Optimization of Drug Therapy for Heart Failure With Reduced Ejection Fraction Based on Gender

Over the last decades, several classes of drugs have been introduced for the treatment of patients with heart failure with reduced ejection fraction (HFrEF). Their use has been supported by randomized controlled trials that have demonstrated improved patient outcomes. However, these trials enrolled a small number of female patients and sometimes have reported gender-related differences regarding the efficacy of the treatments. The aim of this review is to revise the available data about the influence of gender on the optimal treatment and drug dose in patients with HFrEF.

Several gender-related differences in terms of pharmacokinetic and pharmacodynamic characteristics of the drugs have been described. These characteristics could be responsible for a different response and tolerability in men and women also when current recommended treatment of HFrEF is considered. Some studies have shown that, in women, lower doses of beta-blockers and inhibitors of renin angiotensin aldosterone system could be equally effective than higher doses in men, whereas sacubitril/valsartan could exert its favorable effect at greater values of left ventricular ejection fraction. Although there is evidence about differences in the response to treatment of HFrEF in men and women, this has not been sufficient for differentiating current recommended therapy. Further studies should better clarify if the treatment of HFrEF should be based also on the patients' gender.