Kidney, limb and ophthalmic complications, and death in patients with nonvalvular atrial fibrillation and type 2 diabetes prescribed rivaroxaban or warfarin: an electronic health record analysis

Abstract

Background

Patients with nonvalvular atrial fibrillation (NVAF) and type 2 diabetes are at risk of kidney, limb, and ophthalmic complications. We evaluated the rate of these complications and death in patients with NVAF and type 2 diabetes prescribed rivaroxaban or warfarin.

Methods

We analyzed Optum de-Identified electronic health record (EHR) data from 11/2010–12/2019. We included adults with NVAF and T2D newly initiated on rivaroxaban or warfarin with ≥12 months of prior EHR activity. Patients with another indication for anticoagulation, valve disease, history of end-stage renal disease, major adverse limb events (MALE), diabetic retinopathy or pregnancy were excluded. We evaluated the incidence rate of developing a composite outcome of >40% decrease in estimated glomerular filtration incidence rate (eGFR) from baseline, eGFR < 15 mL/minute/1.73 m2, need for dialysis or kidney transplant, MALE, diabetic retinopathy or death. Overlap weighting was used to balance baseline characteristics between cohorts while preserving sample size. Hazard ratios with 95% confidence intervals were calculated using propensity score-overlap weighted Cox regression.

Results

We included 24,912 rivaroxaban and 58,270 warfarin users. The mean ± standard deviation (SD) CHA2DS2VASc score was 4.3 ± 1.5 and modified HASBLED score was 1.5 ± 0.8. Thirty percent of rivaroxaban patients were started on 15 mg once daily, with the rest prescribed 20 mg once daily. Warfarin patients had a mean time in therapeutic range of 47 ± 28%. Patients were followed for a mean of 2.89 ± 1.95 years. Rivaroxaban was associated with a reduced hazard of the composite outcome (HR = 0.93, 95%CI = 0.91–0.95; absolute risk reduction = 1.97 events per 1000 patient-years; number needed-to-treat = 51) versus warfarin. Rivaroxaban was also associated with significant reductions in the relative hazard of > 40% decrease in eGFR from baseline (HR = 0.96), need for dialysis or renal transplant (HR = 0.81), and limb revascularization or major amputation (HR = 0.85). Death occurred at a lower incidence rate with rivaroxaban (HR = 0.92, 95%CI = 0.89–0.95).

Conclusions

Rivaroxaban was associated with reduced incidence rates of kidney and limb complications, and death in NVAF patients with type 2 diabetes compared to warfarin. ClinicalTrials.gov Identifier: NCT04509193

Keywords:

• Anticoagulation
• atrial fibrillation
• diabetes
• rivaroxaban
• kidney
• adverse limb events

Transparency

Declaration of funding

Funding for this study was provided by Bayer AG, Berlin, Germany. In their role as coauthors, Khaled Abdelgawwad, MBA, MSc and Burcu Vardar, MD of the funding body contributed to design and conduct of the study; management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Declaration of financial/other relationships

CIC has received grant funding and consultancy fees from Janssen Scientific Affairs LLC, Titusville, NJ, Bayer AG, Berlin, Germany; Portola Pharmaceuticals, South San Francisco, CA; and speaker fees from Medscape Inc. OSC has received speaker fees from Janssen Scientific Affairs LLC, Titusville, NJ. BV and KA are employees of Bayer AG, Berlin, Germany. CWB, BO, and NS have no conflicts of interest to disclose. Peer reviewers on this manuscript have received an honorarium from CMRO for their review work but have no other relevant financial relationships to disclose.

Author contributions

All authors contributed substantially to the conception, design, acquisitions, analysis or interpretations of data for this study. CIC and OSC drafted the written manuscript. All authors revised the manuscript for important intellectual content.

Acknowledgements

None.

Data availability statement

Data used in this study were obtained from Optum under a license to Bayer AG (and provided to Dr. Coleman under a third-party agreement) and are not publicly available.