Background: Chronic kidney disease (CKD) is both a prothrombotic state and a condition with an elevated bleeding risk that increases in a linear fashion as estimated glomerular filtration rate (eGFR) decreases. These features of the disease along with the exclusion of patients with CKD from most anticoagulation trials have resulted in uncertainty about overall risks and benefits of anticoagulant use in this population.
Study design: Systematic review and meta-analysis.
Setting: Variable across included trials.
Synopsis: Forty-five randomized, controlled trials of anticoagulation covering a broad range of anticoagulants, doses, indications, and methodologies were included in this meta-analysis, representing 34,082 patients with CKD or end-stage kidney disease.
The most compelling data were seen in the management of atrial fibrillation in early-stage CKD (five studies representing 11,332 patients) in which high-dose DOACs were associated with a lower risk for stroke or systemic embolism (risk ratio, 0.79; 95% confidence interval, 0.66-0.92), hemorrhagic stroke (RR, 0.48; 95% CI, 0.30-0.76), and all-cause death (RR, 0.88; 95% CI, 0.78-0.99). Overall stroke reduction was primarily hemorrhagic, and DOACs were equivalent to vitamin K antagonists (VKAs) for ischemic stroke risk.
The analysis also suggests that, in CKD, DOACs may reduce major bleeding when compared with VKAs across a variety of indications, though that finding was not statistically significant.
Efficacy of DOACs, compared with VKAs, in treatment of venous thromboembolism was uncertain, and patients with end-stage kidney disease and advanced CKD (creatinine clearance, less than 25 mL/min) were excluded from all trials comparing DOACs with VKAs, with limited overall data in these populations.
Bottom line: For patients with atrial fibrillation and early-stage CKD, direct oral anticoagulants show a promising risk-benefit profile when compared with vitamin K antagonists. Very few data are available on the safety and efficacy of anticoagulants in patients with advanced CKD and end-stage kidney disease.
Citation: Ha JT et al. Benefits and harms of oral anticoagulant therapy in chronic kidney disease. Ann Intern Med. 2019 Aug 6;171(3):181-9.
Dr. Herrle is a hospitalist at Maine Medical Center in Portland and at Stephens Memorial Hospital in Norway, Maine.