Real-World Risks of Mavacamten Use for Obstructive Hypertrophic Cardiomyopathy

Many adults with obstructive hypertrophic cardiomyopathy (oHCM) taking mavacamten experienced new atrial fibrillation or flutter, new-onset heart failure, and frequent acute care use within months of starting treatment, according to real-world findings published in the Journal of the American Heart Association.¹

“Despite almost 3 years since the approval of mavacamten in the United States, there is a paucity of large‐scale evaluations of patient outcomes,” researchers said.^2,1 “The single‐center studies are informative, but they suffer from small sample size and selection and reporting biases.”

The study included national claims data from 2440 US patients and more than 18,000 mavacamten dispenses. The cohort was 63% female with a median (IQR) age of 66 (55-73) years; most patients were from the South (37%) and Northeast (24%). Patients had more than 7 years of data available before starting mavacamten and were followed for a median of 240 days or 8 months on mavacamten.

During follow-up:

• 5.1% of participants developed new atrial fibrillation or flutter
• 4.1% developed new heart failure
• 12.5% had at least 1 acute care episode, most often for heart failure or atrial arrhythmias

Treatment Discontinuation and Adjustments

The most common dosage of mavacamten was 5 mg, with a median of 6 prescription fills during the study period. During the 8-month follow-up period, nearly half of all patients required dose adjustments, the majority of which were downtitrations, reflecting the need for ongoing monitoring and individualized dosing. Chest pain or angina occurred in 191 patients, while new stress-induced cardiomyopathy was rare, occurring in only 2 patients.

About 17% of patients stopped mavacamten for 90 days or more after their first acute care episode, suggesting potential tolerability, safety, or REMS-related monitoring challenges. Another 3.5% took a break from treatment for more than 90 days after an initial episode but started again for at least 1 prescription fill.

“These longer‐term discontinuations likely signal permanent discontinuation of mavacamten,” the authors said. “Although temporary hold of mavacamten typically lasts 4 to 6 weeks for LVEF <50%, we felt that it is difficult to discern these short‐term temporary holds.”

It was also common for patients to be prescribed new medications, including loop diuretics (6%), oral anticoagulants (4%), and antiarrhythmics like amiodarone (3%), sotalol (0.7%), and dofetilide (0.2%).

Heart Failure, Atrial Fibrillation Drive Acute Care Episodes

From the cohort, 306 patients with oHCM required acute care with 428 total episodes. The most common claims were heart failure (n = 80) and atrial fibrillation (n = 74), with 16 diagnoses of flutter. The median time to event was about 3 months for atrial fibrillation and 3.5 months for heart failure.

AF and flutter are common with HCM, with prevalence as high as 20% to 30% and a typical annual incidence of 2%.³ In this study, the annual incidence of new AF and flutter were 7.6% in the first year—more than triple the typical rate.¹ Although causality remains unclear, the investigators highlighted a potential mechanism for future research.

“It remains unclear if there is an association between mavacamten, or cardiac myosin inhibition, and AF/AFL,” they said. “However, there are some clues that the incidence of new‐onset AF/AFL might be higher than expected, especially with how effective mavacamten is in lowering left ventricular outflow tract gradients and improving left atrial volume.”

References

1. Mahana I, Mejia AT, Elman MR, et al. Characteristics and outcomes of mavacamten use in 2440 patients with obstructive hypertrophic cardiomyopathy. J Am Heart Assoc. 2025;14(21):e042488. doi:10.1161/JAHA.125.042488
2. AJMC Staff. What we’re reading: mavacamten approved for HCM; Oklahoma abortion bans; baby formula whistleblower. AJMC^®. April 29, 2022. Accessed November 25, 2025. https://www.ajmc.com/view/what-we-re-reading-mavacamten-approved-for-hcm-oklahoma-abortion-bans-baby-formula-whistleblower
3. Weissler-Snir A, Saberi S, Wong TC, et al. Atrial fibrillation in hypertrophic cardiomyopathy. JACC Adv. 2024;3(9):101210. doi:10.1016/j.jacadv.2024.101210