Efficacy and safety of direct oral anticoagulants in patients with venous thrombosis and inherited thrombophilia.

Introduction: Inherited thrombophilia screening is widely performed in patients with venous thromboembolism (VTE). Although recent studies suggest that direct oral anticoagulants (DOACs) may provide comparable efficacy and safety to Vitamin K antagonists (VKAs) in this population, robust evidence to support their extensive use is still lacking. We aimed to evaluate the rates of VTE recurrence and overall bleeding in patients with inherited thrombophilia treated with DOACs versus VKAs, with particular interest in those with severe thrombophilia. Methods: Using the electronic database of the largest healthcare provider in Israel, we conducted a retrospective search for patients with a recorded VTE between 2012 and 2021 (the index event). Patients aged 18 or older at the time of diagnosis were included if they began treatment with either a DOAC or a VKA within 30 days of the index event, provided they had laboratory evidence of inherited thrombophilia. Patients were followed up for two independent outcomes (VTE recurrence and overall bleeding) until December 31, 2022 or until termination of follow-up due to death, switching from one oral anticoagulation class to another, or discontinuation of oral anticoagulation. Rates of VTE recurrence and overall bleeding were compared using Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Results: A total of 398 patients (median age 50.9±17.8, males 51.8%, severe thrombophilia 24.9%) were included. Among these, 230 patients (57.8%) were prescribed DOACs, while 168 patients (42.2%) received VKAs. The median follow-up for VTE recurrence and overall bleeding was 21.1 months and 20 months, respectively. Using the VKAs group as a reference, the hazard ratio for VTE recurrence on DOACs was 1.25 (95% CI, 0.23-6.7), and the hazard ratio for overall bleeding on DOACs was 0.33 (95% CI, 0.03-3.7). Restricting the analysis to 99 patients with severe thrombophilia (46 on DOACs, 53 on VKAs) showed no substantial differences in both efficacy and safety. Conclusions: Among patients with inherited thrombophilia treated with DOACs or VKAs, this study found no significant difference in the risk of recurrent VTE and observed a non-significant trend toward a lower risk of bleeding with DOACs.