Benefits of combination pharmacotherapy for HFrEF
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In patients with heart failure with reduced ejection fraction (HFrEF), ?-blockers, mineralocorticoid-receptor antagonists (MRAs) and sodium–glucose cotransporter 2 (SGLT2) inhibitors have shown benefit in placebo-controlled trials, and angiotensin receptor–neprilysin inhibitors (ARNIs) provide incremental benefit compared with angiotensin-converting enzyme (ACE) inhibitors.

However, because these agents were generally tested in parallel and not incrementally, the additive benefits of combining these therapies are untested. Moreover, ARNIs, SGLT2 inhibitors and MRAs remain suboptimally prescribed in clinical practice. In a new cross-trial analysis, researchers predict that a comprehensive strategy combining several drugs reduces hospitalization and mortality compared with conventional therapy.

- The analysis included patient-level data from three randomized, controlled trials (EMPHASIS-HF, PARADIGM-HF and DAPA-HF) with a combined total of 15,880 patients with HFrEF (78% men).
- Compared with conventional therapy (a ?-blocker and an ACE inhibitor or angiotensin-receptor blocker), a comprehensive strategy (combining an ARNI, ?-blocker, MRA and SGLT2 inhibitor) was predicted to reduce the primary end point of cardiovascular death or hospitalization for heart failure as well as each of these end point individually and all-cause mortality.
- With the comprehensive strategy, a patient aged 80 years was estimated to gain 2.7 additional years free from a primary end point event and would survive for an additional 1.4 years. These outcomes increased to 8.3 and 6.3 additional years, respectively, for a patient aged 55 years.

“There are incremental benefits of treating patients with HFrEF with all four agents impacting five pathways (angiotensin II, aldosterone, noradrenaline, neprilysin and SGLT2), and this approach should be considered the standard of care,” said researchers.

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