ADVERSE-EFFECTS OF LOW-DOSE AMIODARONE - A METAANALYSIS

Objectives. We sought to assess the odds of experiencing adverse effec ts with low dose amiodarone therapy compared,vith placebo. Background. An estimate of the likelihood of experiencing amiodarone-related adve rse effects with exposure to low daily doses of the drug is lacking in the published reports, and little information is available on adverse effect event rates in control groups not receiving the drug. Methods. Data from four published trials involving 1,465 patients were include d in a meta analysis design. The criteria for inclusion were 1) double blind, placebo-controlled design; 2) absence of a crossover design be tween patient groups; 3) mean follow-up of at least 12 months; 4) main tenance amiodarone dose less than or equal to 400 mg/day; and 5) prese nce of an explicit description of adverse effects. Data were pooled af ter testing for homogeneity of treat ment effects across trials, and s ummary odds ratios mere calculated by the Peto-modified Mantel-Haensze l method for each adverse effect. Results. The mean amiodarone dose pe r day ranged from 152 to 330 mg; 738 patients were randomized to recei ve amiodarone and 727 placebo. Exposure to amiodarone in this dose ran ge, for a minimal duration of 12 months, resulted in odds similar to t hose of placebo for hepatic and gastrointestinal adverse effects, but in significantly higher odds than those of placebo (p < 0.05) for expe riencing thyroid (odds ratio [OR] 4.2, 95% confidence interval [CI] 2. 0 to 8.7), neurologic (OR 2.0, 95% CI 1.1 to 3.7), skin (OR 2.5, 95% C I 1.1 to 6.2), ocular (OR 3.4, 95% CI 1.2 to 9.6) and bradycardic (OR 2.2, 95% CI 1.1 to 4.3) adverse effects. A trend toward increased odds of pulmonary toxicity was noted (OR 2.0, 95% CI 0.9 to 5.3), but this did not reach statistical significance (p = 0.07). The unadjusted tot al incidence of drug discontinuation was 22.9% in the amiodarone group and 15.4% in the placebo group. The odds of discontinuing the drug in the amiodarone group was approximately 1.5 times that of the placebo group (OR 1.52, 95% CI 1.2 to 1.9) (p = 0.003). Conclusions. Compared with placebo, there is a higher likelihood of experiencing several ami odarone-related adverse effects with exposure to low daily doses of th e drug. Thus, although low dose amiodarone may be well tolerated, it i s not free of adverse effects. (C) 1997 by the American College of Car diology.