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Kidney Week

Abstract: PO1007

Effects of Canagliflozin on Major Adverse Cardiovascular Events in Patients with Different Baseline Levels of Type 2 Diabetes Disease Severity: Results from the CANVAS Program

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Young, Tamara K., The George Institute for Global Health, Sydney, New South Wales, Australia
  • Li, Jingwei, The George Institute for Global Health, Sydney, New South Wales, Australia
  • Kang, Amy, The George Institute for Global Health, Sydney, New South Wales, Australia
  • L Heerspink, Hiddo Jan, The George Institute for Global Health, Sydney, New South Wales, Australia
  • Hockham, Carinna, The George Institute for Global Health, Sydney, New South Wales, Australia
  • Arnott, Clare Gabrielle, The George Institute for Global Health, Sydney, New South Wales, Australia
  • Neuen, Brendon Lange, The George Institute for Global Health, Sydney, New South Wales, Australia
  • Zoungas, Sophia, Monash University, Clayton, Victoria, Australia
  • Mahaffey, Kenneth W., The George Institute for Global Health, Sydney, New South Wales, Australia
  • Perkovic, Vlado, The George Institute for Global Health, Sydney, New South Wales, Australia
  • de Zeeuw, Dick, Rijksuniversiteit Groningen, Groningen, Groningen, Netherlands
  • Fulcher, Greg, University of Sydney - Camperdown and Darlington Campus Burkitt-Ford Library, University of Sydney - AU, Sydney, New South Wales, Australia
  • Neal, Bruce, The George Institute for Global Health, Sydney, New South Wales, Australia
  • Jardine, Meg J., The George Institute for Global Health, Sydney, New South Wales, Australia
Background

Patients with type 2 diabetes mellitus (T2DM) included in trials of sodium-glucose cotransporter 2 inhibitors are heterogeneous in terms of disease severity. We assessed the effects of canagliflozin compared to placebo on cardiovascular and renal outcomes in the CANVAS program according to severity of T2DM as indicated by intensity of treatment, duration of diabetes and glycaemic control.

Methods

We compared effects on major adverse cardiovascular events ([MACE], defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) according to three indicators of T2DM severity at study baseline: number of glucose lowering treatments or insulin therapy (0-1, 2, 3+, insulin), duration of diabetes (<10, 10-16, >16 years) and HbA1c (<7.0, 7.0-7.5, 7.5-8.0, 8.0-8.5, 8.5-9, >9.0%). We also assessed effects on other pre-specified cardiovascular outcomes, and an adjudicated composite of end-stage kidney disease, renal death or sustained 40% decline in estimated glomerular filtration rate. We assessed for constancy of hazard ratios across subgroups by fitting an interaction term that tested for linear trend.

Results

Of 10,142 participants in the CANVAS Program, 1011 experienced a MACE during a mean follow-up of 3.6 years. The effect of canagliflozin on MACE in the overall population (HR 0.86, 95 % CI 0.75-0.97) was consistent irrespective of the number of glucose lowering treatments (p=0.509), duration of diabetes (p=0.174) and baseline HbA1c (p =0.314). Effects were also consistent across different levels of T2DM disease severity for all other outcomes studied.

Conclusion

The proportional risk reductions achieved with canagliflozin were comparable regardless of diabetes duration, number of therapies or HbA1C at baseline.

Funding

  • Commercial Support