European Myocardial Infarction Project—Free Radicals - EMIP-FR


The EMIP-FR trial was a randomized, double-blinded, placebo-controlled trial designed to assess whether treatment with trimetazidine, an agent that reduces oxidative stress and reperfusion injury in experimental models, would improve outcomes in patients with symptoms suggestive of acute myocardial infarction (MI).


Treatment with trimetazidine during the acute phase of MI would reduce total mortality due to reperfusion injury compared to placebo.

Study Design

Study Design:

Patients Enrolled: 19,725
Mean Follow Up: mean 458 days
Mean Patient Age: adults
Female: 30%

Patient Populations:

Suspected acute MI with onset of symptoms within the previous 24 hours. Diagnosis was based on two criteria: chest pain of over 30 minutes' duration within the last 24 hours or resistance to nitrates; and a typical electrocardiogram (ST elevation of 2 mm in at least two leads) or atypical electrocardiogram, but with a known history of coronary disease.


Prior trimetazidine within the previous 48 hours or fibrinolytic within the last 24 hours, treatment with an established or experimental, pregnancy, serious renal or liver failure, recent resuscitation, previously included in the trial, refusal of consent, or any other reason at the discretion of the investigator

Primary Endpoints:

Total mortality at 35 days

Secondary Endpoints:

Hospital death, long-term mortality, cardiovascular mortality, and combined cardiovascular endpoint (including severe heart failure, ventricular fibrillation, asystole, electromechanical dissociation, and cardiovascular death)

Drug/Procedures Used:

Intravenous bolus of 40 mg of trimetazidine, followed by an infusion of trimetazidine at 60 mg/day for 48 hours. Treatment was to be started before or simultaneously with fibrinolytic therapy and not beyond 15 minutes after the beginning of fibrinolytic therapy, and as soon as possible for patients not receiving fibrinolysis.

Concomitant Medications:

Standard care; 56% of patients received fibrinolytic therapy.

Principal Findings:

A total of 19,725 patients were enrolled. More patients received fibrinolytic therapy than not (11,039 vs. 8,686), and MI was confirmed at discharge in 93% of patients. There was no statistically significant difference in 35-day mortality (12.5% in both groups, p=0.98) or long-term mortality (21.5% for trimetazidine vs. 21.1% for placebo, p=0.42, mean follow-up 458 days).

There were no significant differences between trimetazidine and placebo groups in the intention-to-treat analysis of the subgroups of patients receiving fibrinolytic therapy or those receiving placebo. The incidence of other endpoints and the duration of hospital stay was similar in both the trimetazidine and placebo groups.


This very large randomized trial of trimetazidine, a potentially attractive agent acting against free radical-mediated reperfusion injury, demonstrated no clinical benefit when trimetazidine was used in patients presenting with symptoms suggestive of acute MI. Although there were minor differences between treatment groups in the subgroup of patients not receiving fibrinolytic therapy, these differences were not statistically significant in an intention-to-treat analysis.


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. Eur Heart J 2000;21:1537-46.

Clinical Topics: Prevention, Vascular Medicine, Stress

Keywords: Thrombolytic Therapy, Myocardial Infarction, Trimetazidine, Oxidative Stress, Electrocardiography, Length of Stay, Reperfusion Injury, Free Radicals, Chest Pain, Nitrates, Fibrinolysis, Intention to Treat Analysis, Models, Theoretical

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