This report showed that there was a high prevalence of CVD in CKD and that mortality due to CVD was 10 to 30 times higher in dialysis patients than in the general population (Figure 1 and Table 2).6–18 The task force recommended that patients with CKD be considered in the “highest risk group” for subsequent CVD events and that treatment recommendations based on CVD risk stratification should take into account the highest-risk status of patients with CKD. The major goal of this statement is to review CKD as a risk factor for development of CVD. As background, we shall also review the definition of CKD and classification of stages of severity of CKD, the spectrum of CVD in CKD and differences from the general population, and risk factors for CVD in CKD.
Background—The prognostic importance of renal insufficiency (RI) in patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) has not been well characterized. Methods and Results—PCI was performed in 2082 AMI patients without shock presenting within 12 hours of symptom onset in a prospective, multicenter randomized trial. RI was defined as a calculated (Cockroft-Gault) creatinine clearance (CrCl) 60 mL/min. RI at baseline was present in 18% of patients. Compared with patients without RI, patients with RI were older and were more likely to be female; to have hypertension, peripheral vascular disease, or cerebrovascular disease; and to present in heart failure. Mortality was markedly increased in patients with versus without baseline RI both at 30 days (7.5% versus 0.8%, P0.0001) and at 1 year (12.7% versus 2.4%, P0.0001). Mortality rates increased incrementally for every 10-mL/min decrease in baseline CrCl. By multivariate analysis, reduced baseline CrCl was a powerful independent predictor of 30-day mortality (hazard ratio, 5.77; P0.0001) and remained associated with reduced survival at 1 year (hazard ratio, 1.98; P0.08). Hemorrhagic complications and transfusion requirements were also increased more than 2-fold in patients with RI, as were severe restenosis (diameter stenosis 70%; 20.6% versus 11.8%, P0.024) and infarct artery reocclusion (14.7% versus 7.3%, P0.02). Conclusions—Baseline RI in patients with AMI undergoing primary PCI is associated with a markedly increased risk of mortality, as well as bleeding and restenosis. Novel approaches are needed to improve the otherwise poor prognosis of patients with RI and AMI. (Circulation. 2003;108:2769-2775.)
Chronic kidney disease (CKD) adversely affects cardiovascular outcomes and mortality in the general population. We sought to determine the impact of renal function on angiographic and clinical results in ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (pPCI). Analyses were based on the prospective ‘all-comer’ registry of 1,064 consecutive STEMI patients treated with pPCI in our tertiary centre between February 2001 and October 2002. Admission serum creatinine concentration was known in 894 patients (84%). Mean serum creatinine was 105 ± 27 µmol/L and estimated glomerular filtration rate (eGFR) was 67 ± 18 ml/min/1.73 m2. Thrombolysis in Myocardial Infarction grade 3 (TIMI3) flow was achieved in 751 patients (84%). During hospitalisation, 29 (3%) major bleedings, five (1%) strokes and 12 (1%) re-infarctions occurred. By day 30, two patients were lost to follow-up and 41 (5%) were dead. Renal function was independently associated with 30-day mortality (hazard ratio [HR] 1.6, 95% confidence interval [CI] 1.2–2.1, p=0.003). In CKD patients (eGFR <60 ml/min/1.73 m2), TIMI3 flow was restored less frequently (79% vs. 87%), in-hospital major adverse cardiac and cerebrovascular events (MACCE) were more frequent (15% vs. 4%) and 30-day mortality was higher than in non-CKD patients (9% vs. 2%). Lower eGFR was associated with increased risk of major bleeding (HR 1.6, 95% CI 1.3–2.1, p<0.0005). In the subgroup of conscious patients with normal serum creatinine, eGFR remained significantly associated with 30-day mortality. In conclusion, renal function expressed by eGFR is an independent predictor of procedural success and short-term outcomes in STEMI patients treated with pPCI, even in patients with normal serum creatinine. Thus, eGFR should be estimated in all STEMI patients to help identify a high-risk subgroup.
Introduction Myocardial infarction with persistent ST-elevation (STEMI) continues to be a major public health problem. In a recent report, the incidence of hospital admissions for STEMI in Europe varied between 44 and 142 per 100,000 inhabitants per year, and in-hospital mortality reached 13.5%.1 More than 30% of STEMI patients have chronic kidney disease (CKD).2 On the other hand, half of deaths in advanced CKD patients are of cardiovascular causes with myocardial infarction (MI) being the most frequent event.3 Patients with CKD are routinely excluded from cardiovascular clinical trials, and certain medications and treatment modalities are less frequently employed in this group;4 often these patients are treated less aggressively, possibly making proven life-saving therapies underused in this population.5 The objective of this study was to evaluate the impact of renal function on angiographic and short-term clinical outcomes in a homogenous, real-life cohort of patients with STEMI treated with primary percutaneous coronary intervention (pPCI), as this has not been extensively studied so far. Methods Study design and patient population This prospective, observational, single-centre study was conducted at the Institute of Cardiology in Warsaw (Anin). All consecutive patients with STEMI (diagnosed according to European Society for Cardiology [ESC]/American College of Cardiology [ACC] guidelines current at the time6) treated with pPCI between February 2001 and October 2002 were included in a prospective registry (ANIN Myocardial Infarction Registry). There were no exclusion criteria; in particular, patients with cardiogenic shock, pulmonary oedema, known renal failure or advanced age were not excluded. The study complies with the Declaration of Helsinki and the ethics committee approved its research protocol. Clinical setting The Institute of Cardiology in Warsaw is a tertiary cardiology centre performing about 4,000 coronary angiographies and 2,500 PCIs, including about 700 pPCI for STEMI, per year, where round-the-clock interventional duty for acute coronary syndrome patients was started in February 2001. The majority of patients were transferred to our centre from non-PCI hospitals. Informed consent for interventional procedures was obtained in the emergency department, and patients were transported directly to the cath lab (not via the cardiac care unit [CCU]). The aim was to reduce door-to-balloon time. Blood samples for baseline serum creatinine were drawn from the arterial sheath prior to contrast administration. The operator was unaware of the lab results while performing the procedure. Primary angioplasty was performed in all patients in accordance with generally accepted standards. At the time of this study, the pre-procedure protocol included a loading dose (300–500 mg orally) of acetylsalicylic acid. Unfractionated heparin (bolus intravenous injection of 100 IU per kg body weight or 70 IU if prophylactic abciximab was planned) and a loading dose of clopidogrel (at that time 300 mg orally) were usually given at the start of the procedure. Prophylactic abciximab use was left to the discretion of the operator. Reperfusion success was defined as a Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow. Data collection Baseline demographic, clinical, laboratory and angiographic data were collected on admission and angiographic data on completion of the pPCI using pre-printed forms. Data regarding in-hospital course (death, major bleeding, stroke, re-infarction) were obtained from patients’ charts. Major adverse cardiac and cerebrovascular events (MACCEs) were defined according to the approved criteria (in particular, major bleeding as in TIMI bleeding score, and re-infarction as in the GUSTO-I trial). Vital status at 30 days was established by telephone calls to patients or their cardiologists. Missing data were obtained from the National Census Registry. A dedicated computerised database was set up and regularly updated. Estimation of renal function Renal function was assessed by estimation of glomerular filtration rate (eGFR) using abbreviated Modification of Diet in Renal Disease formula, as recommended by the National Kidney Foundation: eGFR = 32,788 × (serum creatinine)–1.154 × age–0.0203 × (1.210 if black) × (0.742 if female). Patients were staged according to Kidney Disease Outcomes Quality Initiative (K-DOQI) guidelines.7 CKD was defined as eGFR below 60 ml/min/1.73 m2 with or without evidence of kidney damage. The clinical laboratory at our institution reported creatinine values greater than 133 µmol/L as abnormal for either gender. Statistics Typical statistical methods were used. Continuous data were expressed as means ± standard deviation (SD) and categorical data as numeric values and percentages. Additionally, age was expressed as a range. Comparison of continuous variables was performed by means of student t-test. Chi square test or Fisher exact test was used for comparison of categorical variables, as appropriate. Time-to-event data were summarised as Kaplan–Meier estimates and compared with log-rank test. To adjust for baseline differences between study groups, all variables associated with the clinical end points at univariate analysis (p<0.1 for selection) were tested in multi-variate analyses; Cox proportional hazards model and logistic regression were used to identify independent predictors of mortality and final TIMI grade 3 flow, respectively (tested variables were sex, age, history of hypertension, diabetes mellitus, smoking status, prior MI or PCI, heart rate [HR] and systolic blood pressure [SBP] on admission, eGFR, Killip class, localisation of MI, abciximab usage, multi-vessel disease [MVD], initial TIMI grade flow and final TIMI grade flow exclusively for mortality). Final models were built by forward stepwise variable selection, with a p value <0.05 used as a criterion for entry and p >0.1 for removal of variables. Results were presented as hazard ratios (HRs) with 95% confidence intervals (CIs). All reported p values are two-tailed, and a p value <0.05 was considered statistically significant unless otherwise specified. All statistical analyses were carried out using the Statistical Package for Social Sciences version 15.0 (SPSS Inc., Chicago, IL, USA). Results Baseline characteristics In 894 of 1,064 consecutive patients enrolled in the registry, blood samples for baseline serum creatinine (SCr) were taken before the administration of the contrast media, and they formed the study group. The baseline characteristics of studied patients are shown in table 1. Angiographic and procedural characteristics and outcomes Angiographic characteristics and procedural results were typical for a cohort of STEMI patients treated with pPCI. Most often the infarct-related artery (IRA) was the right coronary artery. More than half of patients had multi-vessel disease (MVD). On the initial angiography, TIMI 0 or 1 flow in the IRA was observed in 732 patients (82%). In most patients, only the IRA was treated, and the majority of procedures (78%) included stent implantation. Abciximab was given in almost 50% of patients, mostly prophylactically. Final TIMI grade 3 flow was achieved in 751 cases (84%). CKD patients had MVD more often (60% vs. 48%, p=0.004), and received stents less often (73% vs. 80%, p=0.03). They required intra-aortic balloon pump (IABP) more frequently (3% vs. 1%, p=0.02) and had a lower procedural success rate (79% vs. 87%, p=0.004) when compared with patients with normal renal function. The independent predictors of procedural failure (final TIMI grade <3), after adjustment for covariates, were decreased eGFR (HR 1.1, 95% CI 1.0–1.3, p=0.01), initial TIMI flow <2 (HR 2.9, 95% CI 1.6–5.6, p=0.001) and history of smoking (HR 2.5, 95% CI 1.7–3.3, p<0.0005). Clinical outcomes During a mean of 8 ± 7 days of hospitalisation, MACCEs occurred in 69 patients (8%). Vital status at day 30 was known in 892 out of 894 patients. Forty-one patients (5%) died by day 30. Major bleeding was significantly associated with renal function. Any decrease in eGFR by 10 ml/min/1.73 m2 increased the risk of major bleeding (HR 1.6, 95% CI 1.3–2.1, p<0.0005). Frequency of re-infarction or stroke was not statistically different with regard to eGFR. Both mortality and MACCE rates increased in higher stages of CKD (table 2). Cumulative mortality was higher in higher stages of CKD as demonstrated by Kaplan–Meier method (figure 1). Prognostic factors for short-term mortality After adjustment for covariates, 30-day mortality was significantly associated with eGFR (HR 1.6, 95% CI 1.2–2.1, p=0.001 for each 10 ml/min/1.73 m2), age (HR 1.1, 95% CI 1.0–1.1, p=0.005 for each 10 years), prior PCI (HR 5.8, 95% CI 1.7–20.0, p=0.005), unconscious state (HR 18.6, 95% CI 6.7–51.8, p<0.0005) and use of IABP (HR 40.0, 95% CI 9.7–166.7, p<0.0005). After exclusion of unconscious patients from the analyses, eGFR continued to demonstrate statistically significant independent association with short-term mortality (HR 1.6, 95% CI 1.2–2.3, p=0.004). Estimated GFR remained an independent predictor of short-term mortality in conscious patients with