Warfarin may benefit CKD patients without adding bleeding risk

Compared with non-users, Swedish patients with advanced chronic kidney disease (CKD) and atrial fibrillation who received warfarin therapy were less likely to die, have an MI or stroke at no added risk of bleeding in an observational study published March 5 in JAMA.

Patients with impaired kidney function and atrial fibrillation are at higher risk of stroke and thromboembolism than patients without CKD. Clinical trials for anticoagulants don’t include patients with renal dysfunction for ethical reasons, leaving physicians to rely on observational studies for guidance for this patient population. The results from observational studies have been conflicting, though.

Juan Jesus Carrero, PhD, of Karolinska University Hospital in Stockholm, and colleagues designed a registry-based study based on comprehensive data resources in Sweden. They used 2003-2010 data from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, which includes all 72 Swedish hospitals that treat patients for acute cardiac diseases.

The registry captures patient clinical characteristics, with atrial fibrillation confirmed both in the patient history and by electrocardiography. They linked that data with the National Inpatient Registry to track hospitalizations due to MI, ischemic stroke or bleeding. The registries also are updated with death dates and causes.   

They identified 24,317 patients admitted for acute MI who had atrial fibrillation. Of those, 21.8 percent were prescribed warfarin at discharge. More than half had moderate to end-stage CKD: 41.7 percent were CKD stage 3 (estimated glomerular filtration rate [eGFR] 30 to 60 mL/min/1.73 m2); 8.1 percent were CKD stage 4 (eGFR 15 to 60 mL/min/1.73 m2); and 2 percent were CKD stage 5 (eGFR less than 15 mL/min/1.73 m2).

The outcomes were a composite of death, readmission for MI and ischemic stroke within one year of discharge; readmission due to bleeding within one year of discharge; and the aggregate of the two outcomes. They found that outcomes increased with CKD severity.

Compared with patients not treated with warfarin, the warfarin patients in all CKD categories had a lower number of composite outcome events, aggregated events and lower incidence rates at one year. Patients treated with warfarin did not have a higher bleeding risk compared with patients who did not receive warfarin.

“[W]arfarin treatment was associated with a lower one-year risk of the composite end point of death, myocardial infarction, and ischemic stroke without a higher risk of bleeding,” they wrote. “This association was observed in patient strata with moderate, severe, or end-stage CKD.”

As an observational study, the findings do not provide conclusive evidence and may include residual confounding. The results are not generalizable to other patient populations, they cautioned, and the one-year follow-up period may be too short to capture warfarin’s longer-term effects.