EXPLORING THE MINIMAL DOSE OF AMIODARONE WITH ANTIARRHYTHMIC AND HEMODYNAMIC ACTIVITY

Amiodarone in doses of 200 to 400 mg/day has shown promise in secondar y prevention trials for reducing mortality in patients surviving myoca rdial infarction who have complex ventricular ectopy or nonsustained v entricular tachycardia, or both. In an attempt to explore the lowest d ose of amiodarone with antiarrhythmic and hemodynamic activity, we stu died 48 patients (mean age 53 +/- 11 years, ejection fraction 23 +/- 9 %, clinical heart failure in 85%) with nonsustained ventricular tachyc ardia. This was a 3-month, randomized, parallel, double-blind pilot st udy 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 th e 12 weeks, amiodarone (100 mg) significantly reduced ventricular prem ature 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 ven tricular tachycardia compared with 4 of 15 taking placebo, p = 0.021. Left ventricular lar ejection fraction improved by greater than or equ al to 7% (absolute) in 11 of 29 patients taking amiodarone as com pare d with only 1 of 15 placebo patients (0 = 0.02). In these 11 patients with the greatest measurable hemodynamic improvement, amiodarone signi ficantly increased ejection fraction (21 +/- 7% to 33 +/- 11%, p <0.01 ), stroke volume index (28 +/- 9 to 40 +/- 7 ml/m(2), p <0.01) and dec reased end-systolic volume index (116 +/- 48 to 92 +/- 44 ml/m(2), p < 0.01). It is concluded that amiodarone, given at a dose of 100 mg/day, has antiarrhythmic and hemodynamic activity without toxicity and meri ts testing in long-term efficacy trials.