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Chronic Stable Angina
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3. Atherosclerosis Timeline Foam Cells Fatty Streak Intermediate Lesion Atheroma Fibrous Plaque Complicated Lesion/ Rupture Adapted from Pepine CJ. Am J Cardiol. 1998;82(suppl 104). From First Decade From Third Decade From Fourth Decade Endothelial Dysfunction
62. NCEP Primary CHD Risk Goals for Lowering LDL-C 1/00 medslides.com LDL-C Goal No CHD <2 RF <160 mg/dL No CHD 2 RF <130 mg/dL CHD 100 mg/dL The NCEP recommends lowering LDL-C even further than these goals, if possible. Risk Category NHLBI; September 1993
63. HOPE: Study Design 1/00 medslides.com The HOPE Study Investigators. N Engl J Med . 2000;342:145-153. Inclusion Criteria: Age 55 y, history: CAD, stroke, PAD OR diabetes + 1 CVD risk factor Exclusion Criteria: CHF, known EF < 0.40; MI, stroke w/in 4 wk; current ACE inhibitor, vit E 267 Centers: US, Europe, Canada, Central America ALTACE Placebo Patients Randomized N=9297
64. HOPE: Primary Outcome Reductions in MI, Stroke, or Cardiovascular Death 1/00 medslides.com Note: Trial halted early due to the highly significant risk reductions seen with ALTACE 0.20 0.15 0.10 0.05 0 0 500 1000 1500 Days of Follow-up % of Patients Reaching Endpoints Placebo ALTACE ® (ramipril) 15% Reduction in Events at 1 year 22% Reduction in Events P=.0001*
82. Patient Follow Up Monitoring of Symptoms and Anti-anginal Therapy 1/00 medslides.com
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97. The Progressive Development of Cardiovascular Disease Endstage Heart Disease Congestive Heart Failure Ventricular Dilation Remodeling Arrhythmia & Loss of Muscle Myocardial Infarction Myocardial Ischemia CAD Atherosclerosis Endothelial Dysfunction Risk Factors Coronary Thrombosis
Notes de l'éditeur
9 Atherosclerosis is a progressive disease involving the development of arterial wall lesions. As they grow, these lesions may narrow or occlude the arterial lumen. Complex lesions may also become unstable and rupture, leading to acute coronary events, such as unstable angina, myocardial infarction, and stroke. Pepine CJ. The effects of angiotensin-converting enzyme inhibition on endothelial dysfunction: potential role in myocardial ischemia. Am J Cardiol . 1998; 82(suppl 10A):244-275.
11 The HOPE (Heart Outcomes Prevention Evaluation) study was a double-blind, randomized multinational clinical trial. Patients, 55 years or older, at high risk of cardiovascular events (history of either coronary artery disease, stroke, or peripheral vascular disease, or of diabetes and at least one additional cardiovascular disease risk factor) were recruited from 267 centers in 19 countries. Exclusion criteria included heart failure, known low ejection fraction (<0.40), uncontrolled hypertension or overt nephropathy, myocardial infarction or stroke within 4 weeks of study entry, and current use of an angiotensin-converting enzyme inhibitor or vitamin E. Of the 10,576 patients entering the run-in phase, 9,541 were eligible for randomization to treatment. A small subset (244 patients) were randomized to treatment with ALTACE 2.5 mg, given once daily. The remaining 9,297 patients were randomized to treatment with once daily ALTACE (4,645) or placebo (4,652). All patients randomized to the main treatment group (ALTACE) or placebo were included in the main study analyses. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000; 342:145-153.
13 The primary endpoint in the HOPE (Heart Outcomes Prevention Evaluation) study was a composite outcome that included myocardial infarction, stroke, or death from cardiovascular causes. This landmark trial was halted early, after an average treatment duration of 4.5 years, due to the highly significant risk reductions seen with ALTACE for the primary endpoint. Of the 4,645 patients randomized to ALTACE, 651 (14%) reached the primary endpoint; 826 (17.8%) of the 4,652 randomized to placebo reached the primary endpoint. The relative risk of reaching the composite endpoint in the ALTACE group as compared to the placebo group was 0.78 (95% confidence interval, 0.70 to 0.86) (P=0.0001), a 22% reduction. The reduction in risk was evident in the ALTACE group at the end of 1 year: 169 patients and 198 patients in the ALTACE and placebo groups, respectively, reached the endpoint (relative risk: 0.85; 95% confidence interval, 0.70 to 1.05), a 15% reduction. Package Insert, Altace Prescribing Information as of September 2000
14 Each of the outcomes in the primary composite outcome was analyzed separately. A number of secondary outcomes, including all-cause mortality, were also analyzed. The relative risks of myocardial infarction (MI), death from cardiovascular (CV) causes, and stroke were significantly reduced (P=0.0001) by 20% (95% CI, 0.70-0.90), 26% (95% CI, 0.64-0.87), and 32% (95% CI: 0.56-0.84), respectively, in the ALTACE group as compared to the placebo group. The relative risk of death from any cause was also significantly reduced (P=0.005) by 16% (95% CI, 0.75-0.95) in the ALTACE group as compared to the placebo group. Notably, treatment with ALTACE was beneficial among patients who were already receiving a number of effective CV risk-reduction medications, including aspirin, beta-blockers, and lipid-lowering agents.
10 Atherosclerotic disease is a progressive disease as shown in this slide. Many therapeutic interventions are aimed at specific cardiovascular conditions. These interventions may be directed at alleviating symptoms or preventing progression to more serious stages or both. Angiotensin-converting enzyme (ACE) inhibitors have been studied, for example, in patients with hypertension, who are at the top of this progression pathway. These studies looked only at the effects on blood pressure, however, and did not address the long-term question of risk reduction. Other clinical trials with ACE inhibitors have been designed to investigate the effects of these agents on the morbidity and mortality following an acute myocardial infarction.