Dose-response curves in antihypertensive combination therapy: results of a controlled clinical trial

We studied the dose-response relationship for hydrochlorothiazide + triameterene and verapamil, comparing monotherapy with combined treatment in 216 hypertensive patients over 3 weeks of active treatment following a 2-week washout period with placebo. The study was a double-blind, randomly allocated, clinical trial using a two-factorial analysis of variance design. The results showed that the highest dose (a combination of 160 mg verapamil with 25 mg hydrochlorothiazide and 50 mg triameterene) also had the maximum antihypertensive effect. We further conclude that multifactorial trial designs are the most useful designs for analyzing the effects of combination therapy and therefore should be used more often.