Background: Disopyramide, used in obstructive hypertrophic cardiomyopathy (oHCM) for its negative inotropic properties mediated by its reduction in cytosolic calcium, has been recommended for decades as an option to relieve resistant obstruction. Aficamten is a selective cardiac myosin inhibitor that reduces hypercontractility directly by reducing myosin-actin interaction. Objectives: This study aims to investigate the safety and efficacy of concomitant use and withdrawal of disopyramide in patients with symptomatic oHCM receiving aficamten. Methods: Patients with oHCM enrolled in REDWOOD-HCM Cohort 3 (open-label), SEQUOIA-HCM (placebo-controlled), and FOREST-HCM (open-label) were analyzed. The authors identified 4 groups, each with patients symptomatic despite background therapy with disopyramide who received: 1) disopyramide plus aficamten and subsequent aficamten withdrawal per protocol (Diso-Afi Withdrawal); 2) disopyramide plus placebo (Diso-Pbo); 3) aficamten plus disopyramide with subsequent disopyramide withdrawal (Afi-Diso Withdrawal); and 4) continued both disopyramide and aficamten (Diso+Afi Continuous). Assessments were performed at baseline, after aficamten or placebo add-on therapy, and after washout (except at week 24 for Diso+Afi Continuous group). For such oHCM patients, aficamten treatment may be considered with an option to discontinue disopyramide. (Dose-finding Study to Evaluate the Safety, Tolerability, PK, and PD of CK-3773274 in Adults With HCM [REDWOOD-HCM]; NCT04219826) (Aficamten vs Placebo in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy [SEQUOIA-HCM]; NCT05186818) (Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of Aficamten in Adults With HCM [FOREST-HCM]; NCT04848506)
Concomitant Aficamten and Disopyramide in Symptomatic Obstructive Hypertrophic Cardiomyopathy / Masri A., Maron M.S., Abraham T.P., Nassif M.E., Barriales-Villa R., Bilen O., Coats C.J., Elliott P., Garcia-Pavia P., Massera D., Olivotto I., Oreziak A., Owens A.T., Saberi S., Solomon S.D., Tower-Rader A., Heitner S.B., Jacoby D.L., Melloni C., Wei J., et al.. - In: JACC. HEART FAILURE. - ISSN 2213-1779. - ELETTRONICO. - 14:(2025), pp. 0-0. [10.1016/j.jchf.2025.03.008]
Concomitant Aficamten and Disopyramide in Symptomatic Obstructive Hypertrophic Cardiomyopathy
Masri A.;Olivotto I.;Wei J.;Shu Y.;Cheng X.;Halabi M.;Targetti M.;Amin A.;Alvarez A. G.;Cooper R.;Sen S.;Hussain Z.;
2025
Abstract
Background: Disopyramide, used in obstructive hypertrophic cardiomyopathy (oHCM) for its negative inotropic properties mediated by its reduction in cytosolic calcium, has been recommended for decades as an option to relieve resistant obstruction. Aficamten is a selective cardiac myosin inhibitor that reduces hypercontractility directly by reducing myosin-actin interaction. Objectives: This study aims to investigate the safety and efficacy of concomitant use and withdrawal of disopyramide in patients with symptomatic oHCM receiving aficamten. Methods: Patients with oHCM enrolled in REDWOOD-HCM Cohort 3 (open-label), SEQUOIA-HCM (placebo-controlled), and FOREST-HCM (open-label) were analyzed. The authors identified 4 groups, each with patients symptomatic despite background therapy with disopyramide who received: 1) disopyramide plus aficamten and subsequent aficamten withdrawal per protocol (Diso-Afi Withdrawal); 2) disopyramide plus placebo (Diso-Pbo); 3) aficamten plus disopyramide with subsequent disopyramide withdrawal (Afi-Diso Withdrawal); and 4) continued both disopyramide and aficamten (Diso+Afi Continuous). Assessments were performed at baseline, after aficamten or placebo add-on therapy, and after washout (except at week 24 for Diso+Afi Continuous group). For such oHCM patients, aficamten treatment may be considered with an option to discontinue disopyramide. (Dose-finding Study to Evaluate the Safety, Tolerability, PK, and PD of CK-3773274 in Adults With HCM [REDWOOD-HCM]; NCT04219826) (Aficamten vs Placebo in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy [SEQUOIA-HCM]; NCT05186818) (Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of Aficamten in Adults With HCM [FOREST-HCM]; NCT04848506)
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