BACKGROUND: Canagliflozin is a sodium glucose co-transporter 2 inhibitor that reduces the risk of heart failure (HF) in patients with type 2 diabetes and high cardiovascular risk. It is not known if canagliflozin has effects on both HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF).
METHODS: The CANVAS Program included 10,142 patients with type 2 diabetes and high cardiovascular risk randomized to canagliflozin or placebo. Mean follow-up was 188 weeks. Documentation describing fatal and hospitalized HF events was reviewed for data about ejection fraction and events were adjudicated as HFpEF, HFrEF, or HF with unknown ejection fraction (HFuEF). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for the effects of canagliflozin versus placebo on the first HF event of each type.
RESULTS: 276 participants were hospitalized and/or died from HF, and 52 experienced >1 HF outcome during follow up. 101 HF outcomes were defined as first HFpEF events, 122 were defined as first HFrEF events, and 61 were defined as first HFuEF events. Overall, canagliflozin reduced fatal or hospitalized HF compared to placebo (HR 0.70; 95% CI 0.55 – 0.89; Figure). The HR for HFpEF events was 0.80 (95% CI 0.54 – 1.20), for HFrEF events was 0.67 (95% CI 0.47 – 0.97), and for HFuEF events was 0.54 (95% CI 0.32 – 0.89).
CONCLUSIONS: In patients with type 2 diabetes and high cardiovascular risk, canagliflozin reduced the overall risk of HF events, with similar effects on HFpEF, HFrEF, and HFuEF events.