Duration of vitamin K antagonist therapy for venous thromboembolism: a systematic review of the literature

Abstract

Purpose: The aim of this study was to evaluate the evidence on the optimal duration of vitamin K antagonist (VKA) therapy for venous thromboembolism (VTE).

Methods: Randomized controlled trials of VKA for VTE were identified by a computerized database search. Summary event rates for relevant outcomes were calculated using a random effects model with 95% confidence intervals (95% CI).

Results: Ten studies met inclusion criteria. The incidence of recurrent VTE (3 months, 7.9 VTE per 100 patient-years [95% CI, 5.2 to 10] versus 4-12 months, 4.9 VTE per 100 patient-years [95% CI, 3.6 to 6.2] versus continuous therapy, 0.7 VTE per 100 patient-years [95% CI, 0.3 to 1.1]) and total adverse events (3 months, 11.2 events per 100 patient-years [95%CI, 7.1 to 15.4] versus 4-12 months, 7.4 events per 100 patient-years [95%CI, 6.2 to 8.5] versus continuous therapy 3.1 events per 100 patient-years [95%CI, 2.2 to 4.0] declined as VKA therapy duration increased. Continuous reduced intensity therapy (INR 1.5-2) was associated with more recurrent VTE (2.3 VTE per 100 patient-years [95%CI, 1.5 to 3.0]). Continuous VKA therapy (INR 2-3) was beneficial for patients with a second VTE and antiphospholipid antibodies. The incidence of recurrent VTE was similar with 6 or 12 weeks of therapy for isolated calf DVT.

Conclusion: Randomized controlled trials indicate that continuous VKA therapy (INR 2-3) for VTE is associated with better clinical outcomes than shorter durations. Patients with a second VTE or antiphospholipid antibodies also benefit from continuous anticoagulation. Patients with calf DVT should be treated for at least 6 weeks.