Patients with symptomatic nonobstructive hypertrophic cardiomyopathy (HCM) who were treated with aficamten vs. placebo saw significantly greater improvement in exercise capacity and self-reported health status at 36 weeks, according to findings from the ACACIA-HCM trial presented at ESC Congress 2026 and simultaneously published in NEJM.

A total of 258 patients were randomly assigned to either aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for up to 72 weeks. The mean age was 55 years and more than half were women.

At 36 weeks, the change from baseline in the KCCQ-CSS was 11.4 points in the aficamten group compared with 8.4 points in the placebo group. During that same period, the mean change in peak oxygen uptake was 0.64 ml per kilogram of body weight per minute in the aficamten group and −0.03 ml per kilogram per minute in the placebo group.

Beyond the primary endpoints, significant improvements with aficamten were also seen in secondary endpoints including New York Heart Association functional class, submaximal exercise performance and NT-proBNP, a marker of heart strain.

Researchers noted that "despite the phenotypic variety in patients with nonobstructive HCM, prespecified sub-group analyses showed consistency of the treatment effects and generalizability of these findings across the spectrum of patients."

Regarding safety, there was an increased incidence of patients having LVEF less than 50% with aficamten vs. placebo (10.5% vs. 0.8%) but this was managed with dose adjustment. Patients in the aficamten group also experienced more serious adverse events (20.2%) compared with in those in the placebo group (14.7%).

"Results from the ACACIA-HCM trial provide really positive news for patients with symptomatic non-obstructive HCM," said Principal Investigator Ahmad Masri, MD, from the Oregon Health and Science University in Portland. "For the first time, we have shown clinically meaningful improvements in symptoms and exercise capacity with a treatment that targets the cause of the disease."

Clinical Topics: Heart Failure and Cardiomyopathies

Keywords: ESC Congress, ESC26, Cardiomyopathy, Hypertrophic, Cardiomyopathies