2026-07-24T06:25:19Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/165542024-09-27T08:04:06Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Maron, Martin S author Masri, Ahmad author Choudhury, Lubna author Olivotto, Iacopo author Saberi, Sara author Wang, Andrew author Garcia-Pavia, Pablo author Lakdawala, Neal K author Nagueh, Sherif F author Rader, Florian author Tower-Rader, Albree author Turer, Aslan T author Coats, Caroline author Fifer, Michael A author Owens, Anjali author Solomon, Scott D author Watkins, Hugh author Barriales-Villa, Roberto author Kramer, Christopher M author Wong, Timothy C author Paige, Sharon L author Heitner, Stephen B author Kupfer, Stuart author Malik, Fady I author Meng, Lisa author Wohltman, Amy author Abraham, Theodore author 2023-01-03 BACKGROUND Left ventricular outflow tract (LVOT) obstruction is a major determinant of heart failure symptoms in obstructive hypertrophic cardiomyopathy (oHCM). Aficamten, a next-in-class cardiac myosin inhibitor, may lower gradients and improve symptoms in these patients. OBJECTIVES This study aims to evaluate the safety and efficacy of aficamten in patients with oHCM. METHODS Patients with oHCM and LVOT gradients ≥30 mm Hg at rest or ≥50 mm Hg with Valsalva were randomized 2:1 to receive aficamten (n = 28) or placebo (n = 13) in 2 dose-finding cohorts. Doses were titrated based on gradients and ejection fraction (EF). Safety and changes in gradient, EF, New York Heart Association functional class, and cardiac biomarkers were assessed over a 10-week treatment period and after a 2-week washout. RESULTS From baseline to 10 weeks, aficamten reduced gradients at rest (mean difference: -40 ± 27 mm Hg, and -43 ± 37 mm Hg in Cohorts 1 and 2, P = 0.0003 and P = 0.0004 vs placebo, respectively) and with Valsalva (-36 ± 27 mm Hg and -53 ± 44 mm Hg, P = 0.001 and <0.0001 vs placebo, respectively). There were modest reductions in EF (-6% ± 7.5% and -12% ± 5.9%, P = 0.007 and P < 0.0001 vs placebo, respectively). Symptomatic improvement in ≥1 New York Heart Association functional class was observed in 31% on placebo, and 43% and 64% on aficamten in Cohorts 1 and 2, respectively (nonsignificant). With aficamten, N-terminal pro-B-type natriuretic peptide was reduced (62% relative to placebo, P = 0.0002). There were no treatment interruptions and adverse events were similar between treatment arms. CONCLUSIONS Aficamten resulted in substantial reductions in LVOT gradients with most patients experiencing improvement in biomarkers and symptoms. These results highlight the potential of sarcomere-targeted therapy for treatment of oHCM. J Am Coll Cardiol. 2023 Jan 3;81(1):34-45. 10.1016/j.jacc.2022.10.020 1558-3597 Journal of the American College of Cardiology 36599608 http://hdl.handle.net/20.500.12105/16554 Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy.