Morbidity and Mortality Following Early Administration of Amiodarone in Myocardial Infarction - GEMICA
The goal of this study was to assess the safety and efficacy of amiodarone therapy compared with placebo among patients with acute myocardial infarction (AMI).
The initiation of amiodarone therapy within 24 hours of the onset of AMI would be associated with a decrease in all-cause mortality at six months.
Patients Screened: 2,083
Patients Enrolled: 1,073
Mean Follow Up: 6 months
MI within 24 hours
Follow-up not feasible, systolic blood pressure <100 mm Hg, heart rate <60 beats per minute, second or third degree atrioventricular block, intraventricular conduction blocks, corrected QT intervals >500 ms, severe heart failure, supraventricular or ventricular arrhythmias requiring amiodarone therapy, clinically significant liver disease, presence of other diseases affecting short-term survival, women who were pregnant or nursing or suspected of child-bearing, epilepsy with uncontrolled seizures, psychiatric condition likely to limit cooperation, hypersensitivity to amiodarone, amiodarone therapy within the last three months, or current or previous significant thyroid dysfunction
All-cause mortality at six months
Sudden death, heart failure death, reinfarction death, development or progression of heart failure, postinfarction angina, reinfarction, nonfatal arrhythmias, and rehospitalization
Eligible patients were randomized to receive amiodarone or placebo in a double-blind fashion as soon as possible after onset of symptoms or immediately after fibrinolytic administration in patients who received it. Initially, patients in the amiodarone group received a loading dose of 2400 mg intravenously (IV) over 48 hours, as well as an oral dose of 600 mg every 12 hours for four days, followed by 400 mg per day on days 5 though 90 and 200 mg per day thereafter.
After enrollment of 516 patients, an interim analysis revealed higher mortality in patients receiving amiodarone. Consequently, the dose of amiodarone was decreased to 1200 mg IV with an oral dose of 800 mg per day in one dose for the first 48 hours, followed by an oral dose of 400 mg per day on days 3 through 90 and 200 mg per day thereafter.
Patients who received the initial "high dose" amiodarone therapy had a higher mortality than those who received placebo (16.3% vs. 10.16%, p=0.04). Patients who received the "low dose" amiodarone therapy had a trend towards reduced mortality compared to patients who received placebo (6.61% vs. 9.47%, p=0.20).
There was no significant difference among the secondary endpoints except that patients in the amiodarone group had significantly less postinfarction angina than the placebo group with both high (odds ratio [OR] 0.55, p=0.003) and low (OR 0.56, p=0.004) dose amiodarone.
Among patients with AMI, high dose amiodarone therapy was associated with an increase in all-cause mortality at six months. In contrast, there was no statistically significant difference between lower dose amiodarone therapy and placebo in all-cause mortality at six months.
These results suggest that while high dose amiodarone therapy is associated with increased mortality in the setting of AMI, low dose amiodarone therapy is not and may be used in this setting if necessary for treating supraventricular or ventricular arrhythmias.
Elizari MV, Martinez JM, Belziti C, et al. Morbidity and mortality following early administration of amiodarone in acute myocardial infarction. GEMICA study investigators, GEMA Group, Buenos Aires, Argentina. Grupo de Estudios Multicentricos en Argentina. Eur Heart J 2000;21:198-205.
Keywords: Myocardial Infarction
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