A plain language summary of the SEQUOIA-HCM study: aficamten for symptomatic obstructive hypertrophic cardiomyopathy

Plain Language Summary: What is this summary about? This summary explains the main findings from the SEQUOIA-HCM study, which was published in the New England Journal of Medicine. Researchers wanted to find out how well aficamten works and how safe it is compared to a placebo in people with obstructive hypertrophic cardiomyopathy (called oHCM). In the oHCM heart, a heart muscle protein called myosin is more active than normal. This causes the muscle to contract too strongly. Also, when it contracts, it briefly disrupts blood flow out of the heart (called obstruction). Obstruction causes the pressure on the left side of the heart to increase. Aficamten is an investigational treatment for people with oHCM that causes symptoms. It is a type of cardiac myosin inhibitor that works by reducing myosin activity to normal levels and decreasing how strongly the heart contracts. In SEQUOIA-HCM, 142 people with oHCM took aficamten and 140 took a placebo, along with their standard medicine(s), for about 6 months (24 weeks). A placebo looks the same and is taken in the same way as the treatment being tested but does not contain any active ingredients. During the study, people did exercise tests and researchers collected information about their quality of life and symptoms, how well their heart worked, and the side effects they had. Quality of life refers to a person’s overall well-being. People in this study completed a survey to report their quality of life. A side effect is something (expected or unexpected) that you feel was caused by a medicine or treatment you take. Side effects may or may not be caused by the medicine or treatment you take. What are the key takeaways? After 6 months of treatment, people who took aficamten had greater improvements in study outcomes than those who took placebo. They had a greater increase in how much physical activity they could do (called exercise capacity). They had an important increase in their quality of life and a decrease in their symptoms. They also had a positive change in how well their heart worked. During the 6-month treatment period, people who took aficamten had a shorter amount of time during which they were eligible for septal reduction therapy than people who took placebo. Septal reduction therapy can include heart surgery or a non-surgical procedure to reduce the thickness of the heart muscle. This removes the obstruction to blood flowing out of the heart. People who took aficamten did not have any more side effects than people who took a placebo. What were the main conclusions reported by the researchers? Aficamten could provide a new treatment option that improves exercise capacity, symptoms, and quality of life in people with oHCM. It may also provide an alternative treatment option to septal reduction therapy for oHCM. This is an abstract of the Plain Language Summary of Publication article. View the full Plain Language Summary PDF of this article to read the full-text.