Efficacy and Bleeding Risk of Newer Anticoagulants Compared to Conventional Treatment in Patients with Chronic Kidney Disease- a Meta-Analysis of Randomized Controlled Trials

Background

Multiple newer oral anticoagulants (NOAC) are currently approved for the prevention, treatment of venous thromboembolism (VTE) and prevention of stoke in atrial fibrillation (AF). Most of the clinical trials with NOAC have excluded patients with severe renal insufficiency. There is a paucity of safety and efficacy data of NOAC in comparison with conventional treatment (CT) in patients with mild or moderate renal impairment. We performed a meta-analysis of the randomized control trials (RCTs) comparing NOAC to CT in patients with renal insufficiency to understand the safety and efficacy of NACs.

Methods

Medline, PubMed, EMBASE, EBSCO, CINAHL and Cochrane databases were queried with the keywords - “newer anticoagulants”, “renal insufficiency”, “dabigatran”, “rivaroxaban”, “apixaban”, and “edoxaban”. RCTs comparing NOAC to CT (warfarin, low molecular weight heparin, heparin, aspirin or placebo) were included. Non-randomized single arm trials were excluded. Authors of RCTs with missing pertinent data were contacted through electronic mail. The safety end point analyzed was clinically significant or major bleeding risk. The efficacy end points analyzed were incidence of arterial embolism in AF studies and venous thromboembolism in VTE studies.  European Medical Agency classification of renal insufficiency was used, with mild renal insufficiency defined as estimated glomerular filtration rate (eGFR) from 50 to 79 and moderate renal insufficiency defined as eGFR of 30 to 49 and severe renal insufficiency defined as eGFR< 30.

Results

Sixteen RCTs with 115,147 patients fulfilled our inclusion criteria. Rivoroxaban, apixaban, edoxaban and dabigatran were the newer anticoagulants used in these 16 RCTs.  Among these, 48,403 patients had either mild or moderate renal insufficiency. Patients with mild renal insufficiency treated with NAOC had lower bleeding risk [Odds ratio 0.81(CI 0.72-0.90) p<0.0001], lower incidence of arterial thromboembolism [Odds ratio 0.74(CI 0.64-0.85) p<0.0001] compared to conventional treatment. Patients with moderate renal insufficiency treated with NAOC had lower incidence of arterial thromboembolism [Odds ratio 0.74(CI 0.62-0.89) p=0.001] and a trend towards lower bleeding risk [Odds ratio 0.89(CI 0.66-1.18) p=0.41], compared to conventional treatment. Also, a trend of lowered VTE incidence was observed with NOAC compared to conventional treatment in patients with mild [Odds ratio 0.70(CI 0.46 to 1.070) p=0.1] as well moderate [Odds ratio 0.69(CI 0.34 to 1.41) p=0.31] renal insufficiency.

Conclusion:

Newer anticoagulants have decreased odds for VTE, arterial embolism and bleeding in patients with mild to moderate renal insufficiency compared to conventional treatment.