Is chlorthalidone better than hydrochlorothiazide in reducing cardiovascular events in hypertensives?

Hydrochlorthiazide (HCTZ) is the tenth most commonly prescribed drug in recent data. Although no head-to-head trials compare HCTZ with the uncommonly prescribed chlorthalidone (CTDN) in reducing cardiovascular events (CVEs), numerous other data are available. Head-to-head trials have shown CTDN's superiority in antihypertensive potency, particularly during the critical nighttime period (SBP difference 7.1 mmHg), due to the differences in duration of action (16-24 h for HCTZ versus 48-72 h for CTDN). In an observational cohort study, compared with HCTZ, CTDN was associated with lower left ventricular hypertrophy. In another observational cohort analysis (n = 12,866), the percentage risk reduction in CVEs from CTDN versus HCTZ was 21 [95% confidence interval (CI) 8-32], P = 0.002. In network meta-analyses of randomized trials (n = 50,946), CTDN was superior to HCTZ in reducing congestive heart failure and in reducing all CVEs: percentage risk reduction 21 (95% CI 12-28), P < 0.0001. A statistically significant reduction in CVEs by CTDN versus HCTZ persisted even when reduction in office SBP produced by the two diuretics was identical, further strengthening the case for CTDN. Direct and indirect evidence demonstrates that CTDN is superior to HCTZ in reducing CVEs and is congruent with the recent changes in the guidelines for hypertension management.