Apixaban Compares Favorably with Warfarin in Safety, Efficacy

published in JAMA Cardiology concludes that apixaban (Eliquis) tends to be both safer and more effective than warfarin in patients with atrial fibrillation (AF), regardless of their renal function.

The Apixaban for Reduction In Stroke and Other ThromboemboLic Events (ARISTOTLE) trial randomized 18,201 AF patients to apixaban or warfarin and provided ongoing creatinine measurements in 16,869 of those patients.

After a median follow-up of 1.8 years, 2,294 of those patients (13.6%) experienced reductions of 20% or more in their rate of estimated glomerular filtration. Multivariate analysis found that such declines in renal function were associated with older age and more cardiovascular comorbidities but not with use of one medication rather than the other.

Overall, renal deterioration was associated with higher rates of stroke or systemic embolism (hazard ratio, 1.53; 95% confidence interval [CI], 1.17-2.01), major bleeding (HR, 1.56; 95% CI, 1.27-1.93) and all-cause mortality (HR, 2.31; 95% CI, 1.98-2.68).

Still, patients with poor renal function fared better on apixaban than warfarin.

• Among patients whose estimated glomerular filtration rate was less than 50 ml/min, apixaban use was associated with significantly lower rates of major bleeding (HR, 0.59; 95% CI, 0.45-0.77) and a trend toward lower rates of stroke or systemic embolism (HR, 0.70; 95% CI, 0.48-1.03).
• Among patients whose estimated glomerular filtration rate ranged from 50 ml/min to 80 ml/min, apixaban use was associated with significantly lower rates of major bleeding (HR, 0.76; 95% CI, 0.60-0.94) and a trend toward lower rates of stroke or systemic embolism (HR, 0.78; 95% CI, 0.58-1.04).
• Among patients whose estimated glomerular filtration rate was more than 80 ml/min, apixaban use was associated with a trend toward both lower rates of major bleeding (HR, 0.80; 95% CI, 0.60-1.07) and lower rates of stroke or systemic embolism (HR, 0.87; 95% CI, 0.60-1.26).

Overall, the vast majority (86.5%) of the 16,869 patients who underwent tests of renal function every 3 months saw that function decline slowly and steadily — but not, the study authors wrote, to a degree that might necessitate a dosing adjustment for apixaban or any other novel oral anticoagulant.

The study authors suggested that physicians might look for cases of rapid decline by checking each patients renal function at baseline and again after 3 months. If that test showed slow decline (or no decline), annual checks thereafter would likely prove sufficient, except among high-risk patients.

“The study highlighted that the rate of deterioration was variable, with a more rapid reduction at older age and with comorbidities such as heart failure, vascular disease, or diabetes,” the study authors wrote. “The relation between renal dysfunction and poorer prognosis both concerning thromboembolic and major bleeding risk poses a concrete dilemma in clinical practice because better protection against stroke is often counterbalanced by more bleeding.”

The study authors wrote that although poor renal function was associated with relatively poor outcomes no matter which anticoagulant patients took, the relative advantages of apixaban were greatest among patients with poor renal function (compared to middling or good renal function). Apixaban, therefore, deserves particular consideration among such patients.