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Phase 3 randomized clinical trials (RCT) evaluating bupropion, naltrexone, or B\u2010N versus control with reported incidence of MACE. The meta\u2010analysis included 12 RCTs, 69% for weight loss and 29% for smoking cessation, with 19,176 patients and 7354 patient\u2010years who were randomized to an active treatment (bupropion [<jats:italic>n<\/jats:italic>\u2009=\u20092965] or B\u2010N [<jats:italic>n<\/jats:italic>\u2009=\u20096980] or naltrexone [<jats:italic>n<\/jats:italic>\u2009=\u2009249]) versus control (placebo [<jats:italic>n<\/jats:italic>\u2009=\u20096968] or nicotine patch [<jats:italic>n<\/jats:italic>\u2009=\u20092014]). The mean age was 54\u2009\u00b1\u20098 years (55% female), and the baseline BMI was 32\u2009\u00b1\u20095 kg\/m<jats:sup>2<\/jats:sup>. The additive network meta\u2010analysis model for random effects showed no association between bupropion, B\u2010N, or naltrexone and MACE (odds ratio [OR]\u2009=\u20090.90 [95%CI 0.65\u20131.25], <jats:italic>p<\/jats:italic>\u2009=\u20090.52; OR\u2009=\u20090.97 [95%CI 0.75\u20131.24], <jats:italic>p<\/jats:italic>\u2009=\u20090.79; OR\u2009=\u20091.08 [95%CI 0.71\u20131.63], <jats:italic>p<\/jats:italic>\u2009=\u20090.73, respectively; <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> =\u20090%, <jats:italic>p<\/jats:italic>\u2009=\u20090.86). Meta\u2010regression analyses showed no significant association between MACE and potential confounders from RCT demographic disparities (<jats:italic>p<\/jats:italic>\u2009=\u20090.58). The statistical power (post hoc two\u2010tailed) for non\u2010inferiority was 91%, giving a strong probability of validity. Naltrexone, bupropion, or B\u2010N is not associated with the incidence of MACE as compared with placebo.<\/jats:p>","DOI":"10.1111\/obr.13224","type":"journal-article","created":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T03:21:51Z","timestamp":1618284111000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Cardiovascular safety of naltrexone and bupropion therapy: Systematic review and meta\u2010analyses"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7127-2052","authenticated-orcid":false,"given":"Andrei C.","family":"Sposito","sequence":"first","affiliation":[{"name":"Department of Cardiology State University of Campinas  Campinas Brazil"},{"name":"Obesity and Comorbidities Research Center State University of Campinas  Campinas 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