European Heart Journal

European Heart Journal 2000 21(18):1537-1546; doi:10.1053/euhj.1999.2439
Copyright © 2000 by the European Society of Cardiology.

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Effect of 48-h intravenous trimetazidine on short- and long-term outcomes of patients with acute myocardial infarction, with and without thrombolytic therapy. A double-blind, placebo-controlled, randomized trial

revised December 21, 1999; accepted December 22, 1999

Abstract

Aims To compare the effect of trimetazidine (TMZ) versus placebo administered during the acute phase of myocardial infarction on long- and short-term mortality.

Methods and Results EMIP–FR (European Myocardial Infarction Project–Free Radicals) was a prospective, double-blind, European multicentre trial in which 19725 patients, presenting symptoms of acute myocardial infarction within the previous 24h were randomized. Stratification was according to thrombolytic therapy (56%) or not (44%). An intravenous bolus injection of trimetazidine (40mg) was given just before or simultaneously with thrombolysis, followed by continuous infusion (60mg.24h^–1) for 48h. Overall, no difference was found between trimetazidine and placebo for the main end-point, short-term (35-day) mortality, (P=0·98) in an intention-to-treat analysis. This was the result of opposing trends in the two strata. Thrombolysed patients showed a tendency towards more short-term deaths with trimetazidine, compared to placebo (trimetazidine: 11·3%, placebo: 10·5%, P=0·15) and non-thrombolysed patients the converse (trimetazidine: 14·0%, placebo: 15·1%, P=0·14). In a per-protocol analysis the beneficial effect of trimetazidine for non-thrombolysed patients became statistically significant (trimetazidine: 13·3%, placebo: 15·1%,P =0·027).

Conclusion Trimetazidine does not reduce mortality in patients undergoing thrombolytic therapy; however, it might have some beneficial effect for non-thrombolysed patients.

Key Words: Trimetazidine, myocardial infarction, thrombolysis, randomized controlled trial, free radicals

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