Combination therapy with carvedilol and amiodarone in patients with severeheart failure

Background: Carvedilol and at least in some studies, amiodarone have been s hown to improve symptoms and prognosis of patients with heart failure. Ther e are no reports on the outcome of combined treatment with both drugs on to p of angiotensin-converting enzyme inhibitors (ACEI), diuretics and digital is. Methods and Results: In 109 patients with severe heart failure submitte d for heart transplantation at one single center between the years 1996 and 1998 [left ventricular ejection fraction (LVEF) 24.6 +/- 11%, 85% males, 5 2% idiopathic dilated cardiomyopathy (DCM), mean observation time 1.9 +/- 0 .4 years] a therapy with low-dose amiodarone (1000 mg/week) plus titrated d oses of carvedilol (target 50 mg/day) was instituted. In addition, patients received a prophylactic dual chamber pacemaker (PM) in order to protect fr om bradycardia and for continuous holter monitoring. The devices were progr amed in back-up mode with a basal rate of 40 i.p.m. with a hysteresis of 25 %. Significantly, more patients were in sinus rhythm after 1 year than at s tudy entry (85% vs. 63%, P < 0.01). In 47 patients, under therapy over at l east 1 year, the resting heart rate fell from 90 +/- 19 to 59 +/- 5 b.p.m. (P < 0.001). Ventricular premature contractions in 24-h holter ECGs were su ppressed from 1.0 +/- 3 to 0.1 +/- 0.3%/24 h (P < 0.001) as did numbers of tachycardias > 167 b.p.m. detected by the pacemaker (1.2 +/- 2.8 episodes/p atient/3 months vs. 0.3 +/- 0.8 episodes/patient/3 months after 1 year (P < 0.01). The LVEF increased from 26 +/- 10 to 39 +/- 13% (P < 0.001). NYHA c lass improved from 3.17 +/- 0.3 to 1.8 +/- 0.6 (P < 0.001) as well as right heart catheterization data. From the total cohort, seven patients (6%) dev eloped symptomatic documented bradycardic rhythm disturbances requiring rep rogramming of their pacemakers to DDD(R)/VVI(R) mode with higher basic rate s. Two of these patients developed AV block, four sinu-atrial blocks or sin us bradycardia and one patient had bradycardic atrial fibrillation. During the observation period five patients died (3 sudden, 1 due to heart failure and 1 due to mesenteric infarction). Two patients had undergone heart tran splants. The 1-year survival rate (Kaplan-Meier) without transplantation wa s 89%. Compared to historic control patients with amiodarone only (n = 154) or without either agent (n = 283) this rate was 64 and 57% (P < 0.01). Con clusions: Heart failure patients benefit from a combined therapy with carve dilol and amiodarone resulting in a markedly improved NYHA stage, an increa se in LV ejection fraction, a stabilization of sinus rhythm, a significant reduction in heart rate, a delay of electrical signal conduction and a supp ression of ventricular ectopies. Approximately 6% of patients under such a regime became pacemaker-dependent in the first year. Compared to historic c ontrols prognosis was better and the need for heart transplantation was low er. The exact role of either agent in combination or alone should be clarif ied in larger randomized studies. (C) 2000 European Society of Cardiology. All rights reserved.