Oral anticoagulation in patients with chronic kidney disease: A systematic review and meta-analysis

Objective Data regarding the efficacy and safety of warfarin and non-vitamin K antagonist oral anticoagulant (NOAC) among patients with chronic kidney disease (CKD) remain scarce. Methods Systematic review and meta-analysis of studies involving patients with CKD treated with oral anticoagulants were conducted to evaluate the following outcomes: ischemic stroke, intracerebral hemorrhage (ICH), combined ischemic and hemorrhagic stroke (stroke combined ), stroke or systemic embolism, mortality, and major bleeding events. CKD was defined based on creatinine clearance (CrCl) ranging from mild (CrCl: 60–89 mL/min), moderate (CrCl: 30–59 mL/min), to severe (CrCl: 15–29 mL/min). Results Fifteen studies (7 comparing NOAC vs warfarin and 8 comparing warfarin vs no anticoagulant) were identified comprising 78,053 patients. Warfarin (vs no anticoagulant) was associated with reduced risk of ischemic stroke (risk ratio [RR] = 0.68; 95% confidence interval [CI] 0.55–0.84]) and mortality (RR = 0.70; 95% CI 0.62–0.78). In comparison to warfarin, NOAC use lowered the risk of ICH (RR = 0.43; 95% CI 0.33–0.56), stroke combined (RR = 0.83; 95% CI 0.72–0.96), stroke or systemic embolism (RR = 0.73; 95% CI 0.62–0.85), and major bleeding (RR = 0.77; 95% CI 0.66–0.90). In adjusted analyses, warfarin use (vs no anticoagulant) was associated with reduced mortality (HR adj = 0.68; 95% CI 0.61–0.76), whereas NOAC (vs warfarin) use reduced the risk of ICH (HR adj = 0.39; 95% CI 0.30–0.50) and stroke or systemic embolism (HR adj = 0.75; 95% CI 0.65–0.88). Our sensitivity analyses comparing different NOACs exhibited that factor Xa inhibitors (compared to warfarin) consistently reduced stroke combined (RR = 0.84; 95% CI 0.73–0.96), mortality (RR = 0.84; 95% CI 0.70–1.00), ICH (RR = 0.45; 95% CI 0.24–0.85), and major bleeding (RR = 0.76; 95% CI 0.64–0.91). Conclusions Among patients with CKD treated with oral anticoagulants, NOACs present with a more favorable safety and efficacy profile for various cardiovascular outcomes.