Exploring the minimal dose of amiodarone with antiarrhythmic and hemodynamic activity

Abstract

Amiodarone in doses of 200 to 400 mg/day has shown promise in secondary prevention trials for reducing mortality in patients surviving myocardial infarction who have complex ventricular ectopy or nonsustained ventricular tachycardia, or both. In an attempt to explore the lowest dose of amiodarone with antiahrhythmic and hemodynamic activity, we studied 48 patients (mean age 53 ± 11 years, ejection fraction 23 ± 9%, clinical heart failure in 85%) with nonsustained ventricular tachycardia. This was a 3-month, randomized, parallel, double-blind pilot study comparing placebo (n = 16) with amiodarone 50 mg/day (n = 15) and 100 mg/day (n = 17). Patients randomized to amiodarone received a mean loading dose of 422 mg/day for the first study week. At the end of the 12 weeks, amiodarone (100 mg) significantly reduced ventricular premature complexes (177 ± 64 to 98 ± 38/ hour), couplets (8 ± 3 to 4 ± 2/hour), and runs of nonsustained ventricular tachycardia (13 ± 7 to 3 ± 2/day), all p < 0.01 versus baseline. In addition, 10 of 14 patients taking 100 mg/day had total suppression of non-sustained ventricular tachycardia compared with 4 of 15 taking placebo, p = 0.021. Left ventricular ejection fraction improved by ≥7% (absolute) in 11 of 29 patients taking amiodarone as compared with only 1 of 15 placebo patients (p = 0.02). In these 11 patients with the greatest measurable hemodynamic improvement, amiodarone significantly increased ejection fraction (21 ± 7% to 33 ± 11%, p < 0.01), stroke volume index (28 ± 9 to 40 ± 7 ml/m2, p < 0.01) and decreased end-systolic volume index (116 ± 48 to 92 ± 44 ml/m2, p < 0.01). It is concluded that amiodarone, given at a dose of 100 mg/day, has antiarrhythmic and hemodynamic activity without toxicity and merits testing in long-term efficacy trials.