Abstract 114: Effect Of Dose Of Chlorthalidone And Hydrochlorothiazide Dosing On Cardiovascular Outcomes In The Diuretic Comparison Project (DCP)

Background: The Diuretic Comparison Project (DCP) showed chlorthalidone (CTD) to be comparable with hydrochlorothiazide (HCTZ) in cardiovascular prevention among older hypertensive patients. Previous hypertension outcome trials showing benefit for either, higher doses of each were predominant. DCP randomized 13,523 participants to stay on existing HCTZ (25/50mg) or switch to a dose equivalent CTD (12.5/25mg). Such trial data was used to test if CTD was superior to HCTZ when prescribed at a higher dose. Methods: This analysis examined treatment effects with respect to low (25mg HCTZ/12.5mg CTD) and high (50mg HCTZ/25mg CTD) dose regimens. Outcomes including non-fatal MI, stroke, acute heart failure, revascularization for unstable angina and non-cancer death were tested individually and as a composite measure. Results: There were no differences for the composite and all individual outcomes in both low dose (12,781/13,523; 94.5%) and high dose (742/13,523; 5.5%) groups. Mean age (72 y), baseline blood pressure (139 mm Hg), and follow-up time (2.4 y) were similar across doses. High dose participants had a greater prevalence of diabetes and received more antihypertensive drugs. Consistent with DCP results, there was a significant interaction between treatment group and history of MI/stroke in the low dose group (p=0.002); this was not found in the high dose group (p=0.8). Conclusion: As in the main DCP trial results, there were no differences in outcomes between CTD and HCTZ within higher or lower dose subgroups. Treatment interaction with prior mi/stroke was found with lower doses. However, the high dose group was small and might not reflect a true treatment effect at higher doses.