MEK Inhibition Beneficial for Children With Subset of Severe Hypertrophic Cardiomyopathy

MONDAY, Jan. 13, 2025 (HealthDay News) — For children with severe hypertrophic cardiomyopathy caused by gain-of-function RAS/mitogen-activated protein kinase (MAPK) mutations (RASopathy), trametinib reduces mortality and morbidity, according to a study published online Dec. 4 in JACC: Basic to Translational Science.

Cordula M. Wolf, M.D., from the German Heart Center Munich, and colleagues conducted a retrospective analysis of 61 patients younger than 18 years with RASopathy with severe hypertrophic cardiomyopathy. The patients received standard care plus MAPK inhibition (MEKi [trametinib], compassionate use; 30 patients) or standard care (31 patients).

The researchers observed a decrease in mortality and morbidity with improved cardiac status among those receiving trametinib versus standard-of-care treatment. The primary end point (composite of cardiac surgery for outflow tract resection, heart transplantation, or death) occurred in 17 and 87 percent of patients in the MEKi and control groups, respectively (hazard ratio, 0.09). Side effects were manageable and were not life-threatening.

“Taken together, our genotype-specific treatment results establish proof of principle to support the future development of treatment strategies for all RASopathy-associated cardiomyopathy, but potentially also for additional RASopathy manifestations,” the authors write.

Several authors disclosed ties to biopharmaceutical companies, including Novartis, which manufactures trametinib.

Abstract/Full Text

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