Aficamten for Symptomatic Nonobstructive Hypertrophic Cardiomyopathy

BACKGROUND: Nonobstructive hypertrophic cardiomyopathy (HCM) is a common condition that is associated with substantial morbidity and no proven medical therapy. Whether treatment with aficamten, a cardiac myosin inhibitor, can benefit patients with this condition is unknown. METHODS: In this phase 3, multinational, double-blind trial, we randomly assigned adults with symptomatic nonobstructive HCM in a 1:1 ratio to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for up to 72 weeks. The dual primary end points were the change from baseline to week 36 in peak oxygen uptake and in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; range, 0 to 100, with higher scores indicating better health status). RESULTS: A total of 258 patients were assigned to receive aficamten and 259 to receive placebo. The mean age of the patients was 55.1 years, and 53.6% were women. At 36 weeks, the change in the KCCQ-CSS was 11.4 points (95% confidence interval [CI], 9.6 to 13.2) in the aficamten group and 8.4 points (95% CI, 6.6 to 10.2) in the placebo group (least-squares mean difference, 3.0 points; 95% CI, 0.5 to 5.5; P = 0.02). The mean change in the peak oxygen uptake at week 36 was 0.64 ml per kilogram of body weight per minute (95% CI, 0.32 to 0.95) in the aficamten group and -0.03 ml per kilogram per minute (95% CI, -0.35 to 0.28) in the placebo group (least-squares mean difference, 0.67 ml per kilogram per minute; 95% CI, 0.22 to 1.11; P = 0.003). Reversible reductions in left ventricular ejection fraction to less than 50% occurred in 27 patients (10.5%) receiving aficamten and in 2 patients (0.8%) receiving placebo. Serious adverse events occurred in 52 patients (20.2%) and 38 patients (14.7%), respectively. CONCLUSIONS: Among patients with symptomatic nonobstructive HCM, treatment with aficamten resulted in a significantly greater change in exercise capacity and patient-reported health status than placebo at 36 weeks. (Funded by Cytokinetics; ACACIA-HCM ClinicalTrials.gov number, NCT06081894.).

Authors

Institutions

Publication Details

Journal
New England Journal of Medicine
Published
2026-08-28
DOI
https://doi.org/10.1056/nejmoa2603021
Citations
1
Primary Topic
Cardiomyopathy and Myosin Studies
Type
article
Field-Weighted Citation Impact
5.87

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
article

Aficamten for Symptomatic Nonobstructive Hypertrophic Cardiomyopathy

Ankit Bhatia, Carolyn Y. Ho, Punag Divanji, Michael Arad et al.
1 citations
New England Journal of Medicine
Cardiomyopathy and Myosin Studies
5.87
article

Aficamten for Symptomatic Nonobstructive Hypertrophic Cardiomyopathy

Ankit Bhatia, Carolyn Y. Ho, Punag Divanji, Michael Arad, Estêvão Lanna Figueiredo, Amy Wohltman, Shu Zhuo, Joel Salazar‐Mendiguchía, Caroline Coats, Jesus Pino, Juan Pablo Costabel, Edileide de Barros Correia, Scott D. Solomon, Mathew S. Maurer, Jorge E. Silva Enciso, Róbert Sepp, Zi Michael Miao, Sheila M. Hegde, CHARLES TEALE, Lubna Choudhury, Roberto Barriales-Villa, S H Poulsen, Daniel L. Jacoby, Stuart Kupfer, Perry M. Elliott, Gregory D. Lewis, Renato D. Lopes, Pablo Garcia-Pavia, Florian Rader, Matthew W. Martinez, Mark V. Sherrid, Xiaoyan Zhao, Nikhil Sikand, Ethan J. Rowin, P. Christian Schulze, Iacopo Olivotto, Anjali T. Owens, John A. Spertus, Sumeet S. Mitter, Martin S. Maron, Fady I. Malik, Michelle Michels, Maria Luisa Peña-Peña, Ahmad Masri, Junbo Ge, Stephen B. Heitner, Brian L. Claggett
article en
1 citations

