Warfarin Use in Patients With End-Stage Renal Disease May Increase Stroke Risk

Laurie Barclay, MD

September 03, 2009

September 3, 2009 — Use of warfarin as chemoprophylaxis in patients with atrial fibrillation and end-stage renal disease (ESRD) may paradoxically increase stroke risk, according to the results of a cohort study reported in the August 27 Online First issue of the Journal of the American Society of Nephrology.

"Use of warfarin, clopidogrel, or aspirin associates with mortality among patients with ESRD, but the risk-benefit ratio may depend on underlying comorbidities," write Kevin E. Chan, MD, from Fresenius Medical Care NA in Waltham, Massachusetts, and colleagues. "We previously reported a significant excess mortality associated with anticoagulation and/or antiplatelet use in a large, heterogeneous population of incident hemodialysis (HD) patients."

The purpose of this follow-up study was to evaluate the potential risk-benefit ratio of warfarin, clopidogrel, and aspirin specifically in dialysis patients with coexisting atrial fibrillation. The investigators looked at the association between these medications and new stroke, mortality, and hospitalization in a retrospective cohort of 1671 patients with preexisting atrial fibrillation who were receiving hemodialysis. Average follow-up of patient outcomes was 1.6 years from the time dialysis was started.

Patients receiving warfarin therapy had a significantly increased risk for new stroke vs patients not taking warfarin (hazard ratio [HR], 1.93; 95% confidence interval [CI], 1.29 - 2.90). Risk for new stroke was not associated with clopidogrel or aspirin use.

There appeared to be a dose-response relationship between the degree of anticoagulation and new stroke in patients receiving warfarin, based on an analysis using international normalized ratio (INR; P = .02 for trend). Compared with nonusers of warfarin, those users who had no INR monitoring in the first 90 days of dialysis had the highest risk for stroke (HR, 2.79; 95% CI, 1.65 - 4.70). Use of warfarin was not statistically significantly associated with any increases in all-cause mortality or hospitalization rates.

"Warfarin use among patients with both ESRD and atrial fibrillation associates with an increased risk for stroke," the study authors write. "The risk is greatest in warfarin users who do not receive in-facility INR monitoring."

Limitations of this study include retrospective design, potential misclassification bias, confounding by indication, survivorship bias, ascertainment bias, and selection bias from missing data.

"Before definitive conclusions can be drawn, large, prospective, randomized, controlled trials are required," the study authors conclude. "Until then, physicians should be cognizant of the possible risks associated with warfarin use for atrial fibrillation in patients with ESRD, with careful evaluation of the risks and benefits of intervention at the individual patient level. Close monitoring of the degree of anticoagulation (INR) in patients who are on warfarin would also be a reasonable recommendation to minimize the risk for hemorrhagic complications."

The study authors have disclosed no relevant financial relationships.

J Am Soc Nephrol. Published online August 27, 2009. Abstract