{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T01:11:12Z","timestamp":1780535472334,"version":"3.54.1"},"reference-count":8,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Cardiology"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Tadalafil is a long\u2010acting phosphodiesterase\u20105 inhibitor (PDE\u20105i) indicated for erectile dysfunction (ED).<\/jats:p><\/jats:sec><jats:sec><jats:title>Hypothesis<\/jats:title><jats:p>Our hypothesis was that tadalafil will reduce the risk of major adverse cardiovascular events (MACE: composite of cardiovascular death, myocardial infarction, coronary revascularization, unstable angina, heart failure, stroke) and all\u2010cause death in men with ED.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective observational cohort study was conducted in a large US commercial insurance claims database in men with a diagnosis of ED without prior MACE within 1 year. The exposed group (<jats:italic>n<\/jats:italic>\u2009=\u20098156) had \u22651 claim for tadalafil; the unexposed group (<jats:italic>n<\/jats:italic>\u2009=\u200921\u2009012) had no claims for any PDE\u20105i.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Primary outcome was MACE; secondary outcome was all\u2010cause death. Groups were matched for cardiovascular risk factors, including preventive therapy. Over a mean follow\u2010up of 37 months for the exposed group and 29 months for the unexposed group, adjusted rates of MACE were 19% lower in men exposed to tadalafil versus those unexposed to any PDE\u20105i (hazard ratio [HR]\u2009=\u20090.81; 95% confidence intervals [CI]\u2009=\u20090.70\u22120.94; <jats:italic>p<\/jats:italic>\u2009=\u2009.007). Tadalafil exposure was associated with lower adjusted rates of coronary revascularization (HR\u2009=\u20090.69; 95% CI\u2009=\u20090.52\u22120.90; <jats:italic>p<\/jats:italic>\u2009=\u2009.006); unstable angina (HR\u2009=\u20090.55; 95% CI\u2009=\u20090.37\u22120.81; <jats:italic>p<\/jats:italic>\u2009=\u2009.003); and cardiovascular\u2010related mortality (HR\u2009=\u20090.45; CI\u2009=\u20090.22\u22120.93; <jats:italic>p<\/jats:italic>\u2009=\u2009.032). Overall mortality rate was 44% lower in men exposed to tadalafil (HR\u2009=\u20090.56; CI\u2009=\u20090.43\u22120.74; <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001). Men in the highest quartile of tadalafil exposure had the lowest rates of MACE (HR: 0.40; 95% CI: 0.28\u22120.58; <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001) compared to lowest exposure quartile.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In men with ED, exposure to tadalafil was associated with significant and clinically meaningful lower rates of MACE and overall mortality.<\/jats:p><\/jats:sec>","DOI":"10.1002\/clc.24234","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T17:43:37Z","timestamp":1708451017000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The association of tadalafil exposure with lower rates of major adverse cardiovascular events and mortality in a general population of men with erectile dysfunction"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6258-0544","authenticated-orcid":false,"given":"Robert A.","family":"Kloner","sequence":"first","affiliation":[{"name":"Huntington Medical Research Institutes Pasadena California USA"},{"name":"Keck School of Medicine of University of Southern California Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Stanek","sequence":"additional","affiliation":[{"name":"Elevance Health Inc. Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karishma","family":"Desai","sequence":"additional","affiliation":[{"name":"Carelon Research Inc. Wilmington Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.","family":"Crowe","sequence":"additional","affiliation":[{"name":"Carelon Research Inc. Wilmington Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Paige Ball","sequence":"additional","affiliation":[{"name":"Carelon Research Inc. Wilmington Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Haynes","sequence":"additional","affiliation":[{"name":"Carelon Research Inc. Wilmington Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond C.","family":"Rosen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences University of California, San Francisco San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/jsxmed\/qdac005"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2015-309223"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2016-310746"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.01.045"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v8.i3.104"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.201226"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/2047487317718082"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.73.11.1247"}],"container-title":["Clinical Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/clc.24234","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T10:10:20Z","timestamp":1713175820000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/clc.24234"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2]]},"references-count":8,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/clc.24234"],"URL":"https:\/\/doi.org\/10.1002\/clc.24234","archive":["Portico"],"relation":{},"ISSN":["0160-9289","1932-8737"],"issn-type":[{"value":"0160-9289","type":"print"},{"value":"1932-8737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2]]},"assertion":[{"value":"2023-12-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e24234"}}