{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:41:23Z","timestamp":1792014083174,"version":"4.4.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017686","name":"Fujian Provincial Health Technology Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017686","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mavacamten, a cardiac myosin inhibitor for symptomatic obstructive hypertrophic cardiomyopathy (HOCM), carries a risk of excessive negative inotropy. Because mavacamten is metabolized primarily by the cytochrome P450 (CYP) enzymes CYP2C19 and CYP3A4, concomitant CYP inhibitors may increase mavacamten exposure. We evaluated real-world heart failure-related reporting patterns associated with concomitant CYP inhibitor exposure in mavacamten-treated HOCM reports.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective pharmacovigilance study using the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from the second quarter (Q2) of 2022 to the fourth quarter (Q4) of 2025. Mavacamten-treated HOCM reports were screened for concomitant exposure to ten prespecified CYP2C19 and\/or CYP3A4 inhibitors. Heart failure-related signals were defined using seven Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms. Severe outcomes were extracted from FAERS outcome fields; hospitalization was defined as initial or prolonged hospitalization, and death as a reported fatal outcome. Analyses included the reporting odds ratio (ROR), additive signal amplification index (S), time-to-onset modeling, multivariable logistic regression, and 1:4 propensity score matching (PSM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 3,570 mavacamten-treated HOCM reports, 347 involved concomitant CYP inhibitor exposure. Combination therapy showed an elevated heart failure-related reporting signal (ROR = 25.08; 95% confidence interval [CI], 18.63\u201333.76) and potential reporting signal amplification (S = 2.71). Agent-specific reporting signals were heterogeneous across prespecified inhibitors. Weibull modeling showed an early-failure pattern (\u03b2 = 0.88; median onset, 80 days). Compared with mavacamten monotherapy, combination therapy had higher reported proportions of hospitalization (28.5% vs. 13.5%) and death (5.5% vs. 2.3%). Concomitant CYP inhibitor exposure showed higher heart failure-related reporting odds after multivariable adjustment (adjusted odds ratio [aOR], 2.52; 95% CI, 1.10\u20135.62) and in the PSM sensitivity cohort (aOR, 1.99;\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Concomitant use of mavacamten with selected CYP inhibitors was associated with increased heart failure-related reporting in FAERS. Careful medication reconciliation and clinical vigilance are warranted, while recognizing that spontaneous reporting data cannot establish causality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1846852","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:35:10Z","timestamp":1784612110000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Heart failure reporting signals associated with concomitant mavacamten and CYP inhibitors in obstructive hypertrophic cardiomyopathy: a real-world pharmacovigilance study with propensity score matching"],"prefix":"10.3389","volume":"17","author":[{"given":"Daqiu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Cardiology, Nanping First Hospital Affiliated to Fujian Medical University","place":["Nanping, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Nanping First Hospital Affiliated to Fujian Medical University","place":["Nanping, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanxiong","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Nanping First Hospital Affiliated to Fujian Medical University","place":["Nanping, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchao","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Nanping First Hospital Affiliated to Fujian Medical University","place":["Nanping, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomai","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Nanping First Hospital Affiliated to Fujian Medical University","place":["Nanping, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanghua","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Nanping First Hospital Affiliated to Fujian Medical University","place":["Nanping, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunxiang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Nanping First Hospital Affiliated to Fujian Medical University","place":["Nanping, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e003215","DOI":"10.1136\/openhrt-2025-003215","article-title":"Efficacy