Summary: New Drug Combinations Could Cut Heart Failure Mortality by 60%
Summary: New Drug Combinations Could Cut Heart Failure Mortality by 60%
1. Early Initiation of Therapy:
– HF treatment should begin immediately after diagnosis, alongside identifying underlying causes.
– Benefits appear quickly with early intervention.
2. Recommended Quadruple Therapy (ESC 2021):
– For HFrEF (LVEF ≤ 40%) and mildly reduced EF (LVEF 41–49%):
• ACE inhibitors or ARNI
• Beta-blockers
• Mineralocorticoid receptor antagonists (MRAs)
• SGLT2 inhibitors
– Loop diuretics added for volume overload.
3. Supporting Evidence:
– PARADIGM-HF and dapagliflozin trials showed mortality and hospitalization reduction within 30 and 27 days, respectively.
4. Delayed Diagnosis is a Barrier: Only 29% of patients with NT-proBNP > 2000 ng/L were diagnosed with HF within 1 year (REVOLUTION HF study).
• Average time to first echocardiography: 40 days.
• BNP and NT-proBNP are crucial biomarkers in diagnosing HF. Elevated levels indicate increased cardiac wall stress—a hallmark of HF.
• BNP >100 pg/mL → Sensitivity: 90%, Specificity: 76%
• NT-proBNP >900 pg/mL → Sensitivity: 90%, Specificity: 85%
• NT-proBNP <300 pg/mL effectively excludes acute HF with Sensitivity: 99%, Specificity: 68%
– Interpretation must consider age, renal function, and BMI.
5. Diagnostic Gaps Increase Mortality:
– Lower natriuretic peptide levels often lead to missed diagnoses and untreated patients—resulting in higher mortality.
6. Treatment Sequence Recommendation:
– Week 1: Start SGLT2 inhibitors, assess tolerability.
– Week 2: Add MRAs.
– Weeks 3–6: Gradually titrate beta-blockers.
– Weeks 6–10: Start and titrate ARNI once BP is stable.
– Flexibility: SGLT2i + MRAs may start together; beta-blockers may be introduced earlier if tolerated.
7. Survival Benefits:
– Switching from dual to quadruple therapy adds:
• +6.3 years of life for a 55-year-old.
• +1.4 years for an 80-year-old.
– These gains reflect an estimated 60% reduction in heart failure mortality, based on cumulative evidence from key clinical trials.
– Each of the four foundational drug classes has shown the following independent mortality and morbidity reductions:
• ARNI (e.g., sacubitril/valsartan – PARADIGM-HF): ↓ CV death or HF hospitalization by ~20%
• Beta-blockers (e.g., bisoprolol, metoprolol – MERIT-HF, CIBIS-II): ↓ all-cause mortality by ~34%
• MRAs (e.g., spironolactone – RALES, eplerenone – EMPHASIS-HF): ↓ CV mortality by ~30%
• SGLT2 inhibitors (e.g., dapagliflozin – DAPA-HF, empagliflozin – EMPEROR-Reduced): ↓ CV death or HF hospitalization by ~25%
– When used together, these therapies result in a cumulative benefit due to partially overlapping mechanisms and shared outcomes, leading to a powerful overall impact—without simply summing individual effects.
8. Implementation Challenges:
– Quadruple therapy is still underutilized.
– Telemonitoring is not widely adopted, despite its benefits.
9. Device Therapy for Worsening HF:
– Includes pacemakers, ICDs, CRT devices, and remote monitoring.
– Essential for patients unresponsive to drugs.
10. Arrhythmia Control:
– Rhythm control in HF with atrial fibrillation can reduce both mortality and hospitalization.
11. Emerging Drug – Vericiguat:
– A soluble guanylate cyclase stimulator for worsening HF or drug intolerance.
– Effective even at eGFR as low as 15 mL/min.
– VICTOR trial results expected in 2024.
12. Iron Deficiency Management:
– IV ferric carboxymaltose (Class IIa): improves symptoms and reduces rehospitalization.
– Meta-analysis: 28% reduction in HF hospitalization + CV death.
13. HFpEF Management:
– Current: SGLT2 inhibitors, diuretics, comorbidity control.
– Future: Finerenone (non-steroidal MRA) from FINEARTS-HF trial.
• Reduced HF events and CV death.
• May be included in 2026 ESC guidelines.