{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:41:49Z","timestamp":1792813309199,"version":"4.5.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T00:00:00Z","timestamp":1718755200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["224485\/Z\/21\/Z"],"award-info":[{"award-number":["224485\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cardiovascular disease is a leading cause of death globally. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), compared in the ONTARGET trial (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial), each prevent cardiovascular disease. However, trial results may not be generalizable, and their effectiveness in underrepresented groups is unclear. Using trial emulation methods within routine-care data to validate findings, we explored the generalizability of ONTARGET results. For people prescribed an ACEi\/ARB in the UK Clinical Practice Research Datalink GOLD dataset from January 1, 2001, to July 31, 2019, we applied trial criteria and propensity-score methods to create an ONTARGET trial-eligible cohort. Comparing ARB with ACEi, we estimated hazard ratios for the primary composite trial outcome (cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure) and secondary outcomes. Because the prespecified criteria were met, confirming trial emulation, we then explored treatment heterogeneity among 3 trial-underrepresented subgroups: females, persons aged \u226575\u00a0years, and those with chronic kidney disease. In the trial-eligible population (n\u00a0=\u00a0137\u2009155), results for the primary outcome demonstrated similar effects of ARB and ACEi (hazard ratio = 0.97; 95% CI, 0.93-1.01), meeting the prespecified validation criteria. When extending this outcome to trial-underrepresented groups, similar treatment effects were observed by sex, age, and chronic kidney disease. This suggests that ONTARGET trial findings are generalizable to trial-underrepresented subgroups.<\/jats:p>\n               <jats:p>This article is part of a Special Collection on Pharmacoepidemiology.<\/jats:p>","DOI":"10.1093\/aje\/kwae137","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T13:40:10Z","timestamp":1718804410000},"page":"1785-1795","source":"Crossref","is-referenced-by-count":7,"title":["Cardiorenal effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers among people underrepresented in trials: analysis of routinely collected data with emulation of a reference trial (ONTARGET)"],"prefix":"10.1093","volume":"193","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2565-8525","authenticated-orcid":false,"given":"Paris J","family":"Baptiste","sequence":"first","affiliation":[{"name":"Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine , London WC1E 7HT ,","place":["United Kingdom"]},{"name":"Centre for Primary Care , Wolfson Institute of Population Health, , London E1 4NS ,","place":["United Kingdom"]},{"name":"Queen Mary University of London , Wolfson Institute of Population Health, , London E1 4NS ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8618-7333","authenticated-orcid":false,"given":"Angel Y S","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine , London WC1E 7HT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1637-837X","authenticated-orcid":false,"given":"Anna","family":"Schultze","sequence":"additional","affiliation":[{"name":"Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine , London WC1E 7HT ,","place":["United 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Medicine , London WC1E 7HT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6905-876X","authenticated-orcid":false,"given":"Elizabeth","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, London School of Hygiene & Tropical Medicine , London WC1E 7HT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9427-9468","authenticated-orcid":false,"given":"Emma","family":"Powell","sequence":"additional","affiliation":[{"name":"Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine , London WC1E 7HT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3154-5332","authenticated-orcid":false,"given":"Johannes F E","family":"Mann","sequence":"additional","affiliation":[{"name":"Department of Medicine 4 , Faculty of Medicine, , 91054 Erlangen ,","place":["Germany"]},{"name":"Friedrich Alexander University , Faculty of Medicine, , 91054 Erlangen ,","place":["Germany"]},{"name":"KfH Kidney Centre , 80687 M\u00fcnchen-Schwabing ,","place":["Germany"]},{"name":"Population Health Research Institute, McMaster University , Hamilton, ON L8L 2X2 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2398-2281","authenticated-orcid":false,"given":"Marianne","family":"Cunnington","sequence":"additional","affiliation":[{"name":"Analysis Group Inc. , London EC2R 7HJ ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3731-0956","authenticated-orcid":false,"given":"Koon","family":"Teo","sequence":"additional","affiliation":[{"name":"Department of Health Research Methods , Evidence, and Impact, Faculty of Health Sciences, , Hamilton, ON L8S 4L8 ,","place":["Canada"]},{"name":"McMaster University , Evidence, and Impact, Faculty of Health Sciences, , Hamilton, ON L8S 4L8 ,","place":["Canada"]},{"name":"Population Health Research Institute, McMaster University , Hamilton, ON L8L 2X2 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3111-0689","authenticated-orcid":false,"given":"Shrikant I","family":"Bangdiwala","sequence":"additional","affiliation":[{"name":"Department of Health Research Methods , Evidence, and Impact, Faculty of Health Sciences, , Hamilton, ON L8S 4L8 ,","place":["Canada"]},{"name":"McMaster University , Evidence, and Impact, Faculty of Health Sciences, , Hamilton, ON L8S 4L8 ,","place":["Canada"]},{"name":"Population Health Research Institute, McMaster University , Hamilton, ON L8L 2X2 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