Reduced‐ Versus Extended‐Dose Anticoagulation for Venous Thromboembolism in Patients With and Without Cancer: A Systematic Review and Meta‐Analysis

BACKGROUND: Extended-duration anticoagulation reduces recurrent venous thromboembolism (VTE) in cancer and non-cancer patients. Reduced-dose direct oral anticoagulants (DOACs) may be safer if they match efficacy with less bleeding risk. We conducted a systematic review and meta-analysis of trials comparing reduced-dose and extended-dose DOACs. METHODS: Randomized controlled trials comparing reduced-dose with extended-dose anticoagulation for secondary VTE prevention were systematically reviewed. Primary outcomes included recurrent symptomatic VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT). Secondary outcomes included bleeding, adverse events, and all-cause mortality. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Subgroup and leave-one-out sensitivity analyses explored heterogeneity and robustness. All analyses were conducted in R (version 4.3.1). RESULTS: Six RCTs (n = 9382) were included. Reduced-dose anticoagulation showed no statistically significant difference in recurrent VTE (RR 0.98, 95% CI 0.72-1.33), PE (RR 0.96, 95% CI 0.61-1.50), or DVT (RR 0.86, 95% CI 0.56-1.32) compared with extended-dose therapy. Major bleeding was significantly reduced (RR 0.68, 95% CI 0.48-0.98), as were clinically relevant non-major bleeding and any bleeding. All-cause mortality did not differ significantly. Heterogeneity was low to moderate across outcomes, and sensitivity analyses confirmed the stability of results. CONCLUSION: Reduced-dose anticoagulation demonstrated similar efficacy with improved safety compared with extended-dose therapy. These findings support individualized dose reduction strategies after extended anticoagulation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: CRD420251081952.