Canagliflozin Impact on Health Status, Quality of Life, and Functional Status in Heart Failure - CHIEF-HF

Contribution To Literature:

The CHIEF-HF trial showed that canagliflozin is superior to placebo in improving patient-reported HF symptoms among patients with HF, irrespective of diabetes status; the impact on clinical outcomes is unclear.


The goal of the trial was to assess the safety and efficacy of canagliflozin in patients with heart failure (HF), irrespective of diabetes status.

Study Design

Patients were randomized in a 1:1 fashion to either canagliflozin 100 mg (n = 222) or matching placebo (n = 226). All the patients were receiving other treatments for HF.

  • Total screened: 1,333
  • Total number of enrollees: 476 randomized; 448 in final analysis
  • Duration of follow-up: 12 weeks
  • Mean patient age: 64 years
  • Percentage female: 45%

Inclusion criteria:

  • Confirmed HF of any type (based on electronic health record review)
  • Sole access to iPhone (6 or later) or Samsung S7 (or later)
  • Willing to wear a Fitbit (Versa 2)
  • Screening Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score ≤80

Exclusion criteria:

  • Concurrent use of a sodium-glucose cotransporter 2 (SGLT2) inhibitor
  • History of diabetic ketoacidosis
  • Type 1 diabetes
  • Estimated glomerular filtration rate ≤30 ml/min/1.732

Other salient features/characteristics:

  • HF with preserved ejection fraction (HFpEF): 59%
  • White race: 84%
  • Type 2 diabetes mellitus (DM2): 28%

Principal Findings:

The trial was stopped early by the sponsor. The primary outcome, change in KCCQ-Total Symptom Score at 12 weeks for canagliflozin vs. placebo, difference between two groups, was 4.3 points (p = 0.016).

Results were similar for patients with HF with reduced EF (HFrEF) and HFpEF, and for patients with and without DM2.

Secondary outcome:

  • All-cause mortality: 0.9% vs. 1.7% (p > 0.05)


The results of this trial indicate that canagliflozin is superior to placebo in improving patient-reported HF symptoms among patients with HF, irrespective of diabetes status. The impact on clinical outcomes is unclear. The trial follow-up was performed virtually; this trial was also stopped prematurely by the sponsor. Safety data, including amputations, are not available.

Even though the SGLT2 inhibitors were introduced as DM2 management drugs, results of EMPA-REG OUTCOME and other trials indicated a clear benefit in HF management. This trial enrolled a dedicated HF population, and shows a benefit in patient-centered outcomes, irrespective of diabetes status. These drugs will likely have a prominent role in future HF management guidelines. The mechanism of benefit is unclear.


Presented by Dr. John Spertus at the American Heart Association Virtual Annual Scientific Sessions (AHA 2021), November 14, 2021.

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure

Keywords: AHA21, AHA Annual Scientific Sessions, Canagliflozin, Diabetes Mellitus, Type 2, Heart Failure, Metabolic Syndrome, Secondary Prevention, Sodium-Glucose Transporter 2 Inhibitors, Stroke Volume

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