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In Europe and the US, they are only approved if they are bioequivalent to the respective originator product. Nevertheless, the lack of clinical outcomes is sometimes used as the reason for hesitancy in prescribing generics. We performed an observational retrospective study on 17 branded vs. generic pharmaceutical substances for the treatment of hypertension\/heart failure, hyperlipidemia, and diabetes mellitus in a dataset of 9,413,620 insured persons, representing nearly the full population of Austria, from 2007 to 2012. We compared generic vs. branded medications using hazard ratios for all-cause death and major adverse cardiac and cardiovascular events (MACCE) as outcomes of interest. Using patient demographics, health characteristics from hospitalization records, and pharmacy records as covariates, we controlled for confounding in Cox models through inverse probability of treatment weighting (IPTW) using high-dimensional propensity scores. We observed that the unadjusted hazard ratios strongly favor generic drugs for all three pooled treatment indications (hypertension\/heart failure, hyperlipidemia, diabetes mellitus), but were attenuated towards unity with increasingly larger covariate sets used for confounding control. We found that after IPTW adjustment the generic formulation was associated with significantly fewer deaths in 10 of 17 investigated drugs, and with fewer MACCE in 11 of 17 investigated drugs. This result favoring generic drugs was also present in a number of sub-analyses based on gender, prior disease status, and treatment discontinuation. E-value sensitivity analyses suggested that only strong unmeasured confounding could fully explain away the observed results. In conclusion, generic medications were at least similar, and in some cases superior, to their branded counterparts regarding mortality and major cardiovascular events.<\/jats:p>","DOI":"10.1038\/s41598-020-62318-y","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T10:02:55Z","timestamp":1586167375000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Comparative effectiveness of branded vs. generic versions of antihypertensive, lipid-lowering and hypoglycemic substances: a population-wide cohort study"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2126-7199","authenticated-orcid":false,"given":"Yuxi","family":"Tian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berthold","family":"Reichardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1339-0311","authenticated-orcid":false,"given":"Daniela","family":"Dunkler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Hronsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang C.","family":"Winkelmayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5315-0497","authenticated-orcid":false,"given":"Anna","family":"Bucsics","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Strohmaier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1147-8491","authenticated-orcid":false,"given":"Georg","family":"Heinze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,6]]},"reference":[{"key":"62318_CR1","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1111\/j.1365-2125.2010.03718.x","volume":"70","author":"MG Duerden","year":"2010","unstructured":"Duerden, M. 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The study was financed by the Main Association of Austrian Social Security Institutions and the Austrian Agency for Health and Food Safety. We acknowledge the valuable technical support of the cosponsors, of the pharmacoeconomical advisory group of the Austrian social security institutions, and of the \u00d6sterreichische Apotheker-Verlagsgesellschaft mbH. Susanne Strohmaier received funding from the European Union\u2019s Horizon 2020 research and innovation programme under the Marie Sklodwoska-Curie grant agreement No 795292. There were no contractual restrictions to publication. W. C. W. received personal fees for consultancy or for membership in advisory boards from Akebia, Amgen, AstraZeneca, Bayer, Daiichi-Sankyo, Relypsa and Vifer. None of the other authors report any financial conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"5964"}}