For many years warfarin has served as a common anticoagulant therapy and has been helpful in treating patients with atrial fibrillation (AFib). Despite a lack of clinical trials including individuals with renal dysfunction, for some time now the use of warfarin has crossed over to aiding those suffering from chronic kidney disease (CKD), as both AFib and CKD not only share common risk factors, but promote the severity of one another.

In an observational study published March 4 in the Journal of the American Medical Association. Juan Carrero, PHD, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden, and his team of researchers, examined this conflicting association between warfarin and incidents of ischemic stroke in patients with CKD and AFib, and found "that warfarin treatment was associated with a lower 1-year risk of the composite end point of death, myocardial infarction, and ischemic stroke without a higher risk of bleeding... [and the] association was observed in patient strata with moderate, severe, or end-stage CKD."

While it would seem that aggressive treatment of AFib would be paramount in patients with CKD, recent observational studies have prompted concern about the value of warfarin anticoagulation in patients stricken with both ailments. With the therapy being associated with an increased risk of stroke, death, or both, a modification of current guidelines has resulted, calling for caution regarding warfarin use in this particular patient group.

The current study utilized data spanning 2003 to 2010 from the nationwide Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, and drew from 24,317 patients who survived acute myocardial infarction, had AFib, and whose serum creatinine levels were available. From this population 5292 (21.9 percent) were treated with warfarin. Over the course of a one year follow-up, 9002 events were reported, including 3,551 deaths, 4,573 reinfarctions, and 878 strokes.

Ultimately the investigation found that patients with preexisting or new AFib who were prescribed warfarin at discharge experienced fewer incidents of death, myocardial reinfarctions, or ischemic strokes compared with otherwise similar patients who were not administered the treatment. The crude, absolute risk differences were 5.8 percent for death, 2.2 percent for myocardial infarction, and 1.8 percent for stroke in the entire cohort, and were reasonably consistent across all CKD strata.

Wolfgang Winkelmayer, MD, MPH, writes in a related editorial that "there is a paradox at the confluence of these two conditions that is difficult to reconcile: CKD appears to increase both the risk of stroke in patients with AFib and the risk of intracranial and other major hemorrhage... at the same time, CKD has been incorporated in three risk scores used to estimate bleeding risk associated with warfarin in AFib. In light of these findings, does CKD tilt the balance in favor of or against anticoagulation in AFib?"

Winkelmayer adds that, "Although previous analyses have demonstrated efficacy of oral anticoagulation using warfarin in patients with moderate CKD (mostly in patients with an estimated glomerular filtration rate (eGFR) between 60 and 45), the present observational study provides the best evidence to date suggesting that warfarin may be safe and effective in patients with advanced CKD, including those patients with an eGFR below 15. This evidence is important in light of the recent introduction of new target-specific oral anticoagulants, which generally excluded moderate to severe CKD in their pivotal efficacy trials."

Keywords: Myocardial Infarction, Stroke, Follow-Up Studies, Kidney Failure, Chronic, Warfarin, Molecular Medicine, Risk Factors, Creatinine, Registries, Glomerular Filtration Rate, Hemorrhage, Renal Insufficiency, Chronic