Sex-based differences in treatment outcomes in HFpEF: a systematic review

Heart failure with preserved ejection fraction (HFpEF) is the prevailing heart failure phenotype among women. Disease-modifying treatment in HFpEF has proved a challenge and little is known on sex-based differences in treatment outcomes in HFpEF.

This systematic review aimed to identify drug and non-drug exercise randomized controlled trials that stratified treatment outcome by sex.

A systematic literature search of PubMed for randomised controlled trials that assessed treatment outcomes by sex (pre-specified, secondary, post-hoc analysis) for HFpEF was performed until January 2021.

This systematic review included 36 drug and 2 exercise RCTs. There was an increased benefit in reducing the composite outcome of first and recurrent HF hospitalisation and cardiovascular death among women (HR 0.73, 95% CI 0.59–0.90) compared to men (HR 1.03, 95% CI, 0.84–1.25, p-interaction = 0.017) treated with sacubitril-valsartan. However, women (HR 1.41, 95% CI 1.02–1.97) had higher risk of new-onset AF compared to men (HR 0.79, 95% CI 0.55,1.14, p-interaction 0.019) taking sacubitril-valsartan, and men (Δ2.8, 95% CI 1.3–4.3) were more likely to show improvements in the KCCQ-CSS compared to women (Δ-0.6, 95% CI −2.1,0.8, p-interaction=0.003). There may be benefit among women treated with sacubitril-valsartan in lowering blood pressure and characteristic impedance. A superior risk reduction in all-cause mortality was reported in women treated with spironolactone (HR 0.66, 95% CI 0.48–0.90) when compared with men (HR 1.06, 95% CI 0.81–1.39, p-interaction=0.024). No differences in treatment outcomes by sex were reported with SGLT2 inhibitors or with exercise interventions in HFpEF.

Women may respond to HFpEF treatment differently than men. Identifying sex-based differences in treatment outcomes should be prioritised in future research and taken into consideration in the development of guidelines for the management of HFpEF.

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): British Heart Foundation