The sodium glucose cotransporter 2 (SGLT2) inhibitor canagliflozin reduced the risk for cardiovascular death or hospitalizations for heart failure in patients with type 2 diabetes (T2D) and an elevated risk for cardiovascular disease, according to analysis of the CANVAS trial published in Circulation.
Karin Radholm, MD, PhD, from the Department of Medicine and Health Sciences, Division of Community Medicine, Primary Care Faculty of Health Sciences, Department of Local Care West, County Council of Östergötland, Linköping University, Sweden, and colleagues analyzed data from CANVAS (ClinicalTrial.gov identifier: NCT01032629), a phase 3 trial that enrolled 10,142 patients with T2D and randomly assigned them to receive canagliflozin or placebo. They were followed for a mean of 188 weeks. The primary endpoint was adjudicated cardiovascular death or hospitalization for heart failure.
Patients receiving canagliflozin had a significantly lower risk for cardiovascular death or hospitalization for heart failure (hazard ratio [HR], 0.78; 95% CI, 0.67-0.91), fatal or hospitalized heart failure (HR, 0.70; 95% CI, 0.55-0.89), or hospitalized heart failure alone (HR, 0.67; 95% CI, 0.52-0.87).
However, there was no definitive separate effect on fatal heart failure alone (HR, 0.89; 95% CI, 0.49-1.60). The benefit for cardiovascular death or hospitalization for heart failure was borderline significantly greater (P =.021) in patients with a prior history of heart failure (HR, 0.61) compared with those who had no prior history (HR, 0.87).
Absolute risk differences were −106.97 per 1000 patient-years for those with a history of heart failure at baseline (95% CI, −171.59 to −42.34) and −8.36 per 1000 patient-years for those without a history of heart failure (95% CI, −22.08 to 5.36).
The effects of canagliflozin compared with placebo for other cardiovascular outcomes and safety outcomes were similar in patients with or without a history of heart failure at baseline. However, there was a reduced absolute rate of events attributable to osmotic diuresis among participants with a history of heart failure (P =.003).
The authors argue that the CANVAS data offer strong evidence of the protective effects of canagliflozin on heart failure and, considered along with EMPA-REG OUTCOME, suggest an important role for SGLT2 inhibitors in the prevention of heart failure among patients with T2D.
Disclosure: This study was funded by Janssen Research & Development, LLC.
Radholm K, Figtree G, Perkovic V, et al. Canagliflozin and heart failure in type 2 diabetes mellitus [published online March 11, 2018]. Circulation. doi: 10.1161/CIRCULATIONAHA.118.034222