title: Effect of ximelagatran on ischemic events and death in patients with atrial fibrillation after acute myocardial infarction in the efficacy and safety of the oral direct thrombin inhibitor ximelagatran in patients with recent myocardial damage (ESTEEM) trial.
abstract: BACKGROUND
  New-onset trial fibrillation (AF) occurs commonly after acute myocardial infarction (MI) and is associated with a poor prognosis due to stroke or death. The optimal antithrombotic therapy is unknown. The aim of this study was to investigate whether an oral direct thrombin inhibitor, ximelagatran, added to aspirin, reduced the risk of death, myocardial infarction (MI), and stroke in patients who developed AF after their qualifying MI in the efficacy and safety of the oral direct thrombin inhibitor ximelagatran in patients with recent myocardial damage (ESTEEM) trial.
  
  
  METHODS
  The ESTEEM trial evaluated 6 months treatment with ximelagatran together with aspirin, compared to aspirin alone, for prevention of ischemic events in 1883 patients randomized within 14 days after an MI. After their qualifying MI, 174 (9%) patients developed AF in hospital. Multivariate hazard ratios for ximelagatran compared with placebo were calculated by presence AF.
  
  
  RESULTS
  Of 101 patients with AF treated with ximelagatran 7 (6.9%) had either death, MI, or stroke, compared with 15 (20.6%) in 73 patients allocated to placebo. Ximelagatran reduced the risk of death, MI, or stroke by 70% (hazard ratio 0.30, 95% CI 0.12-0.74). For the separate outcome events, we found similar, nonsignificant trends. One major bleeding event occurred in each treatment group.
  
  
  CONCLUSIONS
  For patients with MI complicated by AF, the combination of aspirin and an oral direct thrombin inhibitor seems beneficial. The high risk for death, MI, and stroke in this population and the increasing use of percutaneous interventions in MI patients may suggest a combination of long-term antiplatelet and anticoagulant therapy. Randomized clinical trials are warranted.
authors.affiliation: AstraZeneca R&D, Medical Science, Mölndal, Sweden. marco.tangelder@astrazeneca.com
authors.forename: Marco J D
authors.initials: MJ
authors.lastname: Tangelder
authors.forename: Lars
authors.initials: L
authors.lastname: Frison
authors.forename: Douglas
authors.initials: D
authors.lastname: Weaver
authors.forename: Robbert G
authors.initials: RG
authors.lastname: Wilcox
authors.forename: Anders
authors.initials: A
authors.lastname: Bylock
authors.forename: Håkan
authors.initials: H
authors.lastname: Emanuelsson
authors.forename: Peter
authors.initials: P
authors.lastname: Held
authors.forename: Jonas
authors.initials: J
authors.lastname: Oldgren
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D001241:Aspirin / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D001384:Azetidines / Q000008:administration & dosage*; D001596:Benzylamines / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications* / Q000401:mortality; D017202:Myocardial Ischemia / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; D005343:Fibrinolytic Agents; C426686:ximelagatran; D001241:Aspirin