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

Nov 14, 2021
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Janssen Scientific Affairs
Date Presented:
11/14/2021
Date Updated:
11/14/2021
Original Posted Date:
11/14/2021
References

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.

Description:

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)

Interpretation:

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.

References:

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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