of cardiac myosin inhibitors mavacamten and aficamten in hypertrophic cardiomyopathy: a systematic review and meta-analysis of randomised controlled trials","volume":"12","author":"Aman","year":"2025","journal-title":"Open Heart"},{"key":"B2","doi-asserted-by":"publisher","first-page":"109","DOI":"10.2165\/00002018-199920020-00002","article-title":"The medical dictionary for regulatory activities (MedDRA)","volume":"20","author":"Brown","year":"1999","journal-title":"Drug Safety"},{"key":"B3","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1002\/cpt.3005","article-title":"Physiologically based pharmacokinetic modeling and simulation of mavacamten exposure with drug-drug interactions from CYP inducers and inhibitors by CYP2C19 phenotype","volume":"114","author":"Chiang","year":"2023","journal-title":"Clin. Pharmacology Therapeutics"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1323057","DOI":"10.3389\/fdsfr.2023.1323057","article-title":"Conducting and interpreting disproportionality analyses derived from spontaneous reporting systems","volume":"3","author":"Cutroneo","year":"2023","journal-title":"Front. Drug Safety Regulation"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e017185","DOI":"10.1161\/circimaging.124.017185","article-title":"Serial changes in ventricular strain in symptomatic obstructive hypertrophic cardiomyopathy treated with mavacamten: insights from the VALOR-HCM trial","volume":"17","author":"Desai","year":"2024","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e012441","DOI":"10.1161\/CIRCHEARTFAILURE.124.012441","article-title":"Mavacamten: Real-World experience from 22 months of the risk evaluation and mitigation strategy (REMS) Program","volume":"18","author":"Desai","year":"2025","journal-title":"Circ. Heart Failure"},{"key":"B7","doi-asserted-by":"publisher","first-page":"3492","DOI":"10.1093\/eurheartj\/ehad429","article-title":"The European medicines agency assessment of mavacamten as treatment of symptomatic obstructive hypertrophic cardiomyopathy in adult patients","volume":"44","author":"DeVries","year":"2023","journal-title":"Eur. Heart Journal"},{"key":"B8","volume-title":"FDA Adverse Event Reporting System (FAERS) Public Dashboard","year":"2023"},{"key":"B9","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/j.jchf.2024.11.011","article-title":"Aficamten vs metoprolol for obstructive hypertrophic cardiomyopathy: MAPLE-HCM rationale, Study design, and baseline characteristics","volume":"13","author":"Garcia-Pavia","year":"2025","journal-title":"JACC. Heart Failure"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2518","DOI":"10.1016\/j.jacc.2021.09.1381","article-title":"Effect of mavacamten on echocardiographic features in symptomatic patients with obstructive hypertrophic cardiomyopathy","volume":"78","author":"Hegde","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/1742-5573-3-5","article-title":"Measuring additive interaction using odds ratios","volume":"3","author":"Kalilani","year":"2006","journal-title":"Epidemiologic Perspectives & Innovations EP+I"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e007955","DOI":"10.1161\/CIRCEP.121.007955","article-title":"Drug interactions affecting antiarrhythmic drug use","volume":"15","author":"Mar","year":"2022","journal-title":"Circulation. Arrhythmia Electrophysiology"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1002\/jcph.70072","article-title":"Exposure-Response modeling and simulation to identify optimal mavacamten posology when coadministered with CYP3A4 and CYP2C19 inhibitors in patients with obstructive HCM","volume":"65","author":"Merali","year":"2025","journal-title":"J. Clinical Pharmacology"},{"key":"B14","doi-asserted-by":"publisher","first-page":"eabo7622","DOI":"10.1126\/sciadv.abo7622","article-title":"Mavacamten, a precision medicine for hypertrophic cardiomyopathy: from a motor protein to patients","volume":"9","author":"Nag","year":"2023","journal-title":"Sci. Advances"},{"key":"B15","doi-asserted-by":"publisher","first-page":"4","DOI":"10.3390\/ph14010004","article-title":"Improved detection criteria for detecting drug-drug interaction signals using the proportional reporting ratio","volume":"14","author":"Noguchi","year":"2020","journal-title":"Pharm. (Basel)"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1124\/dmd.111.041293","article-title":"The proton pump inhibitor, omeprazole, but not lansoprazole or pantoprazole, is a metabolism-dependent inhibitor of CYP2C19: implications for coadministration with