Adjunctive antiarrhythmic drug therapy in patients with implantable cardioverter defibrillators
Evidence Summaries Level of Evidence = C
Adjunctive antiarrhytmic drug therapy in patients with implantable cardioverter defibrillators (ICD) may reduce ICD shock therapies. The magnitude of the benefit seems to be higher with amiodarone but its use is associated with potential safety concerns.
A systematic review 1 including 8 studies with a total of 1889 subjects was abstracted in DARE. There was heterogeneity in the type of antiarrhythmic used in the treatment arm (amiodarone, sotalol, azimilide, and dofetilide) as well as in the control group (5 trials compared with placebo and 3 trials compared with beta-blocker). Anti-arrhythmic drug therapy was associated with a significantly lower risk of ICD shock therapy in the one study that evaluated both amiodarone and sotalol compared with beta-blockers (HR 0.42, 95% CI 0.19 to 0.93); there was evidence of statistical heterogeneity for the different drugs. Subgroup analysis by type of anti-arrhythmic drug showed a significant reduction with amiodarone (HR 0.27, 95% CI 0.14 to 0.52), but no significant difference between sotalol and beta-blockers. Class III anti-arrhythmics were significantly more likely to be discontinued compared with beta-blockers (RR 2.57, 95% CI 1.32 to 5.00; 3 studies); there was a significant increase in the discontinuation rate for amiodarone (RR 3.52, 95% CI 1.57 to 7.97). There was a non-significant increase in the risk of new onset or worsening heart failure with anti-arrhythmic compared with beta-blockers (RR 1.44, 95% CI 0.84 to 2.46; 2 studies). Compared with placebo or non-anti-arrhythmic therapy, anti-arrhythmic therapy was associated with a significantly lower risk of all causes of ICD shock therapy (HR 0.67, 95% CI 0.55 to 0.82; 4 studies). No significant differences were found for this outcome between azimilide or dofetilide versus placebo. Sotalol compared with placebo reduced the risk of shock therapy (HR 0.55; 95% CI 0.38 to 0.78). No significant differences were found between the active and placebo groups for discontinuation of therapy or new or worsening heart failure.
Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment and lack of blinding) and by inconsistency (heterogeneity in interventions and outcomes).
1. Ferreira-González I, Dos-Subirá L, Guyatt GH. Adjunctive antiarrhythmic drug therapy in patients with implantable cardioverter defibrillators: a systematic review. Eur Heart J. 2007;28(4):469-77.
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