{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T10:20:00Z","timestamp":1783938000431,"version":"3.55.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":1292,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T00:00:00Z","timestamp":1653264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Recent studies have suggested potential sex differences in treatment response to pharmacological therapies in heart failure (HF). We performed a systematic review and meta-analysis of studies comparing treatment effects between men and women with HF and reduced ejection fraction (HFrEF) using established guideline-directed medical therapy and other emerging pharmacological treatments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Systematic search was performed on PubMed, Embase, and Cochrane Library for randomized controlled trials published in 1990\u20132021. Outcomes were all-cause mortality and combined outcome of all-cause mortality and\/or hospitalization for HF. Of 618 articles identified, 25 articles and 100 213 patients (mean age 62 \u00b1 1.7 years, women 23.1%, mean left ventricular ejection fraction 26.6 \u00b1 1.3%) were included in the systematic review and meta-analysis. For the outcome of all-cause mortality, there was no evidence of treatment heterogeneity by sex for renin-angiotensin system inhibitors (RASi) [hazard ratio (HR) 0.86 (95% confidence interval 0.75\u20130.99) in men; HR 0.97 (0.77\u20131.23) in women; Pinteraction = 0.288], or for beta-blockers (BB) [HR 0.71 (0.59\u20130.86) in men; HR 0.87 (0.73\u20131.03) in women; Pinteraction = 0.345]. Similarly, for the composite outcome of death or HF hospitalization, there was no evidence of treatment heterogeneity by sex for RASi [HR 0.84 (0.77\u20130.93) in men; HR 0.94 (0.81\u20131.08) in women; Pinteraction = 0.210] or BB [HR 0.76 (0.64\u20130.90) in men; HR 0.72 (0.60\u20130.86) in women; Pinteraction = 0.650]. Results for mineralocorticoid receptor antagonists (MRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) from previously published meta-analyses were included in the review. For the combined outcome of cardiovascular death or HF hospitalization, no significant interaction for sex was observed for MRA (Pinteraction = 0.78) or SGLT2i (Pinteraction = 0.37). Results for emerging pharmacological treatments, such as soluble guanylate cyclase stimulators and cardiac myosin activators, were included in the review and showed consistent treatment effects between men and women.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our meta-analysis showed no differences between sex in treatment effect for BB and RASi. Review on previously published trials for MRA, SGLT2i, and emerging therapies presented consistent treatment effects between men and women.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.13974","type":"journal-article","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T04:24:16Z","timestamp":1653279856000},"page":"2753-2761","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Sex Differences in Efficacy of Pharmacological Therapies in Heart Failure with Reduced Ejection Fraction: A Meta-Analysis"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6331-0845","authenticated-orcid":false,"given":"Cecilia","family":"Danielson","sequence":"first","affiliation":[{"name":"National Heart Centre Singapore , 5 Hospital Drive, Level 10, Singapore, 169609 ,","place":["Singapore"]},{"name":"Department of Cardiology, Clinical Sciences, Lund University, Sk\u00e5ne University Hospital , Lund, SE-221 85 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6778-6269","authenticated-orcid":false,"given":"Gabriele","family":"Lileikyte","sequence":"additional","affiliation":[{"name":"National Heart Centre Singapore , 5 Hospital Drive, Level 10, Singapore, 169609 ,","place":["Singapore"]},{"name":"Department of Cardiology, Clinical Sciences, Lund University, Sk\u00e5ne University Hospital , Lund, SE-221 85 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2000-9358","authenticated-orcid":false,"given":"Wouter","family":"Ouwerkerk","sequence":"additional","affiliation":[{"name":"National Heart Centre Singapore , 5 Hospital Drive, Level 10, Singapore, 169609 ,","place":["Singapore"]},{"name":"Department of Dermatology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection & Immunity Institute , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1903-0018","authenticated-orcid":false,"given":"Carolyn","family":"S.P. Lam","sequence":"additional","affiliation":[{"name":"National Heart Centre Singapore , 5 Hospital Drive, Level 10, Singapore, 169609 ,","place":["Singapore"]},{"name":"Duke-NUS Medical School , Singapore ,","place":["Singapore"]},{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3042-5766","authenticated-orcid":false,"given":"David","family":"Erlinge","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Clinical Sciences, Lund University, Sk\u00e5ne University Hospital , Lund, SE-221 85 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8431-9961","authenticated-orcid":false,"given":"Tiew-Hwa Katherine","family":"Teng","sequence":"additional","affiliation":[{"name":"National Heart Centre Singapore , 5 Hospital Drive, Level 10, Singapore, 169609 ,","place":["Singapore"]},{"name":"Duke-NUS Medical School , Singapore ,","place":["Singapore"]},{"name":"School of Allied Health, University of Western Australia , Perth ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,5,23]]},"reference":[{"key":"2026012114151524600_ehf213974-bib-0001","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur Heart 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