{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T13:14:55Z","timestamp":1780060495762,"version":"3.54.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:00:00Z","timestamp":1700179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>This study aimed to determine the 18-year risk of cancer, angioedema, insomnia, depression, and erectile dysfunction in association with antihypertensive drug use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This is a post-trial passive follow-up study of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants between 1994 and 1998 that was conducted by linking their follow-up data with Medicare claims data until 2017 of subjects who were free of outcomes at baseline on 1 January 1999. The main outcomes were the occurrence of cancer (among <jats:italic>n<\/jats:italic>\u2009=\u200917,332), angioedema (among <jats:italic>n<\/jats:italic>\u2009=\u200917,340), insomnia (among <jats:italic>n<\/jats:italic>\u2009=\u200917,340), depression (among <jats:italic>n<\/jats:italic>\u2009=\u200917,330), and erectile dysfunction (among <jats:italic>n<\/jats:italic>\u2009=\u20097,444 men) over 18 years of follow-up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The 18-year cumulative incidence rate of cancer other than non-melanoma skin cancer from Medicare inpatient claims was 23.9% for chlorthalidone, 23.4% for amlodipine, and 25.3% for lisinopril. There were no statistically significant differences in the 18-year risk of cancer, depression, and erectile dysfunction among the three drugs based on the adjusted hazard ratios. The adjusted 18-year risk of angioedema was elevated in those receiving lisinopril than in those receiving amlodipine (hazard ratio: 1.63, 95% CI: 1.14\u20132.33) or in those receiving chlorthalidone (1.33, 1.00\u20131.79), whereas the adjusted 18-year risk of insomnia was statistically significantly decreased in those receiving lisinopril than in those receiving amlodipine (0.90, 0.81\u20131.00).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The 18-year risk of angioedema was significantly higher in patients receiving lisinopril than in those receiving amlodipine or chlorthalidone; the risk of insomnia was significantly lower in patients receiving lisinopril than in those receiving amlodipine; and the risk of cancer, depression, and erectile dysfunction (in men) was not statistically significantly different among the three drug groups.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2023.1272385","type":"journal-article","created":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T10:08:00Z","timestamp":1700302080000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The 18-year risk of cancer, angioedema, insomnia, depression, and erectile dysfunction in association with antihypertensive drugs: post-trial analyses from ALLHAT\u2013Medicare linked data"],"prefix":"10.3389","volume":"10","author":[{"given":"Xianglin L.","family":"Du","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Journey","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose-Miguel","family":"Yamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara M.","family":"Simpson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry R.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,17]]},"reference":[{"key":"B1","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","year":"2002","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2998","DOI":"10.1001\/jama.288.23.2998","article-title":"Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT-LLT)","volume":"288","year":"2002","journal-title":"JAMA"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.1001\/jama.289.19.2560","article-title":"National heart, lung, and blood institute joint national committee on prevention, detection, evaluation, and treatment of high blood pressure, national high blood pressure education program coordinating committee. 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