Early Diabetes and Dyslipidaemia Treatment Optimisation.
Presentation by Dr Chan Wan Xian
Cardiologist, Echocardiologist
Heart Failure Intensivist
Asian Heart & Vascular Centre
www.ahvc.com.sg
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SGLT2 inhibitors in Heart failure: A prized addition to HF treatment options
1. SGLT2 inhibitors in Heart failure:
A prized addition to HF treatment options
Dr Chan Wan Xian
Consultant Cardiologist
Heart Failure Specialist
Echocardiologist
4. Based on the Framingham Heart Study, the mortality rate after diagnosis of HF in the USA was around 10% at 30 days, 20-30% at 1 year and only 45-
60% over 5 years of follow-up, which means only 1 in 2 patients survived after being diagnosed with heart failure in 5 years
5. Cardiac Function Decreases With Each Hospitalization
Adapted from Gheorghiade M et al. Am J Cardiol. 2005;96:6A.
6. Diabetes was 3-fold more common in Southeast Asian compared to white patients with HF, despite
younger age and less obesity, and more strongly associated with poor outcomes in Asian patients
than white patients. These results underscore the importance of ethnicity-tailored aggressive
strategies to prevent diabetes and its complications.
7. Diabetes and heart failure are interlinked
Diabetes Heart Failure
• Patients with HF have a four-
fold higher prevalence of
T2DM (20%) than patients
without HF (4–6%), and this
rises to 40% in T2DM patients
hospitalized for HF
• Metabolic impairment is
intrinsic to HF
pathophysiology, and insulin
resistance is present in up to
60% of patients with HF
• Diabetes is present in 35-45% of
patients with chronic heart
failure, whether they have a
reduced or preserved ejection
fraction
• DM increases hospitalisation
and mortality in HFrEF and
HFpEF patients by 75%
10. Unmet needs in HF Mx
• Prevention of heart failure in individuals with risks
• Disease modifying therapies to reduce mortality and improve
prognosis in HF patients
• Convincing therapeutic options in need for patients with HFpEF
• Managing cardiorenal syndrome
19. 68-year-old woman at high risk for CV events and HF
• Type 2 DM，HBA1C 7.7%
• Hypertension, Hyperlipidemia
• Had PCI a year ago to pLAD, presented with angina
• Currently asymptomatic, mild ankle edema
• BMI 30 BP 145/85
• Creatinine 97umol/L, eGFR 55 mL/min−1/1.73 m−2, microalbuminuria
• Current medications: Aspirin 100mg om, Atorvastatin 40mg ON, Metformin
1000mg bd, Gliclazide 60mg bd, Enalapril 10mg bd, Carvedilol 6.25mg bd
• Comes for regular follow up
• What can we do to further reduce his cardiovascular risks?
20. Impact of Glycemic control
• Intensive glycemic control does not appear to reduce the risk of all-cause mortality, cardiovascular
mortality, heart failure or stroke, it may reduce the risk of nonfatal myocardial infarction (MI)
21. • Optimal glycemic targets for patients with DM and HF should be individualized to reflect comorbidity burden,
including the severity of HF, and to balance the benefits likely to be achieved by lowering HbA1c with the
potential risks
• Treatment decisions need to consider potential benefits and harms of individual glucose-lowering medications
• AHA scientific statement suggest a target range of HbA1c 7% to 8% for most patients with HF ADA/ AHA guidelines
22. 2020 Novel Therapies for CV Risk With T2D Pathway
J A C C V O L . 7 6 , NO . 9 , 2 0 2 0
S E P T E M B E R 1 , 2 0 2 0 : 1 1 1 7 – 4 5
23.
24. Options to reduce CV risks
• Optimise DM glycemic control
• Prescribe glucose lowering medications with evidence based
cardiovascular and mortality benefit
• Optimise cardiovascular risk factors (target HBA1C <7%, BMI <25, BP
<130/80)
• Switch to medications with cardiovascular, renal and mortality
benefits, irrespective of HBA1C (recommend addition of SGLT2
inhibitors)
• Recommend lifestyle modifications options
26. 42 year old lady
• DM, recently diagnosed stage C HFrEF
• Non-ischemic cardiomyopathy (LVEF 30%) ,coros: normal coronary
arteries
• BP 135/75 BMI 28
• Current medications: Entresto 100mg bd, carvedilol 25mg bd,
spironolactone 25mg om
• Cardiovascular exam unremarkable
• HBA1C 6% Creatinine 88umol/L, eGFR 77 mL/min−1/1.73 m−2
• What are the options to reduce risks of future poor outcomes?
29. • Decreased CV death 18%
and HF hospitalisation 30%
• Reduced risk of worsening
HF
• Findings in patients with
diabetes were similar to
those in patients
without diabetes
30. Important SGLT2i trials in HF
Trial Entry criteria No of patients Outcomes
DAPA-HF
NEJM 2019
LVEF≤40%, NYHA II-IV
nt pro-BNP ≥600 pg/L
No DM requirement
4744 pts, 18 mths
Dapagliflozin 10mg om vs
placebo
↓CV death 18%
↓HF hospitalisation 30%
EMPEROR-Reduced
NEJM 2020
LVEF≤40%, NYHA II-IV
LVEF 31-40%, if recent
HHF or ↑BNP levels
No DM requirement
3730 pts, 16 mths
Empagliflozin 10mg om vs
placebo
↓HF hospitalisation 30%
NS CV death
SOLOIST-WHF
NEJM 2021
S/S of heart failure
Type II DM
1222 pts, 9 mths
Sotagliflozin 200mg om vs
placebo
↓HF hospitalisation/
visits 30%
NS CV death
31. Comprehensive quadruple therapy saves lives
• Estimated treatment effects of
comprehensive disease-modifying
pharmacological therapy (ARNI, β
blocker, MRA, and SGLT2
inhibitor) versus conventional
therapy (ACE inhibitor or ARB and
β blocker) in patients with chronic
HFrEF
• Hazard ratio (HR) for the imputed
aggregate treatment effects of
comprehensive disease-modifying
therapy versus conventional
therapy on the primary endpoint of
cardiovascular death or hospital
admission for heart failure was
0·38 (95% CI 0·30-0·47)
Lancet 2020 Jul 11;396(10244):121-128.
