Canagliflozin improves HF symptoms: CHIEF-HF
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The SGLT2 inhibitor canagliflozin improved HF symptoms within 3 months in patients with HF, regardless of ejection fraction or diabetes status, according to results of the fully remote CHIEF-HF trial.
“Benefits were observed as early as 2 weeks and sustained throughout treatment for 3 months,” 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, said during a press conference at the American Heart Association Scientific Sessions.
CHIEF-HF was a fully remote, randomized, placebo-controlled trial. It launched in March 2020 and was completed during the COVID-19 pandemic, Spertus said. Participants were able to complete the trial without a single face-to-face visit by utilizing the self-report Kansas City Cardiomyopathy Questionnaire (KCCQ) on their smartphone.
Participating sites screened electronic medical records to identify patients with HF; those patients were invited to participate in the trial via email, portal phone or visit, and provided with a website to learn more about the trial. If interested, patients opted in for virtual screenings. If eligible (KCCQ score 80), they downloaded an app and provided informed consent via the app. The study medications and a wearable device (Versa 2, Fitbit) were shipped directly to the patient. Patients serially completed the self-report KCCQ over the treatment period, and researchers measured the patients’ symptom reports at weeks 2, 4, 6 and 12 after taking daily canagliflozin 100 mg (Invokana, Janssen) or placebo.
Spertus said planned enrollment was 19,000, but due to shifting priorities the trial was stopped at 476 participants before unblinding. Participants, recruited from 18 health systems across the U.S., had a median age of 65 years and 45% were women. Fifty-nine percent had HF with preserved ejection fraction (HFpEF) and 72% did not have type 2 diabetes. All were recruited from 18 health systems across the United States.
At 12 weeks, there was a 4.3-point difference in the primary outcome, KCCQ total symptom score, favoring canagliflozin. This result suggests “a significant benefit of treatment with 100 mg per day of canagliflozin on the symptoms of patients with HF,” Spertus said.
Results showed a consistent benefit of canagliflozin in all subgroups, including those with HFpEF or HFrEF and those with and without type 2 diabetes, Spertus said.
No new safety concerns were identified. Overall, canagliflozin was well tolerated and the safety events were balanced between the canagliflozin and placebo groups.
CHIEF-HF “models a new approach to the conduct of randomized controlled trials,” Spertus said. The approach yielded more rapid enrollment, had higher completion than traditional randomized controlled trials and addresses many of the Institute of Medicine’s challenges to improving clinical trials, he said.
Spertus noted several limitations of the trial, including its smaller-than-planned sample size; its conduct during the COVID-19 pandemic, which may have altered participants’ usual activities; and it wasn’t powered for clinical events.
Perspective
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Mary Norine Walsh, MD, MACC
Canagliflozin had an impact on a very important, patient-centered endpoint: that of improving patients’ symptoms. Taken together with prior studies and some presented at this meeting, the SGLT2 inhibitors appear to be beneficial for patients with HF regardless of their diabetes status.
How a clinician decides which SGLT2 inhibitor to use for a patient may largely depend on how an individual patient ‘fits’ the trial inclusion criteria for a given drug. Also, as always, insurance payer formularies may play a role in the selection for some patients.
This was an amazing and innovative trial. It was launched at the beginning of the global pandemic. Patients were recruited, enrolled and completed the trial with no in-person visits. This tells us that more trials can be done this way, which may allow for broader patient enrollment. The only drawback is that patients had to go online to find out about the study and enroll. This likely limited enrollment to patients who were internet-savvy or had others in their household that could assist them.
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Spertus J, et al. LBS.05. Building on the Foundations of Treatment: Advances in Heart Failure Therapy. Presented at: American Heart Association Scientific Sessions; Nov. 13-15, 2021 (virtual meeting).
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