The comparative effectiveness of hydrochlorothiazide and chlorthalidone in an observational cohort of veterans.

Indirect evidence suggests that chlorthalidone may be more effective than hydrochlorothiazide (HCTZ), but direct comparisons are lacking. Using national Veterans Administrative pharmacy data from 2003 to 2008, the authors performed a retrospective cohort study examining the effectiveness of chlorthalidone and HCTZ among new thiazide users. For 1 year following the thiazide start, rates of persistence of thiazide use, adequacy of response (defined as the absence of additional new antihypertensive medications following thiazide initiation), and an overall composite of treatment effectiveness incorporating both outcomes were examined. In this cohort of >125,000 individuals, persistence of thiazide use was higher for HCTZ than chlorthalidone (72.0% vs 62.0%; P<.001), but among thiazide-persistent users, more HCTZ users had additional antihypertensives added compared with chlorthalidone (76.4% vs 70.1%; P<.001). The overall composite treatment response (thiazide persistence and no antihypertensive additions) revealed a slight advantage for HCTZ over chlorthalidone (50.7% vs 47.4%; P=.002). These findings remained consistent after adjustment using multivariable logistic regression. This study provides real-world clinical data supporting a potential efficacy advantage of chlorthalidone among patients who tolerate the drug and remain persistent with treatment; however, strategies to optimize the way chlorthalidone is prescribed in clinical practice are necessary to increase its overall effectiveness relative to HCTZ.