Abstract
Increasing the dose of a thiazide diuretic used alone in patients with essential hypertension has little further effect on blood pressure but increases the deleterious metabolic consequences of the diuretic. The effect of a beta-blocker on this flat dose response is not known. In two randomised crossover studies the effect of 12.5 mg, 25 mg, and 50 mg hydrochlorothiazide combined with 400 mg acebutolol was assessed. The mean fall in supine blood pressure was about 15% and was the same whatever dose of thiazide was used with the beta-blocker. As the dose of hydrochlorothiazide was increased, however, there was evidence of increasing metabolic consequences of the diuretic. The study did not define the minimum dose of diuretic, and doses of hydrochlorothiazide lower than 12.5 mg might be as effective. These results suggest that many patients who are being treated with a combination of a beta-blocker and a diuretic are receiving unnecessarily large amounts of the diuretic without benefit to their blood pressure and with adverse metabolic consequences.