Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy.
J Am Coll Cardiol
; 81(1): 34-45, 2023 01 03.
Article
em En
| MEDLINE
| ID: mdl-36599608
ABSTRACT
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 21 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cardiomiopatia Hipertrófica
/
Obstrução do Fluxo Ventricular Externo
/
Insuficiência Cardíaca
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Am Coll Cardiol
Ano de publicação:
2023
Tipo de documento:
Article