Effects of canagliflozin on major adverse cardiovascular events by baseline estimated glomerular filtration rate: Pooled Hispanic subgroup analyses from the CANVAS Program and CREDENCE trial

Diabetes Obes Metab. 2022 Jan;24(1):12-20. doi: 10.1111/dom.14539. Epub 2021 Sep 23.

Abstract

Aim: To assess the risk of major adverse cardiovascular events (MACE) of canagliflozin in Hispanic patients with type 2 diabetes (T2D) and high cardiovascular risk or nephropathy with varying levels of kidney function.

Materials and methods: This post hoc analysis included integrated, pooled data from the CANVAS Program and CREDENCE trial. The effects of canagliflozin versus placebo on major adverse cardiovascular events (MACE; i.e. cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) were assessed in subgroups by baseline estimated glomerular filtration rate (eGFR; <45, 45-60, and >60 mL/min/1.73 m2 ) overall and in the Hispanic cohort. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models, with subgroup by treatment interaction terms added to test for heterogeneity.

Results: A total of 14 543 participants were included; 3029 (20.8%) self-identified as Hispanic. In the overall population, canagliflozin reduced the risk of MACE compared with placebo (HR, 0.83; 95% CI, 0.75, 0.92), with no heterogeneity observed across eGFR subgroups (interaction P = .22). In the Hispanic cohort, canagliflozin also reduced the risk of MACE (HR, 0.71; 95% CI, 0.55, 0.92), with no heterogeneity by baseline eGFR (interaction P = .25), including among the Hispanic participants at highest risk with a baseline eGFR of less than 45 mL/min/1.73 m2 .

Conclusion: Canagliflozin reduced the risk of MACE overall, and among Hispanic participants with T2D and high cardiovascular risk or nephropathy in the CANVAS Program and CREDENCE trial, without heterogeneity by baseline eGFR.

Keywords: canagliflozin; cardiovascular disease; type 2 diabetes.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Canagliflozin / therapeutic use
  • Cardiovascular Diseases* / drug therapy
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / prevention & control
  • Clinical Trials as Topic
  • Diabetes Mellitus, Type 2* / chemically induced
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glomerular Filtration Rate
  • Hispanic or Latino
  • Humans
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Stroke* / chemically induced

Substances

  • Sodium-Glucose Transporter 2 Inhibitors
  • Canagliflozin