Heart Failure Therapy: Lifetime Benefits & Ejection Fraction
- Sodium glucose co-transporter-2 inhibitors (SGLT2i) and non-steroidal mineralocorticoid receptor antagonists (nsMRA) like finerenone have independently demonstrated benefits in patients with heart failure with mildly reduced or preserved ejection...
- However, a recent cross-trial analysis of the DELIVER, FINEARTS-HF, and PARAGON-HF trials investigated the combined impact of these therapies.
- Researchers estimated that using both SGLT2i and nsMRA therapies could reduce the risk of cardiovascular death or a first worsening heart failure event by 31% in the overall...
Combination Therapy Shows Promise in heart Failure Treatment
Table of Contents
Updated October 7, 2025, 07:12:24 AM PDT
Synergistic Effects of Heart Failure Medications
Sodium glucose co-transporter-2 inhibitors (SGLT2i) and non-steroidal mineralocorticoid receptor antagonists (nsMRA) like finerenone have independently demonstrated benefits in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF). Additionally, sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNI), improves outcomes for those with HFmrEF/HFpEF who have a left ventricular ejection fraction (LVEF) below 60%.
However, a recent cross-trial analysis of the DELIVER, FINEARTS-HF, and PARAGON-HF trials investigated the combined impact of these therapies. The analysis, as of October 7, 2025, suggests a significant reduction in cardiovascular risk with combined treatment.
Significant Risk Reduction with combined Therapies
Researchers estimated that using both SGLT2i and nsMRA therapies could reduce the risk of cardiovascular death or a first worsening heart failure event by 31% in the overall patient population (HR 0.69; 95% CI 0.59 to 0.81). For patients with HFmrEF/HFpEF and an LVEF under 60%, combining SGLT2i, nsMRA, and ARNI therapies was projected to reduce risk by 39% (HR 0.61; 95% CI 0.48 to 0.77).
These findings suggest a synergistic effect, where the combination of therapies provides a greater benefit than any single agent alone.
Years of Event-Free Survival
Long-term projections indicate substantial benefits for patients. A 65-year-old patient with HFmrEF/HFpEF receiving combined SGLT2i and nsMRA therapy could gain approximately 3.6 (2.0 to 5.2) additional years free from cardiovascular death or a heart failure event. For a 65-year-old with an LVEF under 60% on combined SGLT2i, nsMRA, and ARNI therapy, the projected gain is even greater, at 4.9 (2.6 to 7.3) years.
Importantly, these benefits where estimated to be consistent across a broad age range, from 55 to 85 years, highlighting the potential for widespread impact.
Implications for Treatment Strategies
The analysis underscores the potential of early combination medical therapy with SGLT2i and nsMRA – and the addition of ARNI for select individuals – to substantially improve long-term outcomes for patients with HFmrEF and HFpEF. These findings suggest a shift towards more aggressive, multi-faceted treatment approaches for heart failure.