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Abstract & Commentary
By Edward P. Gerstenfeld, MD
Professor of Medicine, Chief, Cardiac Electrophysiology, University of California, San Francisco
Dr. Gerstenfeld does research for Biosense Webster, Medtronic, and Rhythmia Medical.
Source: Shah M, et al. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation 2014;129: 1196-1203.
This was a retrospective cohort study from Quebec and Ontario, Canada, examining patients ≥ 65 years of age admitted to a hospital with a diagnosis of atrial fibrillation (AF) between 1998 and 2007. Patients were divided into dialysis patients and non-dialysis patients, as well as warfarin users and nonusers. The association between warfarin use and risk of stroke or bleeding was examined. There were 1626 dialysis patients and 204,210 nondialysis patients included. Among the dialysis patients, 46% were prescribed warfarin. Warfarin use was not associated with a lower risk of stroke in dialysis patients (hazard ratio [HR], 1.14; 95% CI, 0.78-1.67); however, it was associated with a lower stroke risk in nondialysis patients (HR, 0.87; 95% CI, 0.85-0.90). Warfarin use was associated with a significantly increased bleeding risk in dialysis (HR, 1.44; 95% CI, 1.13-1.85) and a slightly increased risk in nondialysis (HR, 1.19; 95% CI, 1.16-1.22) patients. The authors concluded that warfarin therapy in dialysis patients does not reduce stroke risk, but does increase the risk of bleeding.
Multiple prospective, randomized trials have proven that systemic anticoagulants significantly reduce the stroke risk in patients with AF and stroke risk factors. The oral Factor Xa and direct thrombin inhibitors, which have a fixed daily dose and no requirement for blood testing or dietary restriction, have been a welcome addition to our treatment armamentarium. However, since all these agents are predominantly metabolized in the kidneys, they cannot be used in patients with end-stage renal disease on hemodialysis (HD). Warfarin remains the main therapeutic option for HD patients, although it is well known that they have higher bleeding risk because of platelet dysfunction. In addition, repeated access to AV fistulae is needed, and anticoagulation can lead to persistent bleeding after HD catheter removal. However, HD patients also often have diabetes, congestive heart failure, peripheral vascular disease, and older age, which all increase stroke risk. Therefore, most believe that the benefit of systemic anticoagulation in dialysis patients with AF outweighs the risk. In this study, the authors question this wisdom. Interestingly, warfarin use was not associated with a lower stroke risk in HD patients and was associated with a 44% increased risk of bleeding. Were the included patients truly at high stroke risk? Since 73% of their HD patients had a CHADS2 score ≥ 2, this was in fact a high-risk group. Of note, 85% also had a HAS-BLED score ≥ 3, identifying that these patients also had a high risk of bleeding on anticoagulation.
Should we no longer recommend warfarin for HD patients with AF? I think it is premature to change practice based on this retrospective, nonrandomized study. However, in an HD patient with relatively lower risk (CHADS2 = 1) where warfarin might be recommended, it is reasonable to reconsider its use. In addition, in patients with high HAS-BLED scores or those who have already experienced bleeding complications, ongoing use of warfarin should be carefully considered after weighing the risks and benefits. A prospective, multicenter study of HD patients with AF is certainly warranted based on these interesting data.