The primary end point is to assess the efficacy of blood pressure control by each dose of a first-line perindopril/amlodipine combination strategy, and to assess its safety.
Design and method:
A phase 3, multicenter, international, randomized, double-blind study in two parallel groups over 9 months. The uptitration steps were perindopril/amlodipine 3.5/2.5 mg to 7/5 mg, 14/5 mg, and 14/10 mg for one group. The other arm was treated with an irbesartan ± hydrochlorothiazide strategy (irbesartan 150 mg, to irbesartan ± hydrochlorothiazide 150/12.5 mg, 300/12.5 mg, and 300/25 mg).
The baseline population comprised 3270 hypertensive patients with 37.5% grade I hypertension, 50.8% with grade II, and 11.7% with grade III, and a mean body mass index of 29.5. The proportion of patients with controlled blood pressure increased significantly with the first-line combination strategy over each evaluation period until 6 months (primary end point): 21% at 1 month, 30% at 2 months (P < 0.001), 37% at 3 months (P < 0.001), 42% at 6 months (P = 0.003). However, the perindopril 14 mg/amlodipine 5 mg dose seemed to contribute least to the overall efficacy. The proportion of patients with controlled blood pressure remained stable over the period 6 to 9 months. At the last post-baseline assessment over the period 0 to 6 months, the blood pressure reduction was similar for the two strategies (SBP decrease 22.0 mm Hg for the perindopril/amlodipine group and 22.5 mm Hg for the irbesartan ± hydrochlorothiazide group; P = 0.116). A total of 149 patients (9.2%) had severe emergent adverse events in the perindopril/amlodipine group and 121 patients (7.3%) in the irbesartan ± hydrochlorothiazide group. Emergent clinical events of special interest (composite end point of cardiovascular, diabetes and glucose metabolic impairment, and renal impairment) occurred with a significantly lower incidence in the perindopril/amlodipine group, with a statistically significant hazard ratio of 0.811 (95% CI = [0.666–0.986], P = 0.036).
The primary end point was reached: the proportion of patients with controlled blood pressure increased significantly with each dose of the first-line perindopril/amlodipine combination. In view of the efficacy results, the perindopril 14 mg/amlodipine 5 mg dose has been withdrawn from further development studies.