Background Venous thromboembolism (VTE) is a common complication among patients with cancer and is one of the most common causes of increased morbidity and mortality. The use of direct oral anticoagulants (DOACs) for thromboprophylaxis and treatment of cancer-associated venous thromboembolism (CA-VTE) has been evaluated in several randomized clinical trials (RCTs). The aim of this meta-analysis was to assess efficacy and safety of using DOACs for thromboprophylaxis and treatment of CA-VTE and provide a summary for available guidelines’ recommendations. Methods MEDLINE was searched to identify studies evaluating the use of DOACs for thromboprophylaxis or treatment in patients with cancer. Search was limited to peer-reviewed studies published in English. Studies were excluded if they were not RCTs or subgroup analyses of data derived from RCTs, if they did not report efficacy and safety data on patients with active cancer, or if they were published as an abstract. New VTE or VTE recurrence, and major or clinically relevant non-major bleeding (CRNMB) were used to assess the efficacy and safety, respectively. The Mantel-Haenszel random-effects model risk ratios (RRs) and the corresponding 95% confidence intervals (CIs) were calculated to estimate the pooled treatment effects of DOACs. Results Four studies evaluating DOACs use for thromboprophylaxis and four – for treatment of CA-VTE were included. Thromboprophylaxis with DOACs was associated with a significant reduction in the risk of symptomatic VTE (RR = 0.58; 95%CI 0.37,0.91) but with an incremental risk of major bleeding or CRNMB (RR = 1.57; 95%CI 1.10,2.26). CA-VTE treatment with DOACs was linked with a significant reduction in VTE recurrence (RR = 0.62; 95%CI 0.44,0.87) but with an incremental risk of CRNMB (RR = 1.58; 95%CI 1.11,2.24). Conclusions The DOACs are associated with a lower risk of symptomatic VTE and VTE recurrence, but the risk of bleeding remains a considerable concern. Clinical decisions should be made by assessing individual patient’s risk of VTE and bleeding.
ObjectiveCreating an appropriate antithrombotic therapy for patients with atrial fibrillation (AF) who have undergone percutaneous coronary intervention (PCI) remains a dilemma. Several clinical trials compared the use of a dual antithrombotic therapy (DAT) regimen with a direct oral anticoagulants including (apixaban, dabigatran, edoxaban or rivaroxaban) and a P2Y12 inhibitor versus a triple antithrombotic therapy (TAT) that includes a vitamin K antagonist plus aspirin and a P2Y12 inhibitor in patients with AF who have undergone PCI. However, there are no head-to-head trials comparing the DAT regimens to each other. We aimed to compare the efficacy and safety of DAT regimens using a network meta-analysis (NMA) approach.DesignA systematic review and NMA of randomised clinical trials.MethodsWe conducted a systematic literature review to identify relevant randomised clinical trials and performed a Bayesian NMA for International Society on Thrombosis and Haemostasis (ISTH) major or clinically relevant non-major (CRNM) bleeding, all-cause mortality, stroke, myocardial infarction (MI) and stent thrombosis outcomes. We used NetMetaXL V.1.6.1 and WinBUGS V.1.4.3 for the NMA and estimated the probability of ranking the treatments based on the surface under the cumulative ranking curve.ResultsThe comparison between DAT regimens showed no significant difference in the safety or efficacy outcomes. Apixaban regimen was ranked first as the preferred therapy in terms of ISTH major or CRNM bleeding and stroke, with a probability of 52% and 54%, respectively. Rivaroxaban regimen was the preferred therapy in terms of MI and stent thrombosis, with a probability of 34% and 27%, respectively. Dabigatran regimen was ranked first in terms of all-cause mortality, with a probability of 28%.ConclusionThe DAT regimens are as safe and effective as TAT regimens. However, ranking probabilities for the best option in the selected outcomes can be used to guide the selection among these agents based on different patients’ conditions.
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