Comparison of different fixed antihypertensive combination drugs

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Abstract
To compare the effects of fixed-dose preparations containing 180 mg sustained-release verapamil and 2 mg trandolapril, 100/25 mg atenolol/chlorthalidone, 20/12.5 mg lisinopril/hydrochlorothiazide and placebo in patients with essential hypertension. A 4-week placebo run-in period followed by a double-blind, placebo-controlled parallel group study lasting 8 weeks. Office practices (21 centres). Patients with essential hypertension (World Health Organization 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 were assigned randomly to double-blind therapy. Reduction in supine and standing blood pressures. All three active treatments with a single daily dose were significantly more effective 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 comparable: 13 mmHg [95% confidence interval (CI) 16-9] with sustained-release verapamil/trandolapril, 13 mmHg (16-9) with atenolol/chlorthalidone and 12 mmHg (15-8) with lisinopril/hydrochlorothiazide. Normalization of blood pressure (DBP < 90 mmHg) was observed in 48% of patients with sustained-release verapamil/trandolapril, in 46% with atenolol/chlorthalidone and in 40% with lisinopril/hydrochlorothiazide. Response rates (normalization of DBP or a reduction in DBP by > 10 mmHg) with each active treatment were 72% for sustained-release verapamil/trandolapril, 76% for atenolol/chlorthalidone and 69% for lisinopril/hydrochlorothiazide. All three active treatments were tolerated well. This study demonstrates that the low-dose combination sustained-release verapamil/trandolapril may be a suitable alternative for combinations containing a thiazide diuretic or a beta-blocker for longer term management of hypertensive patients for whom combination therapy is indicated.