Efficacy and safety of reduced-dose versus full-dose direct oral anticoagulants for extended treatment of venous thromboembolism: A meta-analysis with trial sequential analysis and reconstructed time-to-event data
Thrombosis Research, cilt.254, 2025 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Derleme
- Cilt numarası: 254
- Basım Tarihi: 2025
- Doi Numarası: 10.1016/j.thromres.2025.109476
- Dergi Adı: Thrombosis Research
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Veterinary Science Database
- Anahtar Kelimeler: Anticoagulants, Apixaban, Meta-analysis, Reduced-dose, Rivaroxaban, Venous thromboembolism
- Ankara Yıldırım Beyazıt Üniversitesi Adresli: Evet
Özet
Background: While current guidelines recommend extended therapeutic anticoagulation for venous thromboembolism (VTE), the optimal dosing strategy for direct oral anticoagulants (DOACs) remains uncertain, particularly in cancer-associated VTE. This meta-analysis evaluates the efficacy and safety of reduced-dose versus full-dose DOACs for extended VTE treatment. Methods: We conducted a comprehensive search of major electronic databases through April 2025 for randomized controlled trials (RCTs) comparing reduced-dose versus full-dose DOACs for VTE treatment. Pooled risk ratios (RR) with 95 % confidence intervals (CI) were calculated using random-effects models. Time-to-event data were reconstructed from Kaplan-Meier curves. Trial sequential analysis (TSA) was employed to assess the conclusiveness of the evidence. Results: Our analysis included five RCTs involving 8781 patients. Reduced-dose DOACs were associated with comparable efficacy to full-dose therapy in preventing recurrent VTE (RR, 0.94; 95 % CI, 0.68–1.29; P = 0.70), supported by time-to-event analysis (HR, 0.89; 95 % CI 0.78–1.02; p = 0.10). However, reduced-dose regimens significantly reduced major or clinically relevant non-major bleeding (RR, 0.71; 95 % CI 0.61–0.82; P < 0.0001), with consistent findings on Kaplan-Meier analysis (HR, 0.61; 95 % CI 0.57–0.66; P < 0.001). Subgroup analyses showed consistent results in patients with and without active cancer, and also across different DOAC types (apixaban and rivaroxaban). No differences were observed in all-cause mortality. TSA confirmed sufficient evidence for both efficacy and safety outcomes. Conclusion: Reduced-dose DOACs were as effective as full-dose regimens in preventing recurrent VTE, with a better safety profile, suggesting they may be preferred for patients requiring extended anticoagulation, especially those at high risk of recurrence. Prospero ID: CRD420251048675.