Impact of renal function on ischemic stroke and major bleeding rates in nonvalvular atrial fibrillation patients treated with warfarin or rivaroxaban: a retrospective cohort study using real-world evidence

Abstract

Objectives: Renal dysfunction is associated with increased risk of cardiovascular disease and is an independent predictor of stroke and systemic embolism. Nonvalvular atrial fibrillation (NVAF) patients with renal dysfunction may face a particularly high risk of thromboembolism and bleeding. The current retrospective cohort study was designed to assess the impact of renal function on ischemic stroke and major bleeding rates in NVAF patients in the real-world setting (outside a clinical trial).

Methods: Medical claims and Electronic Health Records were retrieved retrospectively from Optum’s Integrated Claims–Clinical de-identified dataset from May 2011 to August 2014. Patients with NVAF treated with warfarin (2468) or rivaroxaban (1290) were selected. Each treatment cohort was stratified by baseline estimated creatinine clearance (eCrCl) levels. Confounding adjustments were made using inverse probability of treatment weights (IPTWs). Incidence rates and hazard ratios of ischemic stroke and major bleeding events were calculated for both cohorts.

Results: Overall, patients treated with rivaroxaban had an ischemic stroke incidence rate of 1.9 per 100 person-years (PY) while patients treated with warfarin had a rate of 4.2 per 100 PY (HR = 0.41 [0.21–0.80], p = .009). Rivaroxaban patients with an eCrCl below 50 mL/min (N = 229) had an ischemic stroke rate of 0.8 per 100 PY, while the rate for the warfarin cohort (N = 647) was 6.0 per 100 PY (HR = 0.09 [0.01–0.72], p = .02). For the other renal function levels (i.e. eCrCl 50–80 and ≥80 mL/min) HRs indicated no statistically significant differences in ischemic stroke risks. Bleeding events did not differ significantly between cohorts stratified by renal function.

Conclusions: Ischemic stroke rates were significantly lower in the overall NVAF population for rivaroxaban vs. warfarin users, including patients with eCrCl below 50 mL/min. For all renal function groups, major bleeding risks were not statistically different between treatment groups.

Keywords:

• Renal function
• stroke
• bleeding
• rivaroxaban
• warfarin
• atrial fibrillation

Transparency

Declaration of funding

This study was funded by Janssen Scientific Affairs LLC.

Author contributions: All authors were involved in the conception and design of the study, analysis and interpretation of data, drafting/editing of the manuscript, and final approval. All authors agree to be accountable for all aspects of the work.

Declaration of financial/other relationships

F.L., K.B. and P.L. have disclosed that they are employees of Analysis Group Inc., a consulting company that has received research grants from Janssen Scientific Affairs LLC. V.A. and J.S. have disclosed that they are employees of Janssen Scientific Affairs LLC. M.R.W. and J.S.B. have disclosed that they received consulting fees from Janssen Scientific Affairs LLC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

No assistance in the preparation of this article is to be declared. Parts of this research were presented at the 2016 American College of Cardiology Annual Scientific Session & Expo.