1. Canagliflozin and Heart Failure in Type 2 Diabetes Mellitus: Results From the CANVAS Program.
- Author
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Rådholm K, Figtree G, Perkovic V, Solomon SD, Mahaffey KW, de Zeeuw D, Fulcher G, Barrett TD, Shaw W, Desai M, Matthews DR, and Neal B
- Subjects
- Aged, Biomarkers blood, Blood Glucose metabolism, Canagliflozin adverse effects, Cause of Death, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 mortality, Disease Progression, Europe, Female, Heart Failure diagnosis, Heart Failure mortality, Heart Failure physiopathology, Hospitalization, Humans, Male, Middle Aged, Risk Assessment, Risk Factors, Sodium-Glucose Transporter 2 Inhibitors adverse effects, Time Factors, Treatment Outcome, United States, Blood Glucose drug effects, Canagliflozin therapeutic use, Diabetes Mellitus, Type 2 drug therapy, Heart Failure drug therapy, Sodium-Glucose Transporter 2 Inhibitors therapeutic use
- 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.
- Published
- 2018
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