Abstract

BACKGROUND: Nonobstructive hypertrophic cardiomyopathy (HCM) is a common condition that is associated with substantial morbidity and no proven medical therapy. Whether treatment with aficamten, a cardiac myosin inhibitor, can benefit patients with this condition is unknown. METHODS: In this phase 3, multinational, double-blind trial, we randomly assigned adults with symptomatic nonobstructive HCM in a 1:1 ratio to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for up to 72 weeks. The dual primary end points were the change from baseline to week 36 in peak oxygen uptake and in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; range, 0 to 100, with higher scores indicating better health status). RESULTS: A total of 258 patients were assigned to receive aficamten and 259 to receive placebo. The mean age of the patients was 55.1 years, and 53.6% were women. At 36 weeks, the change in the KCCQ-CSS was 11.4 points (95% confidence interval [CI], 9.6 to 13.2) in the aficamten group and 8.4 points (95% CI, 6.6 to 10.2) in the placebo group (least-squares mean difference, 3.0 points; 95% CI, 0.5 to 5.5; P = 0.02). The mean change in the peak oxygen uptake at week 36 was 0.64 ml per kilogram of body weight per minute (95% CI, 0.32 to 0.95) in the aficamten group and -0.03 ml per kilogram per minute (95% CI, -0.35 to 0.28) in the placebo group (least-squares mean difference, 0.67 ml per kilogram per minute; 95% CI, 0.22 to 1.11; P = 0.003). Reversible reductions in left ventricular ejection fraction to less than 50% occurred in 27 patients (10.5%) receiving aficamten and in 2 patients (0.8%) receiving placebo. Serious adverse events occurred in 52 patients (20.2%) and 38 patients (14.7%), respectively. CONCLUSIONS: Among patients with symptomatic nonobstructive HCM, treatment with aficamten resulted in a significantly greater change in exercise capacity and patient-reported health status than placebo at 36 weeks. (Funded by Cytokinetics; ACACIA-HCM ClinicalTrials.gov number, NCT06081894.).

New England Journal of Medicine
Northwestern University (US), Brigham and Women's Hospital (US), Hartford Hospital (US), St Bartholomew's Hospital (GB), Harvard University (US), Tel Aviv University (IL), Oregon Health & Science University (US), University of Szeged (HU), Columbia University Irving Medical Center (US), Sheba Medical Center (IL), Erasmus MC (NL), Aarhus University Hospital (DK), Morristown Medical Center (US), Spanish National Centre for Cardiovascular Research (ES), Yale University (US), University of California San Diego (US), NYU Langone Health (US), Clinical Research Institute (US), Health Innovations (United States) (US), Queen's Medical Center (US), Hospital Universitario Puerta de Hierro Majadahonda (ES), Lahey Medical Center (US), Meyer Children's Hospital (IT), Centro de Investigación Biomédica en Red (ES), Grupo Santa Casa de Belo Horizonte (BR), Duke Medical Center (US), Zhongshan Hospital (CN), Christ Hospital (US), Saint Luke's Hospital (US), Cytokinetics (United States) (US), Complexo Hospitalario Universitario A Coruña (ES), Cedars-Sinai Smidt Heart Institute (US), Instituto Dante Pazzanese de Cardiologia (BR), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Hospital Universitario Virgen del Rocío (ES), Alaska Heart and Vascular Institute (US), First Affiliated Hospital of Zhengzhou University (CN), Christ Hospital (US), Instituto de Investigación Biomédica de A Coruña (ES), Instituto Cardiovascular de Buenos Aires (AR), Hartford Financial Services (United States), University College London (GB), Mass General Brigham (US), Friedrich Schiller University Jena (DE), University of Glasgow (GB), University of Pennsylvania (US), The University of Texas Southwestern Medical Center (US), Erasmus University Rotterdam (NL)
Cytokinetics
Good health and well-being
Openalex Percentile: Top 3%
Cardiomyopathy and Myosin Studies
5.87
DOISourceOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.