Current 29 - HCTZ and Chlorthalidone Found Similar for Cardiovascular Event Prevention

Summary

A recent study, the Diuretic Comparison Project, found that chlorthalidone did not outperform hydrochlorothiazide (HCTZ) in the prevention of major cardiovascular events in patients with hypertension.¹

More than 13,000 patients 65 years of age or older were randomized 1:1 to the continuation of daily HCTZ 25 mg or 50 mg or a change to chlorthalidone at the equivalent dose. As 95% of the enrolled patients were prescribed HCTZ 25 mg at baseline, the major comparison group was the equivalent dose of chlorthalidone 12.5 mg.

The primary outcome was a composite of major adverse cardiovascular events (MACE). At a median follow-up of 2.4 years, the incidence of MACE did not differ significantly between the HCTZ and chlorthalidone groups (10.0% vs. 10.4%, p = 0.45). Blood pressure trends were comparable between the two groups. Notably, hypokalemia was more common in the chlorthalidone group than the HCTZ group (6.0% vs. 4.4%, p < 0.001).

Study limitations include generalizability to diverse populations (enrollees were 97% men, mean age 72 years, and 15% African American); the lower dosing range of diuretics at baseline, which limits extrapolation to higher doses; and the use of other prescribed antihypertensives used by patients in both groups, which may have influenced the results.²

Sources

¹Ishani A, Cushman WC, Leatherman SM, et al. Chlorthalidone vs. hydrochlorothiazide for hypertension–cardiovascular events. N Engl J Med. 2022;387(26):2401-2410. doi:10.1056/NEJMoa2212270.

²Volpe M, Liuzzo G. The 'cold case' of chlorthalidone vs. hydrochlorothiazide in hypertension closed by the diuretic comparison project?. Eur Heart J. 2023;44(13):1110-1111. doi:10.1093/eurheartj/ehad077.