Estimating the Benefits of the Comprehensive Disease-modifying Pharmacological Treatment in Patients with Heart Failure.

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.