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Combination therapy with carvedilol and amiodarone in patients with severe heart failure
1Abt. Thorax- Herz- und Gefässchirurgie, Universitäts Krankenhaus Hamburg Eppendorf, Martinistr. 52, D-20246, Hamburg, Germany. naegle@uke.uni-hamburg.de
Insights
Combined therapy with carvedilol and amiodarone significantly improved heart failure outcomes, including ejection fraction and NYHA class. This treatment approach demonstrated a better survival rate compared to historic controls, reducing the need for heart transplantation.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Carvedilol and amiodarone show promise in improving heart failure prognosis.
- Limited data exists on the combined effects of carvedilol and amiodarone with standard heart failure medications.
Purpose of the Study:
- To evaluate the efficacy and safety of combined carvedilol and amiodarone therapy in severe heart failure patients.
- To assess the impact on clinical outcomes, cardiac function, and arrhythmias.
Main Methods:
- A prospective study involving 109 severe heart failure patients undergoing heart transplantation evaluation.
- Patients received low-dose amiodarone, titrated carvedilol, and a prophylactic dual-chamber pacemaker.
- Data collected included left ventricular ejection fraction (LVEF), heart rate, rhythm, arrhythmias, and survival rates.
Main Results:
- Significant improvements observed in LVEF (26% to 39%), NYHA class (3.17 to 1.8), and sinus rhythm (63% to 85%).
- Marked reduction in resting heart rate and suppression of ventricular premature contractions.
- A 1-year survival rate of 89% was achieved, significantly higher than historic controls (64% with amiodarone alone, 57% without).
- Approximately 6% of patients required pacemaker reprogramming due to bradycardic rhythm disturbances.
Conclusions:
- Combined carvedilol and amiodarone therapy offers significant benefits for severe heart failure patients.
- The treatment improves cardiac function, stabilizes heart rhythm, and enhances survival rates.
- Larger randomized trials are needed to fully elucidate the role of each agent in combination therapy.
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 programmed 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 (P167 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 reprogramming 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.