{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T19:30:07Z","timestamp":1791833407076,"version":"4.3.4"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,2,3]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">The DCP (Diuretic Comparison Project), a pragmatic trial, evaluated whether chlorthalidone compared with hydrochlorothiazide would reduce the risk of nonfatal cardiovascular disease or noncancer\u2010related death. The intent\u2010to\u2010treat analysis found no difference in such comparison (hazard ratio, 1.04 [95% CI, 0.94\u20131.16]). The objective of the current study is to estimate the per\u2010protocol effect of chlorthalidone (12.5\/25 mg daily) compared with hydrochlorothiazide (25\/50 mg daily) in preventing major adverse cardiovascular events among older patients with hypertension.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">The effect of adhering to treatment strategies was assessed by censoring at first instance of nonadherence, defined as a gap (&gt;90\u2010day gap in drug coverage), switch (switching between study medications), and discontinuation (stop taking chlorthalidone\/hydrochlorothiazide altogether for &gt;90\u2009days before the end of the study). The primary outcome was a composite of nonfatal myocardial infarction, stroke, heart failure resulting in hospitalization, urgent coronary revascularization for unstable angina, and noncancer\u2010related death. Using inverse probability weighting, we evaluated the per\u2010protocol effect of chlorthalidone and hydrochlorothiazide using DCP trial data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Nonadherence was found in 5476 (40%) participants; among 8047 (60%) adherents, 3905 (49%) were randomized to chlorthalidone and 4142 (51%) to hydrochlorothiazide. After censoring time when participants deviated from the assigned treatments, the estimated 5\u2010year risk ratio of the composite primary outcome of nonfatal cardiovascular disease and noncancer\u2010related death was 1.36 (95% CI, 0.96\u20132.12) in chlorthalidone compared with hydrochlorothiazide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">The per\u2010protocol analysis indicated a lower risk with hydrochlorothiazide compared with chlorthalidone in preventing nonfatal cardiovascular disease and noncancer\u2010related death; however, this difference was not statistically significant using dispensation data to identify adherence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT02185417.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.046142","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T10:16:46Z","timestamp":1769768206000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Per\u2010Protocol Analysis of Chlorthalidone Versus Hydrochlorothiazide for Cardiovascular Event Prevention\u2014Diuretic Comparison Project"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5494-1821","authenticated-orcid":false,"given":"Sonia T.","family":"Anand","sequence":"first","affiliation":[{"name":"Cooperative Studies Program Coordinating Center, VA Boston Healthcare System","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4141-9376","authenticated-orcid":false,"given":"Cynthia","family":"Hau","sequence":"additional","affiliation":[{"name":"Cooperative Studies Program Coordinating Center, VA Boston Healthcare System","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5160-2410","authenticated-orcid":false,"given":"Michael J.","family":"Davenport","sequence":"additional","affiliation":[{"name":"Cooperative Studies Program Coordinating Center, VA Boston Healthcare System","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1542-2076","authenticated-orcid":false,"given":"Areef","family":"Ishani","sequence":"additional","affiliation":[{"name":"Minneapolis VA Healthcare System","place":["Minneapolis"]},{"name":"University of Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7162-2972","authenticated-orcid":false,"given":"William C.","family":"Cushman","sequence":"additional","affiliation":[{"name":"Medical Service, Memphis VA Medical Center","place":["Memphis"]},{"name":"University of Tennessee Health Science Center","place":["Memphis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Glassman","sequence":"additional","affiliation":[{"name":"Pharmacy Benefits Management Services, Department of Veterans Affairs","place":["Washington"]},{"name":"VA Greater Los Angeles Healthcare System","place":["Los Angeles"]},{"name":"David Geffen School of Medicine at UCLA","place":["Los Angeles"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3788-3137","authenticated-orcid":false,"given":"Addison A.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Michael E. DeBakey VA Medical Center","place":["Houston"]},{"name":"Baylor College of Medicine","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0389-0566","authenticated-orcid":false,"given":"Robert A.","family":"Lew","sequence":"additional","affiliation":[{"name":"Cooperative Studies Program Coordinating Center, VA Boston Healthcare System","place":["Boston"]},{"name":"Boston University School of Public Health","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan E.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Cooperative Studies Program Coordinating Center, VA Boston Healthcare System","place":["Boston"]},{"name":"Boston University Chobanian and Avedisian School of Medicine","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9821-9646","authenticated-orcid":false,"given":"Sarah M.","family":"Leatherman","sequence":"additional","affiliation":[{"name":"Cooperative Studies Program Coordinating Center, VA Boston Healthcare System","place":["Boston"]},{"name":"Boston University School of Public Health","place":["Boston"]},{"name":"Boston University Chobanian and Avedisian School of Medicine","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0244-2"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjpc\/zwad262"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYP.0000000000000066"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2022.106754"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212270"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsm1605385"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.32049"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2024.104587"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2017.03.007"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2023.107214"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.hjh.0000226211.95936.f5"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000000222"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/pds.4636"},{"key":"e_1_3_2_15_2","first-page":"147","article-title":"Hypomagnesemia and cardiovascular system","volume":"10","author":"Efstratiadis G","year":"2006","unstructured":"Efstratiadis G, Sarigianni M, Gougourelas I. 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