Cardiovascular Effects of Canagliflozin in Relation to Renal Function and Albuminuria
Key result
Canagliflozin cuts CV death or HHF by ~30% versus placebo.
- HR 0.70
- 95% CI 0.62-0.79
Why the study?
The study was conducted to assess the effects of canagliflozin on cardiovascular outcomes according to baseline eGFR and UACR using pooled patient-level data.
Does canagliflozin reduce cardiovascular death or heart failure hospitalization in patients with T2DM and high cardiovascular risk or nephropathy across different levels of baseline renal function and albuminuria?
Key Points
- This study aims to assess how canagliflozin affects cardiovascular outcomes based on renal function and albuminuria levels.
- Pooled patient-level data from CANVAS Program and CREDENCE trial were analyzed.
- Subgroups based on eGFR and UACR were assessed for cardiovascular outcomes.
- Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs).
- Canagliflozin reduced cardiovascular death or hospitalization for heart failure (19.4 vs 28.0 events per 1,000 patient-years; HR: 0.70; 95% CI: 0.62-0.79).
- Rates of cardiovascular death and hospitalization increased with decreasing eGFR and increasing UACR.
- The results were consistent across different categories of renal function and albuminuria.
Study Design
Type
Meta-Analysis
Multicenter
Yes
Structured PICO
Does canagliflozin reduce cardiovascular death or heart failure hospitalization in patients with T2DM and high cardiovascular risk or nephropathy across different levels of baseline renal function and albuminuria?
P
Population
Patients with type 2 diabetes mellitus and high cardiovascular risk or nephropathy.
I
Intervention
Canagliflozin
C
Comparator
Placebo
O
Outcome
Composite of cardiovascular death or hospitalization for heart failure (HHF)composite
Main Result
Hazard Ratio: 0.7 (95% CI 0.62–0.79)
Absolute Event Rate: 19.4% vs 28%
Canagliflozin consistently reduces the risk of cardiovascular death or heart failure hospitalization in patients with T2DM and high cardiovascular risk or nephropathy, regardless of baseline renal function or albuminuria.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Most interestingly, the three other cardiovascular risk markers show no difference in the effect of canagliflozin when we compare them for the four different eGFR groups. Reductions in systolic blood pressure, body weight, and albuminuria were very consistent across the groups.”
WGWilliam G. HerringtonPhysician, University of Oxford
“The findings presented by Neuen and colleagues are promising for patients with diabetes and early CKD, but evidence on broader applications of SGLT-2 inhibition are awaited.”
Implication
Supports canagliflozin across eGFR/UACR strata in high-risk T2DM; confirms and extends RCT consistency to renal subgroups.
Abstract
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: ) 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. 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. (Canagliflozin Cardiovascular Assessment Study [CANVAS], NCT01032629; A Study of the Effects of Canagliflozin [JNJ-24831754] on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus [CANVAS-R], NCT01989754; and Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy [CREDENCE], NCT02065791).
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Cite This Study
Sarraju et al. (2022) conducted a meta-analysis in Type 2 diabetes mellitus with high cardiovascular risk or nephropathy. Canagliflozin vs. Placebo was evaluated on Cardiovascular death or hospitalization for heart failure (HHF) (HR 0.70, 95% CI 0.62-0.79). Canagliflozin significantly reduced cardiovascular death or hospitalization for heart failure compared with placebo (19.4 vs 28.0 events per 1,000 patient-years; HR 0.70; 95% CI 0.62-0.79).