Safety and Efficacy of Mavacamten and Aficamten in Patients With Hypertrophic Cardiomyopathy
Background Cardiac myosin inhibitors were recently developed to address the underlying pathophysiology of hypertrophic cardiomyopathy and to improve symptoms and quality of life. In this review, we evaluated the pharmacologic profile and clinical outcomes for mavacamten and aficamten, 2 cardiac myos...
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Wiley
2025-03-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.124.038758 |
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| author | Bryton J. Davis Hailey Volk Olives Nguyen Daniel Kamna Hongya Chen Roberto Barriales‐Villa Pablo Garcia‐Pavia Iacopo Olivotto Anjali T. Owens Caroline J. Coats Theodore P. Abraham Scott D. Solomon Martin S. Maron Ahmad Masri |
| author_facet | Bryton J. Davis Hailey Volk Olives Nguyen Daniel Kamna Hongya Chen Roberto Barriales‐Villa Pablo Garcia‐Pavia Iacopo Olivotto Anjali T. Owens Caroline J. Coats Theodore P. Abraham Scott D. Solomon Martin S. Maron Ahmad Masri |
| author_sort | Bryton J. Davis |
| collection | DOAJ |
| description | Background Cardiac myosin inhibitors were recently developed to address the underlying pathophysiology of hypertrophic cardiomyopathy and to improve symptoms and quality of life. In this review, we evaluated the pharmacologic profile and clinical outcomes for mavacamten and aficamten, 2 cardiac myosin inhibitors investigated in symptomatic hypertrophic cardiomyopathy. Methods and Results Using a systematic search, 10 clinical trials with safety and efficacy data for either drug in obstructive hypertrophic cardiomyopathy (oHCM) and nonobstructive hypertrophic cardiomyopathy were included. Additionally, we included data from regulatory agencies. Both drugs demonstrated substantial benefit in reducing left ventricular outflow tract obstruction (Valsalva left ventricular outflow tract gradients improved by −45 mm Hg or better), symptom burden (placebo‐corrected New York Heart Association class improvement ≥1 of at least 30%), and cardiac biomarkers (geometric mean ratio of 0.2 for N‐terminal pro‐B‐type natriuretic peptide) while improving exercise parameters (improved placebo‐corrected peak oxygen consumption of at least 1.4 to 1.8 mL/kg per minute) in patients with oHCM. Both drugs were generally well‐tolerated, although patients on mavacamten had higher rates of treatment interruption (partly protocol‐driven, 8.7% versus 0.5%, respectively, in oHCM) due to left ventricular ejection fraction reduction, atrial fibrillation (11.5 versus 4.1 per 100 patient‐years, respectively, in oHCM), and heart failure (1.7 versus 0.0 per 100 patient‐years, respectively, in oHCM) compared with aficamten. These comparisons are limited by a shorter exposure duration to aficamten, and longer follow‐up is needed. The data in nonobstructive hypertrophic cardiomyopathy are derived from phase II trials, with phase III trials ongoing. Conclusions Mavacamten and aficamten represent effective medications for the treatment of symptomatic oHCM. |
| format | Article |
| id | doaj-art-43efed20d4bd4bc6b5fe4da6a44e1f69 |
| institution | Kabale University |
| issn | 2047-9980 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
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| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-43efed20d4bd4bc6b5fe4da6a44e1f692025-08-20T03:24:52ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-03-0114610.1161/JAHA.124.038758Safety and Efficacy of Mavacamten and Aficamten in Patients With Hypertrophic CardiomyopathyBryton J. Davis0Hailey Volk1Olives Nguyen2Daniel Kamna3Hongya Chen4Roberto Barriales‐Villa5Pablo Garcia‐Pavia6Iacopo Olivotto7Anjali T. Owens8Caroline J. Coats9Theodore P. Abraham10Scott D. Solomon11Martin S. Maron12Ahmad Masri13Oregon Health & Science University Portland OR USAOregon Health & Science University Portland OR USAOregon Health & Science University Portland OR USAOregon Health & Science University Portland OR USAOregon Health & Science University Portland OR