Direct oral anticoagulants in patients with venous thromboembolism and thrombophilia: a systematic review and meta-analysis.
Essentials We investigated direct oral anticoagulant (DOAC) use in venous thromboembolism and thrombophilia. A comprehensive search identified 10 studies, 8 of which were included in a meta-analysis. DOACs were overall safe and effective in patients with venous thromboembolism and thrombophilia. Efficacy/safety of DOACs was maintained in low-risk antiphospholipid syndrome patient subgroup. SUMMARY: Background Direct oral anticoagulants (DOACs) are increasingly used in acute and long-term treatment of venous thromboembolism (VTE). However, their role in management of thrombophilia-associated VTE is controversial. Methods Through a comprehensive search on MEDLINE, Cochrane Library, and Clinicaltrials.gov, we identified 10 eligible studies, 8 of which reporting data on 1994 thrombophilia patients were included in a random-effects meta-analysis. Eligible studies were phase 2 to 3 randomized controlled trials comparing DOACs to vitamin K antagonists (VKAs) in patients with VTE, including those with thrombophilia. Results Of eight studies included in meta-analysis, four evaluated rivaroxaban, three dabigatran, and one edoxaban. No results could be obtained on apixaban use. The rates of VTE recurrence (RR, 0.70; 95% CI, 0.34-1.44; I2  = 0%) and major/clinically relevant non-major bleeding events (RR, 0.92; 95% CI, 0.62-1.36; I2  = 23%) were similar between thrombophilia patients treated with DOACs compared to VKAs. Results were comparable to findings in patients without known thrombophilia: RR, 1.02; 95% CI, 0.80-1.30; I2  = 46% for VTE recurrence and RR, 0.72; 95% CI, 0.57-0.90; I2  = 84% for major/clinically relevant non-major bleeding events. Conclusions Rates of VTE recurrence and bleeding events were both low and comparable in patients with various thrombophilias receiving either treatment, suggesting that DOACs are an appropriate treatment option in this population. Due to limited data, it is unclear whether these findings apply to specific subgroups such as high-risk antiphospholipid syndrome, uncommon thrombophilias, or the use of apixaban.
['Elsebaie|Maha A T|MAT|0000-0001-8953-4030', 'van Es|Nick|N|0000-0001-5256-6346', 'Langston|Amelia|A|', 'Büller|Harry R|HR|0000-0002-8374-0930', 'Gaddh|Manila|M|0000-0002-0817-9848']
D000284:Administration, Oral D000925:Anticoagulants D016736:Antiphospholipid Syndrome D001777:Blood Coagulation D017322:Clinical Trials, Phase II as Topic D017326:Clinical Trials, Phase III as Topic D006470:Hemorrhage D006801:Humans D016032:Randomized Controlled Trials as Topic D012008:Recurrence D018570:Risk Assessment D012307:Risk Factors D019851:Thrombophilia D016896:Treatment Outcome D054556:Venous Thromboembolism
direct oral anticoagulants venous thromboembolism thrombophilia direct factor Xa inhibitors direct thrombin inhibitors hypercoagulability