Comparison of the Effects of Cilazapril and of the Combination of Cilazapril Plus Valsartan in Patients with Advanced Heart Failure

Abstract

Background: Combined treatment with angiotensin-converting enzyme inhibitors and angiotensin II antagonists may be a more efficient therapy for cardiac failure than monotherapy with either drug. Objective: We compared the efficacy of the combination of cilazapril and valsartan to cilazapril as monotherapy in 46 patients with advanced heart failure of ischaemic aetiology. Methods: The design of the study is double blind, double dummy, with parallel groups. Diuretics and β-blockers were used as a basal therapy, and many patients were treated with digoxin, spironolactone and nitrates. Concomitant medication was left unchanged and patients were randomised in three groups: placebo (for test drugs), cilazapril, or a combination of cilazapril and valsartan. During 3 weeks, the test drugs were titrated upward, and the highest tolerated dose level was maintained for 6 weeks. At baseline and again at the end of the treatment, left ventricular ejection fraction and regional wall ventricular motility (echocardiography at rest and after pharmacological stress), exercise capacity, signs and symptoms of heart failure and brain natriuretic peptide levels were recorded. Results: Both treatments were well tolerated, however the effects of the combination were superior. Our results show that, in patients who are treated with β-blockers and diuretics, the combination of cilazapril and valsartan is more effective than cilazapril at the highest tolerated dosage in improving global and regional myocardial function both at rest and after stress, and in ameliorating cardiac symptoms and signs of heart failure. We think that the superior effect of the combination is related to a more effective anti-ischaemic effect.