serum creatinine within normal range (HR 1.8, 95% CI 1.16–2.75, p=0.009 for each 10 ml/min/1.73 m2). Discussion The main finding of our study was that every decrease in kidney function as measured by eGFR in STEMI patients was associated with adverse outcomes, even if serum creatinine was within normal range. Thus, eGFR should be considered a continuous parameter, which influences prognosis without any specific cut-off value. Over one-third of our STEMI patients were in stage 3 or 4 of renal disease. Prevalence of CKD (particularly stage 4) among our patients was higher than in randomised clinical trials,8 in which patients with CKD were systematically excluded, and was similar to that found in registries.2,9 One must, however, bear in mind significant variability of definitions of renal dysfunction employed by different studies.10 Of note, many authors used serum creatinine rather than the eGFR recommended by the National Kidney Foundation.7 In the whole cohort of patients, the 30-day mortality rate was relatively low (5%). This could be due to short ‘door-to-balloon time’, which is a recognised prognostic factor.11 This was achieved through round-the-clock presence of an interventional cardiologist on the premises, as opposed to on-call duty, and direct transfer of patients from admissions to the cath lab rather than via CCU. Despite the fact that we included all consecutive patients, regardless of haemodynamic status and renal function, angiographic success was obtained in more than 80% of patients. As a result, prevalence of in-hospital MACCEs was low. This could be an explanation for no significant difference in re-infarction and stroke between groups in different CKD stages. The adverse impact of renal impairment on mortality in various cardiovascular diseases has been previously published by several authors.12 Coronary revascularisation procedures, both surgical and percutaneous, were also shown to have worse results in CKD patients than in patients with normal renal function.13 This might be partly explained by the relatively common co-existence of CKD and atherosclerosis, as most of the classical risk factors for these conditions are shared, e.g. age, diabetes, hypertension, obesity, smoking and dyslipidaemia.14 To make it even worse, kidney failure speeds up development of atherosclerosis; such patients have more extensive coronary and peripheral artery disease, e.g. more often have MVD.15 In our study, it was shown that CKD need not be severe or even mild, as demonstrated in a recent study,16 to worsen the prognosis. Mild decrease of eGFR, even within normal range, was also of importance and, actually, any drop in this parameter worsened the prognosis without a specific cut-off value. We noted more bleeding events in the CKD group. Correlation of renal impairment with bleeding disorders is a well-recognised issue.17 Renal failure may be associated with uraemic platelet dysfunction and decreased thrombopoiesis.18 It also causes impaired aggregability in response to such thrombogenic triggers as adenosine diphosphate (ADP), collagen and epinephrine. In addition to traditional cardiac risk factors, which are highly prevalent in patients with CKD, CKD patients exhibit marked nephroangiosclerosis (intimal hyperplasia, hyalinosis, smooth muscle cell hypertrophy),19 abnormal coronary flow reserve, inflammation, oxidative stress, insulin resistance, accelerated vascular calcification, activation of the renin–angiotensin system, anaemia and vitamin D deficiency, which might contribute directly to adverse outcomes. Moreover, endothelial dysfunction and chronic inflammation, which play an important role in atherothrombosis, are present even with mild impairment of renal function. This may lead to a worse prognosis, not only in patients with early stages of CKD,16 but also in patients with normal renal function, as was demonstrated in our study. The available data on immediate angiographic results of pPCI in STEMI patients with different degrees of kidney failure is inconclusive. However, in some studies, similar to ours, angiographic success rate has been shown to differ between stages of kidney disease.20 It may be related to the combined effect of endothelial dysfunction and higher extent of atherosclerosis. Both in vivo and in vitro studies performed on microvessels obtained from patients with advanced CKD confirmed dysfunction of their endothelium.21 Adverse outcomes in MI patients associated with depressed renal function have already been reported.22 However, there are three features that, taken all together, differentiate our study from the previous. First, it was conducted in a homogenous, single centre cohort of STEMI patients that received uniform treatment. Therefore, the potential influence of some confounding factors (such as diagnosis: non-ST-segment elevation MI [NSTEMI] vs. STEMI, type of treatment: interventional vs. fibrinolytic, experience of the centre, volume of procedures, different algorithms of management of STEMI patients) was avoided. Furthermore, and in opposition to most other studies,7 our population is unselected and represents a high prevalence of kidney disease. It reflects frequency of CKD among acute coronary syndrome in real-life practice.23 All patients received modern reperfusion therapy, without any pre-selection based on renal function or other variables (pPCI with high rate of stenting and abciximab usage). Finally, some prior studies,24 have used serum creatinine rather than the eGFR to detect renal function. The accuracy of serum creatinine level as a marker of renal function is limited, owing to nonlinear associations with eGFR that vary according to age, sex and race.25 We found that the prognostic significance of renal function expressed by eGFR was also present in a subgroup of patients with serum creatinine within the normal range. Thus, eGFR should be determined in all patients with STEMI. Several limitations should be considered when interpreting our results. This was a single-centre study, which may cause an unrecognised bias normally avoided in multi-centre analyses. We had no information about baseline serum creatinine in 170 patients, however, mortality in this excluded subgroup was not significantly different from the study population. We also had no knowledge about renal function before index STEMI, therefore, we were not able to distinguish between the types of renal dysfunction (acute vs. chronic). We were not able to demonstrate the association between renal function and incidence of re-infarction or stroke due to low numbers of events. Adjunctive therapy used at the time of the study differed from the present routine. Although acetylsalicylic acid was given pre-hospital, most of the patients received heparin and clopidogrel only during the procedure and not in the ambulance or in the referring hospital. The loading dose of clopidogrel was 300 mg, and not 600 mg as later recommended in STEMI patients. For obvious reasons newer antiplatelet agents (e.g. prasugrel, ticagrelor), drug-eluting stents or thrombectomy were not used at that time. In conclusion, renal function expressed by eGFR is an independent predictor of procedural success and short-term outcomes in STEMI patients treated with pPCI, even in patients with normal serum creatinine. Thus, eGFR should be estimated in all STEMI patients to help identify a high-risk subgroup. Acknowledgement This work was presented in part at the Congress of the European Society of Cardiology in Stockholm, Sweden, on August 31, 2010. [P4562] Conflict of interest None declared. Key message Renal function expressed by eGFR is an independent predictor of procedural success and short-term outcomes in STEMI patients treated with pPCI. References Widimsky P, Wijns W, Fajadet J et al. Reperfusion therapy for ST elevation acute myocardial infarction in Europe: description of the current situation in 30 countries. Eur Heart J 2010;31:943–57. http://dx.doi.org/10.1093/eurheartj/ehp492 Fox CS, Muntner P, Chen A et al. Use of evidence-based therapies in short-term outcomes of ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction in patients with chronic kidney disease. A report from the National Cardiovascular Data Acute Coronary Treatment and Intervention Outcomes Network Registry. Circulation 2010;121:357–65. http://dx.doi.org/10.1161/CIRCULATIONAHA.109.865352 Ojo A, Hanson JA, Wolfe RA et al. Long-term survival in renal transplant recipients with graft function. Kidney Int 2000;57:307–13. http://dx.doi.org/10.1046/j.1523-1755.2000.00816.x Charytan D, Kuntz RE. The exclusion of patients with chronic kidney disease from clinical trials in coronary artery disease. Kidney Int 2006;70:2021–30. http://dx.doi.org/10.1038/sj.ki.5001934 Dumaine R, Montalescot G, Steg G et al. Renal function, atherothrombosis extent, and outcomes in high-risk patients. Am Heart J 2009;158:141–8. http://dx.doi.org/10.1016/j.ahj.2009.05.011 Antman E, Bassand JP, Klein W et al. Myocardial infarction redefined – a consensus document of The Joint European Society of Cardiology/American College of Cardiology committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000;36:959–69. http://dx.doi.org/10.1016/S0735-1097(00)00804-4 Levey AS, Coresh J, Balk E et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39(2 suppl 1):S1–S266. http://dx.doi.org/10.1016/S0272-6386(02)70081-4 Kim JY, Jeong MH, Ahn YK et al. Decreased glomerular filtration rate is an independent predictor of in-hospital mortality in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Korean Circ J 2011;41:184–90. http://dx.doi.org/10.4070/kcj.2011.41.4.184 El-Menyar A, Zubaid M, Sulaiman K et al. In-hospital major clinical outcomes in patients with chronic renal insufficiency presenting with acute coronary syndrome: data from a registry of 8176 patients. Mayo Clin Proc 2010;85:332–40. http://dx.doi.org/10.4065/mcp.2009.0513 Polonski L, Gasior M, Gierlotka M et al. Polish registry of acute coronary syndromes (PL-ACUTE CORONARY SYNDROME). Characteristics, treatments and outcomes of patients with acute coronary syndromes in Poland. Kardiol Pol 2007;65:861–72; discussion 873–4. McNamara R, Wang Y, Herrin J et al. Effect of door-to-balloon time on mortality in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol 2006;47:2180–6. http://dx.doi.org/10.1016/j.jacc.2005.12.072 Beddhu S, Allen-Brady K, Cheung A et al. Impact of renal failure on the risk of myocardial infarction and death. Kidney Int 2002;62:1776–83. http://dx.doi.org/10.1046/j.1523-1755.2002.00629.x Anderson RJ, O’Brien M, MaWhinney S et al. Renal failure predisposes patients to adverse outcome after coronary artery bypass surgery. VA Cooperative Study #5. Kidney Int 1999;55:1057–62. http://dx.doi.org/10.1046/j.1523-1755.1999.0550031057.x Sarnak MJ, Levey AS, Schoolwerth AC et al. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 2003;108:2154–69. http://dx.doi.org/10.1161/01.CIR.0000095676.90936.80 Yogi H, Kawai M, Komura K et al. Impact of chronic kidney disease on the severity of initially diagnosed coronary artery disease and the patient prognosis in the Japanese population. Heart Vessels 2011;26:370–8. http://dx.doi.org/10.1007/s00380-010-0061-9 Campbell NG, Varagunam M, Sawhney V et al. Mild chronic kidney disease is an independent predictor of long-term mortality after emergency angiography and primary percutaneous intervention in patients with ST-elevation myocardial infarction. Heart 2012;98:42–7. http://dx.doi.org/10.1136/heartjnl-2011-300024 Steg PG, Huber K, Andretti F et al. Bleeding in acute coronary syndromes and percutaneous coronary interventions: position paper by the Working Group on Thrombosis of the European Society of Cardiology. Eur Heart J 2011;32:1854–64. http://dx.doi.org/10.1093/eurheartj/ehr204 Norris, Benign A, Bacardi P et al. Enhanced nitric oxide synthesis in uremia: implications for platelet dysfunction and dialysis hypotension. Kidney Int 1993;44:445–50. http://dx.doi.org/10.1038/ki.1993.264 Perticone F, Maio R, Tripepi G, Zoccali C. Endothelial dysfunction and mild renal insufficiency in essential hypertension. Circulation 2004;110:821–5. http://dx.doi.org/10.1161/01.CIR.0000138745.21879.27 Rubenstein MH, Harrell LC, Sheynberg BV et al. Are patients with renal failure good candidates for percutaneous coronary revascularization in the new device era? Circulation 2000;102:2966–72. http://dx.doi.org/10.1161/01.CIR.102.24.2966 Morris STW, McMurray JJV. Impaired endothelial function in isolated human uremic resistance arteries. Kidney Int 2001;60:1077–82. http://dx.doi.org/10.1046/j.1523-1755.2001.0600031077.x Anavekar NS, McMurray JJ, Velazquez EJ et al. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med 2004;351:1285. http://dx.doi.org/10.1056/NEJMoa041365 Reddan DN, Szczech LA, Tuttle RH et al. Chronic kidney disease, mortality, and treatment strategies among patients with clinically significant coronary artery disease. J Am Soc Nephrol 2003;14:2373–80. http://dx.doi.org/10.1097/01.ASN.0000083900.92829.F5 Saltzman AJ, Stone GW, Claessen BE et al. Long-term impact of chronic kidney disease in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention: the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial. JACC Cardiovasc Interv 2011;4:1011–19. http://dx.doi.org/10.1016/j.jcin.2011.06.012 McClatchey KD. Clinical laboratory medicine. Second edition. Philadelphia: Lippincott Williams & Wilkins, 2002.
