VERAPAMIL SR AND TRANDOLAPRIL COMBINATION THERAPY IN HYPERTENSION - ACLINICAL-TRIAL OF FACTORIAL DESIGN

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.