Evaluation of the Safety and Cardioprotective Effects of Eniporide in Acute Myocardial Infarction - ESCAMI


ESCAMI was a multicenter randomized, double-blinded, placebo-controlled, dose-ranging trial to test the effect of eniporide (an Na+/H+ exchange inhibitor) on infarct size and clinical outcomes in patients treated with either fibrinolytic therapy or primary angioplasty for ST-elevation myocardial infarction (STEMI).


Administration of eniporide, an agent that inhibits the Na+/H+ pump, which may mediate ischemia/reperfusion injury, would be associated with a reduction in infarct size and an increase in myocardial salvage when given as adjunctive therapy to reperfusion.

Study Design

Study Design:

Patients Enrolled: 1,389
Mean Follow Up: Six weeks for clinical events and six-month mortality
Mean Patient Age: Mean of 60
Female: 22

Patient Populations:

Patients aged between 18 and 75 years presenting with chest pain suggesting an acute MI and lasting for at least 30 minutes, and the presence of ST-segment elevation of ≥0.1 mV in at least two limb leads or ≥0.2 mV in two precordial chest leads


Prehospital thrombolysis, Killip class IV on admission, known history of renal failure, history of severe allergic reaction, history of autoimmune diseases, pregnancy, severe concurrent illness with reduced short-term prognosis, inability to give informed consent, and participation in another study within the past 30 days

Primary Endpoints:

Infarct size as determined by the area under the curve for release of alpha-hydroxybutyrate dehydrogenase

Secondary Endpoints:

Creatine kinase and troponin release, clinical events within the first six weeks, and extent of ST-segment resolution

Drug/Procedures Used:

The blinded study medication was administered intravenously over 10 minutes. In patients receiving thrombolytic therapy, the infusion had to be completed at least 15 minutes after the start of treatment. In patients treated with primary angioplasty, the infusion had to be completed at least 10 minutes before the start of the angioplasty.

• Stage 1: 50 mg, 100 mg, 150 mg, and 200 mg of eniporide
• Stage 2: Based on the results of Stage 1, the 100 mg dose and 150 mg dose of eniporide were further tested.

Concomitant Medications:

Reperfusion therapy initiated within six hours of symptoms; the decision to perform primary angioplasty or to treat the patient with thrombolytic therapy was left to the discretion of the treating physician.

Principal Findings:

Four hundred and thirty-three patients were enrolled in Stage 1, and 978 patients were enrolled in Stage 2; a total of 1,389 patients actually received study medication and were included in the analysis. Baseline characteristics were well balanced. Primary angioplasty was performed in 38% of patients, with thrombolysis in 61%. The study drug was well tolerated.

In Stage 1, there was no observed dose-response relationship between increasing doses and reduction in infarct size, but reductions in infarct size were seen for the 100 mg and 150 mg doses (reductions of 25.7% and 41.7%, respectively). However, these findings were not confirmed in Stage 2 of the trial.

There was no effect of the 100 mg or 150 mg doses of eniporide on cardiac enzyme release or on any of the secondary endpoints, including ST-segment resolution or clinical events. Subgroup analyses did not demonstrate any benefit of eniporide, aside from a reduction in patients with abnormal Killip class among patients given the 150 mg dose of eniporide and treated >4 hours after symptom onset.


In this multicenter, placebo-controlled, randomized dose-ranging study of eniporide, an agent that inhibits the Na+/H+ pump, which may mediate ischemia/reperfusion injury, treatment with eniporide was not associated with reductions in infarct size or in the incidence of any secondary endpoints in patients with STEMI.

Although it is possible that the dosing of eniporide was responsible for the negative results, the two-stage trial design tested a variety of doses that had been tested in phase 1 studies. It is possible that eniporide might have been more efficacious if administered earlier (prior to reperfusion), or that other agents that block Na+/H+ exchange will have different effects.


Zeymer U, Suryapranata H, Monassier JP, et al. The Na(+)/H(+) exchange inhibitor eniporide as an adjunct to early reperfusion therapy for acute myocardial infarction. Results of the evaluation of the safety and cardioprotective effects of eniporide in acute myocardial infarction (ESCAMI) trial. J Am Coll Cardiol 2001;38:1644-50.

Clinical Topics: Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Vascular Medicine, Lipid Metabolism, Interventions and Vascular Medicine

Keywords: Thrombolytic Therapy, Myocardial Infarction, Proton Pumps, Reperfusion Injury, Chest Pain, Guanidines, Fibrinolytic Agents, Sulfones, Angioplasty

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