Mixed Results With Metoprolol in Obstructive Hypertrophic Cardiomyopathy

NEW YORK (Reuters Health) – In patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM), treatment with metoprolol led to significant reductions in left ventricular outflow tract (LVOT) gradient at rest and during and after exercise in two-thirds of patients, with related improvements in symptoms and quality of life in the randomized, placebo-controlled TEMPO trial.

Metoprolol also led to minor improvement in the Kansas City Cardiomyopathy Questionnaire Overall Summary score (KCCQ-OS) as compared to placebo, but did not improve exercise capacity, peak oxygen consumption (pVO2), NT-proBNP or measures of diastolic function.

These findings “support the guideline recommendations that beta-blockers should be the first drugs of choice in patients with obstructive HCM who develop symptoms of heart failure,” authors Dr. Anne Dybro of Aarhus University Hospital, in Denmark, and colleagues write in the Journal of the American College of Cardiology.

They note that in the recent EXPLORER-HCM study of patients with obstructive HCM, treatment with mavacamten improved both cardiac structure and function, with significant reduction in symptom burden.

Mavacamten is an investigational, first-in-class, oral cardiac myosin inhibitor designed to target the underlying cause of HCM. It is currently under review at the U.S. Food and Drug Administration.

In an accompanying editorial, Dr. Ahmad Masri of the Hypertrophic Cardiomyopathy Center at Oregon Health & Science University, in Portland, says the TEMPO study team “should be congratulated” for conducting the first comprehensive randomized controlled trial of a beta-blocker in obstructive HCM in more than half a century after the drugs began to be used for this disease.

“The trial provides important data to guide the use of metoprolol in the era of novel therapeutics in oHCM, leaving us wondering whether: 1) the lack of improvement in exercise time, pVO2, and NT-proBNP are related to the short, two-week duration of the study versus the inability of metoprolol to induce positive remodeling (in comparison, NT-proBNP decreased by 65% within four weeks of mavacamten treatment in EXPLORER-HCM); and 2) metoprolol provides hemodynamic benefit by reducing LVOT gradients but possibly masks ongoing negative remodeling and progressive interstitial fibrosis as reflected by lack of improvement in left ventricular hypertrophy, diastolic function, and NT-proBNP.”

Because the Food and Drug Administration requires objective functional improvement in randomized controlled trials of oHCM, “metoprolol would likely not be approved on the basis of the current trial,” Dr. Masri concludes.

The study was supported by the Novo Nordic Foundation and by Skibsreder Per Henriksen, R. og hustrus Foundation. The authors have declared no relevant conflicts of interest.

SOURCE: https://bit.ly/3ISk7L2 and https://bit.ly/3EUVNpr Journal of the American College of Cardiology, online December 13, 2021.

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