SGLT2 inhibitor reduces CV death and hospitalization for HF, especially in those with HF at baseline

ACC 2018 A subanalysis of the CANVAS trial showed a treatment benefit of canagliflozin on CVD death and hospitalized HF in patients with T2DM and at CVD risk, especially in those with history of HF.

Introduction and methods

The randomized CANVAS study evaluated the SGLT2 inhibitor canagliflozin 300 mg and 100 mg in comparison with placebo, in patients with type 2 diabetes (T2DM, HbA1c between 7.0% and 10.5%, eGFR≥30 mL/min/1.73m² and at least 30 years old, with a history of CV event, or at least 50 years old with at least 2 CV risk factors). Of 10142 patients enrolled, 1461 (14.4%) had a prior diagnosis of heart failure (HF) and 85.6% did not.

Effects of canagliflozin on CV and renal outcomes have previously been published, including a 14% reduction in the composite endpoint of CV death, nonfatal MI and nonfatal stroke, lower progression of albuminuria (-27%) and a 40% lower risk of a renal composite endpoint. The objectives of this analysis were to explore in further detail the effects of canagliflozin on HF, and to determine efficacy and safety in patients with and without a history of HF at baseline.

Main results

• The primary outcome of CV death or hospitalization for HF (HHF) was significantly reduced in patients on canagliflozin as compared with placebo (16.3 vs. 20.8 per 1000 patient years (PY), HR: 0.78, 95%CI: 0.67-0.91).
• A secondary outcome was fatal HF or HHF, which showed a significant reduction with canagliflozin (6.4 vs. 9.7 per 1000 PY, HR: 0.70, 955CI: 0.55-0.89), which was mostly driven by a decrease of HHF (5.5 vs 8.7, HR: 0.67, 95%CI: 0.52,0.87).
• Subgroup analyses showed a significant interaction (P=0,03) of BMI with the effect of canagliflozin, such that a treatment effect on CVD death or HHF was seen in those with ≥30 kg/m² (HR: 0.68, 95%CI: 0.56-0.82), but not in those with BMI <30 kg/m².
• Another significant interaction was seen for baseline HbA1c, with a significant treatment effect in those ≥8%, but not in those with HbA1c <8%. Also, patients not on metformin at baseline showed a treatment benefit, while those taking metformin did not. Patients on diuretics at baseline showed a treatment benefit, while those not on diuretics did not.
• When data were stratified according to history of HF, no significant benefit on CV death and HHF of canagliflozin was seen in those without a history of HF, as compared with placebo (13.6 vs. 15.2 per 1000 PY, HR: 0.87, 95%CI: 0.72-1.06). In those with a history of HF, canagliflozin did show a treatment benefit over placebo (35.4 vs 56.8 per 1000 PY, HR: 0.61, 95%CI: 0.46-0.80).
• History of HF did not show significant interactions with the associations between treatment and CV and renal outcomes.
• Safety events did not differ significantly between those with and without HF at baseline.

Conclusion

Disclosures

Our coverage of ACC.18 is based on the information provided during the congress.

This study was published simultaneously in Circulation