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On-Treatment Outcomes in Patients With Worsening Renal Function With Rivaroxaban Compared With Warfarin: Insights
Christopher B Fordyce1, Anne S Hellkamp2, Yuliya Lokhnygina2
1From Duke Clinical Research Institute, Durham, NC (C.B.F., A.S.H., Y.L., S.M.L., J.P.P., M.R.P.); University of Cincinnati College of Medicine, OH (R.C.B.); Bayer HealthCare Pharmaceuticals, Whippany, NJ (S.D.B); Department of Cardiovascular Medicine, Division of Electrophysiology, University Hospital Münster, Germany (G.B.); Centre for Cardiovascular Science, University of Edinburgh and Royal Infirmary of Edinburgh, UK (K.A.A.F.); Department of Medicine, Stanford University, CA (K.W.M.); Janssen Research and Development, Raritan, NJ (C.C.N.); and Massachusetts General Hospital and Harvard Medical School, Boston (D.E.S.). christopher.fordyce@duke.edu.
Background:
Despite rapid clinical adoption of novel anticoagulants, it is unknown whether outcomes differ among patients with worsening renal function (WRF) taking these new drugs compared with warfarin. We aimed to determine whether the primary efficacy (stroke or systemic embolism) and safety (major bleeding and nonmajor clinically relevant bleeding) end points from the ROCKET AF trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation trial) differed among participants with WRF taking rivaroxaban and those taking warfarin.
Methods:
After excluding patients without at least 1 follow-up creatinine measurement (n=1624), we included all remaining patients (n=12 612) randomly assigned to either rivaroxaban or dose-adjusted warfarin. On-treatment WRF (a decrease of >20% from screening creatinine clearance measurement at any time point during the study) was evaluated as a time-dependent covariate in Cox proportional hazards models.
Results:
Baseline characteristics were generally similar between patients with stable renal function (n=9292) and WRF (n=3320). Rates of stroke or systemic embolism, myocardial infarction, and bleeding were also similar, but WRF patients experienced a higher incidence of vascular death versus stable renal function (2.21 versus 1.41 events per 100 patient-years; P=0.026). WRF patients who were randomized to receive rivaroxaban had a reduction in stroke or systemic embolism compared with those taking warfarin (1.54 versus 3.25 events per 100 patient-years) that was not seen in patients with stable renal function who were randomized to receive rivaroxaban (P=0.050 for interaction). There was no difference in major or nonmajor clinically relevant bleeding among WRF patients randomized to warfarin versus rivaroxaban.
Conclusions:
Among patients with on-treatment WRF, rivaroxaban was associated with lower rates of stroke and systemic embolism compared with warfarin, without an increase in the composite bleeding end point.
Clinical Trial Registration:
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767.
Insights
Rivaroxaban reduced stroke risk in atrial fibrillation patients with worsening renal function (WRF) compared to warfarin. This benefit was observed without increasing major bleeding events in the WRF group.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Novel anticoagulants are increasingly used, but their comparative effectiveness in patients with worsening renal function (WRF) remains unclear.
- Warfarin has been the traditional standard, but newer agents like rivaroxaban offer different mechanisms of action.
Purpose of the Study:
- To compare the efficacy and safety of rivaroxaban versus warfarin in atrial fibrillation patients experiencing worsening renal function during treatment.
- To analyze primary efficacy (stroke/systemic embolism) and safety (major/nonmajor bleeding) endpoints in the ROCKET AF trial based on renal function status.
Main Methods:
- Analysis of 12,612 patients from the ROCKET AF trial, including those with and without on-treatment worsening renal function (WRF).
- WRF defined as a >20% decrease in creatinine clearance from baseline.
- Cox proportional hazards models used to evaluate WRF as a time-dependent covariate.
Main Results:
- Patients with WRF had similar rates of stroke, embolism, and bleeding compared to those with stable renal function, but a higher incidence of vascular death.
- In WRF patients, rivaroxaban showed a reduction in stroke or systemic embolism compared to warfarin (1.54 vs. 3.25 events per 100 patient-years).
- No significant difference in major or nonmajor clinically relevant bleeding was observed between rivaroxaban and warfarin in WRF patients.
Conclusions:
- Rivaroxaban demonstrated superior efficacy in preventing stroke and systemic embolism among atrial fibrillation patients with worsening renal function compared to warfarin.
- The improved efficacy of rivaroxaban in WRF patients was achieved without a corresponding increase in the composite bleeding endpoint.
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