title: Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months.
abstract: BACKGROUND
  The influence of the duration of anticoagulant therapy after venous thromboembolism (VTE) on the long-term morbidity and mortality is unclear.
  
  
  OBJECTIVE
  To investigate the long-term sequelae of VTE in patients randomized to different duration of secondary prophylaxis.
  
  
  METHODS
  In a multicenter trial comparing secondary prophylaxis with vitamin K antagonists for 6 weeks or 6 months, we extended the originally planned 2 years follow-up to 10 years. The patients had annual visits and at the last visit clinical assessment of the post-thrombotic syndrome (PTS) was performed. Recurrent thromboembolism was adjudicated by a radiologist, blinded to treatment allocation. Causes of death were obtained from the Swedish Death Registry.
  
  
  RESULTS
  Of the 897 patients randomized, 545 could be evaluated at the 10 years follow-up. The probability of developing severe PTS was 6% and any sign of PTS was seen in 56.3% of the evaluated patients. In multivariate analysis, old age and signs of impaired circulation at discharge from the hospital were independent risk factors at baseline for development of PTS after 10 years. Recurrent thromboembolism occurred in 29.1% of the patients with a higher rate among males, older patients, those with permanent triggering risk factor - especially with venous insufficiency at baseline - signs of impaired venous circulation at discharge, proximal deep vein thrombosis, or pulmonary embolism. Death occurred in 28.5%, which was a higher mortality than expected with a standardized incidence ratio (SIR) of 1.43 (95% CI 1.28-1.58), mainly because of a higher mortality than expected from cancer (SIR 1.83; 95% CI 1.44-2.23) or from myocardial infarction or stroke (SIR 1.28; 95% CI 1.00-1.56). The duration of anticoagulation did not have a statistically significant effect on any of the long-term outcomes.
  
  
  CONCLUSIONS
  The morbidity and mortality during 10 years after the first episode of VTE is high and not reduced by extension of secondary prophylaxis from 6 weeks to 6 months. A strategy to reduce recurrence of VTE as well as mortality from arterial disease is needed.
authors.affiliation: Department of Hematology, Coagulation Unit, Karolinska University Hospital, Stockholm, Sweden. schulms@mcmaster.ca
authors.forename: S
authors.initials: S
authors.lastname: Schulman
authors.forename: P
authors.initials: P
authors.lastname: Lindmarker
authors.forename: M
authors.initials: M
authors.lastname: Holmström
authors.forename: G
authors.initials: G
authors.lastname: Lärfars
authors.forename: A
authors.initials: A
authors.lastname: Carlsson
authors.forename: P
authors.initials: P
authors.lastname: Nicol
authors.forename: E
authors.initials: E
authors.lastname: Svensson
authors.forename: B
authors.initials: B
authors.lastname: Ljungberg
authors.forename: S
authors.initials: S
authors.lastname: Viering
authors.forename: S
authors.initials: S
authors.lastname: Nordlander
authors.forename: B
authors.initials: B
authors.lastname: Leijd
authors.forename: K
authors.initials: K
authors.lastname: Jahed
authors.forename: M
authors.initials: M
authors.lastname: Hjorth
authors.forename: O
authors.initials: O
authors.lastname: Linder
authors.forename: M
authors.initials: M
authors.lastname: Beckman
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011186:Postphlebitic Syndrome / Q000209:etiology*; D012008:Recurrence; D012307:Risk Factors; D013923:Thromboembolism / Q000175:diagnosis; D013997:Time Factors; D020246:Venous Thrombosis / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D014812:Vitamin K / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D014859:Warfarin