Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/19367
Título
Mavacamten Treatment for Symptomatic Obstructive Hypertrophic Cardiomyopathy: Interim Results From the MAVA-LTE Study, EXPLORER-LTE Cohort.
Autor(es)
Rader, Florian | Oręziak, Artur | Choudhury, Lubna | Saberi, Sara | Fermin, David | Wheeler, Matthew T | Abraham, Theodore P | Garcia-Pavia, Pablo CNIC | Zwas, Donna R | Masri, Ahmad | Owens, Anjali | Hegde, Sheila M | Seidler, Tim | Fox, Shawna | Balaratnam, Ganesh | Sehnert, Amy J | Olivotto, Iacopo
Fecha de publicación
2024-01
Cita
JACC Heart Fail. 2024 Jan;12(1):164-177.
Idioma
Inglés
Tipo de documento
journal article
Resumen
BACKGROUND
Data assessing the long-term safety and efficacy of mavacamten treatment for symptomatic obstructive hypertrophic cardiomyopathy are needed.
OBJECTIVES
The authors sought to evaluate interim results from the EXPLORER-Long Term Extension (LTE) cohort of MAVA-LTE (A Long-Term Safety Extension Study of Mavacamten in Adults Who Have Completed EXPLORER-HCM; NCT03723655).
METHODS
After mavacamten or placebo withdrawal at the end of the parent EXPLORER-HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT03470545), patients could enroll in MAVA-LTE. Patients received mavacamten 5 mg once daily; adjustments were made based on site-read echocardiograms.
RESULTS
Between April 9, 2019, and March 5, 2021, 231 of 244 eligible patients (94.7%) enrolled in MAVA-LTE (mean age: 60 years; 39% female). At data cutoff (August 31, 2021) 217 (93.9%) remained on treatment (median time in study: 62.3 weeks; range: 0.3-123.9 weeks). At 48 weeks, patients showed improvements in left ventricular outflow tract (LVOT) gradients (mean change ± SD from baseline: resting: -35.6 ± 32.6 mm Hg; Valsalva: -45.3 ± 35.9 mm Hg), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (median: -480 ng/L; Q1-Q3: -1,104 to -179 ng/L), and NYHA functional class (67.5% improved by ≥1 class). LVOT gradients and NT-proBNP reductions were sustained through 84 weeks in patients who reached this timepoint. Over 315 patient-years of exposure, 8 patients experienced an adverse event of cardiac failure, and 21 patients had an adverse event of atrial fibrillation, including 11 with no prior history of atrial fibrillation. Twelve patients (5.2%) developed transient reductions in site-read echocardiogram left ventricular ejection fraction of <50%, resulting in temporary treatment interruption; all recovered. Ten patients discontinued treatment due to treatment-emergent adverse events.
CONCLUSIONS
Mavacamten treatment showed clinically important and durable improvements in LVOT gradients, NT-proBNP levels, and NYHA functional class, consistent with EXPLORER-HCM. Mavacamten treatment was well tolerated over a median 62-week follow-up.
MESH
Atrial Fibrillation | Cardiomyopathy, Hypertrophic | Heart Failure | Adult | Female | Humans | Male | Middle Aged | Stroke Volume | Ventricular Function, Left
Descripción
This study was funded by Bristol Myers Squibb, Princeton, New Jersey, USA. Bristol Myers Squibb’s policy on data sharing is available
online at https://www.bms.com/researchers-and-partners/clinicaltrials-and-research/disclosure-commitment.html. Dr Rader has
received consulting fees from Medtronic, Bristol Myers Squibb, and
ReCor Medical. Dr Ore˛ziak has received personal fees from Bristol
Myers Squibb. Dr Saberi has received personal fees from Bristol Myers
Squibb. Dr Fermin has received consulting fees from Alnylam, Eidos
Therapeutics, Bristol Myers Squibb, and Pfizer. Dr Wheeler has
received personal fees and research support from Bristol Myers
Squibb. Dr Garcia-Pavia has received consulting and speaking fees
from Bristol Myers Squibb, Rocket Pharmaceuticals, and Cytokinetics
and speaking fees from Bristol Myers Squibb and Cytokinetics. Dr
Zwas has received personal fees from Bristol Myers Squibb. Dr Masri
has received grants from Akcea, Pfizer, and Ultromics and consulting
fees from Alnylam, Cytokinetics, Eidos Therapeutics, Ionis, and
Pfizer. Dr Owens has received consulting fees from Bristol Myers
Squibb, Cytokinetics, and Pfizer. Dr Hegde serves on the faculty of the
Cardiovascular Imaging Core Laboratory at Brigham and Women’s
Hospital, and her institution has received payments for her consulting work from Bristol Myers Squibb. Dr Seidler has received
consulting fees or honoraria for lectures from Bristol Myers Squibb
and Cytokinetics. Dr Balaratnam and Dr Sehnert are employees of
Bristol Myers Squibb and own stock of Bristol Myers Squibb. Shawna
Fox is an employee of IQVIA, a partner providing statistics services to
Bristol Myers Squibb. Dr Olivotto has received grants from Amicus,
Boston Scientific, Bristol Myers Squibb, Cytokinetics, Genzyme, and
Menarini International and consulting fees from Amicus, Cytokinetics, Genzyme, MS Pharma, Rocket Pharmaceuticals, and Tenaya
Therapeutics.
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