Key result
Comprehensive disease-modifying therapy cuts CV death or first HF hospitalization ~66% vs. conventional therapy.
Why the study?
No head-to-head clinical trials have been performed to determine the total effect of comprehensive disease-modifying pharmacological treatments in patients with HFrEF.
Does comprehensive disease-modifying pharmacological therapy (quintuple therapy including vericiguat) reduce the composite of cardiovascular death or heart failure hospitalization in patients with HFrEF compared to conventional therapy?
Meta-Analysis (n=30,808)
Does comprehensive disease-modifying pharmacological therapy (quintuple therapy including vericiguat) reduce the composite of cardiovascular death or heart failure hospitalization in patients with HFrEF compared to conventional therapy?
A comprehensive disease-modifying pharmacological approach utilizing five drug classes (including vericiguat) is estimated to yield a profound 66% relative risk reduction for cardiovascular death or heart failure hospitalization in patients with HFrEF compared to older standard therapy.
To determine the effects of the comprehensive disease-modifying pharmacological approach among patients with heart failure with reduced ejection fraction, a cross-trial, aggregate-data analysis was performed to estimate the expected combined effect of quintuple therapy by multiplying trial-level HRs, assuming independent and multiplicative treatment effects from Phase III randomised clinical trials: EMPHASIS-HF, PARADIGM-HF, pooled DAPA-HF and EMPEROR-Reduced, and pooled VICTORIA and VICTOR. The imputed aggregate treatment effects on the primary endpoint of cardiovascular death or first heart failure hospitalisation were favourable to the quintuple compared with conventional therapy (HR 0.34; 95% CI [0.27-0.42]). This also occurred for cardiovascular death alone (HR 0.47; 95% CI [0.35-0.63]), first heart failure hospitalisation (HR 0.31; 95% CI [0.23-0.40]) and all-cause mortality (HR 0.51; 95% CI [0.39-0.67]). The numbers needed to treat per year for the primary outcome, cardiovascular death and first heart failure hospitalisation were 10, 23 and 15, respectively. Our findings support the potential benefit of comprehensive therapy, with the incremental role of vericiguat likely greatest in higher-risk patients or those with recent worsening heart failure.
No takes yet. Share an insight, caveat, or question.
Escobar et al. (2026) conducted a meta-analysis in Heart failure with reduced ejection fraction (HFrEF) (n=30,808). Comprehensive disease-modifying pharmacological therapy (ARNI, beta-blocker, MRA, SGLT2I, and vericiguat) vs. Conventional therapy (ACEI or ARB plus beta-blocker) was evaluated on Composite of cardiovascular death or first heart failure hospitalisation (HR 0.34, 95% CI 0.27-0.42). Comprehensive disease-modifying therapy reduced the estimated risk of cardiovascular death or first heart failure hospitalization by 66% (HR 0.34) compared with conventional therapy, with an annualized number needed to treat of 10.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: