Incidence of cancer after prophylaxis with warfarin against recurrent venous thromboembolism. Duration of Anticoagulation Trial

N Engl J Med. 2000 Jun 29;342(26):1953-8. doi: 10.1056/NEJM200006293422604.


Background: The length of time after an episode of venous thromboembolism during which the risk of newly diagnosed cancer is increased is not known, and whether vitamin K antagonists have an antineoplastic effect is controversial.

Methods: In a prospective, randomized study of the duration of oral anticoagulation (six weeks or six months) after a first episode of venous thromboembolism, patients were questioned annually about any newly diagnosed cancer. After a mean follow-up of 8.1 years, we used the Swedish Cancer Registry to identify all diagnoses of cancer and causes of death in the study population. The observed numbers of cases of cancer were compared with expected numbers based on national incidence rates, and the standardized incidence ratios were calculated.

Results: A first cancer was diagnosed in 111 of 854 patients (13.0 percent) during follow-up. The standardized incidence ratio for newly diagnosed cancer was 3.4 (95 percent confidence interval, 2.2 to 4.6) during the first year after the thromboembolic event and remained between 1.3 and 2.2 for the following five years. Cancer was diagnosed in 66 of 419 patients (15.8 percent) who were treated for six weeks with oral anticoagulants, as compared with 45 of 435 patients (10.3 percent) who were treated for six months (odds ratio, 1.6; 95 percent confidence interval, 1.1 to 2.4). The difference was mainly due to the occurrence of new urogenital cancers, of which there were 28 cases in the six-week group (6.7 percent) and 12 cases in the six-month group (2.8 percent) (odds ratio, 2.5; 95 percent confidence interval, 1.3 to 5.0). The difference in the incidence of cancer between the treatment groups became evident only after two years of follow-up, and it remained significant after adjustment for sex, age, and whether the thromboembolism was idiopathic or nonidiopathic. Older age at the time of the venous thrombosis and an idiopathic thromboembolism were also independent risk factors for a diagnosis of cancer. No difference in the incidence of cancer-related deaths was detected.

Conclusions: The risk of newly diagnosed cancer after a first episode of venous thromboembolism is elevated during at least the following two years. Subsequently, the risk seems to be lower among patients treated with oral anticoagulants for six months than among those treated for six weeks.

Publication types

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

MeSH terms

  • Administration, Oral
  • Age Factors
  • Anticoagulants / therapeutic use*
  • Drug Administration Schedule
  • Humans
  • Incidence
  • Neoplasms / epidemiology
  • Neoplasms / etiology
  • Neoplasms / mortality
  • Prospective Studies
  • Pulmonary Embolism / complications
  • Pulmonary Embolism / drug therapy
  • Retrospective Studies
  • Risk Factors
  • Thromboembolism / complications
  • Thromboembolism / drug therapy*
  • Time Factors
  • Urogenital Neoplasms / epidemiology
  • Urogenital Neoplasms / etiology*
  • Urogenital Neoplasms / mortality
  • Venous Thrombosis / complications
  • Venous Thrombosis / drug therapy
  • Vitamin K / antagonists & inhibitors
  • Warfarin / therapeutic use*


  • Anticoagulants
  • Vitamin K
  • Warfarin