AHA 2021. Heart failure patients, across ejection fraction and diabetes status, reported improved QOL as early as 3 months in CHIEF-HF trial.
In patients with heart failure (HF) canagliflozin rapidly improved health status, including symptoms, function, and quality of life (QOL), regardless of baseline ejection fraction status or presence of type 2 diabetes (T2D), according to findings from the CHIEF-HF trial, presented during a late-breaking science session at the American Heart Association 2021 Scientific Sessions.
Study authors, led by John A. Spertus, MD, MPH, professor and Daniel J. Lauer Endowed Chair in Metabolism and Vascular Disease Research at the University of Missouri-Kansas City School of Medicine, report that improvements in health status were observed within 3 months of reporting and that separation between treatment and placebo groups began as early as 2 weeks after the study began.
The study findings were notable for the swift clinical effect of the sodium glucose cotransporter-2 inhibitor (SGLT2-2i) and for its completely “virtual” design, using remote symptom tracking and mail delivery of canagliflozin or placebo.
The CHIEF-HF (Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure) trial was launched just prior to the COVID-19 lockdown as a centralized, randomized controlled trial without any face-to-face visits
Spertus et al enrolled 448 participants from 18 US health systems between March 2020 and February 2021. For inclusion patients were required to have a history of HF, a Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS ) ≤80 and a smartphone compatible with the self-administered KCCQ application. Patients were excluded for SGLT-2i use within 3 months, type 1 diabetes, and GFR ≤30 ml/min/1.73m2.
Permuted block 1:1 randomization was used, stratified by HF with reduced ejection fraction (HFrEF) vs HF with preserved EF (HFpEF), to assign patients to receive canagliflozin 100 mg (n=222) or placebo (n=226) daily. Study medications were provided to patients by mail. Data were collected remotely via smartphone application, wearable accelerometers, and through claims.
Researchers measured symptom reports from the participants' KCCQ app at 2, 4, 6, and 12 weeks after randomization. The primary outcome of interest was change in KCCQ Total Symptom Scores (KCCQ-TSS) at 12 weeks which the research team assessed using a mixed effects model of repeated measures, adjusting for treatment, stratification (HFrEF vs HFpEF), time by study intervention, and baseline KCCQ-TSS.
The overall mean age of participants was 63.4 years; 44.9% were female and 14.5% were African American. Approximately 3 in 10 (27.9%) had T2D and more than half (59.6%) had HFpEF. Participants in the canagliflozin group had a baseline KCCQ-TSS of 57.4 and the placebo group KCCQ-TSS was 58.0.
Overall, patients in the canagliflozin group reported significantly improved KCCQ-TSS at 12 weeks vs patients receiving placebo (difference of 4.3 points [95% CI 0.80-7.80], P=.016). Spertus and colleagues highlight that the separation between the groups was evident as early as 2 weeks after symptom reporting began.
They also found the benefits of taking canagliflozin were consistent across the study's key pre-specified subgroups, including participants with both HFrEF and HFpEF, and in those with and without T2D (pinteraction=.35 and .90, respectively).
"These findings, together with the results of other SGLT2 inhibitor trials, are transformational and should have a significant impact on care," said Spertus in an American Heart Association press statement. "The impact of this class of medicines on patients' function and quality of life is larger than many other medications used to treat heart failure, and they are very safe. Since improvement in health status is such a key goal for many patients, these findings support increasing the use of SGLT2 inhibitors for people with heart failure."
“We did not know if a completely ‘virtual’ clinical trial, especially one where randomized treatment was delivered to participants and the outcomes were collected through a smartphone app, could work,” said Spertus in the statement. “Demonstrating the success of a decentralized clinical trial opens opportunities for applying this approach to the testing of other cardiovascular therapies that focus on health status.”
Reference: Spertus J, Birmingham M, Damaraju CV, et al. The canagliflozin impact on health status, quality of life and functional status in heart failure (CHIEF-HF) clinical trial. Paper presented at the American Heart Association 2021 Scientific Sessions, held virtually November 13-15, 2021.