J. Scholze et al., VERAPAMIL SR AND TRANDOLAPRIL COMBINATION THERAPY IN HYPERTENSION - ACLINICAL-TRIAL OF FACTORIAL DESIGN, British journal of clinical pharmacology, 45(5), 1998, pp. 491-495
Aims To investigate the dose-response relationship and contribution of
verapamil SR and trandolapril given in combination once a day for the
treatment of essential hypertension. Methods A randomized, double-bli
nd, placebo controlled, factorial, 12 arm parallel group comparison wi
th placebo, verapamil SR (120, 180 mg), trandolapril (0.5, 1.0, 2.0 mg
) covering all combinations of both drugs. A 4 week placebo run-in per
iod followed by 6 weeks of treatment. Four hundred and fifty-six patie
nts from office practice (22 centres) with mild to moderate hypertensi
on enrolled and 426 with diastolic pressure greater than or equal to 1
00 mm Hg at the end of run-in period were randomized. Main outcome mea
sures were reduction in sitting systolic (SBP) and sitting diastolic (
DBP) blood pressure. Results The combination of verapamil SR and trand
olapril, particularly verapamil SR 180 mg and trandolapril 0.5 or 1.0
mg was significantly superior to both monocomponents at the same dose
(P<0.05). For these combinations, the adjusted mean reductions in DBP
from baseline to last visit were 14.1 and 16.0 nlm Hg, respectively. R
esponse surface analysis provided further evidence that these combinat
ions were optimal for antihypertensive efficacy. All treatments were w
ell tolerated. The incidence of adverse events did not differ signific
antly between treatment groups; the profile of adverse events on combi
nation therapy was mild and consistent with that of each monocomponent
. Conclusions All dosage combinations of verapamil SR and trandolapril
produced significantly greater reduction of blood pressure than the m
onotherapy at the same dosage. However, verapamil SR 180 mg in combina
tion with trandolapril 1.0 mg was the dosage with the greatest: blood
pressure reduction and had the greatest effects compared with the mono
components.