Low-dose Amiodarone Is Safe: A Systematic Review and Meta-analysis

Abstract

Amiodarone is commonly used for a variety of arrhythmias and, in some parts of the world, is the only available antiarrhythmic drug (AAD). Yet, amiodarone is known to have a wide range of potential side effects, many of which are dose-and duration-dependent. We sought to study the incidence of side effects leading to the discontinuation of low-dose amiodarone, arbitrarily defined as 200 mg/day or less, and very-low-dose amiodarone, defined as 100 mg/ day or less. In this study, literature databases were searched through June 2019. Studies that reported the incidence or prevalence of side effects of amiodarone were included. Effect estimates from individual studies were extracted and combined using the random-effects generic inverse variance method of DerSimonian and Laird. A total of 10 observational cohort studies involving 901 patients were included in the analysis. The pooled estimated incidence of overall side effects for low-dose amiodarone was 0.17 [95% confidence interval (CI): 0.12-0.22]. In addition, the pooled estimated incidence of side effects requiring medication discontinuation was 0.06 (95% CI: 0.03-0.11). As compared with 200 mg/day of amiodarone, the pooled estimated incidence of overall side effects was 0.11 (95% CI: 0.04-0.27), while the incidence of side effects requiring medication discontinuation was 0.02 (95% CI: 0.01-0.06) for the dose of 100 mg/day. In conclusion, verylow-dose amiodarone displays a low incidence of significant side effects requiring medication discontinuation.

Reduced-dose Antiarrhythmic Drugs: Valuable or Valueless?

“…In my view, the abovementioned findings do not seem to support the very low numbers reported by Chokesuwattanaskul et al 1 Further, the trials that these authors appeared to have missed also do not support their conclusion. Most striking is the data from the Cardiac Arrest in the Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE) study.…”

“…That having been said, I applaud the attempts by Chokesuwattanaskul et al 1 to undertake an effort to encourage us to use amiodarone in reduced doses when possible. When the use of amiodarone first became widespread and worldwide, its primary rhythm-related indication was for ventricular tachyarrhythmias and its most common maintenance dose was 400 mg/day, following a variable loading regimen.…”

“…Chokesuwattanaskul et al 1 suggest that low-dose amiodarone is appropriate to consider in the management of cardiac tachyarrhythmias because, in their dataset, it appeared to be safe. However, is their conclusion correct?…”

“…The paper by Chokesuwattanaskul et al 1 notes that its authors initially identified 2,312 papers but subsequently eliminated almost all of them from consideration, leaving only 10 papers from which to draw their conclusions. One could reasonably question how representative such a low number of papers can be.…”

“…In their conclusion, Chokesuwattanaskul et al 1 state that they have demonstrated "the safety of very low-dose amiodarone, which has been prescribed worldwide. In addition, the incidence of side effects from our study is lower than that of a prior meta-analysis, which might encourage physicians to begin or continue to use this useful medication, albeit with limitations as appropriate.…”