Apixaban Tops Other DOACs, Warfarin for Stroke Events in AF Patients with CKD

Results of an analysis comparing direct oral anticoagulants (DOACS) is shedding new light on what may be the more effective agent in older patients with atrial fibrillation and chronic kidney disease.

Using Medicare data, investigators found use of apixaban was associated with a decrease in risk of stroke and systemic embolism, as well as major bleeding when compared against warfarin in this patient population, but noted this effect was not seen with other agents in the DOAC class.

“We found that rates of stroke/systemic embolism and of major bleeding did not appear to differ between rivaroxaban and warfarin or between dabigatran and warfarin. Apixaban, compared with warfarin, appeared to be associated with decreased risk of both stroke/systemic embolism and of major bleeding,” wrote study investigators.

With no studies examining the comparative effectiveness of DOACS against warfarin in Medicare beneficiaries with atrial fibrillation and nondialysis-dependent chronic kidney disease, a team of physicians led by Charles Herzog, MD, of Hennepin Healthcare sought to address this apparent gap in knowledge. To do so, the investigators designed the current study to assess the effects of apixaban, rivaroxaban, and dabigatran against warfarin on risk of stroke and systemic embolism as well as major bleeding.

Choosing 2011-2017 as a study period, investigators identified a cohort of 22,739 subjects for inclusion in their analysis. Of these, 46.3% had a prescription for warfarin, 29.6% had a prescription for apixaban, 17.2% had a prescription for rivaroxaban, and 6.9% had a prescription for dabigatran.

The mean age among groups of anticoagulant users ranged from 78.4-79.0 years, the proportion of women ranged from 50.3%-51.4%, and prevalence of stage 3 chronic kidney disease ranged from 80.3%-82.8%.

For inclusion in the study, patients needed to have a diagnosis of stage 3, 4, or 5 chronic kidney disease and a new diagnosis for atrial fibrillation. Diagnoses were determined through the use of ICD-9-CM or ICD-10-CM codes. Patients with valvular heart disease or end-stage renal disease within a year preceding the index date and those with other potential indications for anticoagulation, such as surgery or a venous thromboembolic event within 60 days of atrial fibrillation diagnosis, were excluded from the analysis.

Of note, investigators planned to compare the effectiveness of each agent for the outcomes of interest using inverse-probability-of-treatment weighted Cox proportional hazards models in as-treated and intention-to-treat analyses.

In the as-treated analysis, both apixaban (HR, 0.70; 95% CI, 0.51-0.96) and rivaroxaban (HR, 0.80; 95% CI, 0.54-1.17) were associated with a lower risk of stroke and systemic embolism when compared against warfarin. This effect was not seen with dabigatran (HR, 1.15; 95% CI, 0.69-1.94). When assessing risk for major bleeding, investigators noted use of apixaban (HR, 0.47; 95% CI, 0.37-0.59) was associated with a reduction in risk. In comparison, use of rivaroxaban was associated with a hazard ratio of 1.05 (95% CI, 0.85-1.30) and use of dabigatran was associated with a hazard ratio of 0.95 (95% CI, 0.70-1.31).

Due to limitations within the study, investigators caution against over-generalizing the results of their analysis.

“These agents may possibly have a modest beneficial association with mortality compared with warfarin, but this should be considered hypothesis-generating only in the absence of clinical trial data,” wrote investigators.

This study, “Direct-Acting Oral Anticoagulants Versus Warfarin in Medicare Patients With Chronic Kidney Disease and Atrial Fibrillation,” was published in Stroke.