Characteristics and Outcomes of Mavacamten Use In 2440 Patients with Obstructive Hypertrophic Cardiomyopathy

Aims To assess real-world characteristics, outcomes, and healthcare utilization associated with commercial mavacamten use in patients with oHCM.

and Results We used the Symphony Dataverse to study patients receiving mavacamten between May 25, 2022 and June 30, 2024. Safety outcomes were prespecified and individual hospital-level claims manually reviewed to categorize cardiovascular hospitalizations. We included 2,440 patients and 18,494 mavacamten dispenses (63% females, median age 66 years [Interquartile range (IQR): 55, 73]). Patients were followed for a median of 3,037.0 days (IQR: 2,808, 3,221) prior to mavacamten initiation, and for 240 days (IQR: 117, 407) on mavacamten. Atrial fibrillation or flutter (AF/AFL) at baseline were present in 536 (22%) of patients, while new-onset AF/AFL requiring therapy occurred in 125 patients (5%) and new heart failure (HF) in 100 patients (4%). During follow-up, 154 patients (6%) received new dispenses of loop diuretics, 102 (4%) oral anticoagulants, 78 (3%) amiodarone, 17 (0.7%) sotalol, and 6 (0.2%) dofetilide. There was a total of 306 patients (13%) with 428 acute care episodes (most common claims were HF (n= 80, 26%), AF (n=74, 24%), and AFL (n= 16, 5%)). Predictors of safety outcomes (new HF, new AF/AFL, ventricular tachycardia, or transient ischemic attack [TIA]/stroke claim) were: age at mavacamten start, obesity, and TIA/stroke history.

With 8 month median follow-up in this study, healthcare utilization for patients on mavacamten appeared substantial. New AF/AFL and HF occurred in 5% and 4%, respectively. Further work is needed to understand longer-term outcomes of mavacamten use in oHCM. Competing Interest Statement Ahmad Masri received research grants from Pfizer, Ionis, Attralus, Cytokinetics and Janssen and consulting fees from Cytokinetics, BMS, BridgeBio, Pfizer, Ionis, Lexicon, Attralus, Alnylam, Haya, Alexion, Akros, Edgewise, Rocket, Lexeo, Prothena, BioMarin, AstraZeneca, and Tenaya. Other coauthors have no disclosures. Funding Statement No funding Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Oregon Health & Science University IRB waived oversight for the insurance claims database research I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability Data are available through Symphony and authors are not allowed to share the data directly.