Cardiovascular Effects of Canagliflozin in Relation to Renal Function and Albuminuria

Ashish Sarraju, George Bakris, Christopher P. Cannon, David Cherney, C. V. Damaraju, Gemma A. Figtree, Jagadish Gogate, Tom Greene, Hiddo J.L. Heerspink, James L. Januzzi, Bruce Neal, Meg J. Jardine, Jaime Blais, Mikhail Kosiborod, Adeera Levin, Ildiko Lingvay, Matthew R. Weir, Vlado Perkovic, Kenneth W. Mahaffey

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background: People with type 2 diabetes mellitus (T2DM) have elevated cardiovascular (CV) risk, including for hospitalization for heart failure (HHF). Canagliflozin reduced CV and kidney events in patients with T2DM and high CV risk or nephropathy in the CANVAS (CANagliflozin cardioVascular Assessment Study) Program and the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial. Objectives: The aim of this study was to assess the effects of canagliflozin on CV outcomes according to baseline estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (UACR) in pooled patient-level data from the CANVAS Program and CREDENCE trial. Methods: Canagliflozin effects on CV death or HHF were assessed by baseline eGFR (<45, 45-60, and >60 mL/min/1.73 m2) and UACR (<30, 30-300, and >300 mg/g). HRs and 95% CIs were estimated by using Cox regression models overall and according to subgroups. Results: A total of 14,543 participants from the CANVAS Program (N = 10,142) and the CREDENCE (N = 4,401) trial were included, with a mean age of 63 years, 35% female, 75% White, 13.2% with baseline eGFR <45 mL/min/1.73 m2, and 31.9% with UACR >300 mg/g. Rates of CV death or HHF increased as eGFR declined and/or UACR increased. Canagliflozin significantly reduced CV death or HHF compared with placebo (19.4 vs 28.0 events per 1,000 patient-years; HR: 0.70; 95% CI: 0.62-0.79), with consistent results across eGFR and UACR categories (all P interaction >0.40). Conclusions: Risk of CV death or HHF was higher in those with lower baseline eGFR and/or higher UACR. Canagliflozin consistently reduced CV death or HHF in participants with T2DM and high CV risk or nephropathy regardless of baseline renal function or level of albuminuria.

Original languageEnglish (US)
Pages (from-to)1721-1731
Number of pages11
JournalJournal of the American College of Cardiology
Issue number18
StatePublished - Nov 1 2022


  • SGLT2 inhibitor
  • canagliflozin
  • cardiovascular outcomes
  • diabetes
  • heart failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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