A new analysis from the CANVAS program has shown that canagliflozin (Invokana, Janssen) demonstrated a reduced risk of cardiovascular (CV) outcomes in patients with and without a history of CV disease. The drug also achieved similar and proportional risk reductions for hospitalization due to heart failure (HHF) and renal outcomes in each of the primary and secondary prevention groups. The late-breaking results were presented at the American Heart Association Scientific Sessions 2017 in Anaheim, California, and simultaneously published in Circulation.
This analysis of CANVAS examined two high-CV-risk type-2 diabetes patient groups: those with a history of CV disease (secondary prevention) and those with only risk factors for CV disease (primary prevention). In this analysis, both patient groups showed CV outcomes consistent with the overall reduction seen in CV events: primary (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.74–1.30) and secondary (HR, 0.82; 95% CI, 0.72–0.95), with no statistical evidence of between-group heterogeneity (P = 0.18). Comparable effects were also observed for other CV and renal outcomes across the primary and secondary prevention groups.
As previously reported, in the total cohort of the CANVAS program, canagliflozin reduced the combined risk of CV death, nonfatal myocardial infarction (MI), and nonfatal stroke by 14%, compared to placebo (HR, 0.86; 95% CI, 0.75–0.97; P = 0.0158).
The new analysis also found:
Patients with prior CV events had an overall greater primary endpoint event rate compared to those who had two or more CV risk factors (36.9 versus 15.7/1,000 patient-years; P < 0.001). Canagliflozin lowered the risk of HHF in both patient groups: primary (HR, 0.64; 95% CI, 0.35–1.15) with interaction P = 0.91 and secondary (HR, 0.68; 95% CI, 0.51–0.90). The drug also achieved a reduction in the risk of the composite renal endpoint in both patient groups: primary (HR, 0.63; 95% CI, 0.39–1.02) and secondary (HR, 0.59; 95% CI, 0.44–0.79) with interaction P = 0.73.
The overall adverse event profile for canagliflozin compared with placebo was consistent in the primary and secondary prevention participants (P interactions all > 0.07)
No new adverse events were observed during this additional analysis beyond what was previously reported from the CANVAS program.
The primary prevention cohort was comprised of patients 50 years of age or older with at least two risk factors for CV events; the secondary prevention cohort was comprised of individuals 30 years of age or older with a prior CV event. Primary prevention participants (N = 3,486; 34%) were younger (63 versus 64 years), more often female (45% versus 31%), and had longer duration of diabetes (14 versus 13 years) compared to secondary prevention participants (N = 6,656; 66%).
Source: Janssen; November 14, 2017.