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Mavacamten maintenance dose determination: insights into individualised therapy for hypertrophic cardiomyopathy
Smita Scholtz1, Cédric Coppée2, Kawa Mohemed2
1Clinic for General and Interventional Cardiology/Angiology, Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany sscholtz@hdz-nrw.de.
Insights
Mavacamten effectively treats obstructive hypertrophic cardiomyopathy (oHCM) by reducing left ventricular outflow tract (LVOT) obstruction and improving symptoms. Individualized dosing based on CYP2C19 status and echocardiographic response ensures safety and optimizes patient outcomes.
Area of Science:
- Cardiology
- Pharmacogenomics
- Clinical Therapeutics
Background:
- Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by hypercontractility and left ventricular outflow tract (LVOT) obstruction.
- Mavacamten is the first approved myosin inhibitor targeting these mechanisms.
Purpose of the Study:
- To evaluate the real-world effectiveness and safety of mavacamten in patients with symptomatic oHCM.
- To assess the process of determining maintenance mavacamten doses for optimized individual therapy.
Main Methods:
- Analysis of 36 symptomatic oHCM patients completing mavacamten initiation.
- Assessment of echocardiographic parameters (LVOT gradient, LVEF) and biomarkers (NT-proBNP, troponin I) at baseline and 3 months.
- Evaluation of clinical status using NYHA class and KCCQ scores, with CYP2C19 genetic testing for metabolic status.
Main Results:
- Significant reduction in resting and provoked LVOT gradients (p<0.001).
- Improved cardiac biomarkers (NT-proBNP, troponin I) and diastolic function.
- Significant clinical improvement in NYHA class and KCCQ scores, with mild LVEF decrease (p=0.0004).
- Over 50% of patients required dose adjustments to reach maintenance levels within 14 weeks.
Conclusions:
- Mavacamten initiation therapy is safe and effective for symptomatic oHCM.
- CYP2C19 metabolic status guides initial dosing, while echocardiographic response informs individual dose adjustments for safety.
- Real-world data supports personalized mavacamten therapy for oHCM management.
Aims:
Mavacamten, the first approved myosin inhibitor for symptomatic obstructive hypertrophic cardiomyopathy (oHCM), addresses hypercontractility and left ventricular outflow tract (LVOT) obstruction. This study evaluates real-world experience with mavacamten, focusing on maintenance dose determination to optimise individual therapy and enhance patient safety.
Methods:
36 patients with symptomatic oHCM who completed the initiating phase of mavacamten therapy were analysed. CYP2C19 genetic testing determined metabolic status prior to treatment. Echocardiographic measurements (eg, LVOT gradient, left atrial volume index, left ventricular ejection fraction (LVEF) and E/E') and biomarkers (high-sensitivity troponin I, N-terminal pro B-type natriuretic peptide (NT-proBNP)) were assessed at baseline and after 3 months. Clinical status was evaluated using New York Heart Association (NYHA) class and Kansas City Cardiomyopathy Questionnaire (KCCQ) score.
Results:
The mean age of patients was 60.6±12.1, and all had normal CYP2C19 metabolic status. LVEF was 68% (IQR 8) at baseline and decreased mildly to 60.5% (IQR 7.25; p=0.0004) without cases dropping below 50%. Resting and provoked LVOT gradients decreased from 65 mm Hg (IQR 43.75) and 105 mm Hg (IQR 36.25) to 12 mm Hg (IQR 15.5; p<0.001) and 52.5 mm Hg (IQR 46.5; p<0.001), respectively. NT-proBNP and high-sensitivity troponin I decreased significantly from 1040 ng/mL (IQR 1255) to 285 ng/mL (IQR 483; p=0.0005) and from 11 ng/mL (IQR 15.5) to 10 ng/mL (IQR 5; p<0.0001). Diastolic function improved slightly; and clinically, patients improved significantly, with improvement in NYHA class and increase in KCCQ score. Mean time to reach maintenance dose was 14 weeks, with the necessity of dose adjustments in more than 50% of cases.
Conclusion:
Mavacamten therapy is safe and effective in the initiating phase. Determination of starting and maximum dose is based on CYP2C19 metabolic status, while individualised dose adjustments are guided by echocardiographic response to optimise patient safety.
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