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Kidney Week

Abstract: PO2630

Canagliflozin Across the Spectrum of Kidney Function and Albuminuria: Integrated Data from CANVAS and CREDENCE

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Neuen, Brendon Lange, The George Institute for Global Health, Newtown, New South Wales, Australia
  • Yu, Jie, The George Institute for Global Health, Newtown, New South Wales, Australia
  • Li, Qiang, The George Institute for Global Health, Newtown, New South Wales, Australia
  • Perkovic, Vlado, UNSW Sydney, Sydney, New South Wales, Australia
  • Arnott, Clare Gabrielle, The George Institute for Global Health, Newtown, New South Wales, Australia
  • Neal, Bruce, The George Institute for Global Health, Newtown, New South Wales, Australia
  • L Heerspink, Hiddo Jan, Rijksuniversiteit Groningen, Groningen, Groningen, Netherlands
  • Agarwal, Rajiv, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Bakris, George L., University of Chicago, Chicago, Illinois, United States
  • Cannon, Christopher P., Harvard University, Cambridge, Massachusetts, United States
  • de Zeeuw, Dick, Rijksuniversiteit Groningen, Groningen, Groningen, Netherlands
  • Charytan, David M., New York University School of Medicine, New York, New York, United States
  • Levin, Adeera, The University of British Columbia, Vancouver, British Columbia, Canada
  • Di Tanna, Gian Luca, The George Institute for Global Health, Newtown, New South Wales, Australia
  • Matthews, David R., University of Oxford, Oxford, Oxfordshire, United Kingdom
  • Pollock, Carol A., The University of Sydney, Sydney, New South Wales, Australia
  • Wheeler, David C., University College London, London, London, United Kingdom
  • Mahaffey, Kenneth W., Stanford University School of Medicine, Stanford, California, United States
  • Jardine, Meg J., The George Institute for Global Health, Newtown, New South Wales, Australia
Background

People with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) are at very high risk of cardiovascular events and kidney failure. While canagliflozin reduces the risk of these outcomes, the consistency of this effect across all levels of estimated glomerular filtration rate (eGFR) and urinary albumin:creatinine ratio (UACR) remains uncertain.

Methods

We pooled individual participant data from the CANVAS Program (n=10,142) and CREDENCE trial (n=4,401) to assess the effect of canagliflozin on a primary composite outcome of myocardial infarction, stroke, heart failure, doubling of serum creatinine, kidney failure, cardiovascular or kidney death. The effect of canagliflozin was assessed using Cox regression models with treatment by subgroup interaction terms stratified by trial.

Results

2,051/14,543 (14%) participants experienced the primary outcome over a median follow-up of 2.5 years. Overall, canagliflozin reduced the risk of the primary outcome (HR 0.77, 95% 0.70-0.84; Figure). The magnitude of relative benefit increased as eGFR declined (P-trend=0.0067; Figure) with some evidence of greater relative benefit at higher UACR (P-trend=0.057; Figure). Lower eGFR and higher UACR levels were independently associated with cardio-renal risk. Consequently, absolute risk reductions increased more than 5-fold across lower eGFR categories and more than 9-fold across higher UACR categories (Figure).

Conclusion

Canagliflozin reduces the risk of cardio-renal outcomes in people with T2DM; the magnitude of relative and absolute protection varies by severity of CKD.

Funding

  • Commercial Support