Darexaban Maleate

Direct oral anticoagulants (DOACs) combined with antiplatelet therapy for acute coronary syndrome (ACS) may reduce ischemic events, but there is no consensus on bleeding risk. Moreover, the effect of DOACs on stable coronary artery disease (CAD) needs to be elucidated. We conducted a meta-analysis to summarize the efficacy and safety of DOACs combined with antiplatelet therapy in the treatment of stable CAD and ACS.

We searched PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials, then performed a systematic review of all 17 randomized controlled trials.

For patients with stable CAD, DOACs combined with antiplatelet therapy significantly reduced the rate of major adverse cardiovascular events (MACE) (risk ratio; 95% confidence interval: 0.88; 0.81-0.95) and ischemic stroke (0.62; 0.50-0.77), with a relatively low risk of major bleeding (1.72; 1.42-2.07). For patients with ACS, the combination of DOACs reduced the risk of MACE (0.91; 0.85-0.97), myocardial infarction (MI) (0.90; 0.83-0.98), and ischemic stroke (0.75; 0.58-0.97), accompanied by increased non-fatal bleeding events and intracranial hemorrhage (3.42; 1.76-6.65). Results were similar when restricting the analysis to phase III studies except for the rate of stroke in patients with ACS.

Combination therapy reduced the incidence of MI in ACS patients, but the risk of bleeding from intracranial hemorrhaging outweighs the benefit of MACE driven by MI. That is due to combination therapy having no positive impact on mortality; thus, the benefit-risk balance may be more favorable  in patients with stable CAD.

Anticoagulants are essential in the prevention of venous thromboembolism. However, the effectiveness and safety of different anticoagulants have always been controversial. Therefore, we aimed to expand the sample of anticoagulant results and rank the efficacy and safety of 19 anticoagulants in the prevention of venous thromboembolism when total knee or total hip arthroplasty procedure is performed.

A systematic review and network meta-analysis of randomized trials of adult patients undergoing total hip or knee arthroplasty were conducted. The trials were identified from PubMed, Web of Science, Cochrane Library, and Embase databases, in which anticoagulants were used as interventions randomized controlled trial. The incidence of venous embolism and bleeding are the key outcomes of assessing the efficacy of intervention drugs. We used the Physical Therapy Evidence Database (PEDro) to assess risk bias and used pairwise comparison and network meta-analysis with random effects to estimate the summary relative risk. The study has been registered with PROSPERO, number CRD42020200747.

From the 4083 identified manuscripts, 45,067 participants from 53 randomized trials were included in the analysis and randomly assigned to 19 anticoagulants. With Enoxaparin as a control, Rivaroxaban (risk difference 0.07, 95 % credible interval 0.06 to 0.08), Edoxaban (RD 0.09, 95 % CrI 0.08 to 0.11), and Apixaban (RD 0.05, 95 % CrI 0.04 to 0.06) had the best effect in preventing VTE. However, in terms of comprehensive bleeding rate, Apixaban, Edoxaban, and Darexaban were the most effective and stable. Although effective in preventing VTE, bleeding remains relatively high in Rivaroxaban. Enoxaparin is low-molecular-weight heparin that is widely used in clinics, and although its overall efficacy is not the best, its efficacy and safety are very stable.

According to the available data, Apixaban, Edoxaban, and Darexaban are better than any anticoagulants in the prevention of VTE and bleeding during total knee or total hip arthroplasty. In our study, Fondaparinux, Eribaxaban, Dalteparin, Betrixaban, Bemiparin, Reviparin, Acenocoumarol, and Tinzaparin were scarce in the included studies, therefore, more evidence is needed to prove their efficacy and safety.