“Drug quadruple drug combination” Could Cut Heart Failure Mortality by 60%
“Drug quadruple drug combination” Could Cut Heart Failure Mortality by 60%
Source: Medscape.
Published: May 15, 2025
Key Points:
1. Impact of Optimized Treatment:
• Quadruple drug therapy can reduce chronic heart failure (HF) mortality by up to 60%.
• Early initiation is crucial—start treatment immediately after diagnosis.
2. ESC 2021 Guidelines for HFrEF (LVEF ≤ 40%) and HFmrEF (41–49%):
• Quadruple regimen includes:
• ACE inhibitors or ARNI
• Beta-blockers
• MRAs
• SGLT2 inhibitors
• Loop diuretics added for volume overload.
• Supported by studies like PARADIGM-HF and DAPA-HF.
3. Delayed Diagnosis Is Common:
• Only 29% of high-risk patients were diagnosed within 1 year in the REVOLUTION HF study.
• Average delay: 40 days to get an echocardiogram.
• Delayed diagnosis = delayed treatment = higher mortality.
4. Treatment Initiation Sequence (Best Outcomes in 1 Year):
• Week 1: Start SGLT2 inhibitors.
• Week 2: Add MRAs (can be combined with SGLT2i).
• Weeks 3–6: Titrate beta-blockers.
• Weeks 4–9: Introduce ARNI, after BP stabilizes.
5. Life Expectancy Gains:
• +6.3 years for a 55-year-old switching to quadruple therapy.
• +1.4 years even at age 80.
6. Beyond Drugs – Device Therapy:
• Consider pacemakers, ICDs, CRT and telemonitoring (often underused).
• Treat arrhythmias proactively in HF patients with AF.
7. Emerging Therapies:
• Vericiguat (soluble guanylate cyclase stimulator) shows promise in those not responding to standard therapy.
• Usable down to eGFR 15 mL/min.
• VICTOR trial results expected soon.
8. Iron Deficiency in HF:
• IV iron carboxymaltose improves exercise tolerance and reduces hospitalizations.
• Meta-analysis of 6 trials shows 28% reduction in combined HF hospitalization/CV death.
9. HF with Preserved EF (HFpEF):
• Current therapy includes SGLT2 inhibitors + diuretics, in addition to managing comorbidities.
• However, the 2026 guidelines may also include new options.
• The FINEARTS-HF study showed that finerenone (a nonsteroidal MRA) significantly reduced HF events and cardiovascular death, mainly by decreasing HF-related hospitalizations.
• Finerenone is also used to prevent HF in diabetic nephropathy with albuminuria, and may have broader HF-specific roles in the future.
