1. Efficacy and Safety of Aficamten in Symptomatic Nonobstructive Hypertrophic Cardiomyopathy: Results From the REDWOOD-HCM Trial, Cohort 4.
- Author
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MASRI, AHMAD, SHERRID, MARK V., ABRAHAM, THEODORE P., CHOUDHURY, LUBNA, GARCIA-PAVIA, PABLO, KRAMER, CHRISTOPHER M., BARRIALES-VILLA, ROBERTO, OWENS, ANJALI T., RADER, FLORIAN, NAGUEH, SHERIF F., OLIVOTTO, IACOPO, SABERI, SARA, TOWER-RADER, ALBREE, WONG, TIMOTHY C., COATS, CAROLINE J., WATKINS, HUGH, FIFER, MICHAEL A., SOLOMON, SCOTT D., HEITNER, STEPHEN B., and JACOBY, DANIEL L.
- Abstract
• Doses of aficamten were assessed for nonobstructive hypertrophic cardiomyopathy. • Treatment with aficamten was well tolerated. • Improvements in symptoms and angina were observed. • Changes in clinical status paralleled improvements in cardiac biomarkers. • Our findings support a larger pivotal phase 3 trial (ACACIA-HCM, NCT06081894). This open-label phase 2 trial evaluated the safety and efficacy of aficamten in patients with nonobstructive hypertrophic cardiomyopathy (nHCM). Patients with symptomatic nHCM (left ventricular outflow tract obstruction gradient ≤ 30 mmHg, left ventricular ejection fraction [LVEF] ≥ 60%, N-terminal pro-B-type natriuretic peptide [NT-proBNP] > 300 pg/mL) received aficamten 5–15 mg once daily (doses adjusted according to echocardiographic LVEF) for 10 weeks. We enrolled 41 patients (mean ± SD age 56 ± 16 years; 59% female). At Week 10, 22 (55%) patients experienced an improvement of ≥ 1 New York Heart Association class; 11 (29%) became asymptomatic. Clinically relevant improvements in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores occurred in 22 (55%) patients. Symptom relief was paralleled by reductions in NT-proBNP levels (56%; P < 0.001) and high-sensitivity cardiac troponin I (22%; P < 0.005). Modest reductions in LVEF (mean ± SD) of −5.4% ± 10 to 64.6% ± 9.1 were observed. Three (8%) patients had asymptomatic reduction in LVEF < 50% (range: 41%–48%), all returning to normal after 2 weeks of washout. One patient with prior history of aborted sudden cardiac death experienced a fatal arrhythmia during the study. Aficamten administration for symptomatic nHCM was generally safe and was associated with improvements in heart failure symptoms and cardiac biomarkers. ClinicalTrials.gov Identifier: NCT04219826 Summary of results from REDWOOD-HCM Cohort 4: Data in panel C are presented as mean and 95% CI; data in panel D are presented as mean and SD. Horizontal dotted lines represent the thresholds at which IP was down-titrated to the previous dosage (yellow) or was discontinued (red). CI, confidence interval; HCM, hypertrophic cardiomyopathy; hs-cTnI, high-sensitivity cardiac troponin T and I; KCCQ-CSS, Kansas City Cardiomyopathy Questionnaire clinical summary score; LVEF, left ventricular ejection fraction; LVOT, left ventricular outflow gradient; NT-proBNP, N-terminal pro B-type natriuretic peptide; NYHA, New York Heart Association; SD, standard deviation. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2024
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