BACKGROUND AND PURPOSE:

• Data is unclear regarding the ideal time point to discontinue anticoagulation treatment after unprovoked venous thromboembolism (VTE)
  • Discontinuation after 3-6 months vs treating indefinitely
  • Previous meta-analysis did not address male vs female | Follow-up only up to 2 years
• In patients with first episode unprovoked DVT, Kahn et al. (BMJ, 2019) studied
  • The rate of a first recurrent VTE event after anticoagulation treatment was stopped
  • The total incidence for recurrent VTE up to 10 years

METHODS:

• Systematic review and meta-analysis
• Inclusion criteria
  • RCTs and prospective cohort studies
  • Patients were those with first unprovoked VTE at least three months of treatment
  • VTE included both DVT and PE
• Data extraction and synthesis
  • Two investigators independently screened potential studies, extracted data, and appraised risk of bias
    • Data clarifications were sought from authors of eligible studies
    • Data pooled using random effects meta-analysis
  • Sex and site of initial VTE were also investigated

RESULTS:

• 18 studies | 7515 patients
• After discontinuation of anticoagulation treatment: Pooled rate of recurrent VTE per 100 person years
  • First year: 10.3 events (95% confidence interval 8.6 to 12.1)
  • Second year: 6.3 events (5.1 to 7.7)
  • Years 3-5: 3.8 events/year (3.2 to 4.5)
  • Years 6-10: 3.1 events/year (1.7 to 4.9)
• Cumulative incidence for recurrent VTE was
  • At 2 years: 16% (95% CI, 13% to 19%)
  • At 5 years: 25% (95% CI, 21% to 29%)
  • At 10 years: 36% (95:% CI, 28% to 45%)
• Women vs men
  • Pooled rate of recurrent VTE per 100 person years in the first year
    • Women: 8.9 events (95% CI, 6.8 to 11.3)
    • Men 11.9 events (95% CI, 9.6 to 14.4)
  • Cumulative incidence for recurrent VTE at 10 years
    • Women: 29% (95% CI, 20% to 38%)
    • Men: 41% (95% CI, 28% to 56%)
  • Overall recurrence rate, comparing men to women
    • Rate ratio 1.4 (95% CI, 1.3 to 1.6; P<0.001)
• Distal DVT: Risk of recurrence
  • 1.9% (95% CI, 0.5% to 4.3%)
• Proximal DVT: Risk of recurrence
  • 1.4 times the rate of recurrent VTE compared to pulmonary embolism (P=0.004)
• Case fatality rate for recurrent VTE was 4% (95% CI, 2% to 6%)

CONCLUSION:

• Men vs women: Authors calculated long-term mortality risks over a 10 year period
  • Men: Net long-term mortality benefit to continuing anticoagulation (1.64% risk of fatal recurrent VTE vs 1.32% risk of fatal major bleeding) due to greater recurrent VTE risk
  • Women: Net long-term benefit not found (1.16% risk of fatal recurrent VTE vs 1.32% risk of fatal major bleeding)
• Determination of whether to continue anticoagulation treatment will depend on several factors
• Because recurrence risk declines over time, the authors state

Our results suggest that patients who have not experienced a recurrence within two years of discontinuing anticoagulant treatment are unlikely to experience a net long term mortality benefit from restarting anticoagulation

Learn More – Primary Sources:

Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and meta-analysis

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