Compared to chlorthalidone, amlodipine, lisinopril, and doxazosin resulted in higher heart failure rates in hypertensive patients with metabolic syndrome (e.g., amlodipine RR 1.50, 95% CI 1.18-1.90).
RCT (n=42,418)
double-blind
randomized
Effect estimate: RR 1.50 (95% CI 1.18-1.90)
BACKGROUND: Antihypertensive drugs with favorable metabolic effects are advocated for first-line therapy in hypertensive patients with metabolic/cardiometabolic syndrome (MetS). We compared outcomes by race in hypertensive individuals with and without MetS treated with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), an alpha-blocker (doxazosin mesylate), or an angiotensin-converting enzyme inhibitor (lisinopril). METHODS: A subgroup analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind hypertension treatment trial of 42 418 participants. We defined MetS as hypertension plus at least 2 of the following: fasting serum glucose level of at least 100 mg/dL, body mass index (calculated as weight in kilograms divided by height in meters squared) of at least 30, fasting triglyceride levels of at least 150 mg/dL, and high-density lipoprotein cholesterol levels of less than 40 mg/dL in men or less than 50 mg/dL in women. RESULTS: Significantly higher rates of heart failure were consistent across all treatment comparisons in those with MetS. Relative risks (RRs) were 1.50 (95% confidence interval, 1.18-1.90), 1.49 (1.17-1.90), and 1.88 (1.42-2.47) in black participants and 1.25 (1.06-1.47), 1.20 (1.01-1.41), and 1.82 (1.51-2.19) in nonblack participants for amlodipine, lisinopril, and doxazosin comparisons with chlorthalidone, respectively. Higher rates for combined cardiovascular disease were observed with lisinopril-chlorthalidone (RRs, 1.24 1.09-1.40 and 1.10 1.02-1.19, respectively) and doxazosin-chlorthalidone comparisons (RRs, 1.37 1.19-1.58 and 1.18 1.08-1.30, respectively) in black and nonblack participants with MetS. Higher rates of stroke were seen in black participants only (RR, 1.37 1.07-1.76 for the lisinopril-chlorthalidone comparison, and RR, 1.49 1.09-2.03 for the doxazosin-chlorthalidone comparison). Black patients with MetS also had higher rates of end-stage renal disease (RR, 1.70 1.13-2.55) with lisinopril compared with chlorthalidone. CONCLUSIONS: The ALLHAT findings fail to support the preference for calcium channel blockers, alpha-blockers, or angiotensin-converting enzyme inhibitors compared with thiazide-type diuretics in patients with the MetS, despite their more favorable metabolic profiles. This was particularly true for black participants.
Jackson T. Wright (Mon,) conducted a rct in hypertension with and without metabolic syndrome (n=42,418). amlodipine, doxazosin, or lisinopril vs. chlorthalidone was evaluated on heart failure (RR 1.50, 95% CI 1.18-1.90). Compared to chlorthalidone, amlodipine, lisinopril, and doxazosin resulted in higher heart failure rates in hypertensive patients with metabolic syndrome (e.g., amlodipine RR 1.50, 95% CI 1.18-1.90).