Mavacamten treatment led to LVOT gradient reduction in 93% of patients, with slow/intermediate metabolizers showing significantly lower residual obstruction than rapid metabolizers (p=0.029).
Does CYP2C19 metabolic profile impact the clinical response to mavacamten in patients with obstructive hypertrophic cardiomyopathy?
CYP2C19 metabolic profiles significantly impact the degree of residual LVOT obstruction in patients with obstructive hypertrophic cardiomyopathy treated with mavacamten.
Absolute Event Rate: 0% vs 0%
Abstract Background Mavacamten is currently used as early access drug in obstructive hypertrophic cardiomyopathy and its exposure is affected by CYP2C19 polymorphisms. Genotyping of CYP2C19 is then recommended before treatment initiation. Aims The objective of this study was to describe CYP2C19 genetic polymorphisms observed in patients treated with mavacamten and evaluate their impact on clinical outcomes. Methods A prospective study was performed during 2024 in the Cardiology Unit of our hospital (France). CYP2C19*2, *3 and *17 alleles were determined using LAMP assays on LightCycler®480. Patients were categorized as poor, intermediate (IM), extensive (EM), rapid (RM) or ultra-rapid (UM) metabolizers. Impact of CYP2C19 metabolic profiles on clinical outcomes at the end of the titration period were studied using Kruskal-Wallis and Dunn tests. Results CYP2C19 genotyping was performed in 101 patients. Allelic frequencies of 40% and 14% were described for CYP2C19*17 and CYP2C19*2, respectively. Titration period was achieved in 56 patients (33/23 females/males), with a median age of 66 years (20-88). We identified 14 (25%) IM, 13 (23%) RM, 1 (2%) UM and 28 (50%) EM patients, with initial dose of 5mg/d for all patients. Titration period delay, dose at the end of titration and Left Ventricular Ejection Fraction (LVEF) were not different between metabolic profiles. Good response to therapy (residual Left Ventricular Outflow Tract (LVOT) gradient 30 mmHg) was achieved in 52 of 56 titrated patients. However, a significant difference in residual LVOT obstruction after titration was observed between these profiles (p=0.033), especially between RM and IM (residual gradient = 19.2 vs 11.6 mmHg; p=0.029). Conclusion Although regression of LV obstruction was achieved in most patients, our results suggest that the CYP2C19 genotyping profile may impact the degree of response to therapy by mavacamten. These results need to be confirmed in a larger population including extreme metabolizers.
Lucas et al. (Sat,) reported a other. Mavacamten treatment led to LVOT gradient reduction in 93% of patients, with slow/intermediate metabolizers showing significantly lower residual obstruction than rapid metabolizers (p=0.029).
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