Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis

N Engl J Med. 1982 Dec 30;307(27):1676-81. doi: 10.1056/NEJM198212303072704.


We have previously reported that long-term therapy with warfarin is effective for preventing recurrent venous thromboembolism in patients with proximal-vein thrombosis but that there is an appreciable risk of hemorrhage. To determine whether that risk could be reduced without a loss of effectiveness, we randomly allocated 96 patients with proximal-vein thrombosis to a group receiving less intense anticoagulant therapy, with a mean prothrombin time of 26.9 seconds using the Manchester comparative reagent (corresponding Simplastin time, 15 seconds), or a group given more intense therapy, with a mean Simplastin time of 19.4 seconds (corresponding prothrombin time 41 seconds with the Manchester comparative reagent) (P less than 0.001). Two of 47 patients (4 per cent) in the less intensely treated group had hemorrhagic complications, as compared with 11 of 49 patients (22 per cent) in the more intensely anticoagulated group (P = 0.015 by the two-tailed test). This difference was due to minor bleeding episodes. The frequency of recurrent venous thromboembolism was low in both groups (2 per cent). Our findings indicate that less intense anticoagulant therapy is associated with a low frequency of recurrent venous thromboembolism (2 per cent) and a reduced risk of hemorrhage.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Anticoagulants / administration & dosage*
  • Clinical Trials as Topic
  • Female
  • Hemorrhage / chemically induced
  • Heparin / administration & dosage
  • Humans
  • Indicators and Reagents
  • Infusions, Parenteral
  • Male
  • Middle Aged
  • Partial Thromboplastin Time
  • Prothrombin Time
  • Random Allocation
  • Recurrence
  • Risk
  • Thromboembolism / epidemiology
  • Thrombophlebitis / drug therapy*
  • Time Factors
  • Warfarin / administration & dosage


  • Anticoagulants
  • Indicators and Reagents
  • Warfarin
  • Heparin