COMPARISON OF DIFFERENT FIXED ANTIHYPERTENSIVE COMBINATION-DRUGS - A DOUBLE-BLIND, PLACEBO-CONTROLLED PARALLEL-GROUP STUDY

Objective To compare the effects of fixed-dose preparations containing 180 mg sustained-release verapamil and 2 mg trandolapril, 100/25 mg a tenolol/chlorthalidone, 20/12.5 mg lisinopril/ hydrochlorothiazide and placebo in patients with essential hypertension, Design A 4-week plac ebo run-in period followed by a double-blind, placebo-controlled paral lel group study lasting 8 weeks. Setting Office practices (21 centres) . Patients Patients with essential hypertension (World Health Organiza tion grades I or II); supine diastolic blood pressure 101-114 mmHg in week 4 of the run-in period; 215 patients were enrolled, of whom 205 w ere assigned randomly to double-blind therapy, Main outcome measures R eduction in supine and standing blood pressures. Results All three act ive treatments with a single daily dose were significantly more effect ive than was placebo in reducing the blood pressure of seated subjects (P = 0.0001), The reductions in sitting diastolic blood pressure (DBP ) from baseline to the last visit with each active treatment were comp arable: 13 mmHg [95% confidence interval (CI) 16-9] with sustained-rel ease verapamil/trandolapril, 13 mmHg (16-9) with atenolol/chlorthalido ne and 12 mmHg (15-8) with lisinopril/hydrochlorothiazide. Normalizati on of blood pressure (DBP < 90 mmHg) was observed in 48% of patients w ith sustained-release verapamil/trandolapril, in 46% with atenolol/chl orthalidone and in 40% with lisinopril/hydrochlorothiazide. Response r ates (normalization of DBP or a reduction in DBP by > 10 mmHg) with ea ch active treatment were 72% for sustained-release verapamil/trandolap ril, 76% for atenolol/chlorthalidone and 69% for lisinopril/ hydrochlo rothiazide. All three active treatments were tolerated well, Conclusio n This study demonstrates that the low-dose combination sustained-rele ase verapamil/trandolapril may be a suitable alternative for combinati ons containing a thiazide diuretic or a beta-blocker for longer term m anagement of hypertensive patients for whom combination therapy is ind icated.