Mavacamten for hypertrophic cardiomyopathy: effectiveness and value : final evidence report and meeting summary
- Collection:
- Health Policy and Services Research
- Author(s):
- Wasfy, Jason H., author Walton, Surrey M., author Beinfeld, Molly, author Nhan, Emily, author Sarker, Jyotirmoy, author Whittington, Melanie D., author Pearson, Steven D., author Rind, David M., author
- Contributor(s):
- Institute for Clinical and Economic Review, issuing body.
- Publication:
- [Boston, Massachusetts] : Institute for Clinical and Economic Review, November 16, 2021
- Language(s):
- English
- Format:
- Text
- Subject(s):
- Cardiac Myosins -- antagonists & inhibitors Cardiomyopathy, Hypertrophic -- drug therapy United States
- Genre(s):
- Technical Report
- Abstract:
- Hypertrophic cardiomyopathy (HCM) is a genetic disorder involving sarcomeres in heart muscle that can cause symptoms such as chest discomfort and shortness of breath, particularly with exertion. Additional symptoms can include palpitations, dizziness, and syncope (passing out). Although many patients with HCM have a normal life expectancy without symptoms, even patients without symptoms are at risk of sudden cardiac death. Apart from managing symptoms, key components of therapy include placement of implanted cardioverter defibrillators (ICDs) for patients at high risk of sudden death, and anticoagulation for patients who have both HCM and atrial fibrillation. For patients with a specific subtype of HCM, hypertrophic obstructive cardiomyopathy (HOCM), obstruction of the left ventricular outflow tract (LVOT) can be an important contributor to exertional symptoms. The LVOT is the conduit through which blood exits the heart to the rest of the body. Among the effects of dynamic narrowing of the LVOT are increased pressure within the left ventricle, increased myocardial oxygen demand, and increased mitral regurgitation. While LVOT obstruction is one important target for therapy to reduce symptoms, there are other causes of symptoms that can also affect non-obstructive HCM patients. Those symptoms include diastolic dysfunction, microvascular angina (obstruction of small heart artery vessels), and irregular heart rhythms. For HOCM patients with shortness of breath related to LVOT obstruction, medications can improve symptoms. Beta blockers and calcium channel blockers reduce the forcefulness of the heart’s contraction, reducing the LVOT gradient, thus improving symptoms. However, beta blockers and calcium channel blockers have important side effects, including fatigue that can interfere with work or daily activities, dizziness, and sexual dysfunction. When these first-line therapies are insufficient or not well tolerated, second-line treatment options include adding disopyramide or performing septal reduction procedures. Disopyramide has important side effects as well, and drug shortages limit access to the long-acting version. Septal reduction procedures include surgical myectomy (a type of open-heart surgery) or alcohol septal ablation, a controlled heart attack that reduces the thickness of the heart muscle causing LVOT obstruction. Those procedures can have substantial benefit, but they have a low but meaningful risk of death. Furthermore, clinical outcomes following these procedures may be worse outside centers of excellence. As such, there is substantial unmet need for the management of exertional symptoms in patients with symptomatic HOCM, particularly among patients that do not have good access to specialized centers. A novel agent, mavacamten, has been tested in clinical trials. Mavacamten reduces adenosine triphosphatase activity in cardiac myosin heavy chain, one of the proteins in heart muscle cells, and thus reduces the contraction of the heart that can contribute to obstruction. A United States (US) Food and Drug Administration (FDA) decision on approval of mavacamten is expected in early 2022. This report examines the comparative effectiveness and cost effectiveness of mavacamten in patients with symptomatic HOCM.
- Copyright:
- Reproduced with permission of the copyright holder. Further use of the material is subject to CC BY license. (More information)
- Extent:
- 1 online resource (1 PDF file (various pagings))
- Illustrations:
- Illustrations
- NLM Unique ID:
- 9918401085806676 (See catalog record)
- Permanent Link:
- http://resource.nlm.nih.gov/9918401085806676