Does amiodarone or ICD therapy reduce the risk of thromboembolism compared to placebo in patients with moderate heart failure and no history of atrial fibrillation?
In patients with moderate heart failure without atrial fibrillation, treatment with amiodarone or an ICD was associated with a significantly lower risk of thromboembolic events compared to placebo.
BACKGROUND: In patients with heart failure, rates of clinically apparent stroke range from 1.3% to 3.5% per year. Little is known about the incidence and risk factors in the absence of atrial fibrillation. In the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), 2521 patients with moderate heart failure were randomized to receive amiodarone, implanted cardioverter-defibrillators (ICDs), or placebo. METHODS AND RESULTS: We determined the incidence of stroke or peripheral or pulmonary embolism in patients with no history of atrial fibrillation (n=2114), predictors of thromboembolism and the relationship to left ventricular ejection fraction. Median follow-up was 45.5 months. Kaplan-Meier estimates (95% CIs) for the incidence of thromboembolism by 4 years were 4.0% (3.0% to 4.9%), with 2.6% (1.1% to 4.1%) in patients randomized to amiodarone, 3.2% (1.8% to 4.7%) in patients randomized to ICD, and 6.0% (4.0% to 8.0%) in patients randomized to placebo (approximate rates of 0.7%, 0.8%, and 1.5% per year, respectively). By multivariable analysis, hypertension (P=0.021) and decreasing left ventricular ejection fraction (P=0.023) were significant predictors of thromboembolism; treatment with amiodarone or ICD treatment was a significant predictor of thromboembolism-free survival (P=0.014 for treatment effect; hazard ratio 95% CI versus placebo, 0.57 0.33 to 0.99 for ICD; 0.44 0.24 to 0.80 for amiodarone). Inclusion of atrial fibrillation during follow-up in the multivariable model did not affect the significance of treatment assignment as a predictor of thromboembolism. CONCLUSIONS: In the SCD-HeFT patient cohort, which reflects contemporary treatment of patients with moderately symptomatic systolic heart failure, patients experienced thromboembolism events at a rate of 1.7% per year without antiarrhythmic therapy. Those treated with amiodarone or ICDs had lower risk of thromboembolism than those given placebo. Hypertension at baseline and lower ejection fraction were independent predictors of risk.
Freudenberger et al. (Tue,) studied this question.