Canaglifozin associated with Improved Quality of Life, Regardless of Ejection Fraction or Diabetes

CHIEF-HF

Key Points:

• In the CHIEF-HF study, patients with HF of any ejection fraction with or without diabetes were treated with either canagliflozin or placebo for 12 weeks. The primary outcome was 12-week change in Kansas City Cardiomyopathy Questionnaire (KCCQ) total summary score. Secondary analyses included subgroup analysis for the primary outcome by ejection fraction and presence of diabetes, as well as 6- and 9- month repeated KCCQ screening.
• Treatment with canagliflozin reduced the 12-week KCCQ score relative to placebo, with similar results seen across EF and diabetes subgroups.

Patients with heart failure have high morbidity and mortality, and the advent of guideline-directed medical therapy has significantly ameliorated the burden of symptoms and complications patients with HF face. Many recent trials have demonstrated the efficacy of SGLT2 inhibitors in reducing cardiovascular mortality and HF hospitalizations across both HFrEF (EMPEROR-REDUCED, DAPA-HF, etc) and HFpEF (EMPEROR-PRESERVED, PRESERVED-HF). More evidence is needed regarding the effect of SGLT2 inhibitors on HF symptomatology. In a breaking presentation at the 2021 American Heart Association Scientific Sessions today, Dr. John Spertus (Saint Luke’s Hospital, Kansas City) and his team presented the results of the Canagliflozin: Impact on Symptoms, Physical Limitations and Quality of Life in Heart Failure (CHIEF-HF) Trial.

The CHIEF-HF study (NCT04252287) was a multicenter randomized trial, conducted at 18 centers across the United States. Patients were treated with either a 100mg daily canagliflozin for 12 weeks or a NOAC. All recruited patients were required to have a) confirmed HF of any type, b) access to a qualifying smartphone for data collection, c) a Fitbit, and d) an initial screening Kansas City Cardiomyopathy Questionnaire (KCCQ) score of less than 80. Some relevant exclusion criteria included the use of another SGLTi or a previous history of diabetic ketoacidosis.

A total of 476 patients were randomized; 222 received canagliflozin and 226 received placebo. The median age was 65, and 59% of patients had HFpEF. 72% of patients were non-diabetic. Patients were followed for 9 months. The primary outcome was a 12-week change in KCCQ total summary score, which represented the patients’ perception of their HF symptoms. Pre-specified secondary analyses included subgroup analysis for the primary outcome by ejection fraction and presence of diabetes, as well as 6- and 9- month repeated KCCQ screening. All outcome data were collected virtually, without in-person visits. Canagliflozin reduced the 12-week KCCQ score relative to placebo (mean difference 4.3, p=0.016). The NNT for a large improvement in symptoms was 27. There was a consistent magnitude of mean difference in KCCQ across all subgroups, although likely due to low sample size none reached significance individually. There were 27 (12.7%) serious adverse events in the canagliflozin group, compared to 18 (7.8%) in placebo.

This trial represents a new model of conducting RCTs; the lack of requirement for any in-person visits or data collection increases the speed of enrollment and potentially completion. When discussing the implications of the study at the AHA, Dr. Spertus stated: “Canagliflozin improved patients’ heart failure symptoms. It did so regardless of their ejection fraction or diabetes status. Effects were observed as early as 2 weeks and sustained as far as 3 months…[these results] highlight the efficacy and safety of beginning SGLT2i in this patient population.”