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. The EMIP-FR Group. European Myocardial Infarction Project--Free Radicals.
OBJECTIVE
To compare the effect of trimetazidine (TMZ) versus placebo administered during the acute phase of myocardial infarction on long- and short-term mortality.


RESULTS
EMIP-FR (European Myocardial Infarction Project - Free Radicals) was a prospective, double-blind, European multicentre trial in which 19 725 patients, presenting symptoms of acute myocardial infarction within the previous 24 h were randomized. Stratification was according to thrombolytic therapy (56%) or not (44%). An intravenous bolus injection of trimetazidine (40 mg) was given just before or simultaneously with thrombolysis, followed by continuous infusion (60 mg. 24 h(-1)) for 48 h. 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).


CONCLUSIONS
Trimetazidine does not reduce mortality in patients undergoing thrombolytic therapy; however, it might have some beneficial effect for non-thrombolysed patients.
D000328:Adult; D000368:Aged; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016019:Survival Analysis; D015912:Thrombolytic Therapy; D016896:Treatment Outcome; D014292:Trimetazidine / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D014665:Vasodilator Agents; D014292:Trimetazidine