Does Sex Affect the Efficacy, Safety, and Quality of Life Outcomes for Patients Using Angiotensin Receptor Neprilysin Inhibitor, Soluble Guanylate Cyclase Stimulators, and Cardiac Myosin Activators in Heart Failure? A Systematic Review.

Background: Heart failure (HF) is a condition with significant differences between men and women, due to pathophysiology disparities attributed to hormonal factors and different comorbidities rates. There are no guidelines specifically tailored for women. The objective of the study is to summarise the current evidence of efficacy, safety, and impact on quality of life associated with angiotensin receptor neprilysin inhibitor, guanylate cyclase stimulators, and cardiac myosin activators drugs across different sexes.

Methods: We performed a systematic search on PubMed, EMBASE, Cochrane Central, and Google Scholar databases for randomised controlled trials (RCTs), including patients with HF with reduced ejection fraction or HF with preserved ejection fraction. The outcomes were N-terminal pro-B-type natriuretic peptide hormone levels, functional capacity, ventricular remodelling, safety results, and quality of life. The risk of bias was assessed using the Risk of Bias 2 tool.

Results: This review included data from eight RCTs (10 studies), involving a total of 15,021 patients, of whom 48% were women. HF with preserved ejection fraction was studied in five RCTs, and HF with reduced ejection fraction in three RCTs. Regarding clinical outcomes, six RCTs evaluated N-terminal pro-B-type natriuretic peptide hormone levels, all comparing sacubitril-valsartan with standard therapy, while two others compared functional capacity between the sexes, two analysed safety outcomes by sex subgroups, and only one RCT compared men and women for the ventricular remodelling outcome. Two RCTs assessed differences in quality of life between men and women. None of the studies showed any statistical difference between the subgroups and most outcomes demonstrated a low risk of bias.

Conclusions: This review shows consistent efficacy, safety and quality of life across both sexes for HF treatments.