Hydrochlorothiazide-amiloride versus hydrochlorothiazide alone for essential hypertension: effects on blood pressure and serum potassium level

Abstract

In a double-blind randomized controlled trial the effects on the blood pressure and the serum potassium concentration of hydrochlorothiazide-amiloride hydrochloride (Moduret) and hydrochlorothiazide alone were compared in 266 adults who were normokalemic and had a diastolic blood pressure greater than 95 mm Hg at the time of entry into the study. The mean ages (52.2 and 53.8 years) and the proportions of men (66% and 56%) in the groups given the combination drug and hydrochlorothiazide alone respectively were similar. In the group given the combination drug the mean blood pressure, measured while the patients were supine, and the mean serum potassium level fell significantly, from 156/99 to 138/88 mm Hg and from 4.23 to 3.91 mmol/L, after 8 weeks of treatment. In the other group both measures also fell significantly, the blood pressure from 157/99 to 138/87 mm Hg and the potassium level from 4.16 to 3.69 mmol/L. The proportions of patients in the two groups with hypokalemia (14% and 29% respectively), defined as a serum potassium level below 3.5 mmol/L, differed significantly (p = 0.0026), whereas the proportions with a potassium level exceeding 4.5 mmol/L (4.5% and 3.9% respectively) were similar. Thus, the combination drug reduced the blood pressure to the same extent as hydrochlorothiazide alone but significantly less often caused hypokalemia. In light of growing concerns about the cardiovascular complications of hypokalemia, hydrochlorothiazide-amiloride appears preferable to hydrochlorothiazide alone for the treatment of some patients with hypertension.