Are NOACs Safe for Afib Patients with Worsening Renal Function?

Most atrial fibrillation (AF) patients require oral anticoagulation for stroke prevention. Although warfarin is the historical standard of care, the FDA has approved 4 novel oral anticoagulants (NOACs) for the same indication.

AF patients with renal dysfunction face higher risks of both thromboembolism and bleeding during antithrombotic therapy. This is important because all of the available NOACs have some component of renal elimination, and each has specific dose adjustments in the setting of moderate renal impairment.

Although fixed daily doses of NOACs have demonstrated favorable efficacy and safety compared with warfarin, the impact of worsening renal function (WRF) on these medications over time hasn’t been evaluated.

Recently, 2 post-hoc analyses explored the impact of WRF on clinical event rates in patients taking NOACs and warfarin.

The first dataset was from the ARISTOTLE trial, which randomized 18,201 AF patients to apixaban or warfarin. Serial creatinine measurements were available in 16,869 patients, and WRF was defined as an annual decrease in estimated glomerular filtration rate (eGFR) >20%.¹

WRF was observed in 13.6% of patients and was associated with older age and more cardiovascular comorbidities. The risks of stroke or systemic embolism, major bleeding, and mortality were higher in WRF patients.¹

In those patients, apixaban consistently demonstrated similar relative risk of stroke or systemic embolism, ischemic or unspecified stroke, and major bleeding versus warfarin throughout a 12- month period.¹

The second analysis of the ROCKET AF trial included 12,612 patients randomly assigned to either rivaroxaban or dose-adjusted warfarin. Upon treatment, WRF was again measured as a decrease >20% from screening creatinine clearance measurement at any point during the study.²

WRF patients experienced a higher incidence of vascular death versus stable renal function (2.21 vs. 1.41 events per 100 patient-years), but rates of stroke or systemic embolism, myocardial infarction, and bleeding were similar between groups.²

WRF patients who received rivaroxaban saw a reduction in stroke or systemic embolism compared with those taking warfarin (1.54 vs. 3.25 events per 100 patient-years), but this wasn’t seen in patients with stable renal function who received rivaroxaban. There was no difference in major or nonmajor clinically relevant bleeding among WRF patients on warfarin versus rivaroxaban.²

Taken together, these 2 studies carry several important implications for clinicians managing AF. First, the heightened risk of adverse outcomes in patients with AF and WRF was further reinforced. Second, despite dependence on renal elimination, both NOACs (rivaroxaban and apixaban) appeared at least as good as (if not slightly better than) warfarin in WRF patients. Finally, these analyses showed WRF is common among those with AF, particularly older patients with other morbid conditions. Pharmacists should bear this in mind and ensure patients taking NOACs have regular assessment of renal function to ensure adequate dose adjustment should WRF develop.

It’s also noteworthy that neither study included patients with severe renal impairment (eGFR< 30 mL/min) at baseline. Given this absence of evidence, I personally wouldn’t be comfortable using any NOAC in a patient with advanced renal disease (including hemodialysis) until further data are available.

References

1. Hijazi Z, et al. Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation in Relation to Renal Function Over TimeInsights From the ARISTOTLE Randomized Clinical Trial. JAMA Cardiol. 2016;1(4):451-460.

2. Fordyce CB, et al. On-Treatment Outcomes in Patients With Worsening Renal Function With Rivaroxaban Compared With Warfarin: Insights From ROCKET AF. Circulation. 2016;134(1):37-47.