Duration of primary/secondary treatment to prevent recurrent venous thromboembolism: a systematic review and meta-analysis

Antithrombotic therapy can prevent recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE). It is, however, associated with an increased risk for major bleeding. This meta-analysis systematically reviewed the evidence regarding the duration of antithrombotic therapy to assess benefits and harms. We systematically searched for randomized controlled trials (RCTs) that compared shorter (3-6 months) with longer (>6 months) courses of anticoagulation for the primary treatment of venous thromboembolism (VTE) or that compared discontinued with indefinite antithrombotic therapy for the secondary prevention of VTE. Pairs of reviewers screened the eligible trials and collected data. This study included 22 RCTs (11 617 participants). Pooled estimates showed that, for the primary treatment of unprovoked VTE, VTE provoked by chronic risk factors or transient risk factors, treating patients with a longer course (>6 months) of anticoagulation, as opposed to a shorter course (3-6 months), probably reduced recurrent PE (risk ratio [RR], 0.66; 95% confidence interval [CI], 0.42-1.02) and DVT (RR, 0.85; 95% CI, 0.63-1.14), but it was associated with increased mortality (RR, 1.43; 95% CI, 0.85-2.41) (moderate certainty) and a higher risk for major bleeding (RR, 2.02; 95% CI, 1.02-3.98; high certainty). For the secondary prevention of unprovoked VTE and VTE provoked by chronic risk factors, when compared with discontinuing treatment, indefinite anticoagulation therapy was associated with decreased mortality (RR, 0.54; 95% CI, 0.36-0.81), a reduction in recurrent PE (RR, 0.25; 95% CI, 0.16-0.41) and DVT (RR, 0.15; 95% CI, 0.10-0.21), and an increase in the risk for bleeding (RR, 1.98; 95% CI, 1.18-3.30), all supported by high certainty. Indefinite antiplatelet therapy may be associated with decreased mortality (RR, 0.95; 95% CI: 0.53-1.68; low certainty), probably a reduction in recurrent PE (RR, 0.65; 95% CI, 0.41-1.03) and DVT (RR, 0.44; 95% CI, 0.17-1.13) (moderate certainty), and may increase the risk for bleeding (RR, 1.28; 95% CI, 0.48-3.41; low certainty). In summary, for the primary treatment of all types of VTE, shorter (3-6 months) duration of anticoagulation is more beneficial. For the secondary prevention of unprovoked VTE or VTE provoked by chronic risk factors, indefinite antithrombotic treatment is more beneficial.