Evaluation of direct oral anticoagulant lead-in therapy duration on clinical outcomes in venous thromboembolism: a systematic review and meta-analysis

Direct oral anticoagulants (DOACs) such as apixaban and rivaroxaban require a high-dose “lead-in” phase to ensure timely therapeutic anticoagulation for venous thromboembolism (VTE). However, some real-world clinical practice often deviates from full “lead-in” protocol due to prior parenteral anticoagulation or patient-specific bleeding risks. This review aims to evaluate the evidence comparing full versus reduced DOAC lead-in strategies in acute VTE treatment. This meta-analysis was conducted according to the PRISMA guidelines. Data were extracted from MEDLINE, Web of Science, Embase, and Cochrane Library. The primary out-come was major bleeding. Secondary outcomes included VTE recurrence and mortality. The risk ratio (RR) with a 95% confidence interval (95% CI) was used to evaluate study outcomes and heterogeneity was assessed using I 2 and Cochran Q statistics. A total of seven retrospective cohort studies were included in the analysis with a total sample size of 1,651 patients. The risk of major bleeding was a significantly lower in the full lead-in group compared with the reduced lead-in group (RR = 0.49; 95% CI 0.27–0.86). No significant differences were observed between the groups in terms of VTE recurrence (RR = 0.99; 95% CI 0.45–2.18), or mortality (RR = 0.50; 95% CI 0.15–1.65). Our results show that a full DOAC lead-in regimen is associated with a significantly lower risk of major bleeding compared to reduced lead-in, without increasing the risk of VTE recurrence or death. However, significant gaps still exist, especially in high-risk groups emphasizing the need for further prospective, randomized studies.