Background—Patients with end-stage renal disease undergoing conventional balloon angioplasty have reduced procedural success and increased complication rates. This study was designed to determine the immediate and long-term outcomes of patients with varying degrees of renal failure undergoing percutaneous coronary intervention in the current device era. Methods and Results—We compared the immediate and long-term outcomes of 362 renal failure patients (creatinine 1.5 mg/dL) with those of 2972 patients with normal renal function who underwent percutaneous coronary intervention between 1994 and 1997. Patients with renal failure were older and had more associated comorbidities. They had reduced procedural success (89.5% versus 92.9%, P0.007) and greater in-hospital combined major event (death, Q-wave myocardial infarction, emergent CABG; 10.8% versus 1.8%; P0.0001) rates. Renal failure was an independent predictor of major adverse cardiac events (MACEs) (OR, 3.41; 95% CI, 1.84 to 6.22; P0.00001). Logistic regression analysis identified shock, peripheral vascular disease, balloon angioplasty strategy, and unstable angina as independent predictors of in-hospital MACEs in the renal group. Compared with 362 age- and sex-matched patients selected from the control group, patients with renal failure had a lower survival rate (27.7% versus 6.1%, P0.0001) and a greater MACE rate (51% versus 33%, P0.001) at long-term follow-up. Cox regression analysis identified age and PTCA strategy as independent predictors of long-term MACEs in the renal group. Finally, within the renal failure population, the dialysis and nondialysis patients experienced remarkably similar immediate and long-term outcomes. Conclusions—Although patients with renal failure can be treated with a high procedural success rate in the new device era, they have an increased rate of major events both in hospital and at long-term follow-up. Nevertheless, utilization of stenting and debulking techniques improves immediate and long-term outcomes. (Circulation. 2000;102:2966-2972.)
In-Hospital Results Procedural success and in-hospital outcomes are shown in Table 4. Procedural success was lower in the renal group than in the control and the matched groups. MACE rate was greater in the renal group than in the control and the matched groups. This difference was entirely attributable to an in- creased death rate in the renal group. There was no statisti- cally significant difference in emergent CABG or Q-wave myocardial infarction among the 3 groups of patients. When patients in cardiogenic shock were excluded from the analy- sis, the MACE rate decreased to 6.0% but was still signifi- cantly higher than for either the control or matched group (6.0%, 1.4%, and 1.7% for the renal, control, and matched groups, respectively; P0.001). In addition, renal patients had a higher incidence of blood transfusion and vascular repair. Median postprocedure length of hospital stay was greater in the renal group than in the control and the matched groups. Finally, there were no statistically significant differ- ences in in-hospital outcomes between the dialysis patients and the remainder of the renal group (Table 5). Again, in-hospital MACE rate was almost entirely a function of mortality, with a negligible contribution from emergent CABG and Q-wave myocardial infarction. Predictors of In-Hospital MACE in theRenal GroupCardiogenic shock (OR, 17.7; 95% CI, 6.1 to 56.9; P0.00001), conventional balloon angioplasty strategy (OR, 4.38; 95% CI, 1.4 to 19.4; P0.02), presence of vascular disease (OR, 2.89; 95% CI, 1.1 to 8.0; P0.03), and unstable angina (OR, 0.11; 95% CI: 0.02 to 0.4; P0.004) were identified as independent predictors of in-hospital MACE rates in the renal failure group. Of note, diabetes mellitus was not an independent predictor of in-hospital MACE in patients with renal failure.
Long-Term Follow-Up Results Long-term follow-up outcomes are shown in Table 6. Follow-up information was successfully obtained in 78.7% of the renal group patients and in 77.8% of the matched group patients (PNS). Follow-up MACE rate was significantly greater in the renal group than in the control group. This difference was due to an increased rate of mortality and myocardial infarction in the renal group. Kaplan-Meier analysis showed that both survival (Figure 1) and event-free survival (Figure 2) were significantly worse in the renal failure group. One-year actuarial survival was lower for the renal than the matched group (75% [95% CI, 70 to 80] versus 97% [95% CI, 93 to 99], P0.00001). One-year actuarial event-free survival was also lower for the renal than the matched group (55% [95% CI, 49 to 61] versus 78% [95% CI, 71 to 84], P0.00001). The curves separated very early after the index procedure and continued to diverge over the course of follow-up, with a steeper slope noted in the initial 6 to 10 months. The incidence rate of survival was 0.16% and 1.97% for the renal and the matched groups, respectively (P0.00001). The incidence rate of event-free survival was 1.07% and 4.53% for the renal and the matched groups, respectively (P0.00001). Cox regression analysis identified age 74 years (RR, 1.8; 95% CI, 1.3 to 2.5; P0.001), PTCA strategy (RR, 1.7; 95% CI. 1.1 to 2.5; P0.01), and female sex (RR, 1.4; 95% CI, 1.0 to 2.0; P0.07) as independent predictors of MACE at long-term follow-up in the renal group. Finally, long-term outcomes were similar in the dialysis patients compared with the remainder of the renal population. Follow-up information was obtained in 74% of the dialysis patients compared with 78% in the nondialysis renal population (PNS). Kaplan-Meier analyses showed no statistically signif- icant difference in survival or event-free survival between the dialysis and nondialysis renal failure patients (Figure 3).
Discussion The present study demonstrates that patients with varying degrees of renal failure can be treated with a high procedural success rate in the current era of percutaneous coronary revas- cularization. However, despite this high procedural success rate, these patients continue to suffer significant in-hospital and long-term morbidity and mortality. Importantly, utilization of stenting and debulking techniques improves immediate and long-term outcomes in this complicated patient population. Although coronary revascularization in end-stage renal dis- ease patients has been studied extensively in the past decade, little is known about the impact of coronary intervention on the complex and diverse population of patients with varying degrees of renal failure.3-7,17,18 In our study, 92.5% of the patients with renal failure were not on chronic dialysis. Additionally, the renal failure cohort constitutes 11% of the entire population undergo- ing PCI at our institution during the study period. A thorough assessment of the characteristics, outcomes, and predictors of failure or success in this growing population is long overdue. The renal failure population was a high-risk group. They were older and presented more frequently with clinical syndromes associated with increased periprocedural complications, such as diabetes, hypertension, chronic obstructive pulmonary disease, congestive heart failure, cardiogenic shock, multivessel coronary artery disease, history of previous myocardial infarction, a history of previous CABG, and a higher incidence of saphenous vein graft and AHA/ACC type C lesion interventions. Consequently, compared with patients with normal renal function, renal failure patients exhibit inferior immediate and long-term outcomes. They have a lower procedural success rate, increased in-hospital MACE rates, and increased noncardiac postprocedural complications. Interestingly, these inferior results are present within both the dialysis cohort and the nondialysis cohort, with no statistically significant differences. These poor outcomes in the overall renal failure population are largely the result of complex lesion morphology and the multitude of comorbid conditions previously identified as factors associated with an increased risk during PCI.15,19 Thus, renal failure is a marker for clinical and morphological characteristics associated with lower chances of successful percutaneous intervention and a higher incidence of in-hospital and follow-up adverse events. Nevertheless, complex lesion morphology and comorbidities do not solely account for the poor outcomes in patients with renal failure. We identified renal disease itself as an independent predictor of in-hospital MACE. In fact, renal disease was the strongest predictor after cardiogenic shock and increased age. Furthermore, this finding was independent of the increased incidence of diabetes mellitus in the renal failure population. Over the last decade, new lesion-specific coronary devices have resulted in improved angiographic outcomes for complex lesions.11-13 Because patients with renal failure have a higher incidence of complex coronary lesion morphology, which is less amenable to conventional balloon angioplasty,8 these new de- vices may offer hope to this population. In our study, percutaneous interventional methods changed considerably during the period of observation. In particular, over the 3 years analyzed in the present study, we witnessed the evolution of stent utilization from its limited initial role to its current widespread use. In our population, stent placement in our overall population increased from 12.9% in 1994 to 70% by the beginning of 1997, thus overtaking conventional balloon angioplasty as the principal coronary interventional strategy. Regression analysis showed that those patients who received stents were significantly less likely to experience an adverse outcome. A similar trend was observed in the renal group during this time period, as stent utilization increased from 9% in 1994 to 56% by the beginning of 1997. This increase in stent utilization in the renal group was associated with a concurrent increase in procedural success from 84% to 95%. Regression analysis identified the use of conventional balloon angioplasty strategy as an independent predictor of in-hospital MACE rates in the renal failure group. In fact, it was the second strongest predictor of a poor outcome after cardiogenic shock. Thus, the use of new devices (ie, stenting and debulking techniques) improves out- comes in the renal failure population. The long-term results of our patients with renal failure were also inferior compared with a matched group of patients with normal renal function. Despite a high initial procedural success rate, the renal group experienced a significantly lower survival and event-free survival compared with the matched group. These inferior long-term outcomes were experienced by both the dialysis and nondialysis patients within the renal failure popu- lation, as evidenced by their almost superimposable Kaplan- Meier curves. Increased rates of mortality and myocardial infarction in the renal population accounted for the disparity between the 2 groups. This difference was evident very early after the index procedure and continued to increase over the course of follow-up. Again, in the renal group, regression analysis identified PTCA strategy as the second strongest pre- dictor of long-term follow-up MACE after age 74 years. Thus, new devices not only affect procedural success and in-hospital outcomes but also improve long-term outcomes. With the advent of advanced stent technology, greater experience with combined debulking-stenting techniques,20,21 ongoing and exciting devel- opment of coronary brachytherapy,22,23 and the use of adjunctive pharmacological therapy,24,25 we expect that the outcomes of renal failure patients undergoing PCI will continue to improve. Study Limitations The present study is a retrospective analysis based on data from our registry. The matched group was a computer- generated match of the renal failure patients by age and sex. We obtained follow-up information from telephone inter- views with patients and their family members for 78% of patients in both the renal and matched groups. Because it is possible that patients may have been lost to follow-up as a result of an adverse event, we may have underestimated the long-term follow-up rates. However, a similar percentage of patients was lost to follow-up in both groups. Furthermore, we compared baseline characteristics of the patients lost to follow-up with those of the entire group and found no appreciable differences.
Angiographic analysis. Patients with a lower creatinine clearance more frequently had multivessel disease, vein graft disease, more complex lesions (according to the modified American College of Cardiology/American Heart Associa- tion classification) and greater use of rotational atherectomy (Table 2). Glycoprotein IIb/IIIa inhibitors were given before or during the procedure in 24.4% of the interventions, with no difference in the frequency of use of these agents in the different creatinine clearance groups. A dis- section occurred 20.6% of the time, and the frequency was similar in all groups (p 0.60). The angiographic success rate was similar in the groups. However, patients with a lower creatinine clearance and those on dialysis had more frequent complications, including death, non–Q-wave MI or the need for CABG during the hospital period, and thus the procedural success rate was lower. Furthermore, those patients with a lower creatinine clearance were less likely to have been completely revascularized after the procedure. The frequency of adverse events in the hospital and at one-year follow-up is shown in Table 3. Patients with a lower creatinine clearance had an increased risk of death or MI (both Q-wave and non–Q-wave) in the hospital and in the year following the procedure, both including and ex- cluding the in-hospital events. Of note, the marked increase in the frequency of in-hospital death in the lower creatinine clearance groups and in dialysis patients was associated with only a small increase in both Q-wave and non–Q-wave MI. Furthermore, there was a marked increase in acute renal failure in the lower creatinine clearance groups. The Kaplan-Meier curves demonstrating mortality and cardiac mortality are shown in Figures 1 and 2. The mean follow-up time was 2.7 1.6 years. These figures demonstrate that creatinine clearance was significantly associated with mor- tality and cardiac mortality in patients after successful PCI. Using a univariate model, the risk ratios (RR) for death after successful PCI were significant (p 0.001) for all of the following variables: creatinine clearance in 10-ml/min units (RR 0.75, 95% confidence interval [CI] 0.7 to 0.8), age in 10-year units (RR 1.61, 95% CI 1.5 to 1.8), weight in 10-kg units (RR 0.86, 95% CI 0.8 to 0.9), diabetes (RR 2.43, 95% CI 2.0 to 2.9), previous MI (RR 1.68, 95% CI 1.4 to 2.0), previous stroke or transient ischemic attack (RR 2.09, 95% CI 1.7 to 2.7), congestive heart failure on presentation (RR 5.19, 95% CI 4.2 to 6.4), peripheral vascular disease (RR 2.93, 95% CI 2.4 to 3.6), multivessel disease (RR 1.94, 95% CI 1.6 to 2.3), right coronary artery intervention (RR 0.65, 95% CI 0.5 to 0.8) and vein graft intervention (RR 2.44, 95% CI 1.9 to 3.0). In the multi- variate model (Table 4), the RR of death during follow-up was highest for dialysis patients, followed by patients with moderate renal dysfunction (creatinine clearance 50 ml/ min). Moderate or severe renal insufficiency was associated with a greater risk of death than even diabetes. The association between renal dysfunction and death was dose- dependant. The use of a stent was not a significant factor in the multivariate model (p 0.10).