clopidogrel","volume":"39","author":"Ogilvie","year":"2011","journal-title":"Drug Metabolism Disposition The Biological Fate Chemicals"},{"key":"B17","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/j.jchf.2023.04.018","article-title":"Cardiac myosin inhibitors for managing obstructive hypertrophic cardiomyopathy: JACC: heart failure state-of-the-art review. JACC","volume":"11","author":"Ostrominski","year":"2023","journal-title":"Heart Failure"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1002\/cpdd.1332","article-title":"Effects of omeprazole and verapamil on the pharmacokinetics, safety, and tolerability of mavacamten: two drug-drug interaction studies in healthy participants","volume":"12","author":"Perera","year":"2023","journal-title":"Clin. Pharmacology Drug Development"},{"key":"B19","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1177\/2047487319828474","article-title":"Risk factors for atrial fibrillation in hypertrophic cardiomyopathy","volume":"28","author":"Philipson","year":"2021","journal-title":"Eur. Journal Preventive Cardiology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1002\/cpt.3701","article-title":"FDA adverse event reporting system (FAERS) essentials: a guide to understanding, applying, and interpreting adverse event data reported to FAERS","volume":"118","author":"Potter","year":"2025","journal-title":"Clin. Pharmacology Therapeutics"},{"key":"B21","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.pcad.2026.01.004","article-title":"The new life of myectomy in the era of myosin inhibitors","volume":"95","author":"Quarta","year":"2026","journal-title":"Prog. Cardiovascular Diseases"},{"key":"B22","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.jchf.2023.09.028","article-title":"Mavacamten treatment for symptomatic obstructive hypertrophic cardiomyopathy: interim results from the MAVA-LTE study, EXPLORER-LTE cohort. JACC","volume":"12","author":"Rader","year":"2024","journal-title":"Heart Failure"},{"key":"B23","doi-asserted-by":"publisher","first-page":"91","DOI":"10.17925\/HI.2022.16.2.91","article-title":"Mavacamten: a first-in-class oral modulator of Cardiac Myosin for the treatment of symptomatic hypertrophic obstructive cardiomyopathy","volume":"16","author":"Reyes","year":"2022","journal-title":"Heart International"},{"key":"B24","doi-asserted-by":"publisher","first-page":"8181","DOI":"10.3390\/jcm14228181","article-title":"Long-Term real-world outcomes of mavacamten in symptomatic obstructive hypertrophic cardiomyopathy up to 108 weeks","volume":"14","author":"Reza","year":"2025","journal-title":"J. Clinical Medicine"},{"key":"B25","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1016\/j.hrthm.2024.11.041","article-title":"Managing drug-drug interactions with mavacamten: a focus on combined use of antiarrhythmic drugs and anticoagulants","volume":"22","author":"Ricci","year":"2025","journal-title":"Heart Rhythm."},{"key":"B26","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1002\/pds.1001","article-title":"The reporting odds ratio and its advantages over the proportional reporting ratio","volume":"13","author":"Rothman","year":"2004","journal-title":"Pharmacoepidemiol. Drug Safety"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1007\/s00228-020-02909-w","article-title":"Borrowing external information to improve Bayesian confidence propagation neural network","volume":"76","author":"Tada","year":"2020","journal-title":"Eur. Journal Clinical Pharmacology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1016\/j.jchf.2023.07.030","article-title":"Mavacamten for obstructive hypertrophic cardiomyopathy with or without hypertension: Post-Hoc analysis of the EXPLORER-HCM trial","volume":"12","author":"Wang","year":"2024","journal-title":"JACC. Heart Failure"},{"key":"B29","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1007\/s40256-024-00672-2","article-title":"A real-world pharmacovigilance Study of FDA Adverse Event Reporting System (FAERS) for mavacamten","volume":"24","author":"Yukselen","year":"2024","journal-title":"Am. Journal Cardiovascular Drugs Drugs, Devices, Other Interventions"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1846852\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:35:11Z","timestamp":1784612111000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1846852\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":29,"alternative-id":["10.3389\/fphar.2026.1846852"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1846852","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]},"article-number":"1846852"}}