{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T22:02:54Z","timestamp":1788559374392,"version":"build-2803163510"},"reference-count":13,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>The long-term relative risk of antihypertensive treatments with regard to mortality and morbidity is not well understood.<\/jats:p><\/jats:sec>Objective<\/jats:title>To determine the long-term posttrial risk of primary and secondary outcomes among trial participants who were randomized to either a thiazide-type diuretic, calcium channel blocker (CCB), or angiotensin-converting enzyme (ACE) inhibitor with up to 23 years of follow-up.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This prespecified secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a multicenter randomized, double-blind, active-controlled clinical trial, followed up with participants aged 55 years or older with a diagnosis of hypertension and at least 1 other coronary heart disease risk factor for up to 23 years, from February 23, 1994, to December 31, 2017. Trial participants were linked with administrative databases for posttrial mortality (N\u2009=\u200932\u202f804) and morbidity outcomes (n\u2009=\u200922\u202f754). Statistical analysis was performed from January 2022 to October 2023.<\/jats:p><\/jats:sec>Interventions<\/jats:title>Participants were randomly assigned to receive a thiazide-type diuretic (n\u2009=\u200915\u202f002), a CCB (n\u2009=\u20098898), or an ACE inhibitor (n\u2009=\u20098904) for planned in-trial follow-up of approximately 4 to 8 years and posttrial passive follow-up for up to 23 years.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary end point was mortality due to cardiovascular disease (CVD). Secondary outcomes included all-cause mortality, combined fatal and nonfatal (morbidity) CVD, and both mortality and morbidity for coronary heart disease, stroke, heart failure, end-stage renal disease, and cancer.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 32\u202f804 participants (mean [SD] age, 66.9 [7.7] years; 17\u202f411 men [53.1%]; and 11\u202f772 Black participants [35.9%]) were followed up for all-cause mortality and a subgroup of 22\u202f754 participants (mean [SD] age, 68.7 [7.2] years; 12\u202f772 women [56.1%]; and 8199 Black participants [36.0%]) were followed up for fatal or nonfatal CVD through 2017 (mean [SD] follow-up, 13.7 [6.7] years; maximum follow-up, 23.9 years). Cardiovascular disease mortality rates per 100 persons were 23.7, 21.6, and 23.8 in the diuretic, CCB, and ACE inhibitor groups, respectively, at 23 years after randomization (adjusted hazard ratio [AHR], 0.97 [95% CI, 0.89-1.05] for CCB vs diuretic; AHR, 1.06 [95% CI, 0.97-1.15] for ACE inhibitor vs diuretic). The long-term risks of most secondary outcomes were similar among the 3 groups. Compared with the diuretic group, the ACE inhibitor group had a 19% increased risk of stroke mortality (AHR, 1.19 [95% CI, 1.03-1.37]) and an 11% increased risk of combined fatal and nonfatal hospitalized stroke (AHR, 1.11 [95% CI, 1.03-1.20]).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this secondary analysis of a randomized clinical trial in an adult population with hypertension and coronary heart disease risk factors, CVD mortality was similar between all 3 groups. ACE inhibitors increased the risk of stroke outcomes by 11% compared with diuretics, and this effect persisted well beyond the trial period.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT00000542<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.44998","type":"journal-article","created":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T16:01:06Z","timestamp":1701705666000},"page":"e2344998","source":"Crossref","is-referenced-by-count":12,"title":["Mortality and Morbidity Among Individuals With Hypertension Receiving a Diuretic, ACE Inhibitor, or Calcium Channel Blocker"],"prefix":"10.1001","volume":"6","author":[{"given":"Jose-Miguel","family":"Yamal","sequence":"first","affiliation":[{"name":"Coordinating Center for Clinical Trials, Department of Biostatistics and Data Science, School of Public Health, The University of Texas Health Science Center at Houston, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Journey","family":"Martinez","sequence":"additional","affiliation":[{"name":"Coordinating Center for Clinical Trials, Department of Biostatistics and Data Science, School of Public Health, The University of Texas Health Science Center at Houston, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikala C.","family":"Osani","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston"},{"name":"Zimmer Biomet, Warsaw, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianglin L.","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara M.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Coordinating Center for Clinical Trials, Department of Biostatistics and Data Science, School of Public Health, The University of Texas Health Science Center at Houston, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry R.","family":"Davis","sequence":"additional","affiliation":[{"name":"Coordinating Center for Clinical Trials, Department of Biostatistics and Data Science, School of Public Health, The University of Texas Health Science Center at Houston, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2023,12,4]]},"reference":[{"issue":"4, pt 1","key":"zoi231315r1","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/0895-7061(96)00037-4","article-title":"Rationale and design for the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).","volume":"9","author":"Davis","year":"1996","journal-title":"Am J Hypertens"},{"issue":"15","key":"zoi231315r2","doi-asserted-by":"publisher","first-page":"1967","DOI":"10.1001\/jama.283.15.1967","article-title":"Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).","volume":"283","author":"ALLHAT Collaborative Research Group","year":"2000","journal-title":"JAMA"},{"issue":"23","key":"zoi231315r3","doi-asserted-by":"publisher","first-page":"2981","DOI":"10.1001\/jama.288.23.2981","article-title":"Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).","volume":"288","author":"ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group; 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