DISCUSSION The principal finding of this study is that renal dysfunction significantly increases the risk of death and cardiac death during and after PCI in a dose-dependent manner. Even mild renal insufficiency (creatinine clearance 70 ml/min) has an important association with one-year mortality (relative risk 1.46) and is nearly as predictive as diabetes mellitus. Moderate renal failure (creatinine clearance 50 ml/min) has a higher association with death than any variable, except for congestive heart failure on presentation. Severe renal failure has the highest association with one-year mortality, in both patients not requiring dialysis (creatinine clearance 30 ml/ min) and those on dialysis (relative risk 3.70 and 8.91, respectively). In this study, the use of a stent did not significantly alter the high mortality of patients with renal insufficiency. Renal failure and cardiovascular risk factors. The asso- ciation between renal failure and CAD is well established, but the precise mechanisms of this interaction are not clearly understood. Explanations of this interaction include the greater frequency of risk factors, such as diabetes mellitus and hypertension, in patients with renal insufficiency, as well as the effects of renal failure on lipids, oxidative stress, homocysteine and fibrinogen (7–10). Diabetes mellitus and hypertension are the leading causes of end-stage renal disease (11). Previous studies have dem- onstrated that the increased prevalence of CAD in patients on dialysis or with chronic renal insufficiency is partly due to the increased presence of these well-established cardiac risk factors (7,12,13). In our study, patients with renal dysfunc- tion had a greater number of diseased coronary vessels. Diabetes mellitus and hypertension were associated with progressive renal dysfunction and also with the extent and severity of CAD. However, when renal failure is treated with renal transplantation, the risk of future cardiovascular events decreases, despite the persistence of these high-risk characteristics (1). Thus, advanced renal dysfunction inde- pendently contributes to cardiovascular mortality and in- creased cardiac risk. In our study, even mild renal insuffi- ciency doubled the risk of death at one year. Despite the association of diabetes mellitus and hyper- tension with renal dysfunction, our study did not identify an association with hyperlipidemia (defined as total cholesterol 240 mg/dl). Although total cholesterol levels were not increased with renal dysfunction in our study population, lipid profiles tend to be more atherogenic in patients with renal insufficiency, even when patients are not hyperlipid- emic (14,15). Renal dysfunction increases homocysteine and oxidative stress, which enhance the oxidation of low-density lipoprotein, making it even more atherogenic (16,17). Hy- perhomocysteinemia also promotes atherosclerotic plaque formation by increasing free apolipoprotein(a) (9,18). Thus, regardless of the similar rates of hyperlipidemia between the groups in our study, the atherogenic risk of cholesterol is higher in patients with renal dysfunction. Percutaneous coronary interventions in patients with chronic renal failure. Management of CAD in patients on dialysis or with mild renal insufficiency is more difficult than that in patients with normal renal function. Medical man- agement in patients with renal dysfunction has been based on therapy shown to be beneficial in other patient popula- tions. Currently, these medications include aspirin, beta- blockers, nitrates, hydroxymethylglutaryl coenzyme A re- ductase inhibitors (statins) and angiotensin-converting enzyme inhibitors. However, because of the routine exclu- sion of this patient population from clinical trials, the efficacy of these agents in patients with renal dysfunction is not proven. Treatment of CAD by PCI in patients with chronic renal failure is feasible but is associated with poor long-term results (3,5). Restenosis rates are as high as 60% to 81% when evaluated by repeat angiography. However, clinical restenosis is not increased in patients with chronic renal failure, compared with patients with normal renal function (19). Thus, the absence of symptoms of restenosis in patients with chronic renal failure may lead to severe silent ischemia and contribute to the high risk of subsequent cardiac events. Other studies have not evaluated the role of stenting in patients with renal insufficiency. In our study population, stenting did not significantly improve survival after a successful intervention. In the only randomized study of dialysis patients comparing an invasive revascularization approach (including both PCI and CABG) with medical therapy, the invasive approach had a clear survival benefit (20). However, the medical therapy consisted of a calcium channel blocker and aspirin, which does not reflect current practice. Moreover, this study only evaluated diabetic pa- tients on dialysis, which further limits the applicability of this study. With regard to milder renal insufficiency, little is known about the clinical outcome of patients after PCI. Such patients have been excluded from randomized studies. Increased restenosis after PCI in patients with mild renal insufficiency may account for part of the increased mortality rate after PCI in this population. Coronary artery bypass graft surgery in patients with chronic renal failure. Coronary artery bypass graft surgery is also associated with a poor outcome in patients with chronic renal failure, with in-hospital mortality rates as high as 20% (21,22). Even mild renal insufficiency is associated with a doubling of hospital mortality after CABG (23). Coronary artery disease is more diffuse in patients with renal dysfunction, which undoubtedly contributes to the higher complication rate and worse outcomes after interventions. Newer surgical techniques, such as the minimally invasive direct CABG, have been successful in high-risk patients with renal failure, but the long-term results, compared with other surgical and non-surgical techniques, have yet to be determined (24). When comparing PCI with CABG in patients on dialysis, retrospective studies suggest that CABG improves survival (25,26). Because these studies were retrospective, the bias toward treatment allocation limits the usefulness of these results. No studies have compared CABG or PCI with medical therapy in more mild forms of renal insufficiency. Thus, a better understand- ing of treatment options in patients with established CAD is necessary in patients with chronic renal failure and renal insufficiency.
PCI in chronic renal failure First reports addressing the impact of chronic renal failure on the outcome after PCI appeared in 2000 and were based on a small case-control study with 66 patients  and on a large cross-sectional study of 362 patients by Rubenstein et al. . Both trials assessed in-hospital complications and long-term survival in patients with serum creatinine levels of >1.5 mg/dl without previous history of haemodialysis. They found a markedly higher in-hospital and long-term mortality in these patients, with an overall survival of only 60% after 3–4 years. However, in these two studies the patients were not separated according to the degree of renal impairment. Three subsequent studies also focused on the impact of the degree of renal failure on outcome after PCI. In a subgroup analysis of their previous study, Rubenstein et al.  compared patients with a serum creatinine level of 1.6–2.0 mg/dl to those with a level of >2.0 mg/dl. They found a significantly higher mortality after 2 years in those with the higher serum creatinine levels (55 vs 75%) but also noted that the outcome of those with less severe renal failure was worse than that of patients with normal renal function.
Best et al.  analysed the outcome after PCI as a function of the calculated creatinine clearance in subgroups with clearances of 70, 50–69, 30–49 and <30 ml/min, respectively. They found a significantly higher mortality for each of the three latter subgroups compared to that with a clearance of 70 ml/min (Figure 1, lower). Finally, a recent analysis from our institution  focused on PCI patients with marginally reduced renal function. We observed an increment in mortality with each stepwise increase in the serum creatinine level of 0.1 mg/dl above 1.0 mg/dl, with differences in survival becoming significant at a level of 1.3 mg/dl (Figure 1, upper). Even though the approaches of all these studies were different, the mortality rates observed were similar and consistently indicated a reduced outcome of chronic renal failure patients after PCI. From these reports the issue arose of whether a threshold in terms of GFR could be defined above which no negative impact on mortality might be expected. The implication from our analysis, which showed that even patients with serum creatinine levels of 1.1 and 1.2 mg/dl had a nonsignificant trend towards higher mortality (Figure 1, upper), is that the possible threshold may be lower than previously expected and that the number of patients at risk may therefore be higher. One has to bear in mind that in many subjects a serum creatinine level of 1.3 mg/dl signifies a reduction in renal function by 50%, which obviously impacts on the clinical outcome of PCI in those patients. Thus, the terms ‘mild’ or ‘moderate’ renal failure will have to be redefined, as they appear to be too imprecise. The new Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines recommend a more rigorous definition of various stages of chronic kidney disease . A wide application of these new definitions will improve comparisons between clinical studies.
It is of note that, in all of the five studies mentioned above, the mortality curves after PCI separated very early, and at 1 year cumulative survival was already significantly lower in renal failure patients. Therefore, it is debatable whether PCI is effective and acceptable in patients with reduced GFRs, since 25–40% of patients with serum creatinine levels of 1.6 mg/dl will have died within the next 3–4 years [13–17].
PCI vs bypass surgery: and the winner is . . . Are patients with renal failure good candidates for percutaneous coronary revascularization in the new device era?’ This question was asked in the abovementioned landmark study by Rubenstein et al. . When considering only patients with end-stage renal failure, the situation appears to be clear. In their analysis of >10 000 patients from the US Renal Data System database, Herzog et al.  showed that coronary bypass grafting was associated with a significantly higher 2 year survival than PCI (56 vs 48%). In addition, other studies demonstrated that the risk for recurring revascularization and the efficacy to reduce angina were also clearly in favour of bypass surgery [20–22]. However, there are not enough data available presently to decide whether these results can be extrapolated from end-stage kidney disease to less advanced stages of chronic renal failure.
Moreover, all PCI studies, as well as the analyses of bypass surgery trials, were retrospective in nature. Apart from general limitations inherent in this approach, one major caveat has to be taken into consideration. PCI, but not bypass surgery, is feasible in patients with advanced cardiovascular disease and in those with a markedly reduced general condition or with acute myocardial infarction, and it has even marked benefits in patients with cardiogenic shock . Such high-risk patients have actually been included in the above-mentioned trials. In contrast, bypass surgery is almost exclusively limited to patients who are considered to be ‘fit for surgery’. Patients with acute infarction and cardiogenic shock are usually excluded or only treated in rare instances. Thus, always a substantial bias will remain between patients selected for bypass surgery and those submitted to PCI. This bias has most likely affected patients’ outcome in the above-mentioned trials. However, since most patients with renal failure undergo elective coronary revascularization in an acceptable general condition, randomized prospective trials seem to be feasible. Finally, the increasing use of coated coronary stents (e.g. with sirolimus) will influence acute and long-term outcome of PCI patients with or without chronic renal failure. Even in the above-mentioned PCI in chronic renal failure trials, the implantation of conventional coronary stents (used in only 50% of cases) was associated with a significantly better survival [17,24].
Moreover, coated stents were found to have very low rates of restenosis (0–3% of cases), myocardial infarction or mortality . Accordingly, benefits have also been observed in high-risk patients, e.g. those with unfavourable coronary anatomy or diabetes mellitus [26,27]. Taking into account the dismal outcome of PCI in renal failure patients, one may speculate that this is due to coronary restenosis with subsequent fatal or non-fatal infarctions, which may be prevented by these new coronary devices.
The increased prevalence of CVD in patients with renal dysfunction has been attributed to lack of effective prevention and low utilization of effective therapy. Despite great advances in the treatment of coronary artery disease and acute myocardial infarction and a noticeable decline in related morbidity and mortality, the long-term survival of patients with CKD, especially those receiving dialysis (Fig. 1) (5), remains very poor in comparison with the general population. Even more striking is the poor survival of patients treated in the “era of reperfusion”: in 1990-1995, the 1- and 2-year mortality rates for patients with acute myocardial infarction were 62% and 74%, respectively. The poor outcome for dialysis patients who have had an acute myocardial infarction may partly reflect inadequate treatment, including underutilization of intravenous thrombolytic therapy (6) and beta-blockers (7, 8). The optimal treatment of ischemic heart disease in ESRD patients before renal transplantation is controversial. The paucity of our knowledge results from the consistent exclusion of patients with CKD from major trials. Consequently, we must depend on small, mostly non-randomized trials to formulate our recommendations. In small trials comparing medical therapy with revascularization, revascularization appeared to offer symptom relief and mortality benefit (9). However, a definite conclusion is not possible, especially given that most of the medical therapy administered in these trials is far from that considered current standard of treatment used in coronary artery disease. Despite the debate regarding the relative merits of revascularization and medical therapy, the number of coronary revascularization procedures in ESRD patients is certain to increase.
