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Cleveland Clinic-led trial shows effect of drug

EMBARGOED UNTIL 9:30 AM. ET, Saturday, April 2, 2022, Cleveland: Results from a clinical trial led by the Cleveland Clinic showed that using an investigational drug in patients with severely symptomatic hypertrophic cardiomyopathy significantly reduced the need for invasive procedures.

The trial assessed whether the drug, mavacamten, could be used as an alternative to heart surgery or alcohol septal ablation, therapies used to reduce thickening of the septum, the wall separating the right and left sides of the heart.

Results from the “Valor-HCM Study: Myosin Inhibition as an Alternative to Surgical Myectomy or Alcohol Septal Ablation in Obstructive Hypertrophic Cardiomyopathy” were presented today at a late-breaking scientific session at American College of Cardiologyit’s 71st Annual Scientific Session in Washington DC

Hypertrophic cardiomyopathy is a complex type of heart disease that causes thickening of the heart muscle, left ventricular stiffness, and mitral valve changes. It affects approximately 600,000 to 1.5 million Americans, or one in every 500 people, but many of these patients go undiagnosed until the disease has progressed.

The cause of hypertrophic cardiomyopathy may be unknown or attributed to genetics, high blood pressure, or aging, making it difficult to identify a high-risk population. Symptoms include chest pain, palpitations, shortness of breath, fatigue, and syncope (fainting). Most people with hypertrophic cardiomyopathy have a low risk of sudden cardiac death. However, the condition is the most common cause of sudden cardiac death in people under the age of 30.

Medications such as beta blockers, calcium channel blockers, and antiarrhythmics are often prescribed to treat the symptoms of hypertrophic cardiomyopathy and prevent further complications. Patients with persistent symptoms may also have a septal myectomy, in which a surgeon removes a small portion of the thickened septal wall to widen the outflow tract (the path that blood takes) from the left ventricle to the aorta. Another option is alcohol ablation, a cardiac catheterization procedure where a tiny amount of pure alcohol is injected into the septum, causing it to shrink to a more normal size and widening the passageway for blood flow.

The Phase 3 Valor HCM trial enrolled 112 patients with symptomatic hypertrophic cardiomyopathy at 19 sites across the United States. All patients were referred for surgical myectomy or alcohol ablation. They were randomized to receive an oral myosin inhibitor, mavacamten (5 to 15 mg daily) or a placebo. Mavacamten works by reducing excessive contraction of the heart muscle, making it more effective. It also reduces heart muscle stiffness.

After 16 weeks, 43 of 56 (76.8%) placebo-treated patients continued to meet guideline criteria for surgery or elected to undergo surgery compared to 10/56 (17.9%) patients treated with mavacamten. The study demonstrated a significant reduction in left ventricular outflow tract pressure slope in patients treated with mavacamten, as well as improvements in quality of life measures. The long-term safety and results of mavacamten will continue to be studied.

“These results could give what may be a very sick patient population a noninvasive treatment alternative,” said Milind Desai, MD, MBA, director of the Hypertrophic Cardiomyopathy Center and director of clinical operations at the Heart Vascular & Thoracic Institute of the Cleveland Clinic, and principal investigator of the trial. “There are few high-volume centers that perform septal myectomies or alcohol ablations, which can limit a patient’s access to optimal outcomes and patients may require repeat procedures. This is why it is vital to explore non-invasive options for these patients.

Steven E. Nissen, MD, academic director of the Heart, Vascular & Thoracic Institute at the Cleveland Clinic and senior author of the trials, said, “The vast majority of patients, even those in the placebo group, elected to continue treatment with the medication. after 16 weeks, suggesting a strong desire for this type of treatment option.

The trial was funded by MyoKardia, Inc, a wholly owned subsidiary of Bristol Myers Squibb (Brisbane, CA) and coordinated by the Cleveland Clinic Coordinating Center for Clinical Research (C5Research) and Medpace (Cincinnati, OH).

Dr. Desai is a consultant for Bristol Myers Squibb and Medtronic, and sits on the Scientific Advisory Board of Caristo Diagnostics.

Dr. Nissen has consulted for numerous pharmaceutical companies and has overseen clinical trials for Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Esperion, Novartis, Novo Nordisk, Ordemanden, Takeda and Pfizer. However, it does not accept fees, consulting fees or other compensation from commercial entities.

About the Cleveland Clinic

Cleveland Clinic is a non-profit, multi-specialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision to provide exceptional patient care based on the principles of cooperation, compassion and innovation. The Cleveland Clinic has pioneered many medical breakthroughsincluding coronary bypass surgery and the first face transplant in the United States. US News and World Report consistently names the Cleveland Clinic as one of the best hospitals in the nation in its annual “America’s Best Hospitals” survey. The Cleveland Clinic’s 72,500 employees worldwide include more than 5,050 salaried physicians and researchers, and 17,800 registered nurses and advanced practice providers, representing 140 medical specialties and subspecialties. Cleveland Clinic is a 6,500-bed health system that includes a 173-acre main campus near downtown Cleveland, 21 hospitals, more than 220 ambulatory care facilities, including locations in northeast Ohio; southeast Florida; Las Vegas, Nevada; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2021, there were 10.2 million total outpatient visits, 304,000 hospital admissions and observations, and 259,000 surgical cases across the Cleveland Clinic health system. Patients came for treatment from every state and 185 countries. Visit us at clevelandclinic.org. follow us on twitter.com/ClevelandClinic. News and resources available at newsroom.clevelandclinic.org.

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