Warfarin Use in End-Stage Renal Disease Raises Concerns

A meta-analysis of warfarin use in patients with atrial fibrillation (AF) and end-stage renal disease (ESRD) finds that the medication increases all-cause bleeding risk without reducing strokes. Those findings, the study authors write, “call into question the use of warfarin” for such patients.

Investigators combined data from 20 observational cohorts with 56,146 AF patients with ESRD. The pooled estimates from meta-analysis found no association between warfarin use and all-cause stroke.

Despite a trend toward increased risk, warfarin use also showed no significant association with major bleeding, gastrointestinal bleeding, or any bleeding. There was, however, a significant association between warfarin use and all-cause bleeding.

“We attempted to evaluate warfarin use vs aspirin or [direct oral anticoagulants] which was not examined in previously published systematic reviews and meta-analyses, but there were not enough studies to draw conclusions regarding these comparisons,” the study authors wrote in BMC Nephrology.

The authors had also planned to evaluate all-cause mortality, but the statistical heterogeneity was so high across the 12 studies that documented mortality that it was impossible to make an accurate calculation.

However, “despite the degree of heterogeneity across studies and the bias in selected studies, our study showed that warfarin use was not associated with a lower risk of ischemic stroke, consistent with recent studies and was associated with a significant higher risk for bleeding among patients undergoing hemodialysis.”

Trials have definitively proven the benefits of warfarin use in AF patients with mild to moderate chronic kidney disease. Additional trials of direct oral anticoagulants such as dabigatran and rivaroxaban have generally found that they work even better, offering more stroke protection and lower bleeding risk.

Such trials, however, have all excluded patients whose more advanced kidney disease requires dialysis, the authors of the new study wrote.

The lack of randomized trials has led a number of research teams to undertake observational studies that follow outcomes for AF patients with ESRD who do and do not use anticoagulation — studies whose significantly heterogeneous outcomes led inspired investigators to attempt the new meta-analysis.

They searched online research databases and screened 2,022 titles and abstracts, but they only found 20 studies that met their quality criteria, all of them observational cohorts. Of those, 19 compared warfarin use to no warfarin use, while 2 studies also compared warfarin use to aspirin and 1 study compared warfarin use to dabigatran and rivaroxaban.

The included studies had a median of 690 AF patients with ESRD and a median follow-up of 7.0 years.

The analysis authors identified several strengths to their work including the use of “the recently developed Cochrane Risk of Bias Assessment Tool for Non-Randomized Studies of Interventions, which was designed specifically for non-randomized studies that compare the health effects of 2 or more interventions, and unlike the Newcastle-Ottawa scale, does not require modification for use in reviews of effectiveness of interventions.”

They also identified several limitations to their work, most notably the high heterogeneity among the underlying studies.