The use of direct oral anticoagulants for thromboprophylaxis or treatment of cancer-associated venous thromboembolism: a meta-analysis and review of the guidelines.

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.

Safety and efficacy of dual versus triple antithrombotic therapy (DAT vs TAT) in patients with atrial fibrillation following a PCI: a systematic review and network meta-analysis.

OBJECTIVE: Creating 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. DESIGN: A systematic review and NMA of randomised clinical trials. METHODS: We 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. RESULTS: The 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%. CONCLUSION: The 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.

The use of direct oral anticoagulants for extended duration thromboprophylaxis in medically ill patients: a systematic review and meta-analysis.

The extended use of thromboprophylaxis with direct oral anticoagulants (DOACs) for more than 30 days has been evaluated as an alternative for the standard duration thromboprophylaxis (7-10 days) with low molecular weight heparin in medically ill patients to reduce the risk of venous thromboembolism (VTE) after hospital discharge. EMBASE and MEDLINE were searched for studies evaluating extended duration thromboprophylaxis with DOACs versus standard thromboprophylaxis with enoxaparin in medically ill patients through October 2018. Search was limited to randomized-controlled trials. Symptomatic VTE, VTE-related death, and death from any cause, and major and clinically relevant non-major bleeding were used to assess the efficacy and safety, respectively. The Mantel-Haenszel random-effects model risk ratio (RR) and corresponding 95% CIs were calculated using the metan routine in Stata (version 14.2) to estimate the pooled treatment effects. Heterogeneity was assessed by the I2 statistics. Four studies met the inclusion criteria. DOACs were superior to enoxaparin in preventing symptomatic VTE (RR = 0.59, 95% CI 0.44-0.79). There were no significant differences in thromboprophylactic efficacy between extended and standard thromboprophylaxis as to VTE-related death (RR = 0.81, 95% CI 0.60-1.10) and death from any cause (RR = 0.98, 95% CI 0.87-1.09). Compared to the standard duration, extended thromboprophylaxis was associated with approximately two-fold greater risk of major (RR = 1.95, 95% CI 1.25-3.04), and clinically relevant non-major (RR = 1.81, 95% CI 1.29-2.53) bleeding. The superior efficacy was diminished by the unfortunate safety profile. Therefore, we continue to support both the American Society of Hematology (ASH) and the American College of Chest Physicians (ACCP) guidelines recommendation against the extended use of thromboprophylaxis beyond the hospital stay.