Concomitant Aficamten and Disopyramide in Symptomatic Obstructive Hypertrophic Cardiomyopathy.

Area of Science:

• Cardiology
• Pharmacology

Background:

• Disopyramide has been a long-standing treatment for obstructive hypertrophic cardiomyopathy (oHCM) due to its negative inotropic effects.
• Aficamten, a selective cardiac myosin inhibitor, offers a novel approach by directly reducing myosin-actin interaction and hypercontractility.

Purpose of the Study:

• To evaluate the safety and efficacy of combining disopyramide with aficamten.
• To assess the impact of withdrawing disopyramide in patients with symptomatic oHCM receiving aficamten.

Main Methods:

• Analysis of patients from three clinical trials (REDWOOD-HCM, SEQUOIA-HCM, FOREST-HCM).
• Four patient groups were defined based on treatment: disopyramide plus aficamten with withdrawal, disopyramide plus placebo, aficamten plus disopyramide with withdrawal, and continuous combination therapy.
• Assessments included left ventricular outflow tract (LVOT) obstruction, symptoms (NYHA class, KCCQ-CSS), and NT-proBNP levels.

Main Results:

• Aficamten addition to disopyramide significantly reduced LVOT obstruction, improved symptoms, and lowered NT-proBNP.
• Withdrawal of aficamten led to a return of obstruction and symptoms.
• Withdrawal of disopyramide while on aficamten did not compromise efficacy, with no safety events or atrial fibrillation reported.

Conclusions:

• Combination therapy of aficamten and disopyramide is safe and well-tolerated in symptomatic oHCM patients.
• Aficamten alone demonstrates significant clinical efficacy, and disopyramide can be discontinued without loss of benefit.
• Aficamten represents a viable treatment option for oHCM, potentially allowing for disopyramide cessation.