MULTICENTER, RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND-STUDY OF THE SAFETY AND EFFICACY AT ORAL DELAPRIL IN PATIENTS WITH CONGESTIVE-HEART-FAILURE

A total of 101 patients (67 delapril, 34 placebo) with congestive heart failure, New York Heart Association (NYHA) classes II and III, entered a multicenter, randomized (2:1), double-blind, placebo-controlled study to determine the minimum effective and maximum tolerated doses of delapril. Patients received placebo or increasing doses of delapril. After a 2-week run-in period on placebo, patients were randomly assigned to delapril or placebo. The dose of delapril was 7.5 mg twice daily for 2 weeks, 15 mg twice daily for another 2 weeks, followed by 30 mg twice daily for 4 weeks. The dose was increased only if the patient did not present any symptoms of orthostatic hypotension. if such symptoms developed, the code was broken and an open treatment was continued on the minimum effective dose (delapril group). Patients with symptoms of orthostatic hypotension in the placebo group were withdrawn. At the end of the 8-week treatment, 36 (54.5%) patients in the delapril group completed the study on 30 mg twice daily, 12 (18.2%) on 15 mg twice daily, and 18 (27.3%) on 7.5 mg twice daily. Seven patients on placebo were withdrawn because of insufficient therapeutic response; one patient on delapril was lost to follow-up. Them was a significant improvement (p < 0.01) in bicycle ergometric performance involving an increase in the exercise duration and the maximum workload tolerated in those patients completing the study on delapril 30 mg twice daily acid those finishing on 15 mg twice daily. At the end of the 8-week period, delapril also produced a significant (p < 0.01) reduction in left ventricular end-systolic and end-diastolic volume, which was most marked during the period on delapril 30 mg twice daily. This was confirmed by a significant (p < 0.01) reduction in left ventricular wall stress as well as an increase in systolic volume (p < 0.01), cardiac output (p < 0.01), and election fraction (p < 0.05). Treatment with delapril wets well tolerated; only 1 patient experienced adverse reactions (nausea and headache). No significant changes in biochemical, hematologic, or urine laboratory parameters were seen in the 2 treatment groups. In conclusion, delapril exerts a beneficial effect on left ventricular performance in patients with congestive heart failure acid is well tolerated. The dosage of delapril producing the best symptom control without clinically relevant effects on the arterial blood pressure in patients with CHF is 15 mg twice daily. The dosage of 30 mg twice daily may be indicated in more severe cases and 7.5 mg twice daily is useful to test the initial response of patients to the drug.