Mavacamten linked to improvements in cardiac biomarkers in HFpEF patients

Mavacamten, a drug originally developed to treat hypertrophic cardiomyopathy, has shown signs of reducing cardiac stress in patients with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) affects almost half of all patients with heart failure. It is characterized by the inability of the heart to fill properly with blood despite normal pumping force.

Patients with a left ventricular ejection fraction (LVEF) of 60% or greater account for 43% to 46% of patients with HFpEF. These individuals often have a reduced response to standard heart failure treatments, limiting effective treatment options.

Mavacamten is a cardiac myosin inhibitor already approved for the treatment of hypertrophic cardiomyopathy (HCM) and has demonstrated the ability to lower specific biomarkers in non-obstructive cases of HCM. Researchers hypothesized that similar mechanisms could benefit patients with HFpEF by improving heart muscle relaxation and reducing stress on the heart.

In a brief report titled “Cardiac Myosin Inhibition in Heart Failure With Normal and Supranormal Ejection Fraction: Primary Results of the EMBARK-HFpEF Trial,” published in JAMA Cardiologythe multicenter team led by the Feinberg School of Medicine at Northwestern University details its preliminary results.

The team reports that 26 weeks of treatment with mavacamten was associated with statistically significant reductions in cardiac biomarkers indicating cardiac stress and damage in patients with HFpEF and LVEF of 60% or greater.

EMBARK-HFpEF is a single-arm, open-label, Phase IIa study conducted at 20 sites. It included 30 patients with symptomatic HFpEF and an LVEF of 60% or more. Patients were treated with mavacamten for 26 weeks, starting with a daily dose of 2.5 mg, with the option to increase up to 5 mg based on assessment of their cardiac function at week 14.

The study found that mavacamten treatment was associated with significant reductions in cardiac biomarkers indicating cardiac stress. Levels of N-terminal pro-B-type natriuretic peptide decreased by an average of 26%.

High-sensitivity troponin T levels dropped by 13% and high-sensitivity troponin I levels saw a 20% reduction. These changes suggest reduced stress and injury to the heart wall during treatment. Eight weeks after the end of treatment, these biomarkers tend to return to baseline levels, indicating a potential direct effect of mavacamten.

Using the New York Heart Association classification, which measures the severity of heart failure symptoms, 41.7% of patients improved by at least one class at the end of the treatment period.

The safety profile of mavacamten was generally favorable. While three patients experienced a decrease in LVEF requiring temporary discontinuation of the drug, all recovered cardiac function and treatment was resumed without major complications. No serious adverse events or deaths related to mavacamten were reported during the study period.

The results should be interpreted with caution. The research team emphasized that further randomized controlled trials are needed to confirm the effectiveness and safety of mavacamten in this patient population.

A new randomized phase II clinical trial, the AURORA-HFpEF trial, is underway to further evaluate the impact of mavacamten on HFpEF with preserved ejection fraction. Researchers hope these upcoming studies will provide clearer evidence regarding the drug’s potential role in managing this difficult form of heart failure.

© 2024 Science X Network