32. Options to further reduce risks
• Optimise heart failure medications according to good evidence based
medications
• Addition of SGLT2 inhibitors, Dapagliflozin (CV death reduction)
• Lifestyle modifications
• Cardiac rehabilitation for heart failure
33.
34. Safety considerations in SGLT2i use
JA C C V O L . 7 6 , NO . 9 , 2 0 2 0 Das
et al.
S E P T E M B E R 1 , 2 0 2 0 : 1 1 1 7 –
4 5
35.
36.
37. Conclusion
• SGLT2 inhibitors have changed the management of patients with
diabetes and cardiovascular diseases or heart failure
• Now SGLT2 inhibitors have been shown to be beneficial also in heart
failure patients without diabetes and potentially in those with chronic
kidney disease
• It is important to be familiar with the benefit and prescribing details
of this important class of medications so they can be utilised to
improve the clinical outcome of patients
38. Thank you
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Notes de l'éditeur
26 million heart failure patients worldwide
1-2% of Health care expenditure attributed to heart failure in Europe and North America
The cost of HF is driven by hospitalisation
Heart failure (HF) is a growing public health issue. As many as 1 in 5 people are expected to develop HF during their lifetime
Once admitted for clinical heart failure, there is increased risk of rehospitalisation
1 out of 4 in 30days and 1 in 2 46% in 60days
Together with a reduced in quality of life
1.Median Survival in Years by Age Group in HF Patients Compared With the
Life Expectancy in the United States, lower across all HF EF range
2. Overall survival rates for the heart failure group were 81.3% (95%CI 80.9–81.6), 51.5% (95%CI 51.0–52.0) and
29.5% (95%CI 28.9–30.2) at 1, 5 and 10 years respectively and did not change over time.
3.In general, the mortality following hospitalization for patients with heart failure is 10.4% at 30 days, 22% at 1 year, and 42.3% at 5 years, despite marked improvement in medical and device therapy
4. Based on the Framingham Heart Study, the mortality rate after diagnosis of HF in the USA was around 10% at 30 days, 20-30% at 1 year and 45-60% over 5 years of follow-up
Important to decrease HF and hospitalisation episodes
Can be optimised by compliance to meds, dietary and fluid restrictions, close monitoring
Singaporean HF patients are younger, less obese, 3x more have DM, associated with poorer outcomes in the diabetic patients
Pathophysiologically,
In heart failure, neuroendocrine activation alters haemodynamics and metabolism, predisposing to the development of diabetes through insulin resistance.
In diabetes, hyperglycaemia induces macro- and microvascular dysfunction, and myocardial ischaemia and/or infarction bias towards systolic dysfunction (heart failure with reduced ejection fraction), while in
the absence of ischaemia, diastolic dysfunction (heart failure with preserved ejection fraction) prevails through a combination of sarcomere stiffness and fibrosis.
Inflammation is a key systemic factor that contributes to several of these processes
Importance of prevention of a chronic condition
Studies indicate that patients hospitalized forHF have a 10%mortality rate
at30 dayspostdischarge23andthat themortality rateat1 yearfor
patients admitted to a hospital is 20%.24 Furthermore, the
readmission rate for HF at 6 months is 50%,25,26 and the risk of
mortality increases with each hospitalization
Mortality for patients with HFrEF remains high,31 with recent US registry data showing extremely poor 5-year mortality (75%) and hospital readmission (82%) rates
Subsequently were trials involving Dapagliflozin, Canaglifozin, ertugliflozin all showing absolute risk reduction in CV death/ HF hospitalisation
First SGLT2i cardiovascular outcomes trial (7) was the EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes) trial
first trial in T2DM that showed a significant 14% reduction (hazard ratio [HR]: 0.86; p ¼ 0.04) of MACE, which is a composite of myocardial infarction, stroke, and cardiovascular death (Figure 1) (7).
It reported a significant 38% reduction of cardiovascular death, a 32% reduction in all-cause death, and a 32% reduction of hospitalization for HF.
CANVAS (Canagliflozin Cardiovascular Assessment Study) program, which also reported a significant 14% reduction of MACE in patients randomized to canagliflozin when compared with those on placebo
a significant 33% reduction of hospitalization for HF was observed in canagliflozin-treated patients
consistent with DM clinical practice guidelines for patients with DM and serious comorbidities. For patients
with advanced, stage D HF not pursuing mechanical circulatory
support or transplantation, less stringent goals
may be appropriate.
Recent preventive guidelines
HRs were also favourable for cardiovascular death alone (HR 0·50 [95% CI 0·37-0·67]), hospital admission for heart failure alone (0·32 [0·24-0·43]), and all-cause mortality (0·53 [0·40-0·70]). Treatment with comprehensive disease-modifying pharmacological therapy was estimated to afford 2·7 additional years (for an 80-year-old) to 8·3 additional years (for a 55-year-old) free from cardiovascular death or first hospital admission for heart failure and 1·4 additional years (for an 80-year-old) to 6·3 additional years (for a 55-year-old) of survival compared with conventional therapy.
