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

Abstract

Abstract Background 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. Purpose This systematic review aimed to identify drug and non-drug exercise randomized controlled trials that stratified treatment outcome by sex. Methods 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. Results 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. Conclusions 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. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): British Heart Foundation