DOUBLE-BLIND COMPARISON OF ANTIHYPERTENSIVE TREATMENT WITH RAMIPRIL AND PIRETANIDE, GIVEN ALONE OR IN COMBINATION

In a double-blind, randomized, multicenter trial, we compared the effi cacy and safety of the fixed combination of 5 mg ramipril and 6 mg pir etanide and the respective component monotherapies in hypertensive pat ients [supine diastolic blood pressure (DBP) 100-114 mm Hg]. After a s ingle-blind run-in period on placebo, 611 patients were randomized to ramipril (n = 209), piretanide(n = 201), or the combination therapy (n = 201). At randomization, the three groups had the same characteristi cs (51% men, age 55 +/- 10 years, BP 165 +/- 18/104 +/- 6 mm Hg). At 4 weeks, BP decreased more with combined therapy than with monotherapy. As compared with piretanide monotherapy, the gain in the antihyperten sive effect in the supine position averaged 2.1 mm Hg [90% confidence interval (CI) -0.8-5.0 mm Hg; p = 0.07] systolic BP (SEP) and 1.9 mm H g (CI 0.3-3.5 mm Hg, p = 0.02) DBP and, as compared with ramipril mono therapy, these differences were 4.2 mm Hg (CI 1.3-7.0 mm Hg, p = 0.008 ) and 2.0 mm Hg (CI 0.5-3.6 mm Hg, p = 0.009). The incidence of advers e events (AE) and the changes in biochemical measurements were similar in the three treatment groups with the exception of spontaneously rep orted polyuria and serum uric acid concentration. Polyuria was reporte d more frequently (p < 0.001) with piretanide therapy (n = 23) and com bined therapy (n = 19) than with ramipril therapy (n = 1). Similarly, serum uric acid increased more (p < 0.001) in the piretanide group (+2 4 mu M) and in the group receiving combined therapy (+18 mu M) as comp ared with the ramipril group (+0 mu M). However, serum uric acid level s and the incidence of polyuria were similar with piretanide and combi ned therapy. As compared with the respective monotherapies, combined t reatment with ramipril and piretanide produced an additional BP-loweri ng effect and did not lead to more frequent side effects.