title: The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. The Duration of Anticoagulation Trial Study Group.
abstract: BACKGROUND
  A consensus has not been reached about the optimal duration of oral anticoagulant therapy after a second episode of venous thromboembolism.
  
  
  METHODS
  In a multicenter trial, we compared six months of oral anticoagulant therapy with anticoagulant therapy continued indefinitely in patients who had had a second episode of venous thromboembolism. Of 227 patients enrolled, 111 were randomly assigned to six months of anticoagulation and 116 were assigned to receive anticoagulant therapy indefinitely; for both groups, the target international normalized ratio was 2.0 to 2.85. The initial episodes of deep-vein thrombosis (n = 193) and pulmonary embolism (n = 34), as well as recurrent episodes, were all objectively confirmed.
  
  
  RESULTS
  After four years of follow-up, there were 26 recurrences of venous thromboembolism that fulfilled the diagnostic criteria, 23 in the group assigned to six months of therapy (20.7 percent) and 3 in the group assigned to continuing therapy (2.6 percent). The relative risk of recurrence in the group assigned to six months of therapy, as compared with the group assigned to therapy of indefinite duration, was 8.0 (95 percent confidence interval, 2.5 to 25.9). There were 13 major hemorrhages, 3 in the six-month group, (2.7 percent) and 10 in the infinite-treatment group (8.6 percent). The relative risk of major hemorrhage in the six-month group, as compared with the infinite-treatment group was 0.3 (95 percent confidence interval, 0.1 to 1.1). There was no difference in mortality between the two groups.
  
  
  CONCLUSIONS
  Prophylactic oral anticoagulation that was continued for an indefinite period after a second episode of venous thromboembolism was associated with a much lower rate of recurrence during four years of follow-up than treatment for six months. However, there was a trend toward a higher risk of major hemorrhage when anticoagulation was continued indefinitely.
authors.affiliation: Department of Internal Medicine at Karolinska Hospital, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Schulman
authors.forename: S
authors.initials: S
authors.lastname: Granqvist
authors.forename: M
authors.initials: M
authors.lastname: Holmström
authors.forename: A
authors.initials: A
authors.lastname: Carlsson
authors.forename: P
authors.initials: P
authors.lastname: Lindmarker
authors.forename: P
authors.initials: P
authors.lastname: Nicol
authors.forename: S G
authors.initials: SG
authors.lastname: Eklund
authors.forename: S
authors.initials: S
authors.lastname: Nordlander
authors.forename: G
authors.initials: G
authors.lastname: Lärfars
authors.forename: B
authors.initials: B
authors.lastname: Leijd
authors.forename: O
authors.initials: O
authors.lastname: Linder
authors.forename: E
authors.initials: E
authors.lastname: Loogna
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001728:Dicumarol / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011336:Probability; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D012008:Recurrence; D013924:Thrombophlebitis / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D013997:Time Factors; D014859:Warfarin / Q000008:administration & dosage
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D014859:Warfarin; D001728:Dicumarol; D006493:Heparin