New data from the FOREST-HCM trial suggests that aficamten could help patients with obstructive hypertrophic cardiomyopathy (oHCM) avoid undergoing septal reduction therapy (SRT). The findings, presented at the American Heart Association (AHA) Annual Scientific Sessions 2024, indicate a significant reduction in SRT eligibility among patients treated with aficamten.
Impact on SRT Eligibility
The FOREST-HCM trial, an open-label extension study of patients from the phase 2 REDWOOD-HCM or SEQUOIA-HCM trials, included a subgroup analysis focusing on patients initially eligible for SRT. Among 180 patients with oHCM and at least 24 weeks of follow-up, 31.6% (n=57) were considered eligible for SRT at baseline. After 24 weeks of aficamten treatment, only 3.5% (n=2) of this subgroup remained eligible for SRT.
Clinical Observations and NYHA Class Improvements
Further analysis revealed that 35.1% (n=20) of the SRT-eligible patients had a left ventricular outflow obstruction (LVOT) gradient of 50 mmHg or greater but were NYHA Class I/II, while 3.5% (n=2) had NYHA III/IV but an LVOT gradient less than 50 mmHg. Additionally, 92.9% (n=52) of SRT-eligible patients, and 67.8% of the remaining cohort, improved by at least one NYHA class by week 24. Greater improvements were observed among SRT-eligible patients relative to those in the remaining cohort (21.7 [SD, 19.3] vs 13.5 [SD, 13.9]; P = .003).
Expert Commentary
Ahmad Masri, MD, MS, director of the Hypertrophic Cardiomyopathy Center at Oregon Health and Science University, noted the importance of these findings in clinical practice. "This is an open level study, so you can't always take everything from it and say, ‘I have the highest level of evidence [and] that this is being achieved.’ However, what I would argue is day in, day out, in the clinic, this is what we use to treat patients," Masri explained. "We use their symptoms, their LVOT gradient, how they feel, my impression or the physician's impression of what's going on, and we recommend to them surgery or no surgery."
