BARCELONA – A low- and fixed-dose combination of perindopril 3.5 mg/amlodipine 2.5 mg once daily showed considerable promise as a potential first-step treatment in mild to moderate hypertension in a large, international, randomized trial.
The 8-week, double-blind, placebo- and active-controlled trial involved 1,297 patients, of whom 1,073 completed the study. The fixed-dose combo showed reductions in mean 24-hour blood pressure that were clinically meaningful and significantly greater than in patients randomized to perindopril monotherapy at 5 mg/day or placebo, Dr. Gianfranco Parati reported at the annual congress of the European Society of Cardiology.
Twenty-four–hour BP reductions in the lower-dose perindopril/amlodipine combination group were virtually identical to those seen in patients assigned to amlodipine monotherapy at 5 mg/day. However, the fixed-dose combo was better tolerated, with an incidence of peripheral edema of 1.6%, compared with 4.9% in patients on amlodipine at 5 mg/day.
Moreover, the rate of treatment withdrawal due to adverse effects was 1.2% with combination therapy compared to 2.6% with perindopril at 5 mg/day and 3.4% with amlodipine at 5 mg/day, added Dr. Parati of the University of Milan.
The decrease in mean 24-hour systolic BP in the lower-dose combo group was 3.8 mm Hg greater than with higher-dose perindopril monotherapy and 6.2 mm Hg greater than with placebo. The reduction in mean 24-hour diastolic BP with the fixed-dose combo was 2.4 mm Hg greater than with perindopril at 5 mg/day and 4.0 mm Hg more than with placebo.
The lower-dose combination also performed well in terms of the secondary endpoints of diurnal and nocturnal blood pressure lowering, as well as BP lowering during the previous 6 hours and in the morning.
Dr. Parati noted that current guidelines, as well as guidance from regulatory agencies, emphasize the high rate of uncontrolled hypertension and take a favorable view of the early use of fixed-dose combinations in patients with uncomplicated hypertension as a means of addressing the problem.
He received a research grant from Servier, which funded the multicenter study.