Among patients with chronic kidney disease (CKD) treated with oral anticoagulants, nonvitamin K antagonist oral anticoagulants (NOACs) have a more favorable efficacy and safety profile for a range of cardiovascular outcomes when compared with warfarin, according to study results published in Neurology.

This systematic review and meta-analysis sought to illuminate the efficacy and safety of warfarin and NOACs among patients with CKD with regard to the following cardiovascular outcomes: intracerebral hemorrhage (ICH), stroke or systemic embolism, ischemic stroke, combined ischemic and hemorrhagic stroke (stroke combined), major bleeding events, and mortality. Chronic kidney disease was defined according to creatinine clearance (CrCl): mild (CrCl: 60-89 mL/min), moderate (CrCl: 30-59 mL/min), and severe (CrCl: 15-29 mL/min).

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The analysis included 15 studies comprising 78,053 patients: 8 for warfarin vs no anticoagulant and 7 for warfarin vs NOACs. Compared with no anticoagulant, warfarin was associated with a reduced ischemic stroke risk (risk ratio [RR] 0.68; 95% CI, 0.55-0.84; P =.0003) and a reduced risk for mortality (RR 0.7; 95% CI, 0.62-0.78; P <.001). Compared with warfarin, NOACs reduced the risk for stroke or systemic embolism (RR 0.73; 95% CI, 0.62-0.85; P <.001), stroke combined (RR 0.83; 95% CI, 0.72-0.96; P =.01), and ICH (RR 0.43; 95% CI, 0.33-0.56; P <.001). Adjusted analyses showed that warfarin compared with no anticoagulant was associated with reduced mortality risk (hazard ratio [HR] 0.68; 95% CI, 0.61-0.76; P <.001) whereas NOACS compared with warfarin reduced the risk for ICH (HR 0.39; 95% CI, 0.3-0.5; P <.001) and of stroke or systemic embolism (HR 0.75; 95% CI, 0.65-0.88; P =.0004). Sensitivity analyses comparing various NOACs showed that factor Xa inhibitors compared with warfarin consistently lowered the risk for major bleeding (RR 0.76; 95% CI, 0.64-0.91; P =.002), stroke combined (RR 0.84; 95% CI, 0.73-0.96; P =.01), ICH (RR 0.45; 95% CI, 0.24-0.85; P =.01), and mortality (RR 0.84; 95% CI, 0.7-1; P =.05).

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Study limitations include varying equations on the severity of renal impairment, varying cut points between studies, inherent biases in post hoc and retrospective studies, and varying definitions of safety and efficacy.

Study investigators concluded, “NOACs in comparison to warfarin may represent a more effective and safer therapeutic option for patients with CKD requiring anticoagulation. Our findings lend support to current guidelines that advocate the use of NOAC over warfarin in patients with CKD requiring anticoagulation.”


Malhotra K, Ishfaq MF, Goyal N, et al. Oral anticoagulation in patients with chronic kidney disease: a systematic review and meta-analysis. Neurology. 2019;92:e2421-e2431.