As no data from large-scale prospective randomized trials are available, data on outcomes of PCI versus surgical revascularization in patients with CKD and chronic ischemia are limited to those from large national databases and registries or retrospective analyses of relatively small groups of patients treated in single centers. Using the database of the United States Renal Data System, Herzog et al identified the benefit of coronary artery bypass grafting (CABG) in dialysis patients. The in-hospital mortality was 8.6% for 6668 CABG patients, 6.4% for 4836 percutaneous transluminal coronary angioplasty (PTCA) patients, and 4.1% for 4280 stent patients. The 2- year all-cause survival was 56.4% for CABG patients, 48.2% for PTCA patients, and 48.4% for stent patients (6) (Fig. 2). In a series from the New York registry, Szczech et al found the adjusted estimated 2-year survival to be 51.9% after PCI and 77.4% after CABG (10). Similarly, using the Duke University database, Reddan et al found that CABG provided a survival benefit in comparison with both PCI and medical management across the entire spectrum of CKD. Contrarily, PCI provided a survival benefit in comparison with medical management only in patients with mild or moderate renal dysfunction (11). Although no meta-analysis or pooled analysis of the data from the small trials exists, in general it appears that PCI provides excellent angiographic success but is associated with increased restenosis and the need for revascularization and that CABG, while associated with higher in-hospital morbidity and mortality, provides better overall long-term results and freedom from angina (12). Despite the discouraging results with PCI, one must remember that the studies in question were small, retrospective, inherently limited by the physician’s treatment allocation bias, and do not reflect the current standard of care for percutaneous revascularization.
A more recent study by Rubenstein et al of 350 patients found more promising short- and long-term outcomes using advances in interventional cardiology such as stents and debulking devices (13). Also, a retrospective analysis of 1654 patients with a GFR of < 60 ml/min revealed that PCI yielded better results than medical therapy and CABG in CKD patients with acute coronary syndromes (14). Despite suboptimal results for percutaneous interventions in comparison with bypass surgery, PCI remains a viable option, especially for patients who are not candidates for surgery and those with disabling angina despite anti-anginal therapy. The widespread use of stents with PCI has lowered the incidence of subacute vessel closure and restenosis, a benefit that has been extended to patients receiving hemodialysis (15). Although the use of drug-coated stents has not been studied in patients with CKD, the benefits observed with their use in the general population could be expected in patients with CKD, especially given the higher incidence of restenosis with bare metal stents seen in CKD patients. Intracoronary brachytherapy in patients with CKD has yielded reductions in restenosis rates and target lesion revascularization that are similar to the reductions observed in the general population (16).
The use of new thrombectomy devices, chronic total occlusion devices, debulking devices, and distal protection devices may also be of benefit. Anti-thrombotic therapy and anti-platelet therapy offer promise in the management of acute coronary syndromes. Thrombin activity appears to be increased in patients with renal impairment, as evidenced by elevated prothrombin fragment levels and possibly reduced anti-thrombin levels (17). Heparin has been a mainstay therapy for acute coronary syndromes, especially in patients undergoing coronary intervention. Physicians seem comfortable using heparin in patients with CKD partly because of its ease of delivery, its shorter half-life, and the ability to monitor activated clotting time and activated prothrombin time. Emerging data regarding the safety and efficacy of low-molecular- weight heparin in patients with CKD has yielded approval from the United States Food and Drug Administration for the use of enoxaparin in patients with creatinine clearance of < 30ml/min with dosage adjustment (18). Collet et al reported encouraging safety and benefit data with the use of enoxaparin in CKD patients with acute coronary syndromes after renal dose adjustment and anti-factor Xa monitoring (19). Retrospective analysis of the Efficacy Safety Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) and Thrombolysis in Myocardial Infarction (TIMI) 11B trials showed that the use of enoxaparin in patients with acute coronary syndromes resulted in a trend toward lower rates of death/recurrent myocardial infarction and urgent revascularization, as compared with the use of unfractionated heparin (incidence of hemorrhage was similar) (20). Another promising alternative is bivalirudin. In a metaanalysis of 3 major trials, Chew et al found that bivalirudin was associated with a lower rate of death, myocardial infarction, or urgent revascularization (odds ratio, 0.75; P = 0.018); major hemorrhage (odds ratio, 0.40; P = 0.001); and the composite end point of ischemic and bleeding events (odds ratio, 0.55; P = 0.001) compared with heparin. The relative risk reduction with bivalirudin observed in the overall analysis appeared to persist when patients were stratified by renal function (21).
Background—The optimal approach to revascularization in patients with kidney disease has not been determined. We studied survival by treatment group (CABG, percutaneous coronary intervention [PCI], or no revascularization) for patients with 3 categories of kidney function: dialysis-dependent kidney disease, non–dialysis-dependent kidney disease, and a reference group (serum creatinine 2.3 mg/dL). Methods and Results—Data were derived from the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH), which captures information on all patients undergoing cardiac catheterization in Alberta, Canada. Characteristics and patient survival in 662 dialysis patients (1.6%) and 750 non–dialysis-dependent kidney disease patients (1.8%) were compared with the remainder of the 40 374 patients (96.6%). For the reference group, the adjusted 8-year survival rates for CABG, PCI, and no revascularization (NR) were 85.5%, 80.4%, and 72.3%, respectively (P0.001 for CABG versus NR; P0.001 for PCI versus NR). Adjusted survival rates were 45.9% for CABG, 32.7% for PCI, and 29.7% for NR in the nondialysis kidney disease group (P0.001 for CABG versus NR; P0.48 for PCI versus NR) and 44.8% for CABG, 41.2% for PCI, and 30.4% for NR in the dialysis group (P0.003 for CABG versus NR; P0.03 for PCI versus NR). Conclusions—Compared with no revascularization, CABG was associated with better survival in all categories of kidney function. PCI was also associated with a lower risk of death than no revascularization in reference patients and dialysis-dependent kidney disease patients but not in patients with non– dialysis-dependent kidney disease. The presence of kidney disease or dependence on dialysis should not be a deterrent to revascularization, particularly with CABG. (Circulation. 2004;110:1890-1895.)
After excluding 6156 patients (12.7%) with normal coronary anatomy and 520 (1.1%) with missing data, the final study population was 41 786. Of these, 662 (1.6%) were on dialysis (dialysis kidney disease), 750 (1.8%) had serum creatinine 2.3 mg/dL but were not on dialysis (nondialysis kidney disease), and 40 374 (96.6%) had serum creatinine 2.3 mg/dL (reference patients). The prevalence of clinical risk factors, by treatment group and category of kidney function, are listed in Table 1. Other than known hyperlipidemia, the prevalence of clinical risk factors was significantly higher in patients with kidney disease, both nondialysis and dialysis dependent, than in the reference patient group. Overall, the most common indication for cardiac catheterization was myocardial infarction in the reference and nondialysis kidney disease patients; in the dialysis kidney disease patients, other indications were cited. Other indications most frequently cited were congestive heart failure, suspected silent ischemia, and atypical symptoms. The majority of dialysis and nondialysis kidney disease patients did not undergo revascularization after their cardiac catheterization despite results of the catheterization showing that these patients had more severe coronary anatomy (Table 2). The median follow-up time after cardiac catheterization was 3.7 years for the reference patient group, 1.9 years for patients with nondialysis kidney disease, and 2.1 years for dialysis patients. The risk-adjusted survival curves for the reference patient group, nondialysis kidney disease patient group, and dialysis patient group are shown in the Figure. Treatment with CABG was associated with the best adjusted survival rates and no revascularization with the worst for each of the 3 categories of kidney function. The adjusted 8-year survival rates in the reference patient group associated with CABG, PCI, and no revascularization were 85.5%, 80.4%, and 72.3%, respectively (Figure, A). For patients with non- dialysis kidney disease, the adjusted 8-year survival rates were 45.9% with CABG, 32.7% with PCI, and 29.7% with no revascularization (Figure, B). For patients on dialysis, the adjusted 8-year survival rates were 44.8% with CABG, 41.2% with PCI, and 30.4% with no revascularization (Fig- ure, C). A summary of 8-year unadjusted and adjusted survival rates for CABG and PCI, with their associated adjusted survival differences and hazard ratios relative to no revascu- larization, are provided in Table 3. CABG was associated with a survival advantage compared with no revascularization for all 3 categories of kidney function, with nondialysis kidney disease patients experiencing the greatest survival advantage for CABG compared with no revascularization, at 16.2%. PCI was not associated with as positive a survival advan- tage as CABG, particularly for patients with nondialysis kidney disease (Table 3; Figure, B). In both the reference patient group and the dialysis patient group, PCI was associ- ated with a statistically significant lower risk of death than no revascularization. However, nondialysis kidney disease pa- tients experienced a similar outcome regardless of whether they were treated with PCI or no revascularization (adjusted hazard ratio 0.91; 95% CI 0.69 to 1.19). When we addition- ally controlled for the propensity to be selected for CABG or PCI, the adjusted hazard ratios changed little (Table 3). Compared with PCI, CABG was associated with a statisti- cally significant lower risk of death in both the reference and nondialysis kidney disease groups, with adjusted hazard ratios (95% CIs) of 0.69 (0.63 to 0.75) and 0.75 (0.56 to 0.99), respectively, whereas the dialysis kidney disease group experienced a nonsignificant lower risk of death (adjusted hazard ratio 0.89, 95% CI 0.59 to 1.32). Intheseanalyses,weusedtimeofcatheterizationasacommon “timezero”acrosstreatmentgroups.ForthePCIgroup,thisreflects the treatment time, given a median waiting time of only 1 day, but the CABG median waiting time was longer, at 48 days. To assess the impact of including this waiting time, we performed a sensitivitanalysis using the date of CABG or PCI as time zero. This sensitivity analysis yielded almost identical results to the analysis that used time of catheterization as time zero.
Objectives This study sought to evaluate ischemic and bleeding outcomes in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES).
Background Previous studies have shown that CKD is associated with poor outcomes after PCI. However, these studies were largely conducted before the introduction of DES and aggressive antithrombotic therapy or were performed in the setting of randomized trials. With data from a contemporary registry, we evaluated the influence of CKD on major cardiovascular events and bleeding complications in unselected “real-world” patients undergoing PCI.
Methods Data from 4,791 patients enrolled in the EVENT (Evaluation of Drug Eluting Stents and Ischemic Events) Registry between July 2004 and September 2005 were analyzed. Patients were stratified into 4 groups: creatinine clearance (CrCl) 75, 50 to 75, 30 to 49 and 30 ml/min. Results During the index hospital stay, there was a step-wise increase in bleeding complications with decreasing CrCl (3.3%, 5.0%, 8.8%, and 14.3%; p 0.0001 for trend). Lower CrCl was also associated with more frequent death or myocardial infarction (MI) during the initial hospital stay (p 0.001) and at 1 year (p 0.001). These findings were confirmed in multivariate analyses that adjusted for baseline differences in demographic, clinical, and angiographic factors. Use of guideline recommended medications at 1 year, including aspirin, clopidogrel, angiotensin-converting enzyme inhibitors, and statins, also decreased with declining renal function.
Conclusions Renal function is an independent and powerful predictor of bleeding and ischemic complications in the era of DES and contemporary antithrombotic therapy in patients undergoing PCI. The low use of guideline-recommended drugs among patients with CKD undergoing PCI might contribute to these adverse outcomes and warrants further evaluation.
Baseline characteristics. A total of 5,053 consecutive patients were enrolled in Waves 1 and 2 of the EVENT registry between July 2004 and September 2005. After excluding 262 patients with missing baseline renal function assessment, 4,791 patients constituted the study cohort. Approximately 59% (2,827) of patients had normal renal function (CrCl 75 ml/min), whereas 26% (1,253) had mild renal impairment (CrCl 50 to 75 ml/min), 12% (571) had moderate renal impairment (CrCl 30 to 49 ml/min), and 3% (140) had severe renal impairment (CrCl 30 ml/min). Of the 140 patients with severe renal impairment, 51 (approximately 1% of the total sample) were dependent on renal dialysis.
On average, patients with a CrCl below 75 ml/min were older than those with a CrCl above 75 ml/min and were more likely to be female and have a history of congestive heart failure, coronary artery bypass grafting, diabetes, hypertension, stroke, and peripheral arterial disease. Patients with lower CrCl were less likely to be current smokers and to have presented with a STEMI. Other potential indications for PCI did not differ according to renal function. Of note, among patients with at least moderate renal insufficiency, 24% had only a slight increase in serum creatinine (level between 1.5 and 2.0 mg/dl) at baseline (Table 1).
