MUNICH—The novel anticoagulant apixaban is better than warfarin at preventing stroke and reducing mortality independent of renal function, a secondary analysis of the ARISTOTLE trial showed, reported MedPage Today.
Major bleeding was also reduced with apixaban, although the patients with the most impaired renal function appeared to derive the greatest benefit, according to Stefan Hohnloser, MD, of J.W. Goethe University in Frankfurt.
The findings reported at the European Society of Cardiology meeting here and published simultaneously online in the European Heart Journal "suggest that apixaban may be particularly suited to address the unmet need for more effective and safe stroke prevention in patients with atrial fibrillation and renal dysfunction," he said.
Impaired renal function is common in patients with atrial fibrillation and is associated with greater risks of bleeding and poor outcomes. Because of the fear of bleeding, many patients with both renal dysfunction and atrial fibrillation do not receive oral anticoagulation.
Hohnloser and colleagues performed a prespecified secondary analysis of the ARISTOTLE trial, which showed that apixaban—of which about 25 percent is excreted through the kidneys—significantly reduced stroke and systemic embolism by a relative 21 percent, total mortality by a relative 11 percent, and major bleeding by a relative 31 percent versus warfarin in patients with atrial fibrillation and at least one additional risk factor for stroke.
They used three different methods to estimate glomerular filtration rate among 14,884 study participants—the Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, which are both based on serum creatinine, as well as cystatin C measurements.
According to the Cockcroft-Gault equation, at baseline 42 percnt of patients had an eGFR greater than 80 mL/min, 42 percent had an estimate greater than 50 but no greater than 80 mL/min, and 15 percent had an estimate of 50 mL/min or less.
As seen in prior studies, the rates of cardiovascular events, mortality, and bleeding were highest in the patients with impaired renal function (eGFR of 80 mL/min or less).
Compared with warfarin, apixaban was more effective at preventing stroke and systemic embolism and reducing all-cause mortality, regardless of baseline renal function and the method used to calculate it.
Apixaban also reduced major bleeding events across all ranges of eGFR, although there was a significant interaction between treatment effect and renal function indicating greater efficacy in patients with an eGFR of 50 mL/min or less according to the Cockcroft-Gault equation (P=0.005).
The relative risk reduction in major bleeding was greater in patients with an eGFR of ≤50 mL/min using Cockcroft–Gault (HR 0.50 95% CI 0.38 to 0.66, P=0.005).
"This is interesting, important, and needs to be explained," Keith Fox, MBChB, of the Edinburgh Center for Cardiovascular Science in Scotland, said in comments following Hohnloser's presentation.
The researchers conducted sensitivity analyses to see whether the finding was related to use of a half dose of apixaban in some patients. Most patients received 5 mg twice daily but patients 80 and older, those with a body weight of 132 pounds or less, and those with a serum creatinine of 1.5 mg/dL or greater received 2.5 mg twice daily.
The reduced dose did not fully explain the greater reductions in major bleeding seen in the patients with the worst renal function.
"In my view," Fox said, "ARISTOTLE [apixaban] provides a treatment option and advantages over warfarin in patients with moderate renal dysfunction, a group that [is] currently suboptimally treated."
