title: Optimal intensity of oral anticoagulant therapy after myocardial infarction.
abstract: OBJECTIVE
  This study attempted to determine the optimal intensity of anticoagulant therapy in patients after myocardial infarction.
  
  
  BACKGROUND
  Treatment with oral anticoagulant therapy entails a delicate balance between over- (risk of bleeding) and under-anticoagulation (risk of thromboemboli). The optimal intensity required to prevent the occurrence of either event (bleeding or thromboembolic) is not known.
  
  
  METHODS
  A method was used to determine the optimal intensity of anticoagulant therapy by calculating incidence rates for either event associated with a specific international normalized ratio. The numerator included events occurring at given international normalized ratios, and the denominator comprised the total observation time.
  
  
  RESULTS
  The study population included 3,404 myocardial infarction patients enrolled in the ASPECT (Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis) trial. Total treatment was 6,918 patient-years. Major bleeding occurred in 57 patients (0.8/100 patient-years), and thromboembolic complications in 397 (5.7/100 patient-years). The incidence of the combined outcome (bleeding or thromboembolic complications) with international normalized ratio <2 was 8.0/100 patient-years (283 events in 3,559 patient-years), with international normalized ratios between 2 and 3, 3.9/100 patient-years (33 events in 838 patient-years); 3.2/100 patient-years (57 events in 1,775 patient-years) for international normalized ratios between 3 and 4; 6.6/100 patient-years (37 events in 564 patient-years) for international normalized ratios between 4 and 5; and 7.7/100 patient-years (14 events in 182 patient-years) for international normalized ratios >5. After adjustment for achieved international normalized ratio levels, significant predictors were higher levels of systolic blood pressure and age.
  
  
  CONCLUSIONS
  If equal weight is given to hemorrhagic and thromboembolic complications, these results suggest that the optimal intensity of long-term anticoagulant therapy for myocardial infarction patients lies between 2.0 and 4.0 international normalized ratio, with a trend to suggest an optimal intensity of 3.0 to 4.0.
authors.affiliation: Thoraxcenter, Department of Cardiology, University Hospital Dijkzigt, Erasmus University of Rotterdam, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: Azar
authors.forename: S C
authors.initials: SC
authors.lastname: Cannegieter
authors.forename: J W
authors.initials: JW
authors.lastname: Deckers
authors.forename: E
authors.initials: E
authors.lastname: Briët
authors.forename: P F
authors.initials: PF
authors.lastname: van Bergen
authors.forename: J J
authors.initials: JJ
authors.lastname: Jonker
authors.forename: F R
authors.initials: FR
authors.lastname: Rosendaal
mesh_terms: D000284:Administration, Oral; D000367:Age Factors; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure; D062787:Drug Overdose; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D016012:Poisson Distribution; D012015:Reference Standards; D013923:Thromboembolism / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants