title: 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.
abstract: OBJECTIVE
  We conducted an international, prospective, randomized, double-blind, placebo-controlled phase 2 trial in patients undergoing thrombolytic therapy or primary angioplasty for acute ST-elevation myocardial infarction (MI) to investigate the effect of eniporide on infarct size and clinical outcome.
  
  
  BACKGROUND
  Experimental studies suggest that the activity of the Na(+)/H(+) exchange (NHE) plays an important role in the unfavorable sequels of myocardial ischemia and reperfusion. Eniporide specifically inhibits the NHE-1 isoform 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) (area under the curve [AUC] 0 to 72 h). In stage 1, 50, 100, 150 or 200 mg eniporide 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 eniporide were compared with placebo in 959 patients.
  
  
  RESULTS
  In stage 1, the administration of 100 mg and 150 mg eniporide resulted 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 angioplasty group. In contrast, in stage 2 there was no difference in the enzymatic 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-threatening 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 eniporide, before reperfusion therapy in patients with acute ST elevation MI, did not limit infarct size or improve clinical outcome.
authors.affiliation: Medizinische Klinik II, Klinikum Kassel, Kassel, Germany. Uwe.Zeymer@t-online.de
authors.forename: U
authors.initials: U
authors.lastname: Zeymer
authors.forename: H
authors.initials: H
authors.lastname: Suryapranata
authors.forename: J P
authors.initials: JP
authors.lastname: Monassier
authors.forename: G
authors.initials: G
authors.lastname: Opolski
authors.forename: J
authors.initials: J
authors.lastname: Davies
authors.forename: G
authors.initials: G
authors.lastname: Rasmanis
authors.forename: G
authors.initials: G
authors.lastname: Linssen
authors.forename: U
authors.initials: U
authors.lastname: Tebbe
authors.forename: R
authors.initials: R
authors.lastname: Schröder
authors.forename: R
authors.initials: R
authors.lastname: Tiemann
authors.forename: T
authors.initials: T
authors.lastname: Machnig
authors.forename: K L
authors.initials: KL
authors.lastname: Neuhaus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary; D019540:Area Under Curve; D017024:Chemotherapy, Adjuvant; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006146:Guanidines / Q000627:therapeutic use*; D006801:Humans; D006884:Hydroxybutyrate Dehydrogenase / Q000378:metabolism; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000201:enzymology / Q000628:therapy; D015425:Myocardial Reperfusion / Q000379:methods; D011446:Prospective Studies; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000627:therapeutic use*; D015912:Thrombolytic Therapy; D016896:Treatment Outcome
chemical_list: D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C118397:eniporide; C035749:2-hydroxybutyrate dehydrogenase; D006884:Hydroxybutyrate Dehydrogenase