Aficamten Improves Exercise Capacity in Symptomatic Obstructive HCM

Study at a glance:

• Journal: New England Journal of Medicine, 2024

• Population: 282 adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM)

• Method: Phase 3, double-blind RCT comparing aficamten (5–20 mg daily) vs. placebo for 24 weeks

• Key Finding: Aficamten significantly increased peak oxygen uptake and improved all secondary functional outcomes

Summary:
The SEQUOIA-HCM trial tested aficamten, a selective cardiac myosin inhibitor, in adults with symptomatic obstructive HCM. Patients were randomized to aficamten (n=142) or placebo (n=140) for 24 weeks, with dose titration based on echocardiography. Baseline characteristics included mean age 59.1 years, 59.2% men, resting LV outflow tract gradient 55.1 mm Hg, and LVEF 74.8%. At 24 weeks, peak oxygen uptake increased by 1.8 ml/kg/min in the aficamten group vs. 0.0 ml/kg/min in placebo (between-group difference 1.7 ml/kg/min; 95% CI, 1.0–2.4; P<0.001). All 10 prespecified secondary endpoints—including NYHA class, KCCQ-CSS score, and LVOT gradient—also improved significantly. Adverse event rates were similar between groups.

Takeaway:
Aficamten is effective in improving exercise tolerance and multiple functional parameters in patients with obstructive HCM, offering a promising pharmacologic alternative to invasive therapies.

Source:
SEQUOIA-HCM Investigators. Aficamten in Symptomatic Obstructive Hypertrophic Cardiomyopathy. N Engl J Med. 2024. doi:10.1056/NEJMoa2403271. Available at: https://www.nejm.org/doi/10.1056/NEJMoa2401424