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 efficacy and safety of the fixed combination of 5 mg ramipril and 6 mg piretanide and the respective component monotherapies in hypertensive patients [supine diastolic blood pressure (DBP) 100–114 mm Hg]. After a single-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 characteristics (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 antihypertensive 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 (SBP) and 1.9 mm Hg (CI 0.3–3.5 mm Hg, p = 0.02) DBP and, as compared with ramipril monotherapy, 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 adverse events (AE) and the changes in biochemical measurements were similar in the three treatment groups with the exception of spontaneously reported polyuria and serum uric acid concentration. Polyuria was reported more frequently (p < 0.001) with piretanide therapy (n = 23) and combined therapy (n = 19) than with ramipril therapy (n = 1). Similarly, serum uric acid increased more (p < 0.001) in the piretanide group (+ 24 μM) and in the group receiving combined therapy (+ 18 μM) as compared with the ramipril group (+ 0 μM). However, serum uric acid levels and the incidence of polyuria were similar with piretanide and combined therapy. As compared with the respective monotherapies, combined treatment with ramipril and piretanide produced an additional BP-lowering effect and did not lead to more frequent side effects.