title: Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation.
abstract: BACKGROUND
  A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of complications and death.
  
  
  METHODS
  We enrolled 3491 patients, 18 to 75 years of age, who presented within 12 hours after the onset of an ST-elevation myocardial infarction and randomly assigned them to receive clopidogrel (300-mg loading dose, followed by 75 mg once daily) or placebo. Patients received a fibrinolytic agent, aspirin, and when appropriate, heparin (dispensed according to body weight) and were scheduled to undergo angiography 48 to 192 hours after the start of study medication. The primary efficacy end point was a composite of an occluded infarct-related artery (defined by a Thrombolysis in Myocardial Infarction flow grade of 0 or 1) on angiography or death or recurrent myocardial infarction before angiography.
  
  
  RESULTS
  The rates of the primary efficacy end point were 21.7 percent in the placebo group and 15.0 percent in the clopidogrel group, representing an absolute reduction of 6.7 percentage points in the rate and a 36 percent reduction in the odds of the end point with clopidogrel therapy (95 percent confidence interval, 24 to 47 percent; P<0.001). By 30 days, clopidogrel therapy reduced the odds of the composite end point of death from cardiovascular causes, recurrent myocardial infarction, or recurrent ischemia leading to the need for urgent revascularization by 20 percent (from 14.1 to 11.6 percent, P=0.03). The rates of major bleeding and intracranial hemorrhage were similar in the two groups.
  
  
  CONCLUSIONS
  In patients 75 years of age or younger who have myocardial infarction with ST-segment elevation and who receive aspirin and a standard fibrinolytic regimen, the addition of clopidogrel improves the patency rate of the infarct-related artery and reduces ischemic complications.
authors.affiliation: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. msabatine@partners.org
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.forename: C Michael
authors.initials: CM
authors.lastname: Gibson
authors.forename: Jose L
authors.initials: JL
authors.lastname: López-Sendón
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.forename: Pierre
authors.initials: P
authors.lastname: Theroux
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Claeys
authors.forename: Frank
authors.initials: F
authors.lastname: Cools
authors.forename: Karen A
authors.initials: KA
authors.lastname: Hill
authors.forename: Allan M
authors.initials: AM
authors.lastname: Skene
authors.forename: Carolyn H
authors.initials: CH
authors.lastname: McCabe
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001241:Aspirin / Q000627:therapeutic use*; D000077144:Clopidogrel; D017023:Coronary Angiography; D001026:Coronary Artery Bypass; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D055502:Secondary Prevention; D015912:Thrombolytic Therapy; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D014654:Vascular Patency / Q000187:drug effects
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D006493:Heparin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin