Original Articles Long-Term Effects of Incident Diabetes Mellitus on Cardiovascular Outcomes in People Treated

Background—Thiazide-type diuretics are associated with an increased incidence of diabetes compared with other antihypertensive medications. In this study, we determined the long-term cardiovascular disease (CVD) consequences of incident diuretic-associated diabetes compared with the effects of incident diabetes associated with calcium channel blocker and angiotensin-converting enzyme inhibitor use. Methods and Results—A total of 22 418 participants from the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) with baseline diabetes, incident diabetes (7.5 % with chlorthalidone, 5.6 % with amlodipine, and 4.3 % with lisinopril), or no diabetes at 2 years of in-trial follow-up were followed for a mean total of 6.9 years (2.9 years in-trial and 4 additional years posttrial) through the use of national databases. The primary outcome was CVD mortality (death from coronary heart disease [CHD], stroke, heart failure, or other CVD). Among other outcomes were all-cause mortality, non-CVD mortality, and CHD (nonfatal myocardial infarction or fatal CHD). Participants on chlorthalidone with incident diabetes versus no diabetes had consistently lower, nonsignificant risk for CVD mortality (hazard ratio [HR], 1.04; 95 % CI, 0.74–1.47), all-cause mortality (HR, 1.04; 95 % CI, 0.82–1.30), and non-CVD mortality (HR, 1.05; 95 % CI, 0.77–1.42) than participants on amlodipine or lisinopril with incident diabetes (HR range, 1.22–1.53). Participants with incident diabetes had elevated CHD risk compared with those with no diabetes (HR, 1.46; 95 % CI, 1.09–1.96), but those on chlorthalidone had significantly lower risk than those on lisinopril (HR, 1.18 versus 2.57; P0.04 for interaction)