Santema BT, Ouwerkerk W, Tromp J, et al. - Via a post-hoc analysis of BIOSTAT-CHF, a prospective study in 11 European countries of patients with heart failure in whom initiation and up-titration of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) and β blockers was encouraged by protocol, experts hypothesised that there might be gender variations in the optimal dose of ACE inhibitors or ARBs and β blockers in patients (n = 1,308 men and 402 women) with heart failure with reduced ejection fraction (HFrEF). A comparable number of men and women reached guideline-recommended target doses of ACE inhibitors or ARBs. In men, the lowest hazards of death or hospitalization for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and β blockers, however, women exhibited nearly 30% lower risk at only 50% of the recommended doses, with no further reduction in risk at higher dose levels. These gender variations were still present following adjustment in clinical covariates, including age and body surface area. In the ASIAN-HF registry, for both ACE inhibitors or ARBs and β blockers, comparable patterns were noted, with women having nearly 30% lower risk at 50% of the recommended doses, with no additional advantage at higher dose levels. Therefore, this study recommends that women with HFrEF might require lower doses of ACE inhibitors or ARBs and β blockers in comparison with men, and brings into issue what the true optimal medical therapy is for women vs men.