Efficacy and Safety of Direct Oral Anticoagulants in Extended Venous Thromboembolism: A Placebo-Controlled Grade Assessed Meta-Analysis.

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism, is a major cardiovascular condition associated with substantial morbidity, mortality, and risk of recurrence. Extended anticoagulation is frequently required beyond the initial treatment phase, yet the optimal strategy remains uncertain. Direct oral anticoagulants (DOACs) provide practical advantages over vitamin K antagonists, but their role in long-term secondary prevention warrants clarification. We performed a systematic review and meta-analysis of placebo-controlled randomized controlled trials evaluating extended DOAC therapy in VTE. A comprehensive literature search identified 5 eligible trials with a total of 13,802 patients. Data were pooled using random-effects models to calculate risk ratios (RR) and 95% confidence intervals (CI). Outcomes included recurrent VTE, DVT, pulmonary embolism, mortality, stroke, cancer incidence, and bleeding events. Compared with placebo, extended DOAC therapy significantly reduced symptomatic recurrent VTE (RR, 0.26; 95% CI, 0.16-0.41), with consistent findings across sensitivity analyses. DOACs demonstrated strong protection against recurrent DVT, while results for recurrent pulmonary embolism were less consistent. No significant differences were observed in all-cause mortality, ischemic stroke, or cancer incidence. Safety analyses showed no increase in major bleeding. Extended DOAC therapy is highly effective in preventing recurrent VTE, particularly DVT, and maintains an acceptable safety profile. Despite the absence of mortality or stroke benefit, the favorable efficacy-safety balance supports DOACs as a convenient and effective option for prolonged secondary prevention in patients at ongoing risk of recurrence.