Quinapril and hydrochlorothiazide combination for control of hypertension: assessment by factorial design. Quinapril Investigator Group

Abstract

A factorial design method was applied in this multicentre trial of the angiotensin-converting enzyme inhibitor quinapril hydrochloride (Accupril) in combination with the diuretic hydrochlorothiazide (HCTZ) to assess the additive effects of the combination versus monotherapy, to characterise the dose-response relationship of each drug in the presence of the other and to determine if quinapril would attenuate the hypokalemic effect of HCTZ. Following a two to four week placebo-baseline period, 460 qualifying patients with a DBP > or = 100 mmHg and < or = 115 mmHg were randomised to an eight week double-blind phase with one of 16 parallel treatments: placebo, one of three doses of quinapril monotherapy, one of three doses of HCTZ monotherapy or one of nine possible corresponding combinations of quinapril and HCTZ. Mean reductions in sitting SBP/DBP at trough with combination therapy ranged from 7.8 mmHg/7.2 mmHg to 19.6 mmHg/15.1 mmHg (n = 458). Results of the response surface analyses indicate that the effects of the two drugs were additive and that the maximum antihypertensive effect of quinapril in combination with HCTZ within the doses studied is achieved approximately at a dose of 26 mg quinapril and 25 mg HCTZ. The degree of attenuation of the hypokalemic effect of HCTZ was directly related to the dose of quinapril. At 40 mg quinapril, the HCTZ dose-related decreases of serum potassium were not apparent and overall hypokalemic effects were attenuated by quinapril. Thus, the combination of quinapril and HCTZ given once daily provided additive antihypertensive effects of predictable degrees and the addition of quinapril attenuated the hypokalemic effect of HCTZ.