Ramipril and felodipine: a comparison of the efficacy and safety of monotherapy versus combination therapy.

A multinational, double-blind, randomised study was conducted to investigate the efficacy and safety of a low-dose combination of the angiotensin converting enzyme inhibitor, ramipril, and the calcium antagonist, felodipine ER, in 642 patients with mild to moderate hypertension [supine diastolic blood pressure (DBP) = 95-115 mm Hg]. After a 4-week single-blind placebo run-in, patients were randomly allocated to once-daily felodipine extended release (ER; 2.5 mg), ramipril (2.5 mg) or felodipine ER/ramipril (2.5/2.5 mg) for 12 weeks. In the intention-to-treat analysis, mean DBP decreased significantly (p < 0.0001) after felodipine ER, ramipril and the combination (-9.1, -9.8 and -11.4 mm Hg, respectively). The decrease was significantly greater with the combination than with felodipine ER monotherapy (p = 0.02). The number of responding patients (final DBP < or = 90 mm Hg or a decrease of > or = 10 mm Hg) was also higher with the combination than with felodipine ER or ramipril monotherapy (65.1%, 53.1%, 55.7%, respectively). There were no differences between the three groups with respect to the incidence of adverse events overall or those considered treatment-related. There were fewer cases of peripheral oedema with combination therapy than with felodipine ER monotherapy. Thirty-three patients (5.1%) withdrew from the study because of adverse events, but there was no clear pattern with regard to the specific events leading to withdrawal. There were no clinically relevant changes in laboratory or clinical safety variables. Ramipril/felodipine ER 2.5/2.5 mg is an appropriate starting dosage when initiating combination antihypertensive therapy.