An assessment of diltiazem and hydrochlorothiazide in hypertension. Application of factorial trial design to a multicenter clinical trial of combination therapy
J. F. Burris, M. R. Weir, S. Oparil, M. Weber, W. J. Cady and W. H. Stewart
Hypertension Research Unit, Veterans Administration Medical Center, Washington, DC.
This multicenter, factorial-design trial assessed the safety and additive
antihypertensive efficacy of a slow-release (SR) formulation of diltiazem
hydrochloride given alone or in combination with hydrochlorothiazide for
treatment of mild to moderate hypertension. After a 4- to 6-week placebo
run-in period, 297 qualifying patients were randomized to receive placebo,
1 of 4 doses of diltiazem SR monotherapy, 1 of 3 doses of
hydrochlorothiazide monotherapy, or 1 of 12 possible combinations of
diltiazem SR and hydrochlorothiazide for 6 weeks. A dose-related reduction
in blood pressure was demonstrated for each drug as monotherapy and for the
two drugs in combination. Absolute blood pressures of patients who received
combination therapy were lower by an overall mean of 3.0 mm Hg diastolic
and 8.0 mm Hg systolic vs diltiazem SR used alone and 3.5 mm Hg diastolic
and 4.0 mm Hg systolic vs hydrochlorothiazide used alone. At the largest
doses used, 50% of patients achieved goal blood pressure while taking
hydrochlorothiazide, 57% while taking diltiazem SR, and 75% while taking
combination therapy. Combination therapy was well tolerated. This trial
clearly demonstrates that diltiazem SR and hydrochlorothiazide have
additive antihypertensive effects.
