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CHIEF-HF: Canagliflozin improves health status in heart failure

Presented by
Prof. John Spertus, University of Missouri-Kansas City, USA
AHA 2021
Phase 3, CHIEF-HF
Canagliflozin improved heart failure (HF) symptoms compared with placebo, regardless of ejection fraction or diabetes status in patients with any type of HF. Moreover, the effects were observed as early as 2 weeks from treatment initiation. The phase 3 CHIEF-HF trial was conducted without in-person visitations, which resulted in a diverse study population and a high completion rate.

Prof. John Spertus (University of Missouri-Kansas City, MO, USA) explained that canagliflozin has been shown to reduce HF outcomes and improve renal protection in patients with type 2 diabetes [1]. However, the agent has not yet been approved for a primary HF indication. The randomised, double-blind, placebo-controlled, phase 3 CHIEF-HF trial (NCT04252287) assessed the efficacy of canagliflozin on symptom improvement in patients with any type of HF. Participants could register for the trial via a smartphone application, after which the study medication and Fitbit devices were delivered. In total, 448 participants (mean age 63; 45% women) were randomised 1:1 to 100 mg canagliflozin once daily or placebo. The primary outcome was the 12-week change on the Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS).

After 12 weeks, canagliflozin treatment evoked a mean 4.3-point increased change in KCCQ-TSS versus placebo (P=0.016). Notably, the effect was observed as early as 2 weeks after treatment initiation (see Figure). The number needed to treat to avoid a large deterioration in KCCQ-TSS (≥10-point decrease) was 15, and 27 patients needed to be treated to achieve a large improvement on this instrument. The results were similar across ejection fractions and type 2 diabetes status. No new safety issues of canagliflozin emerged during this study.

Figure: 12-week KCCQ-TSS improvement for canagliflozin [1]

Discussant Dr Eldrin Lewis (Stanford University, CA, USA) put the results of the CHIEF-HF trial in perspective. “We have seen a remarkable improvement in mortality rates of HF patients due to therapeutic advances in recent years. Up to 60% reductions in mortality rates can be achieved in these patients if they follow combination therapies. The SGLT2 inhibitors are the latest drug class to add to the progress in HF management. In addition, the current completely decentralised trial recruited a diverse treatment population (14% Black, 45% women, 59% preserved ejection fraction) and established excellent follow-up rates (98%). Therefore, the CHIEF-HF trial design shows benefits over standard randomised controlled trials. I am curious to see the long-term follow-up data of this trial regarding the persistence of established improvements in health-related quality of life.”


    1. Spertus J, et al. Canagliflozin: Impact on Symptoms, Physical Limitations and Quality of Life in Heart Failure (CHIEF-HF) Trial. LBS05, AHA 2021 Scientific Sessions, 13–15 November.


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