Amiodarone for prevention of sudden cardiac death

Evidence Summaries

Level of Evidence = C
Amiodarone may reduce sudden cardiac death, cardiac and all-cause mortality compared to placebo or no intervention in primary prevention (persons with high risk of sudden cardiac death).

The quality of evidence is downgraded and by study limitations (unclear allocation concealment), and by suspected publication bias (asymmetrical funnel plot).

A Cochrane review 1 included 24 studies with a total of 9,997 subjects. Seventeen studies evaluated amiodarone for primary prevention and 6 for secondary prevention of sudden cardiac death; 3 secondary prevention studies used an implantable cardiac defibrillator (ICD) concomitantly with amiodarone. For primary prevention, participants at high risk for sudden cardiac death (SCD) were considered, and for secondary prevention participants recovered from cardiac arrest or syncope due to ventricular arrhythmias were considered. For primary prevention, amiodarone compared to placebo or no intervention reduced SCD, cardiac mortality (RR 0.86, 95% CI 0.77 to 0.96) and all-cause mortality (table T1). Compared to other antiarrhythmics (3 studies, n=540), 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).

Table 1. Amiodarone versus placebo or no treatment in participants with high risk of sudden cardiac death (primary prevention)
Outcome Relative effect (95% CI) Assumed risk - placebo or no treatment Corresponding risk - amiodarone (95% CI) Participants (studies)
Sudden cardiac death RR 0.76 (0.66 to 0.88) 91 per 1000 70 per 1000 (61 to 81) 8,383 (17 studies)
All-cause mortality RR 0.88 (0.78 to 1.00) 203 per 1000 178 per 1000 (158 to 203) 8,383 (17 studies)

For secondary prevention, amiodarone compared to placebo or no intervention (2 studies, n=440) seemed to increase the risk of SCD (RR 4.32, 95% CI 0.87 to 21.49) and increased all-cause mortality (RR 3.05, 1.33 to 7.01). Compared to other antiarrhythmics (4 studies, n=839) amiodarone seemed to increase the risk of SCD (RR 1.40, 95% CI 0.56 to 3.52) although the difference was not statistically significant. There was no effect in all-cause mortality (RR 1.03, 95% CI 0.75 to 1.42).

Amiodarone was associated with an increase in pulmonary and thyroid adverse events.

It is uncertain whether amiodarone increases or reduces the risk of a new episode of cardiac arrest or death in subjects who have already suffered a prior cardiac arrest. ICD implantation is preferable in this group.

References

1. Claro JC, Candia R, Rada G et al. Amiodarone versus other pharmacological interventions for prevention of sudden cardiac death. Cochrane Database Syst Rev 2015;(12):CD008093.  [PMID:26646017]
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