Novel Oral Anticoagulants in Patients with Renal Insufficiency:A Meta-Analysis of Randomized Trials
Recent reports suggest altered antithrombotic efficacy and higher risk of bleeding with new oral anticoagulants (NOAC) in patients with renal insufficiency. A meta-analysis was performed to evaluate the efficacy and safety with recommended doses of NOAC compared to conventional treatment in patients with renal insufficiency.
PubMed, Cochrane Library, EMBASE, EBSCO, Web of Science and CINAHL databases were searched from January 01, 2001 through March 23, 2014. Randomized controlled trials (RCTs) comparing NOACs (rivaroxaban apixaban, and dabigatran) with comparators (vitamin K antagonist/warfarin, low molecular weight heparin, aspirin, placebo) were selected.
There were 40,693 patients with renal insufficiency in ten trials. Compared to other anticoagulants in patients with mild renal insufficiency there was significantly less major or clinically relevant non-major (CRNM) bleeding (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.72- 0.90) and stroke or systemic embolism (OR 0.70, 95% CI 0.54- 0.92), with NOACs. By random effects meta-analysis, there was significantly less stroke or systemic embolism (OR 0.72, 95% CI 0.57- 0.92) and a trend toward less major or CRNM bleeding (OR 0.82, 95% CI 0.59- 1.14) with the NOACs among patients with moderate renal insufficiency, and this became statistically significant when evaluated using a fixed effects model. NOACs showed efficiency comparable to conventional anticoagulants for prevention of venous thromboembolism (VTE) or related mortality.
In patients with renal insufficiency, recommended doses of novel anticoagulants are noninferior and relatively safe compared to conventional anticoagulants.
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ABSTRACT: Venous thromboembolism (VTE) is a major cause of morbidity, mortality, and healthcare expenditure. In the United States, approximately 0.1 % of the population experiences an initial VTE event each year. Anticoagulation therapy is the cornerstone of acute VTE treatment and for prevention of recurrent VTE events. Conventional anticoagulants, including heparin, low-molecular-weight heparins, fondaparinux, and vitamin K antagonists are widely used but have limitations. Newer oral anticoagulant agents, including direct thrombin inhibitors (e.g., dabigatran etexilate) and direct factor Xa inhibitors (e.g., rivaroxaban, apixaban, and edoxaban) have been developed to attempt to overcome some of the limitations of conventional anticoagulant therapy. These new oral agents have been evaluated for safety and efficacy in large, randomized clinical trials in the treatment and secondary prevention of VTE with results that are comparable to conventional therapy. Dabigatran, rivaroxaban, apixaban, and edoxaban are important new treatment options for patients with VTE. In this review, we compare these new agents and their associated clinical trials in VTE treatment.Drugs 10/2014; DOI:10.1007/s40265-014-0301-x · 4.13 Impact Factor
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ABSTRACT: Apixaban is a novel oral anticoagulant which is approved for the management of atrial fibrillation and venous thromboembolism prophylaxis. There have been concerns regarding bleeding risks with apixaban in patients with renal impairment. We performed a systematic review and meta-analysis to evaluate the risk of bleeding with apixaban in these patients. Relevant studies were identified through electronic literature searches of MEDLINE, EMBASE, Cochrane library, and clinicaltrials.gov (from inception to February 24, 2014). Phase III randomized controlled trials that compared apixaban with conventional agents (vitamin K antagonist and/or warfarin, low molecular weight heparin, aspirin, and placebo) were included. We defined mild renal impairment as creatinine clearance of 50 to 80 ml/min and moderate to severe renal impairment as creatinine clearance <50 ml/min. Study-specific risk ratios were calculated, and between-study heterogeneity was assessed using the I(2) statistics. In 6 trials involving 40,145 patients, the risk of bleeding with apixaban in patients with mild renal impairment was significantly less (risk ratio 0.80, 95% confidence interval 0.66 to 0.96, I(2) = 13%) compared with conventional anticoagulants. In patients with moderate to severe renal impairment, the risk of bleeding with was found to be similar (risk ratio 1.01, 95% confidence interval 0.49 to 2.10, I(2) = 72%). In conclusion, compared with the conventional agents, bleeding risk with apixaban in patients with mild and moderate to severe renal insufficiency is lower and similar, respectively. Copyright © 2015 Elsevier Inc. All rights reserved.The American Journal of Cardiology 11/2014; 115(3). DOI:10.1016/j.amjcard.2014.10.042 · 3.43 Impact Factor
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ABSTRACT: The target-specific oral anticoagulants are a class of agents that inhibit factor Xa or thrombin. They are effective and safe compared to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation and for the treatment of venous thromboembolism, and they are comparable to low-molecular-weight heparin for thromboprophylaxis after hip or knee arthroplasty. For other indications, however, such as the prevention of stroke in patients with mechanical heart valves, initial studies have been unfavorable for the newer agents, leaving warfarin the anticoagulant of choice. Further studies are needed before the target-specific anticoagulants can be recommended for patients with cancer-associated thrombosis or heparin-induced thrombocytopenia. Concerns also persist about difficulties with the laboratory assessment of anticoagulant effect and the lack of a specific reversal agent. For these reasons, we anticipate that the vitamin K antagonists will continue to be important anticoagulants for years to come.Annual Review of Medicine 01/2015; 66(1):241-53. DOI:10.1146/annurev-med-051113-024633 · 15.48 Impact Factor