Amiodarone versus other pharmacological interventions for prevention of sudden cardiac death

Sudden cardiac death (SCD) is one of the main causes of cardiac death. There are two main strategies to prevent it: managing cardiovascular risk factors and reducing the risk of ventricular arrhythmias. Implantable cardiac defibrillators (ICDs) constitute the standard therapy for both primary and secondary prevention; however, they are not widely available in settings with limited resources. The antiarrhythmic amiodarone has been proposed as an alternative to ICD.

To evaluate the effectiveness of amiodarone for primary or secondary prevention in SCD compared with placebo or no intervention or any other antiarrhythmic drugs in participants at high risk (primary prevention) or who have recovered from a cardiac arrest or a syncope due to Ventricular Tachycardia/Ventricular Fibrillation, or VT/VF (secondary prevention).

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), EMBASE (OVID), CINAHL (EBSCO) and LILACS on 26 March 2015. We reviewed reference lists of included studies and selected reviews on the topic, contacted authors of included studies, screened relevant meetings and searched in registers for ongoing trials. We applied no language restrictions.

Randomised and quasi-randomised trials assessing the efficacy of amiodarone versus placebo, no intervention, or other antiarrhythmics in adults. For primary prevention we considered participants at high risk for SCD. For secondary prevention we considered participants recovered from cardiac arrest or syncope due to ventricular arrhythmias.

Two authors independently assessed the trials for inclusion and extracted relevant data. We contacted trial authors for missing data. We performed meta-analyses using a random-effects model. We calculated risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CIs). Three studies included more than one comparison.

We included 24 studies (9,997 participants). Seventeen studies evaluated amiodarone for primary prevention and six for secondary prevention. Only three studies used an ICD concomitantly with amiodarone for the comparison (all of them for secondary prevention).For primary prevention, amiodarone compared to placebo or no intervention (17 studies, 8383 participants) reduced SCD (RR 0.76; 95% CI 0.66 to 0.88), cardiac mortality (RR 0.86; 95% CI 0.77 to 0.96) and all-cause mortality (RR 0.88; 95% CI 0.78 to 1.00). The quality of the evidence was low.Compared to other antiarrhythmics (three studies, 540 participants), amiodarone reduced SCD (RR 0.44; 95% CI 0.19 to 1.00), cardiac mortality (RR 0.41; 95% CI 0.20 to 0.86) and all-cause mortality (RR 0.37; 95% CI 0.18 to 0.76). The quality of the evidence was moderate.For secondary prevention, amiodarone compared to placebo or no intervention (two studies, 440 participants) appeared to increase the risk of SCD (RR 4.32; 95% CI 0.87 to 21.49) and all-cause mortality (RR 3.05; 1.33 to 7.01). However, the quality of the evidence was very low. Compared to other antiarrhythmics (four studies, 839 participants) amiodarone appeared to increase the risk of SCD (RR 1.40; 95% CI 0.56 to 3.52; very low quality of evidence), but there was no effect in all-cause mortality (RR 1.03; 95% CI 0.75 to 1.42; low quality evidence).Amiodarone was associated with an increase in pulmonary and thyroid adverse events.

There is low to moderate quality evidence that amiodarone reduces SCD, cardiac and all-cause mortality when compared to placebo or no intervention for primary prevention, and its effects are superior to other antiarrhythmics.It is uncertain if amiodarone reduces or increases SCD and mortality for secondary prevention because the quality of the evidence was very low.