REVISTA CIRCULATION
Canagliflozin and
Heart Failure in Type 2 Diabetes Mellitus: Results From the CANVAS Program
(Canagliflozin Cardiovascular Assessment Study)
Karin Rådholm
Abstract
BACKGROUND: Canagliflozin is a
sodium glucose cotransporter 2 inhibitor that reduces the risk of
cardiovascular events. We report the effects on heart failure and
cardiovascular death overall, in those with and without a baseline history of
heart failure, 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 heart failure.
RESULTS: Participants with a
history of heart failure 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
heart failure 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 heart
failure (HR, 0.70; 95% CI, 0.55-0.89) and hospitalized heart failure alone (HR,
0.67; 95% CI, 0.52-0.87). The benefit on cardiovascular death or hospitalized
heart failure may be greater in patients with a prior history of heart failure (HR,
0.61; 95% CI, 0.46-0.80) compared with those without heart failure 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 heart
failure 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 heart failure (P=0.03).
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