Chlorthalidone for hypertension

Thiazide diuretics are recommended as first-line treatment for hypertension. Hydrochlorothiazide (HCTZ) is the most commonly used diuretic in North America, but some experts have recommended chlorthalidone in this role, suggesting that it may be superior. A new study, however, suggests that chlorthalidone may cause more electrolyte abnormalities than HCTZ. Nearly 30,000 patients ≥ 66 years of age who were newly treated for hypertension were evaluated. About one-third were treated with chlorthalidone and the rest with HCTZ. None of the patients had been hospitalized for heart failure, stroke, or MI within the last year. The primary outcome was a composite of death or hospitalization for heart failure, stroke, or MI, and safety outcomes included hospitalization with hypokalemia or hyponatremia. After 5 years of follow-up, there was no difference in the primary outcome between the two drugs — 3.2 events per 100 person years for chlorthalidone vs 3.4 events per 100 person years for HCTZ. However, patients treated with chlorthalidone were three times more likely to be hospitalized with hypokalemia (adjusted HR, 3.06; CI, 0.81-1.06). Hyponatremia was also more common (HR, 1.68; CI, 1.24-2.28). The findings suggest that in typical doses, chlorthalidone is not associated with fewer adverse cardiovascular events or deaths compared to hydrochlorothiazide, but it is associated with a greater incidence of electrolyte abnormalities, especially hypokalemia (Ann Intern Med 2013;158:447-455).