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Original Research: Cardiovascular Disease |

Stroke, Major Bleeding, and Mortality Outcomes in Warfarin Users With Atrial Fibrillation and Chronic Kidney Disease: A Meta-Analysis of Observational Studies

Khagendra Dahal, MD; Sumit Kunwar, MD; Jharendra Rijal, MD; Peter Schulman, MD; Juyong Lee, MD, PhD
Author and Funding Information

FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

CORRESPONDENCE TO: Juyong Lee, MD, PhD, Calhoun Cardiology Center, University of Connecticut Health Center, 263 Farmington Ave, Floor 2, Farmington, CT 06030


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(4):951-959. doi:10.1378/chest.15-1719
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Background  The use of warfarin in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) can be problematic because of increased bleeding risk. We performed a systematic review and meta-analysis of observational studies that evaluated the use of warfarin in patients with AF and CKD to evaluate the risks of ischemic stroke/thromboembolism, major bleeding, and mortality.

Methods  PUBMED, EMBASE, CINAHL, ProQuest, and Google Scholar databases were electronically searched through January 12, 2015. Additionally, a manual search was performed for relevant references. Random-effects model was used to estimate the pooled hazard ratio (HR) with 95% CI. CKD was divided into non-end-stage CKD and end-stage CKD (on renal replacement therapy) and separate analyses were performed.

Results  Thirteen publications from 11 cohorts (six retrospective and five prospective) including >48,500 total patients with >11,600 warfarin users were included in the meta-analysis. In patients with AF and non-end-stage CKD, warfarin resulted in a lower risk of ischemic stroke/thromboembolism (HR, 0.70; 95% CI, 0.54-0.89; P = .004) and mortality (HR, 0.65; 95% CI, 0.59-0.72; P < .00001), but had no effect on major bleeding (HR, 1.15; 95% CI, 0.88-1.49; P = .31). In patients with AF and end-stage CKD, warfarin had no effect on the risks of stroke (HR, 1.12; 95% CI, 0.69-1.82; P = .65) and mortality (HR, 0.96; 95% CI, 0.81-1.13; P = .60), but increased the risks of major bleeding (HR, 1.30; 95% CI, 1.08-1.56; P = .005).

Conclusions  Based on this meta-analysis, the use of warfarin for AF may have an unfavorable risk/benefit ratio in patients with end-stage CKD but not in those with non-end-stage CKD.

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