Real-world data on 2,440 mavacamten users show new atrial fibrillation in 5% and heart failure in 4%

Obstructive hypertrophic cardiomyopathy (oHCM) accounts for about two-thirds of HCM cases. Hypercontractility drives dynamic outflow obstruction, which can cause exertional symptoms and eventually heart failure. Mavacamten, a cardiac myosin inhibitor, was FDA-approved in 2022 as second-line therapy after β-blockers, non-dihydropyridine calcium channel blockers and disopyramide. In the EXPLORER-HCM and VALOR-HCM trials, some patients developed a reduced ejection fraction (<50%), which led to a restrictive risk mitigation program (REMS). Real-world reports so far come from small studies at experienced centers, and atrial fibrillation/flutter (AF/AFL) is increasingly noticed in patients on mavacamten.

The investigators used the Symphony Health Integrated Dataverse, a national claims database covering commercial, cash, Medicare and Medicaid payers. They included patients with at least one mavacamten claim between May 25, 2022 and June 30, 2024. Claims from 2015 onward established baseline comorbidities and medications. Treatment episodes were consecutive fills with gaps of 35 days or less, and discontinuation meant 90 or more days without mavacamten before the end of recorded activity. Safety outcomes were prespecified. Two composite outcomes were defined: (1) new heart failure, AF, AFL, ventricular tachycardia or TIA/stroke; and (2) the same events plus new loop diuretic use as a surrogate for volume overload. Acute care episodes were manually reviewed. Cox models assessed predictors of the composites.

The cohort had 2,440 patients and 18,494 mavacamten dispenses. Median age was 66 years and 62.7% were women. Baseline comorbidities were common: hypertension 75.5%, coronary artery disease 39.7%, obstructive sleep apnea 33%, diabetes 26.4% and obesity 9.9%. At baseline, 54% were taking β-blockers, 28% calcium channel blockers and 5% disopyramide. Patients had a median of about 3,037 days of data before starting mavacamten and 240 days (IQR 117–407) after.

During follow-up, new AF/AFL requiring therapy occurred in 125 patients (5%) and new heart failure in 100 (4%). New dispenses included loop diuretics in 6%, oral anticoagulants in 4%, amiodarone in 3%, sotalol in 0.7% and dofetilide in 0.2%. In total, 306 patients (13%) had 428 acute care episodes. The most common claims were heart failure (26%), AF (24%) and AFL (5%). Age at mavacamten start, obesity, prior TIA/stroke and residence in the West versus the South predicted the composite outcomes.

The authors conclude that these figures give clinicians realistic estimates for counseling patients and a basis for comparing mavacamten with other oHCM drugs. They also stress that long-term incidence of AF/AFL, heart failure and other outcomes remains uncertain.

The main caveats are the short median follow-up of about 8 months and the absence of an untreated or comparator group. Because baseline AF/AFL prevalence is high in HCM, the new-onset rates cannot be attributed to the drug. Claims data also lack echocardiographic measures such as LVEF and gradients, so efficacy and dose-related LVEF decline cannot be assessed here.