Baseline characteristics. A total of 5,053 consecutive patients were enrolled in Waves 1 and 2 of the EVENT registry between July 2004 and September 2005. After excluding 262 patients with missing baseline renal function assessment, 4,791 patients constituted the study cohort. Approximately 59% (2,827) of patients had normal renal function (CrCl 75 ml/min), whereas 26% (1,253) had mild renal impairment (CrCl 50 to 75 ml/min), 12% (571) had moderate renal impairment (CrCl 30 to 49 ml/min), and 3% (140) had severe renal impairment (CrCl 30 ml/min). Of the 140 patients with severe renal impairment, 51 (approximately 1% of the total sample) were dependent on renal dialysis.
On average, patients with a CrCl below 75 ml/min were older than those with a CrCl above 75 ml/min and were more likely to be female and have a history of congestive heart failure, coronary artery bypass grafting, diabetes, hypertension, stroke, and peripheral arterial disease. Patients with lower CrCl were less likely to be current smokers and to have presented with a STEMI. Other potential indications for PCI did not differ according to renal function. Of note, among patients with at least moderate renal insufficiency, 24% had only a slight increase in serum creatinine (level between 1.5 and 2.0 mg/dl) at baseline (Table 1).
Angiographic characteristics of the study population are displayed in Table 2. A total of 6,655 lesions were treated in 4,791 patients, with a similar number of lesions treated/ patient across groups. Approximately 15% of patients underwent multivessel PCI in each group. Percutaneous coronary intervention was performed more frequently in left main and saphenous vein graft lesions in the lowest Cr Cl group. Additionally, patients with worse renal function had PCI performed in more complex lesions (B2/C per American College of Cardiology classification). Procedural characteristics of the study population are summarized in Table 3. Most patients received only DES. The use of anticoagulants varied significantly among the groups (p 0.0001) as shown in Table 3. Unfractionated heparin or DTI alone was used more frequently in patients with lower CrCl. Conversely, GP IIb/IIIa inhibitors were used less frequently in patients with greater renal impairment. Eptifibatide was the predominant GP IIb/IIIa inhibitor used, irrespective of renal function. However, use of abciximab increased as renal function worsened, (CrCl 75 ml/min, 83% eptifibatide vs. 15% abciximab; CrCl 30 ml/min, 57% eptifibatide vs. 41% abciximab). In patients receiving heparin, higher activated clotting time was seen in patients with CrCl between 30 and 75 ml/min (p 0.03).
Baseline characteristics. A total of 5,053 consecutive patients were enrolled in Waves 1 and 2 of the EVENT registry between July 2004 and September 2005. After excluding 262 patients with missing baseline renal function assessment, 4,791 patients constituted the study cohort. Approximately 59% (2,827) of patients had normal renal function (CrCl 75 ml/min), whereas 26% (1,253) had mild renal impairment (CrCl 50 to 75 ml/min), 12% (571) had moderate renal impairment (CrCl 30 to 49 ml/min), and 3% (140) had severe renal impairment (CrCl 30 ml/min). Of the 140 patients with severe renal impairment, 51 (approximately 1% of the total sample) were dependent on renal dialysis. On average, patients with a CrCl below 75 ml/min were older than those with a CrCl above 75 ml/min and were more likely to be female and have a history of congestive heart failure, coronary artery bypass grafting, diabetes, hypertension, stroke, and peripheral arterial disease. Patients with lower CrCl were less likely to be current smokers and to have presented with a STEMI. Other potential indications for PCI did not differ according to renal function. Of note, among patients with at least moderate renal insufficiency, 24% had only a slight increase in serum creatinine (level between 1.5 and 2.0 mg/dl) at baseline (Table 1). Angiographic characteristics of the study population are displayed in Table 2. A total of 6,655 lesions were treated in 4,791 patients, with a similar number of lesions treated/ patient across groups. Approximately 15% of patients underwent multivessel PCI in each group. Percutaneous coronary intervention was performed more frequently in left main and saphenous vein graft lesions in the lowest CrCl group. Additionally, patients with worse renal function had PCI performed in more complex lesions (B2/C per American College of Cardiology classification). Procedural characteristics of the study population are summarized in Table 3. Most patients received only DES. The use of anticoagulants varied significantly among the groups (p 0.0001) as shown in Table 3. Unfractionated heparin or DTI alone was used more frequently in patients with lower CrCl. Conversely, GP IIb/IIIa inhibitors were used less frequently in patients with greater renal impairment. Eptifibatide was the predominant GP IIb/IIIa inhibitor used, irrespective of renal function. However, use of abciximab increased as renal function worsened, (CrCl 75 ml/min, 83% eptifibatide vs. 15% abciximab; CrCl 30 ml/min, 57% eptifibatide vs. 41% abciximab). In patients receiving heparin, higher activated clotting time was seen in patients with CrCl between 30 and 75 ml/min (p 0.03).
In-hospital outcomes. Impaired renal function was associated with a graded increase in both ischemic and bleeding complications during the index hospital stay (Table 4). Of the 4,791 patients, 227 developed the composite end point of bleeding complications. There was a progressive increase in the frequency of the composite end point of death or MI during the index hospital stay from 5.8% to 10% with worsening renal function (p 0.0016), driven primarily by a greater incidence of in-hospital MI among patients with lower CrCl (p 0.002). Finally, post-procedure length of hospital stay was greater in patients with worse renal function at baseline (Table 4).
One-year outcomes. During 1 year of follow-up, 139 patients (2.9%) died and 395 (8.2%) experienced an MI. The Kaplan-Meier curves for survival are displayed in Figure 1. With decreasing CrCl, there was a stepwise increase in mortality across all groups (unadjusted p value for trend 0.0001) (Table 4). The incidence of MI also increased with worsening renal function (unadjusted p value for trend 0.0007). Stent thrombosis (p 0.99) and repeat revascularization (unadjusted p value for trend 0.51) were not different among the various groups. Trends in cardiovascular medication usage at 6 and 12 months showed a significant decline in use of guideline recommended pharmacotherapy with decreasing CrCl (e.g., CrCl 75 ml/min vs. CrCl 30 ml/min) at 1 year, aspirin (93% vs. 73%), clopidogrel (72% vs. 63%), hydroxymethylglutaryl-coenzyme A reductase inhibitors (86% vs. 65%), and angiotensin-converting enzyme inhibitors (52% in vs. 34%) as shown in Table 5. The follow-up rates were between 95% and 98% at 6 months and between 92% and 94% at 1 year for all CrCl groups
Multivariable analysis. Creatinine clearance was a powerful predictor of bleeding complications. This observation held true even when multiple variables including antithrombotic use and baseline hemoglobin were progressively forced into the model (Table 6). The multivariable-adjusted odds of bleeding complications were more than 3 as high in the 30 ml/min CrCl group compared with the referent group of CrCl 75 ml/min (odds ratio: 3.23, 95% confidence interval: 1.72 to 6.04) (Table 6). At 1 year, renal dysfunction emerged as an independent predictor of mortality after adjustment for the risk factors listed earlier (Table 6). The composite of death and MI also increased across all CrCl groups (p 0.0001). Individuals with CrCl 30 ml/min had more than 5 the risk of dying than those with CrCl 75 ml/min (multivariable-adjusted hazard ratio: 5.35, 95% confidence interval: 2.86 to 10.02). Noticeably, TLR did not increase with renal dysfunction. Analysis of CrCl as a continuous, log-transformed predictor demonstrated similar findings for in-hospital and 1-year outcomes (data not shown).
Our study generated several important results. Renal insufficiency was associated with increased in-hospital death and MI as well as bleeding complications, even after adjustment for other clinical factors that could potentially confound these associations. One-year ischemic outcomes including death and nonfatal MI also increased in a step-wise fashion as CrCl decreased. Despite these important clinical outcomes, renal dysfunction was not associated with an increased risk of stent-specific events, including stent thrombosis or clinical restenosis (i.e., TLR). We also found that guideline-recommended medications were used less frequently as renal function worsened. We found that, consistent with other reports, more than 40% of patients undergoing PCI have impaired renal function. We also found that almost one-fourth of patients with significant renal insufficiency undergoing PCI have only a mild increase in serum creatinine (between 1.5 to 2.0 mg/dl), emphasizing the advantage of using CrCl over serum creatinine, as the dosage of certain antithrombotic medications need to be adjusted on the basis of CrCl. Bleeding complications in CKD. Renal dysfunction has been shown to be a risk factor for bleeding complications in patients undergoing PCI in the setting of STEMI as well as ACS (13,14). Few previous studies have demonstrated a linear increase in bleeding after PCI with a concomitant decrease in CrCl (15,16). However, these analyses were either performed in the setting of randomized controlled trials or were in the era of bare-metal stents and noncontemporary antithrombotic therapy, in contrast to our study, which was performed in the real-world setting.
In our study, patients with CrCl 30 to 49 ml/min had higher peak activated clotting times and were particularly more susceptible to hemorrhagic complications. Whereas there has been increasing emphasis on proper medication dosing in patients with renal insufficiency, one possible explanation for our finding is that moderate degrees of renal insufficiency might have been overlooked in some patients. In particular, estimation of renal function on the basis of serum creatinine alone might have led to inadvertent overdosing of antithrombotic medications that are renally metabolized, including GP IIb/IIIa inhibitors such as eptifibatide. Recently, Alexander et al. (17,18) reported that renal dysfunction was an independent predictor of excessive dosing of heparins and GP IIb/IIIa inhibitors and of TIMI major bleeding among patients presenting with ACS and that this practice was more common in women than in men. The appropriate dosing of heparin in patients with CKD has not been studied very well (19). Although excess dosing of antithrombotic agents could also have played a role in increased bleeding complications of patients with CKD, we were unable to prove this association in the EVENT registry, because doses of GP IIb/IIIa antagonists were not systematically collected in our study cohort. It is also likely that patients with CKD are at increased risk of bleeding, even in the absence of dosing errors. For example, renal insufficiency has been associated with several abnormalities of primary hemostasis, particularly platelet dysfunction characterized by decreased release of adenosine triphosphate and decreased serotonin content in dense granules (20).
Blood transfusions, even after adjusting for baseline hemoglobin, were more often administered in patients with decreased renal function, a finding that could be related to a lower threshold for transfusion in patients with severe CKD. Previous studies have shown an increase in blood transfusions in patients with CKD after PCI (3,21).
Ischemic outcomes in CKD. Our study showed a marked increase in in-hospital and 1-year cardiovascular events after PCI as renal function worsened. Other smaller and retrospective studies have shown increased mortality and MI within 1 year after PCI with DES (22), even when the degree of renal insufficiency is mild (23). However, the large population of patients with varying degrees of renal dysfunction in our study provides greater power to examine a broader spectrum of outcomes, including death as well as increased long-term risk of MI, in this patient population. One of the strengths of our study was that systematic collection of pre- and post-procedure cardiac markers allowed for reliable detection of periprocedural ischemic events without ascertainment bias. Indeed, we observed a stepwise increased incidence of periprocedural MI with worsening renal function. Of note, the use of GP IIb/IIIa antagonists decreased with worsening renal function, which could have played a role in the increased incidence of post-procedural MI in patients with CKD, given their proven role in reducing these complications (24).
Studies have shown that the need for repeat revascularization in patients with CKD has decreased with the advent of DES (21,25). However, a recent study showed that the need for repeat revascularization increases with renal dysfunction, even in patients receiving DES (26). Renal failure has also been implicated as an independent predictor of stent thrombosis with DES, being second only to premature discontinuation of clopidogrel (27). However, repeat revascularization or stent thrombosis was not found to be increased in patients with CKD at 1-year follow-up in our analysis, questioning earlier findings. Recently, more emphasis is being laid on bleeding complications as a determinant of mortality in patients after PCI. However, our results indicate that even after correcting for bleeding complications, outcomes remain worse in patients with lower CrCl. Therefore, in patients with CKD, additional factors attributable to CKD as well as underuse of recommended cardioprotective medications could account for worse outcomes. It has been reported that cardioprotective medications are less often used in the management of patients with CKD (28). To our knowledge, our study is the first to show the paradoxical underuse of cardioprotective drugs after PCI in a CKD population. Use of medications such as aspirin, clopidogrel, statins, and angiotensinconverting enzyme inhibitors decreased in a step-wise fashion with the drop in CrCl at 1 year. Although further studies are needed to evaluate the safety and efficacy of guideline-recommended therapies in patients with CKD, it seems paradoxical that cardiovascular pharmacotherapy is being underused in patients who might benefit the most. Limitations. Although our data were collected prospectively, the current analysis was not specified prospectively. Consequently, the data collected did not include whether the anticoagulants were dosed on the basis of CrCl or serum creatinine or whether renal function was considered at all in dose selection. Similarly, transfusion was a major component of the composite bleeding end point, and we did not collect data regarding indication for transfusion.
