• Areef Ishani, William C Cushman, Sarah M Leatherman, Robert A Lew, Patricia Woods, Peter A Glassman, Addison A Taylor, Cynthia Hau, Alison Klint, Grant D Huang, Mary T Brophy, Louis D Fiore, Ryan E Ferguson, and Diuretic Comparison Project Writing Group.
• From Minneapolis Veterans Affairs (VA) Health Care System, and the Department of Medicine, University of Minnesota - both in Minneapolis (A.I.); Medical Service, Memphis VA Medical Center, and the Department of Preventive Medicine, University of Tennessee Health Science Center - both in Memphis (W.C.C.); the Cooperative Studies Program Coordinating Center, VA Boston Healthcare System (S.M.L., R.A.L., P.W., C.H., A.K., M.T.B., L.D.F., R.E.F.), the Department of Biostatistics, Boston University School of Public Health (S.M.L., R.A.L.), and the Department of Medicine, Boston University School of Medicine (M.T.B., R.E.F.) - all in Boston; Pharmacy Benefits Management Services (P.A.G.) and the Office of Research and Development (G.D.H.), Department of Veterans Affairs, Washington, DC; VA Greater Los Angeles Healthcare System, and the David Geffen School of Medicine, University of California, Los Angeles - both in Los Angeles (P.A.G.); and Michael E. DeBakey VA Medical Center, and the Department of Medicine, Baylor College of Medicine - both in Houston (A.A.T.).
• N. Engl. J. Med. 2022 Dec 29; 387 (26): 240124102401-2410.

BackgroundWhether chlorthalidone is superior to hydrochlorothiazide for preventing major adverse cardiovascular events in patients with hypertension is unclear.MethodsIn a pragmatic trial, we randomly assigned adults 65 years of age or older who were patients in the Department of Veterans Affairs health system and had been receiving hydrochlorothiazide at a daily dose of 25 or 50 mg to continue therapy with hydrochlorothiazide or to switch to chlorthalidone at a daily dose of 12.5 or 25 mg. The primary outcome was a composite of nonfatal myocardial infarction, stroke, heart failure resulting in hospitalization, urgent coronary revascularization for unstable angina, and non-cancer-related death. Safety was also assessed.ResultsA total of 13,523 patients underwent randomization. The mean age was 72 years. At baseline, hydrochlorothiazide at a dose of 25 mg per day had been prescribed in 12,781 patients (94.5%). The mean baseline systolic blood pressure in each group was 139 mm Hg. At a median follow-up of 2.4 years, there was little difference in the occurrence of primary-outcome events between the chlorthalidone group (702 patients [10.4%]) and the hydrochlorothiazide group (675 patients [10.0%]) (hazard ratio, 1.04; 95% confidence interval, 0.94 to 1.16; P = 0.45). There were no between-group differences in the occurrence of any of the components of the primary outcome. The incidence of hypokalemia was higher in the chlorthalidone group than in the hydrochlorothiazide group (6.0% vs. 4.4%, P<0.001).ConclusionsIn this large pragmatic trial of thiazide diuretics at doses commonly used in clinical practice, patients who received chlorthalidone did not have a lower occurrence of major cardiovascular outcome events or non-cancer-related deaths than patients who received hydrochlorothiazide. (Funded by the Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT02185417.).Copyright © 2022 Massachusetts Medical Society.

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