RATIONALE AND DESIGN OF THE 3RD VASODILATOR-HEART FAILURE TRIAL (V-HEFT-III) - FELODIPINE AS ADJUNCTIVE THERAPY TO ENALAPRIL AND LOOP DIURETICS WITH OR WITHOUT DIGOXIN IN CHRONIC CONGESTIVE-HEART-FAILURE

Therapy with angiotensin-converting enzyme inhibitors and nonselective vasodilators (hydralazine and isosorbide dinitrate) has become accept ed treatment in patients with symptomatic, chronic congestive heart fa ilure (CHF), and has been demonstrated in large clinical trials to ame liorate symptoms, improve exercise performance, and reduce cardiac mor tality. Nevertheless, the management of patients with CHF remains a th erapeutic challenge. The second Vasodilator-Heart Failure Trial (V-HeF T II) showed that the average 2-year mortality with enalapril (18%) wa s significantly lower than that with hydralazine-isosorbide dinitrate (25%) but, somewhat surprisingly, the nonspecific vasodilators produce d significantly more improvement in exercise performance and left vent ricular function. Such data suggest that improvement in symptoms, hemo dynamics, and survival may not be afforded by the use of a single clas s of vasodilator therapy, but might be optimized by the combined use o f different agents. This report describes the rationale and design of V-HeFT III, a multicenter, prospective, randomized, double-blind, plac ebo-controlled trial comparing the effects of chronic oral extended-re lease felodipine (felodipine ER) 2.5 to 5 mg twice daily, when added t o a stable regimen of enalapril and loop diuretics, with or without di goxin, on exercise performance, morbidity, and mortality in patients w ith New York Heart Association functional class II to III CHF followed for a minimum of 12 weeks. Felodipine is a second-generation dihydrop yridine calcium antagonist with a high degree of vascular selectivity which, in the doses used in this study, exerts its systemic arterial e ffect by decreasing peripheral vascular resistance without producing n egative inotropic effects. The results of V-HeFT III may shed importan t light on the role of additive vasodilator therapy in the management of patients with CHF.