We had limited power to evaluate some end points such as stent thrombosis and to evaluate dialysis patients separately. Similarly, we did not collect information on post-procedure renal failure or dialysis as complications of PCI. The Cockcroft-Gault equation was used for estimation of CrCl. This formula might overestimate CrCl in obese patients. Although the number of patients who received bare-metal stents was small, we did not compare the outcomes of patients receiving DES with those of patients receiving bare-metal stents.
Cardiovascular disease is the leading cause of death in patients who have chronic kidney disease or end-stage renal disease and are undergoing hemodialysis. Chronic kidney dis- ease is a recognized risk factor for premature atherosclerosis. Unfortunately, most major randomized clinical trials that form the basis for evidence-based use of revascularization procedures exclude patients who have renal insufficiency. Retrospective, observational studies suggest that patients with end-stage renal disease and severe coronary occlusive disease have a lower risk of death if they undergo coronary revascularization rather than medical therapy alone. Due to a lack of prospective studies, however, the relative merits of percutaneous versus surgical revascularization are merely a matter of opinion. Several small, retrospective studies have shown that coronary artery bypass grafting is associated with higher procedural death but better long-term survival than is percutaneous coronary intervention. This difference appears to result from poor long-term results of percutane- ous coronary intervention in patients who have chronic kidney disease or end-stage renal disease. Because randomized trials comparing percutaneous coronary intervention and coronary artery bypass grafting have included patients undergoing balloon angioplasty and place- ment of bare-metal stents, their conclusions are suspect in the era of drug-eluting stents. In this review, we discuss different revascularization options for patients with chronic kid- ney disease, the outcomes of revascularization procedures, and the risk factors for adverse outcomes. (Tex Heart Inst J 2010;37(1):9-18)
Coronary Artery Bypass Grafting In-hospital and long-term outcomes of routine CABG in patients with ESRD have been described in 10 to 15 retrospective studies. Perioperative death ranges from 5% to 20% (Table II) in ESRD patients, which is roughly 3-fold greater than that in non-ESRD pa- tients.8,33-43 Having ESRD increases by about 2-fold the complications of surgery, including mediastinitis (2.3%–4%),36,41,43 stroke (4.3%–8%),41 and the need for prolonged mechanical ventilation.8 These sequelae increase morbidity rates and prolong intensive care unit and hospital stays (Table I). Presumed reasons for the increase in illness include fluid shifts due to CPB, anemia, malfunctioning platelets, and more general- ized atherosclerosis. Decreased left ventricular ejection fraction,36,37 severe distal disease,36 and increased cross- clamp37 and CPB times37 clearly increase in-hospital death, whereas use of the internal mammary artery as a bypass conduit is protective.37 Surprisingly, the risk of perioperative bleeding41 or myocardial infarction is similar to that in populations unaffected by ESRD.36,37 After routine CABG in ESRD patients, survival rates at 1 year range from 71% to 95%; at 3 years, 44% to 84%; and at 5 years, 32% to 82% (Table III). Variables associated with death are similar to those for patients without ESRD and include decreased left ventricu- lar ejection fraction, use of the internal mammary ar- tery graft, advanced age, prior myocardial infarction, chronic obstructive pulmonary disease, nonambulatory state, and emergency surgery.34,36,37,44 After CABG, angi- na and left ventricular ejection fraction are routinely improved over preoperative measurements.36 Although prospective studies comparing the use of venous and arterial grafts in this population are lacking, observa- tional studies have demonstrated excellent 5-year sur- vival (60%–82%) with the use of mammary artery grafts,8,38,39 which are associated with reduced in-hos- pital and long-term mortality rates in ESRD patients, primarily because of reduced thrombosis during the postoperative period.37,45,46 In a study of 7,152 ESRD patients from the Society of Thoracic Surgeons data- base, the OR for 30-day death (calculated in compar- ison with patients who had normal renal function and underwent similar procedures) was lower for ESRD patients who received mammary artery grafts than for ESRD patients who received venous grafts (4.3 vs 3.6; P <0.009).8 However, if the surgeon uses the mamma- ry artery from the same side as the arteriovenous fistu- la, there is a risk of coronary steal during dialysis. This can cause angina during dialysis. Therefore, surgeons might want to choose the contralateral mammary ar- tery for use as the critical conduit to the left anterior descending coronary artery.47 However, there is no evi- dence that this complication erodes the benef icial effect of internal mammary conduit use. Off-Pump Coronary Artery Bypass Surgery In retrospective studies, perioperative death in ESRD patients undergoing OPCAB ranges from 0 to 10.9% (Table IV).16,48-52 Small, nonrandomized studies have re- ported that ONCAB-treated ESRD patients have long- er postoperative mechanical ventilation times (28.3% vs 6.8%; P=0.001)50 and more transfusions (57.4% vs 25.7%; P <0.001)49 than do patients who undergo OPCAB. In a retrospective study of 158 patients from the Society of Thoracic Surgeons database, the use of CPB was an independent risk factor for early perioper- ative death in ESRD patients (OR=13.6; P=0.01).50 In contrast, in a much larger study of the USRDS database (possibly with less selection bias), perioperative death was similar in 540 patients undergoing OPCAB and 3,382 patients undergoing ONCAB (10.9% vs 12%; P = 0.471).48 One disadvantage of OPCAB is the potential diffi- culty in manipulating the heart to place particular distal anastomoses—to the posterior left ventricular branch- es, for example. In addition, creating distal anastomoses on a beating heart is associated with a “learning curve,” and routine conversion to OPCAB in an institution can be associated with a brief increase in complications and procedural failure. There is greater potential for incomplete revascularization, which would erode the long-term protection provided by CABG. A comparison of medi- um-term survival for 540 OPCAB and 3,382 ONCAB patients with ESRD from the USRDS database48 re- vealed no difference at 18 months (61.9% vs 59.5%; P=0.226); but several studies have reported worse long- term survival after OPCAB.50 In these studies, patients undergoing OPCAB received fewer bypasses than did those undergoing ONCAB (2.4 ± 1 grafts vs 3.3 ± 0.9 grafts, respectively; P <0.001).
Herzog data – duplicate with slide 14
Percutaneous Intervention Numerous comorbid conditions, a greater prevalence of diffuse disease, and more severe vascular calcifica- tion increase the likelihood of both short- and long-term treatment failure after percutaneous revascularization in ESRD patients, when comparison is made with patients who have normal kidney function. Although data from prospective studies are lacking, early retrospective stud- ies of PCI indicate that ESRD and non-ESRD popu- lations have similar initial rates of angiographic success (84% –97% vs 78% –97%) and periprocedural myo- cardial infarction (1%–3.7% vs 1%–4%). However, observational studies show highly variable rates of restenosis after PCI in ESRD and non-ESRD pa- tients (20%–60% vs 20%–38%, respectively); of re- vascularization for restenosis at 1 year (22%–35% vs 20%–28%, respectively) and at 4 years (20%–29% vs 18%–19%, respectively); and of revascularization for progression of disease at 1 year (5%–11% vs 5%–7%, respectively).19,53-60 In studies that report a higher rate of restenosis, ESRD patients had a greater percentage of calcified lesions and greater residual stenosis after the procedure. Other procedural complications, such as bleeding, are higher in chronic kidney disease patients when glycoprotein IIb/IIIa receptor antagonists are used during PCI. When eptifibatide or tirofiban is used in patients with chronic kidney disease, the dose must be adjusted, whereas abciximab has the advantage of not requiring dosage adjustment.61 The impact of numerous comorbid conditions and of decreasing GFR on disease progression is manifest in long-term survival. Only 1 year after the index pro- cedure, the mortality rate is almost 3-fold higher in ESRD patients than in non-ESRD patients (31% vs 13%; P=0.001).58 In a study of 5,327 patients under- going PCI (65%, bare-metal stents; 35%, angioplasty without stenting), in-hospital and long-term mortality rates were significantly higher in patients in the ESRD group (6% and 24.4%, respectively; P <0.001) than in patients whose clearance was greater than 70 mL/min (0.5% and 2.1%, respectively; P <0.001).19 The principal disadvantage of percutaneous therapy in the ESRD population is treatment longevity. Place- ment of a bare-metal stent increases the risk of restenosis and leaves untreated sites prone to rapid disease progression. Because drug-eluting stents have substantially re- duced restenosis and the frequency of repeat procedures after stent placement, they offer the possibility of provid- ing ESRD patients with percutaneous revascularization that has a reasonable probability of long-term success, as seen in the general population. In an observation- al study of ESRD (n=72) and non-ESRD (n=3,370) patients undergoing placement of drug-eluting stents, procedural success was lower in the ESRD group. The target-lesion revascularization rate at 1 month was 3.1% compared with 0.4% in non-ESRD patients (P=0.05). At 6 months, target-vessel revascularization was simi- lar for the 2 groups (5.4% in ESRD patients vs 3.8% in non-ESRD patients; P=0.54). Nevertheless, this rea- sonable risk of restenosis was offset by increased death in the ESRD group (16% vs 3.8%; P <0.001), which might mask the true risk of clinically significant restenosis.
Comparison of RevascularizationTechniques in End-Stage Renal Disease Patients Multiple, small, retrospective studies have shown that long-term survival rates are higher in ESRD patients who undergo CABG than in those who undergo per- cutaneous transluminal coronary angioplasty (PTCA) (Table V).25,27,45,63-66 In a large, retrospective study of the USRDS national database, 7,419 ESRD patients un- dergoing CABG were compared with 6,887 ESRD pa- tients undergoing PTCA. Despite higher perioperative mortality rates in the CABG-treated patients (12.5% vs 5.4%), the survival curves crossed each other at about 1 year, and the long-term survival rates at 2 and 5 years were significantly higher for CABG-treated pa- tients than for those who underwent PTCA (Fig. 1). A reduction in all-cause death at 2 years (relative risk [RR]=0.91, 0.83–0.98) and cardiac death at 2 years (RR=0.85, 0.79–0.92) was associated with surgical therapy.64 A similar long-term survival benef it from CABG was seen in a study that examined the New York State Reg- istry, wherein the risk-adjusted survival rate for ESRD patients at 3 years was 46.1% after PTCA compared with 65.9% after CABG.12 However, comparative out- comes after PTCA are no longer clinically relevant due to the almost uniform use of coronary stents for PCI. In another USRDS database study, outcomes after CABG (n=6,688), PTCA (n=4,836), and bare-metal stent placement (n=4,280) were compared in ESRD patients. In-hospital death was lowest for the stent pop- ulation (4.1%), intermediate for PTCA (6.4%), and highest for CABG (8.6%). However, after only 24 months, ESRD patients undergoing CABG (P <0.001) had a signif icant survival benef it when compared with those undergoing PTCA or stent placement (56.4% ± 1.4%, 48.2% ± 1.5%, and 48.4% ± 2%, respectively).27 Compared with bare-metal stents, drug-eluting stents reduce death and repeat target-vessel revascularization in ESRD patients. In a study of 89 consecutive patients who underwent coronary stenting (drug-eluting in 24 patients; bare-metal in 65), drug-eluting stents, when compared with bare-metal stents, were associated at 9 months with significant reductions in target-vessel re- vascularization (4% vs 26%; OR=0.07; P=0.036) and in a composite endpoint comprising death, myocardial infarction, and target-vessel revascularization (33% vs 60%; OR=0.11; 95% CI, 0.022–0.513; P=0.005).67 In a prospective cohort study of the National Heart, Blood and Lung Institute registry of ESRD patients (n=74), drug-eluting stents (n=33) were associated with more freedom from major adverse cardiac events (25.2% vs 57.3%, P=0.01; HR=0.24 [0.1–0.6]; P=0.002), and with a trend towards reduced mortality rates (18.4% vs 36.8%, P=0.09; HR=0.4 [0.15–1.05]; P=0.06) at 1 year, when compared with bare-metal stents (n=41).68 Because these studies are retrospective and the PCI techniques used in some of them do not ref lect the cur- rent standard of treatment, the application of the data to real-life situations is seriously constrained. Without pro- spective studies comparing the surgical and percutane- ous treatment options, we can only conjecture that PCI gives excellent clinical and angiographic revasculariza- tion success and better in-hospital survival but is asso- ciated with increased rates of restenosis and subsequent revascularization. Coronary artery bypass grafting is as- sociated with better long-term survival, despite high- er in-hospital death. However, PCI using drug-eluting stents may be a good choice in patients in whom multi- ple comorbid conditions preclude surgery or in patients in whom the internal mammary artery cannot be used as a bypass conduit.
