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We identified patients newly prescribed fourth\u2010line anti\u2010hypertensive drugs (aldosterone antagonist , beta\u2010blocker, or alpha\u2010blocker). Using propensity score\u2013adjusted Cox proportional hazards models, we compared the incidence of the primary outcome (composite of all\u2010cause mortality, stroke, and myocardial infarction) between patients on different fourth\u2010line drugs. AA was the reference drug in all comparisons. Secondary outcomes were individual components of the primary outcome, blood pressure changes, and heart failure. We used a negative control outcome, Herpes Zoster, to detect unmeasured confounding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 8639 patients were included. In propensity score\u2013adjusted analyses, the hazard ratio for the primary outcome was 0.81 (95% CI, 0.55\u20101.19) for beta\u2010blockers and 0.68 (95% CI, 0.46\u20100.96) for alpha\u2010blockers versus AA. Findings for individual cardiovascular outcomes trended in a more plausible direction, albeit imprecise. A trend for a protective effect for Herpes Zoster across both comparisons was seen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A higher rate of all\u2010cause death in the AA group was likely due to unmeasured confounding in our analysis of the composite primary outcome, supported by our negative outcome analysis. Results for cardiovascular outcomes were plausible, but imprecise due to small cohort sizes and a low number of observed outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.4808","type":"journal-article","created":{"date-parts":[[2019,7,17]],"date-time":"2019-07-17T04:38:55Z","timestamp":1563338335000},"page":"1267-1277","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The comparative effectiveness of fourth\u2010line drugs in resistant hypertension: An application in electronic health record data"],"prefix":"10.1002","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7586-686X","authenticated-orcid":false,"given":"Sarah\u2010Jo","family":"Sinnott","sequence":"first","affiliation":[{"name":"Department of Non\u2010communicable Disease Epidemiology London School of Hygiene and Tropical Medicine  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liam","family":"Smeeth","sequence":"additional","affiliation":[{"name":"Department of Non\u2010communicable Disease Epidemiology London School of Hygiene and Tropical Medicine  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics London School of Hygiene and Tropical Medicine  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Perel","sequence":"additional","affiliation":[{"name":"Department of Non\u2010communicable Disease Epidemiology London School of Hygiene and Tropical Medicine  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothea","family":"Nitsch","sequence":"additional","affiliation":[{"name":"Department of Non\u2010communicable Disease Epidemiology London School of Hygiene and Tropical Medicine  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurie A.","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"Department of Non\u2010communicable Disease Epidemiology London School of Hygiene and Tropical Medicine  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian J.","family":"Douglas","sequence":"additional","affiliation":[{"name":"Department of Non\u2010communicable Disease Epidemiology London School of Hygiene and Tropical Medicine  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,7,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00128-2"},{"key":"e_1_2_10_3_1","unstructured":"World Health Organisation (WHO).A global brief on hypertension: silent killer Global Public Health Crisis [Online]. Available fromhttp:\/\/www.who.int\/cardiovascular_diseases\/publications\/global_brief_hypertension\/en\/.2013."},{"key":"e_1_2_10_4_1","unstructured":"World Health Organisation (WHO).Fact sheet: cardiovasular diseases. Available from:http:\/\/www.who.int\/mediacentre\/factsheets\/fs317\/en\/2017."},{"key":"e_1_2_10_5_1","unstructured":"National Institute for Health and Care Excellence.Hypertension in adults: diagnosis and management. 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