The Na+/H+ exchange inhibitor eniporide as an adjunct to early reperfusiontherapy for acute myocardial infarction - Results of the evaluation of thesafety and cardioprotective effects of eniporide in acute myocardial infarction (ESCAMI) trial

OBJECTIVES We conducted an international, prospective, randomized, double-b lind, placebo-con trolled phase 2 trial in patients undergoing thrombolytic therapy or primary angioplasty for acute ST-elevation myocardial infarctio n (MI) to investigate the effect of eniporide on infarct size and clinical outcome. BACKGROUND Experimental studies suggest that the activity of the Na+/H+ exc hange (NHE) plays an important role in the unfavorable sequels of myocardia l ischemia and reperfusion. Eniporide specifically inhibits the NHE-1 isofo rm and has been shown to limit infarct size in experimental models. METHODS The primary efficacy end point was the infarct size measured by the cumulative release of alpha-hydroxybutyrate dehydrogenase (alpha-HDBH) (ar ea under the curve [AUC] 0 to 72 h). In stage 1, 50, 100, 150 or 200 mg eni poride given as a 10-min infusion before start of reperfusion therapy were compared with placebo in 430 patients, and in stage 2, 100 and 150 mg enipo ride were compared with placebo in 959 patients. RESULTS In stage 1, the administration of 100 mg and 150 mg eniporide resul ted in smaller infarct sizes (mean alpha-HBDH AUC in U/ml X h, placebo: 44. 2, 100 mg eniporide: 40.2, 150 mg eniporide: 33.9), especially in the angio plasty group. In contrast, in stage 2 there was no difference in the enzyma tic infarct size between the three groups (placebo: 41.2, 100 mg eniporide: 43.0, 150 mg eniporide: 41.5). Overall there was no effect of eniporide on clinical outcome (death, cardiogenic shock, heart failure, life-threatenin g arrhythmias). However, there was a significant reduction of the incidence of heart failure in patients reperfused late (>4 h). CONCLUSIONS In this large study administration of the NHE-1 inhibitor enipo ride, before reperfusion therapy in patients with acute ST elevation MI, di d not limit infarct size or improve clinical outcome. (C) 2001 by the Ameri can College of Cardiology.