{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:06:44Z","timestamp":1792786004662,"version":"4.5.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T00:00:00Z","timestamp":1673568000000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Sanofi to HMRI"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Treatment with phosphodiesterase type 5 inhibitors (PDE-5is) is effective in treating erectile dysfunction (ED).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The objective of this study was to determine the effect of PDE-5is on the incidence of major adverse cardiovascular (CV) events (MACE; composite outcome of CV death, hospitalization for myocardial infarction, coronary revascularization, stroke, heart failure, and unstable angina pectoris) and overall mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective observational cohort study was conducted in a large US claims database in men with \u22651 diagnosis of ED without prior MACE within 1\u00a0year, from January 1, 2006, to October 31, 2020. The exposed group had \u22651 claim for PDE-5i and the unexposed group had no claims for PDE-5i, and the groups were matched up to 1:4 on baseline risk variables.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcome<\/jats:title>\n                    <jats:p>The primary outcome was MACE and the secondary outcomes were overall mortality and individual components of MACE, determined by multivariable Cox proportional hazard modeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Matched plus multivariable analyses showed that MACE was lower by 13% in men exposed (n\u2009=\u200923\u2009816) to PDE-5is (hazard ratio [HR] 0.87; 95% CI 0.79-0.95; P\u2009=\u2009.001) vs nonexposure (n\u2009=\u200948\u2009682) over mean follow-up periods of 37 and 29\u00a0months, respectively, with lower incidence of coronary revascularization (HR 0.85; 95% CI 0.73-0.98; P\u2009=\u2009.029), heart failure (HR 0.83; 95% CI 0.72-0.97; P\u2009=\u2009.016), unstable angina (HR 0.78; 95% CI 0.64-0.96; P\u2009=\u2009.021), and CV death (HR 0.61; 95% CI 0.41-0.90; P\u2009=\u2009.014) with PDE-5i exposure. Phosphodiesterase type 5 inhibitor\u2013exposed men had a 25% lower incidence of overall mortality (HR 0.75; 95% CI 0.65-0.87; P\u2009&amp;lt;\u2009.001). Men without coronary artery disease (CAD) but with CV risk factors at baseline showed a similar pattern. In the main study cohort, men in the highest quartile of PDE-5i exposure had the lowest incidence of MACE (HR 0.45; 95% CI 0.37-0.54; P\u2009&amp;lt;\u2009.001) and overall mortality (HR 0.51; 95% CI 0.37-0.71; P\u2009&amp;lt;\u2009.001) vs the lowest exposure quartile. In a subgroup with baseline type 2 diabetes (n\u2009=\u20096503), PDE-5i exposure was associated with a lower MACE risk (HR 0.79; 95% CI 0.64-0.97; P\u2009=\u2009.022).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Implications<\/jats:title>\n                    <jats:p>PDE-5is may have cardioprotective effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Strengths and Limitations<\/jats:title>\n                    <jats:p>Strengths are the large numbers of participants and consistency of the data; limitations include the retrospective nature of the study and unknown confounders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In a large population of US men with ED, PDE-5i exposure was associated with lower incidence of MACE, CV death, and overall mortality risk compared to non-exposure. Risk reduction correlated with PDE-5i exposure level.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jsxmed\/qdac005","type":"journal-article","created":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T17:44:04Z","timestamp":1673631844000},"page":"38-48","source":"Crossref","is-referenced-by-count":41,"title":["Effect of phosphodiesterase type 5 inhibitors on major adverse cardiovascular events and overall mortality in a large nationwide cohort of men with erectile dysfunction and cardiovascular risk factors: A retrospective, observational study based on healthcare claims and national death index data"],"prefix":"10.1093","volume":"20","author":[{"given":"Robert A","family":"Kloner","sequence":"first","affiliation":[{"name":"Huntington Medical Research Institutes , Pasadena, CA, United States"},{"name":"Keck School of Medicine, Department of Medicine, Division of Cardiovascular Medicine , Los Angeles, CA, United 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