AUTHOR=Yan Yi-Dan , Ding Zheng , Pan Mang-Mang , Xia Qing , Cui Jiu-Jie , Wang Li-Wei , Zhang Chi , Gu Zhi-Chun 

TITLE=Net Clinical Benefit of Direct Oral Anticoagulants in Patients With Cancer and Venous Thromboembolism: A Systematic Review and Trade-Off Analysis

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=7

YEAR=2020

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2020.586020

DOI=10.3389/fcvm.2020.586020

ISSN=2297-055X

ABSTRACT=<p><bold>Background:</bold> Venous thromboembolism (VTE) is highly prevalent in cancer patients. Recent guidelines recommend considering direct oral anticoagulants (DOACs) for the treatment of cancer-associated thrombosis (CAT). However, direct head-to-head comparisons among DOACs are lacking, and almost no net clinical benefit (NCB) analysis has been performed in patients with CAT.</p><p><bold>Methods:</bold> We systematically searched PubMed, EMBASE, Cochrane Library, and <ext-link ext-link-type="uri" xlink:href="https://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link> for randomized controlled trials (RCTs) reporting on recurrent VTE, major bleeding, or clinically relevant bleeding events in patients with CAT who received DOACs and low-molecular-weight heparins. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated using a random-effect model. Surface under the cumulative ranking curve (SUCRA) values were calculated, and a trade-off analysis was performed to estimate the NCB.</p><p><bold>Results:</bold> Overall, four RCTs involving 2,894 patients were enrolled. DOACs were more effective than dalteparin in reducing the risk of recurrent VTE (RR: 0.62, 95% CI: 0.44–0.87), with a comparative risk of major bleeding (RR: 1.33, 95% CI: 0.84–2.11) and an increased risk of clinically relevant bleeding (RR: 1.45, 95% CI: 1.05–1.99). No significant difference was observed among individual anticoagulants in terms of recurrent VTE and major bleeding. With respect to the ranking of each anticoagulant for the primary outcome, edoxaban (SUCRA: 69.2) was more effective than dalteparin (SUCRA: 60.7), rivaroxaban (SUCRA: 60.7), and apixaban (SUCRA: 25.5) in reducing VTE recurrence. For major bleeding, apixaban (SUCRA: 76.3) had the highest cumulative ranking probability, followed by edoxaban (SUCRA: 66.4), dalteparin (SUCRA: 28.8), and rivaroxaban (SUCRA: 28.5). Similar results were observed for clinically relevant bleeding. In terms of both benefit and safety outcomes, DOACs, especially edoxaban, seemed to confer a better NCB profile than dalteparin.</p><p><bold>Conclusions:</bold> DOACs are a safe and effective alternative therapy to dalteparin in patients with CAT. Among them, edoxaban might provide a good risk-to-benefit balance. However, because of the lack of head-to-head studies, further investigations are needed to confirm our findings.</p>