Antihypertensive efficacy and safety of perindopril in mild-to-moderate essential hypertension: Results of a double-blind multicenter study versus atenolol

Abstract

A 3-month double-blind multicenter trial compared the efficacy and safety of perindopril, a new angiotensin-converting enzyme (ACE) inhibitor, with atenolol in mild-to-moderate essential hypertension. A total of 190 patients, 49 of whom were diabetic, entered the perindopril-atenolol comparison. Of these, 163 had been previously treated and had a 4-week runin period on placebo; 27 had previously been untreated and received placebo for 2 weeks. At entry, all patients who had a supine diastolic blood pressure (DBP) of 95–115 mm Hg were randomized to receive perindopril 2 mg or atenolol 25 mg, once daily. Patients were assessed at 2 weekly intervals for the first month and then monthly for 2 more months. If supine DBP was >90 mm Hg, treatment was increased by stepwise doubling of dose up to 8 mg perindopril or 100 mg atenolol once daily, and later by the addition of hydrochlorothiazide 25 mg, (indapamide 2.5 mg in diabetic patients) once daily. The two groups were homogeneous prior to treatment except for supine and erect heart rate, which were higher in the perindopril group than in the atenolol group (p <0.05). Mean supine DBP was 101.1 ± 0.6 mm Hg in the perindopril group (n = 94) and 99.9 ± 0.6 mm Hg in the atenolol group (n = 96). After 3 months' active treatment, 74% of patients in the perindopril group achieved a supine DBP of ≤90 mm Hg and 73% of patients in the atenolol group achieved the same goal. Monotherapy controlled supine DBP in 67% of the perindopril group and 63% of the atenolol group. The decrease in supine DBP was not significantly different between the two groups (−12.9 ± 0.9 versus −14.7 ± 0.9 mm Hg) but the decrease in erect DBP was lower in the perindopril group (−10.3 ± 0.9 versus −13.4 ± 1.0 mm Hg, p <0.02). Heart rate was reduced in the atenolol group (p <0.001). Sixteen patients withdrew from the study; nine were attributed to adverse events, two in the perindopril group and seven, including one death, in the atenolol group. Cough was spontaneously reported by 13% patients of the perindopril group and 1% patients of the atenolol group. In 5% of the perindopril cases this was mild and associated with upper respiratory tract infection. The nature and incidence of other symptoms were similar with both drugs. Changes in laboratory parameters were minor and not significantly different between the two groups. Analysis of the subgroup of diabetic patients showed similar efficacy and safety results.