03081nas a2200229   4500000000100000008004100001100002100042700001700063700001600080700001500096700001800111700001900129700001900148700001900167700001800186700001800204700002100222700001500243245014600258520243300404022001402837       2018                            d1 aMahaffey Kenneth1 aFulcher Greg1 aDesai Mehul1 aShaw Wayne1 ade Zeeuw Dick1 aMatthews David1 aPerkovic Vlado1 aRådholm Karin1 aFigtree Gemma1 aSolomon Scott1 aBarrett Terrance1 aNeal Bruce00aCanagliflozin and Heart Failure in Type 2 Diabetes Mellitus: Results From the CANVAS Program (Canagliflozin Cardiovascular Assessment Study).3 a<p>                    
: 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.: 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.: 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<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<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;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 interactionvalues >0.130), except for a possibly reduced absolute rate of events attributable to osmotic diuresis among those with a prior history of heart failure (=0.03).: 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.: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01032629 and NCT01989754.</p>  a1524-4539