© 2000 European Society of Cardiology
Combination therapy with carvedilol and amiodarone in patients with severe heart failure
Abt. Thorax- Herz- und Gefäßchirurgie, Universitäts Krankenhaus Hamburg Eppendorf Martinistr. 52, D-20246 Hamburg, Germany
* Corresponding author. Tel.: +49-40-42803-3471; fax: +49-40-42803-4591. E-mail address: naegele{at}uke.uni-hamburg.de
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Abstract |
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Background: Carvedilol and at least in some studies, amiodarone have been shown to improve symptoms and prognosis of patients with heart failure. There are no reports on the outcome of combined treatment with both drugs on top of angiotensin-converting enzyme inhibitors (ACEI), diuretics and digitalis.
Methods and Results: In 109 patients with severe heart failure submitted for heart transplantation at one single center between the years 1996 and 1998 [left ventricular ejection fraction (LVEF) 24.6±11%, 85% males, 52% idiopathic dilated cardiomyopathy (DCM), mean observation time 1.9±0.4 years] a therapy with low-dose amiodarone (1000 mg/week) plus titrated doses of carvedilol (target 50 mg/day) was instituted. In addition, patients received a prophylactic dual chamber pacemaker (PM) in order to protect from bradycardia and for continuous holter monitoring. The devices were programed 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 study entry (85% vs. 63%, P<0.01). In 47 patients, under therapy over at least 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 suppressed 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/patient/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 class 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%) developed symptomatic documented bradycardic rhythm disturbances requiring reprograming of their pacemakers to DDD(R)/VVI(R) mode with higher basic rates. Two of these patients developed AV block, four sinu-atrial blocks or sinus 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 transplants. The 1-year survival rate (Kaplan–Meier) without transplantation was 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).
Conclusions: Heart failure patients benefit from a combined therapy with carvedilol and amiodarone resulting in a markedly improved NYHA stage, an increase in LV ejection fraction, a stabilization of sinus rhythm, a significant reduction in heart rate, a delay of electrical signal conduction and a suppression of ventricular ectopies. Approximately 6% of patients under such a regime became pacemaker-dependent in the first year. Compared to historic controls prognosis was better and the need for heart transplantation was lower. The exact role of either agent in combination or alone should be clarified in larger randomized studies.
Key Words: ACEI, angiotensin-converting enzyme inhibitor • AT1-AT, angiotensin 1 receptor antagonist • aVDO2 (%), arterio-venous oxygen difference • Captoprileqi, captopril equivalent dose [dosage of ACEI or AT1-AT (mg)x(150/maximal recommended dosage of ACEI or AT1-AT (mg)] • CHF, congestive heart failure • CI (l/minxm2), cardiac index • DCM (%), dilated cardiomyopathy (primary) rate of patients in percent • FS, fractional shortening • HR, heart rate • i.p.m., impulses per minute • LAes (cm), left atrial end-systolic diameter • LVEDD (cm), left ventricular end-diastolic diameter • LVEF (%), left ventricular ejection fraction in percent • MAP (mmHg), mean arterial pressure • NYHA, New York heart association • LVSWI (pm), left ventricular stroke work index • PCP (mmHg), pulmonary capillary wedge pressure • PVR (dyn), pulmonic vascular resistance • RAP (mmHg), right atrial pressure • SD, sudden death • SVR (dyn), systemic vascular resistance • VPCs (%), ventricular premature contractions in percent per 24 h • VT (n), Ventricular tachycardia (three or more consecutive premature ventricular contractions) per 24 h
Received September 16, 1999; Revised November 29, 1999; Accepted December 1, 1999
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