It is unknown whether the efficacy and safety of drug-eluting stents (DES) apply in patients with chronic renal failure (CRF). AIMS:To compare DES with bare metal stents (BMS) for percutaneous coronary intervention (PCI) in CRF patients. METHODS:Consecutive patients treated by PCI were allocated to four groups according to type of stent used (DES versus BMS) and creatinine clearance (CrCl). CRF was defined as CrCl less than 60 mL/minute. Cardiovascular death, major adverse cardiac events (MACE, defined as cardiovascular death, myocardial infarction, stroke and target lesion revascularization [TLR]), TLR and definite stent thrombosis (ST) were recorded at 1 year.RESULTS:We note that 1376 consecutive patients underwent PCI with stent within 18 months: 534 (39%) and 492 (36%) patients without CRF and 224 (16%) and 126 (9%) patients with CRF were treated with BMS and DES, respectively. In the entire cohort, patients treated with DES had a higher restenosis risk profile. BMS were predominantly (87%) used for ST-segment elevation myocardial infarction. At 1 year, 6.2% had cardiovascular death, 15.8% MACE, 7.3% TLR and 1.5% ST. Cardiovascular death and MACE occurred less frequently in DES groups. The TLR rate was not significantly different in the CRF groups (BMS 9.8% vs DES 7.1%; P=0.44). No excess of ST was observed in the DES groups and use of DES was independently associated with absence of MACE and TLR. CONCLUSIONS:In patients with CRF, DES appear to be at least as effective as BMS--despite a higher restenosis risk profile--with no excess of ST at 1 year.
By Yael L. Maxwell Thursday, January 22, 2015
In patients with chronic kidney disease (CKD), CABG is associated with improved early and late clinical outcomes compared with PCI, according to a registry study published in the January 2015 issue of Circulation: Cardiovascular Interventions. Mortality at 30 days was similar between the treatment groups, but survival at 3 years favored surgery. “These data would suggest that patients with CKD would be better served with CABG over PCI,” the authors say, although they acknowledge that there is a paucity of data and to date no randomized controlled trial has compared the strategies in this high-risk group.
Vladimír Džavík, MD, of Toronto General Hospital (Toronto, Canada), and colleagues identified 4,006 patients (average age 75 years) with CKD and multivessel disease who underwent revascularization from October 2008 to September 2011 and were enrolled in the Cardiac Care Network of Ontario Cardiac Registry. Most patients had CABG (n = 3,010), while the rest received PCI with DES (n = 996). Patients from each treatment arm were also sorted into 893 propensity-matched pairs. Baseline clinical and procedural characteristics were similar between the groups with the exception of CABG patients having lower weight and being more likely to be in Canadian Cardiovascular Society angina class IV. Diabetes was present in about 44% of each group.
Higher Long-term Survival With CABG Mortality and admission for stroke were similar between the PCI and CABG groups at 30 days, but MACCE and its components—including repeat revascularization and MI—were higher with PCI. Late follow-up at 3 years showed higher mortality, repeat revascularization, MI, and MACCE with PCI vs CABG (P< .01 for all; table 1).
Kaplan-Meier survival estimates favored CABG over PCI at 1, 2, and 3 years (P< .001 for all). Additionally, CABG resulted in greater freedom from MACCE at each of those time points, driven by a greater occurrence of MI and repeat revascularization in the PCI cohort (P< .001 for all). In the unmatched analysis, PCI with DES was associated with increased late mortality (HR 1.58; 95% CI 1.32-1.90) and MACCE (HR 2.62; 95% CI 2.28-3.01). Other independent predictors of these outcomes included CKD stage, age, diabetes, LV dysfunction, and urgent revascularization priority. DES use resulted in similar late MACCE outcomes across a multitude of subgroups compared with CABG (P < .001 for all). Of the more than 80% of patients who had stage 3 CKD, mortality rates at 30 days and at 1 year were similar between PCI and CABG. However, late mortality and MACCE were higher in the PCI group (P < .05 for both). In those with stage 4 CKD, all adverse outcomes occurred more frequently in the PCI arm with the exception of 30-day death.
Several Advantages to CABG “These important findings underscore the results of 2 recent large RCTs comparing the effectiveness of PCI with DES versus CABG in patients with complex multivessel disease and diabetes mellitus (SYNTAX and FREEDOM),” Dr. Džavík and colleagues write. “In both these trials, CABG demonstrated superiority over PCI with respect to MACCE, MI, and repeat revascularization, particularly in the subset of patients with intermediate to high SYNTAX scores (with mortality reduction at 5 years in FREEDOM).” They offer possible reasons why surgery seems to be favored in this challenging patient group: Complete revascularization may provide a survival advantage, and it is more likely to be achieved with CABG than with PCI In CKD patients, procedural success is less common with PCI, contributing to the risk of incomplete revascularization Surgery may help protect against future coronary events by bypassing vulnerable plaques In an accompanying editorial, Usman Baber, MD, MS, and Roxana Mehran, MD, both of the Icahn School of Medicine at Mount Sinai (New York, NY), confirm the consistency of these data with past studies in patients with diffuse or complex CAD as well as in those receiving dialysis. However, this study is at odds with “a recent network meta-analysis suggesting that newer-generation DESs yield mortality reductions comparable with CABG when either is compared with medical therapy, whereas first-generation DESs confer less benefit.” The editorialists note an outstanding baseline difference even after propensity matching—adherence to dual antiplatelet therapy—that “as a potential mediator of DES-attributable mortality in the setting of CKD, may be particularly relevant given the increased bleeding risk observed in such patients.” Drs. Baber and Mehran also express surprise at the lack of difference in stroke risk between the treatment groups. “Although this rate is comparable with the CABG arms in both FREEDOM and SYNTAX trials, it is much higher than the [approximate] 1.5% stroke rate observed in the PCI arms of these randomized studies,” they write, adding that this may be due to chance or a selection bias favoring PCI.
Patient Choice Always a Factor In a telephone interview with TCTMD, Jeffrey A. Breall, MD, of Indiana University (Indianapolis, IN), said he too was “a little bit surprised” about the stroke rates. “To my knowledge, [this is] the first time that stroke ever [did not favor PCI],” he said. A strength of the study is that it represents real-world practice, according to Richard Solomon, MD, of the University of Vermont (Burlington, VT), who noted that 3 times as many patients underwent surgery as received PCI. He told TCTMD in a telephone interview that patient factors often influence treatment choice since “patients tend to look at the near future rather than long-term” and PCI is less invasive. “For people with lifespans that are already shortened by comorbidities, PCI may be a reasonable choice,” he said. The study authors observe that the best way to approach decision making is “in the framework of a Heart Team to define the optimal revascularization strategy for each individual patient.” Dr. Breall said a randomized trial in the CKD population—much like the FREEDOM trial in diabetics—would be “tremendously valuable” since the majority of PCI and CABG studies previously excluded patients with CKD. Given that “we see patients like this all the time,” he noted, enrollment would be easy. Dr. Solomon agreed but said he doubted that the outcomes would depart from what is seen in the current study. Another question is how the choice of revascularization affects the need for dialysis or worsening kidney function, he suggested.
The value of aggressive coronary artery revascularization compared with no revascularization in improving outcomes for patients with kidney disease is unknown. In the present study, we have shown that revascularization with CABG was associated with a lower risk of death than no revasculariza- tion for all categories of kidney function. Revascularization with PCI was also associated with a lower risk of death than no revascularization in reference patients and dialysis kidney disease patients but not in patients with nondialysis kidney disease. However, regardless of the treatment received, pa- tients with kidney disease had poorer survival than the reference group. These results must be interpreted in view of the observa- tional nature of the data. Although an association between revascularization and outcome has been demonstrated, the observed associations may or may not be causal. Although randomized controlled trials are the best means of confirming causation, large observational studies such as this can also be informative. Previous studies have also suggested a survival benefit for CABG in dialysis patients.13–16 The present study had the added advantage over other studies13,15,16 of being able to adjust for severity of cardiac disease and left ventricular function. The reduced survival for dialysis patients treated with PCI compared with CABG may be related to an increased risk of restenosis.22–24 Despite the reduced survival for dialysis patients treated with PCI compared with CABG, the results of the present study nonetheless suggest a survival advantage for PCI over no revascularization We also found a lower risk of death for CABG over both PCI and no revascularization for patients with nondialysis kidney disease (serum creatinine 2.3 mg/dL). These results are in contrast to those reported by Szczech et al,14 in which CABG was not associated with better survival among patients with a creatinine 2.5 mg/dL (hazard ratio 0.86, 95% CI 0.56 to 1.33). This discrepancy may be explained by their shorter duration of follow-up (3 years).14 To the best of our knowl- edge, only 1 other study of patients with nondialysis kidney disease has included a nonrevascularized group.17 Similar to the present results, CABG was associated with a survival benefit across all levels of kidney function, whereas PCI failed to offer a significant benefit among patients with severe (creatinine clearance 30 mL/min) kidney disease.17 The lack of an improvement in survival for PCI among nondialysis kidney disease patients is less likely to be explained by atherosclerotic risk factors and accelerated atherogenesis, because dialysis patients would also be so exposed, and yet a benefit of PCI over no revascularization was apparent in the dialysis group. A possible mechanism for the poor survival after PCI among nondialysis kidney disease patients is their increased risk of acute renal failure, an event associated with a greater risk of adverse outcomes after coronary intervention.25,26 The potential for increased com- plications after PCI, but not after CABG, in patients with kidney disease has been described.27 Another explanation may be higher rates of incomplete revascularization.28 Com- pleteness of revascularization, as defined by the Duke jeop- ardy score,29 has been shown to vary by level of kidney function in a previous study from the APPROACH data- base,30 with complete revascularization obtained in 67.6% of reference patients, 64.3% of dialysis kidney disease patients, and only 42.4% of nondialysis kidney disease patients. Although speculative, incomplete revascularization in pa- tients with nondialysis kidney disease may be related to conservative use of dye during angiography. Survival after revascularization for dialysis kidney disease patients was better in the present study than previously reported in the United States.13–15 A possible explanation for this finding is that unlike previous studies that included only patients hospitalized after revascularization, the APPROACH database includes both inpatients and outpatients after cath- eterization, thus including patients with less urgent indica- tions for catheterization. A second explanation may be that there are differences in outcomes between healthcare sys- tems, a possibility supported by recent research showing better survival in dialysis patients in Canada than in the United States.31 Given the observational nature of the present study, it has important limitations. First, selection bias is likely in that healthier patients may have been chosen for surgical inter- ventions. Nevertheless, multivariate analysis and propensity adjustment were used to mitigate the impact of selection bias. A selection process and possible bias are also likely in the decision to pursue a cardiac catheterization. Second, the dichotomy of creatinine into values greater or less than 2.3 mg/dL (200 mol/L) in the definition of nondialysis kidney disease limits an assessment of risk for various levels of kidney function. Third, the inception point for the cohort was cardiac catheterization. These patients are a subset of all patients with CVD and do not reflect the outcomes of all patients with CVD. Fourth, information on medication use during follow-up was not available, which prevented us from characterizing the medical treatment provided to the nonre- vascularized group. Finally, we were unable to track patients who may have left the province. This, however, is unlikely to have a major influence given the stability of the population, with a general trend in Alberta for increased inward rather than outward migration. In addition, we limited our study to residents of Alberta, and it would be rather atypical for a patient to move out of the province during a cardiac evaluation.
To summarize, we found a survival advantage for CABG compared with no revascularization for patients with all categories of kidney function. PCI was also associated with a survival advantage over no revascularization except in pa- tients with non–dialysis-dependent kidney disease. These results indicate that the presence of kidney disease or depen- dence on dialysis treatment should not be a deterrent to revascularization, particularly with CABG. A better under- standing of the factors associated with poor outcomes after PCI in patients with non–dialysis-dependent kidney disease may lead to improved management strategies for such patients.
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