Canagliflozin and Heart Failure in Type 2 Diabetes Mellitus: Results From the CANVAS Program
Open accessAbstract
Background: Canagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events. We report the effects on heart failure (HF) and cardiovascular death overall, in those with and without a baseline history of HF, and in other participant subgroups. Methods: The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) enrolled 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk. Participants were randomly assigned to canagliflozin or placebo and followed for a mean of 188 weeks. The primary end point for these analyses was adjudicated cardiovascular death or hospitalized HF. Results: Participants with a history of HF at baseline (14.4%) were more frequently women, white, and hypertensive and had a history of prior cardiovascular disease (all P <0.001). Greater proportions of these patients were using therapies such as blockers of the renin angiotensin aldosterone system, diuretics, and β-blockers at baseline (all P <0.001). Overall, cardiovascular death or hospitalized HF was reduced in those treated with canagliflozin compared with placebo (16.3 versus 20.8 per 1000 patient-years; hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.67–0.91), as was fatal or hospitalized HF (HR, 0.70; 95% CI, 0.55–0.89) and hospitalized HF alone (HR, 0.67; 95% CI, 0.52–0.87). The benefit on cardiovascular death or hospitalized HF may be greater in patients with a prior history of HF (HR, 0.61; 95% CI, 0.46–0.80) compared with those without HF at baseline (HR, 0.87; 95% CI, 0.72–1.06; P interaction =0.021). The effects of canagliflozin compared with placebo on other cardiovascular outcomes and key safety outcomes were similar in participants with and without HF at baseline (all interaction P values >0.130), except for a possibly reduced absolute rate of events attributable to osmotic diuresis among those with a prior history of HF ( P =0.03). Conclusions: In patients with type 2 diabetes mellitus and an elevated risk of cardiovascular disease, canagliflozin reduced the risk of cardiovascular death or hospitalized HF across a broad range of different patient subgroups. Benefits may be greater in those with a history of HF at baseline. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01032629 and NCT01989754.
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SGLT2 inhibitors have been shown to reduce the risk of hospitalizations for heart failure in 8 large-scale trials, including those focused on type 2 diabetes, heart failure with reduced ejection fraction, and chronic kidney disease.
“Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce the risk of hospitalizations for heart failure in 8 large-scale trials, including those that focused on type 2 diabetes, heart failure with a reduced ejection fraction, and chronic kidney disease.1–8”
From Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial (2021) · cites this paper as [2]
Little is known about the effect of SGLT2 inhibitors on the broad spectrum of both inpatient and outpatient worsening heart failure events, because these were not documented in trials with these drugs in type 2 diabetes.
“Little is known about the effect of SGLT2 inhibitors on the broad spectrum of both inpatient and outpatient worsening heart failure events, because these were not documented in trials with these drugs in type 2 diabetes.1–5”
From Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial (2021) · cites this paper as [2]
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- Authors
- Rådholm, K., Figtree, G., Perkovic, V., Solomon, S. D., Mahaffey, K. W., de Zeeuw, D., Fulcher, G., Barrett, T. D., Shaw, W., Desai, M., Matthews, D. R., & Neal, B.
- Affiliations
- Linköping University (SE)
- Royal North Shore Hospital (AU)
- The George Institute for Global Health (GB)
- Brigham and Women's Hospital (US)
- Stanford Medicine (US)
- University of Groningen, University Medical Center Groningen, The Netherlands (D.d.Z.).
- Janssen Research & Development (United States) (US)
- University of Oxford (GB)
- Corresponding author
- Rådholm, Karin
- Figtree, Gemma
- ORCID
- Venue
- Circulation
- Published
- 2018-07-31
- Volume
- 138
- Issue
- 5
- Pages
- 458-468
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC6075881
- OpenAlex
- W2965056983
- Cited by
- 488
- References
- 29
- Citations by year
- 2026: 16 · 2025: 32 · 2024: 36 · 2023: 52 · 2022: 59 · 2021: 82 · 2020: 105 · 2019: 75 · 2018: 30 · 2016: 1
- FWCI
- 58.05
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Circulation (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- Imperial College London
- University of Oxford
- University of New South Wales
- Universitair Medisch Centrum Groningen
- Mitsubishi Tanabe Pharma Corporation
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- canagliflozin, heart failure, type 2 diabetes, SGLT2 inhibitors, cardiovascular mortality, osmotic diuresis, CANVAS trial, subgroup analysis, cardiovascular risk reduction, drug safety, renin-angiotensin-aldosterone system inhibitors, diuretics, beta-blockers
- MeSH terms
- Canagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Aged, Blood Glucose, Cause of Death, Diabetes Mellitus, Type 2, Europe, Female, Heart Failure, Hospitalization, Humans, Male, Middle Aged, Risk Factors, Time Factors, United States, Biomarkers, Treatment Outcome, Disease Progression, Risk Assessment
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