Canagliflozin and Heart Failure in Type 2 Diabetes Mellitus: Results From the CANVAS Program.

Abstract

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.

• Authors: Karin Rådholm, Gemma Figtree, Vlado Perkovic, Scott D Solomon, Kenneth W Mahaffey, Dick de Zeeuw, Greg Fulcher, Terrance D Barrett, Wayne Shaw, Mehul Desai, David R Matthews, Bruce Neal
• Journal: Circulation (Circulation) Vol. 138 Issue 5 Pg. 458-468 (07 31 2018) ISSN: 1524-4539 [Electronic] United States
• PMID: 29526832 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Blood Glucose
• Sodium-Glucose Transporter 2 Inhibitors
• Canagliflozin

Topics

• Aged
• Biomarkers (blood)
• Blood Glucose (drug effects, metabolism)
• Canagliflozin (adverse effects, therapeutic use)
• Cause of Death
• Diabetes Mellitus, Type 2 (blood, diagnosis, drug therapy, mortality)
• Disease Progression
• Europe
• Female
• Heart Failure (diagnosis, drug therapy, mortality, physiopathology)
• Hospitalization
• Humans
• Male
• Middle Aged
• Risk Assessment
• Risk Factors
• Sodium-Glucose Transporter 2 Inhibitors (adverse effects, therapeutic use)
• Time Factors
• Treatment Outcome
• United States