CANAGLIFLOZIN
REVISTA CIRCULATION
Canagliflozin and
Heart Failure in Type 2 Diabetes Mellitus: Results From the CANVAS Program
(Canagliflozin Cardiovascular Assessment Study)
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
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).
CONCLUSIONS: In patients with type 2
diabetes mellitus and an elevated risk of cardiovascular disease, canagliflozin
reduced the risk of cardiovascular death or hospitalized heart failure across a
broad range of different patient subgroups. Benefits may be greater in those
with a history of heart failure at baseline.
