Warfarin offers no protection against ischemic strokes in patients with end-stage kidney disease (ESKD) and atrial fibrillation, but it may increase their risk for hemorrhagic stroke, according to the authors of a new systematic review and meta-analysis.

The meta-analysis included 15 observational studies, 5 of which were conducted within the past 2 years, and involved 47,480 patients. Warfarin users (22.0%) did not have significantly different rates of ischemic stroke (7.7% vs 7.1%, major bleeding (16.1% vs 15.0%), or mortality (43.4% vs 52.5%), compared with nonusers. The rate of hemorrhagic stroke was significantly higher among warfarin users compared with nonusers (2.4% vs 1.9%). Warfarin use, however, was significantly associated with a nearly 1.5-fold increased risk of hemorrhagic stroke compared with nonuse, Mandeep S. Randhawa, MD, of Michigan State University in Kalamazoo, and colleagues reported in JAMA Network Open.

“Available data show that warfarin use is not associated with any benefit in the prevention of ischemic stroke,” Dr Randhawa’s team concluded. “Instead, it is associated with a significant increase in the risk of hemorrhagic stroke, no significant difference in the risk of major bleeding, and no association with overall mortality.”

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Emilie P. Belley-Cote, MD, PhD, and John W. Eikelboom, MBBS, MSc, discussed the clinical implications of the findings in an accompanying editorial. “Although these results are subject to confounding because they are nonrandomized, and although they demonstrate moderate or large amounts of heterogeneity, they suggest that warfarin may not be effective for the prevention of ischemic stroke in patients with AF and ESRD and instead may cause substantial harm,” they wrote.

The editorialists discussed possible alternatives to warfarin, which is a vitamin K antagonist. First, apixaban is FDA-approved for use in ESKD patients, but a recent meta-analysis suggests no benefit or a dose-dependent benefit. The other direct oral anticoagulants, dabigatran nor rivaroxaban, might offer better renal protection, but neither drug is approved for ESKD.

A second option is a left atrial appendage occlusion device, which research suggests is noninferior to anticoagulation. A third option is antiplatelet therapy using aspirin or aspirin with clopidogrel, but this treatment does not appear effective.

According to Dr Belley-Cote and Dr Eikelboom, current investigations may provide some answers on treating ESKD patients. The Strategies for the Management of Atrial Fibrillation in Patients Receiving Hemodialysis (SAFE HD; NCT03987711) trial is comparing warfarin, apixaban, and no anticoagulation, and the Compare Apixaban and Vitamin-K Antagonists in Patients with Atrial Fibrillation and End-Stage Kidney Disease (AXADIA; NCT02933697) trial is comparing phenprocoumon and apixaban.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Randhawa MS, Vishwanath R, Rai MP, et al. Association between use of warfarin for atrial fibrillation and outcomes among patients with end-stage renal disease: A systematic review and meta-analysis. JAMA Netw Open. 2020;3(4):e202175. doi: 10.1001/jamanetworkopen.2020.2175

Belley-Cote EP and Eikelboom JW. Anticoagulation for stroke prevention in patients with atrial fibrillation and end-stage renal disease—First, do no harm. JAMA Netw Open. doi: 10.1001/jamanetworkopen.2020.2237