USAComplexo Hospitalario Universitario A Coruña, INIBIC, CIBERCV Coruña SpainHospital Universitario Puerta de Hierro de Majadahonda, IDIPHISA, CIBERCV, and Centro Nacional de Investigaciones Cardiovasculares (CNIC) Madrid SpainMeyer Children’s Hospital IRCCS Florence ItalyPerelman School of Medicine of the University of Pennsylvania Philadelphia PA USAUniversity of Glasgow Glascow UKUniversity of California San Francisco San Francisco CA USAHarvard Medical School and Brigham and Women’s Hospital Boston MA USATufts University and Lahey Hospital & Medical Center Burlington MA USAOregon Health & Science University Portland OR USABackground Cardiac myosin inhibitors were recently developed to address the underlying pathophysiology of hypertrophic cardiomyopathy and to improve symptoms and quality of life. In this review, we evaluated the pharmacologic profile and clinical outcomes for mavacamten and aficamten, 2 cardiac myosin inhibitors investigated in symptomatic hypertrophic cardiomyopathy. Methods and Results Using a systematic search, 10 clinical trials with safety and efficacy data for either drug in obstructive hypertrophic cardiomyopathy (oHCM) and nonobstructive hypertrophic cardiomyopathy were included. Additionally, we included data from regulatory agencies. Both drugs demonstrated substantial benefit in reducing left ventricular outflow tract obstruction (Valsalva left ventricular outflow tract gradients improved by −45 mm Hg or better), symptom burden (placebo‐corrected New York Heart Association class improvement ≥1 of at least 30%), and cardiac biomarkers (geometric mean ratio of 0.2 for N‐terminal pro‐B‐type natriuretic peptide) while improving exercise parameters (improved placebo‐corrected peak oxygen consumption of at least 1.4 to 1.8 mL/kg per minute) in patients with oHCM. Both drugs were generally well‐tolerated, although patients on mavacamten had higher rates of treatment interruption (partly protocol‐driven, 8.7% versus 0.5%, respectively, in oHCM) due to left ventricular ejection fraction reduction, atrial fibrillation (11.5 versus 4.1 per 100 patient‐years, respectively, in oHCM), and heart failure (1.7 versus 0.0 per 100 patient‐years, respectively, in oHCM) compared with aficamten. These comparisons are limited by a shorter exposure duration to aficamten, and longer follow‐up is needed. The data in nonobstructive hypertrophic cardiomyopathy are derived from phase II trials, with phase III trials ongoing. Conclusions Mavacamten and aficamten represent effective medications for the treatment of symptomatic oHCM.https://www.ahajournals.org/doi/10.1161/JAHA.124.038758aficamtencardiac myosin inhibitorsmavacamtensymptomatic hypertrophic cardiomyopathy |
| spellingShingle | Bryton J. Davis Hailey Volk Olives Nguyen Daniel Kamna Hongya Chen Roberto Barriales‐Villa Pablo Garcia‐Pavia Iacopo Olivotto Anjali T. Owens Caroline J. Coats Theodore P. Abraham Scott D. Solomon Martin S. Maron Ahmad Masri Safety and Efficacy of Mavacamten and Aficamten in Patients With Hypertrophic Cardiomyopathy Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease aficamten cardiac myosin inhibitors mavacamten symptomatic hypertrophic cardiomyopathy |
| title | Safety and Efficacy of Mavacamten and Aficamten in Patients With Hypertrophic Cardiomyopathy |
| title_full | Safety and Efficacy of Mavacamten and Aficamten in Patients With Hypertrophic Cardiomyopathy |
| title_fullStr | Safety and Efficacy of Mavacamten and Aficamten in Patients With Hypertrophic Cardiomyopathy |
| title_full_unstemmed | Safety and Efficacy of Mavacamten and Aficamten in Patients With Hypertrophic Cardiomyopathy |
| title_short | Safety and Efficacy of Mavacamten and Aficamten in Patients With Hypertrophic Cardiomyopathy |
| title_sort | safety and efficacy of mavacamten and aficamten in patients with hypertrophic cardiomyopathy |
| topic | aficamten cardiac myosin inhibitors mavacamten symptomatic hypertrophic cardiomyopathy |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.124.038758 |
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