James Januzzi, MD

An expert cardiologist discusses the importance of healthcare provider education and finding resources around the REMS program.

REMS Program Resources for Clinicians

This is a video synopsis of a discussion involving James L. Januzzi, MD, regarding the importance of healthcare providers and pharmacists educating themselves about the Risk Evaluation and Mitigation Strategy (REMS) program before initiating mavacamten (cardiac myosin inhibitor) therapy for hypertrophic cardiomyopathy (HCM). Preparation is crucial to understand the REMS program's requirements, which can be found on the website of the United States Food and Drug Administration and through resources provided by the drug manufacturer.

Effective coordination with colleagues, especially in the cardiac ultrasound lab, is essential to seamlessly schedule patients and ensure timely follow-up for echocardiograms every four weeks initially and every 12 weeks thereafter. Despite its complexity, institutions like the Massachusetts General Hospital Heart Center have successfully implemented the REMS program, improving safety and patient outcomes.

While navigating the REMS program may be more intricate, its effectiveness in enhancing safety and patient well-being is undeniable. Patient feedback underscores the significant improvement in symptoms and quality of life experienced with mavacamten therapy, highlighting the program's value in managing HCM effectively and safely.

Video synopsis is AI-generated and reviewed by HCPLive® editorial staff.

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mavacamten as the first approved cardiac myosin inhibitor for oHCM, balancing the increased risk of heart failure with the medication, REMS program.

Role of Mavacamten in Treating oHCM

This is a video synopsis of a discussion involving James L. Januzzi, MD, detailing the use of mavacamten (cardiac myosin inhibitor) in obstructive hypertrophic cardiomyopathy (HCM) and the associated Risk Evaluation and Mitigation Strategy (REMS) program. Mavacamten is the first approved drug for adults with symptomatic NYHA class 2-3 obstructive HCM, aiming to improve functional capacity and symptoms. Despite favorable efficacy and safety data from clinical trials, the FDA mandated inclusion in the REMS program due to philosophical concerns regarding the potential for an excessive drop in ejection fraction.

The REMS program requires prescribers and patients to follow specific steps to ensure safe administration and monitoring of mavacamten. Prescribers must enroll in the program and educate patients about its requirements, emphasizing that it's not a one-and-done therapy. Patients undergo baseline echocardiograms before initiating treatment and at four-week intervals until reaching a maximally tolerated dose. Regular echocardiograms continue every 12 weeks or with any changes in drug regimen or use of cytochrome P450 inhibitors.

Close therapeutic alliance with patients is crucial, necessitating their active engagement in the REMS program. Patient selection prioritizes those with obstructive HCM, and shared decision-making sessions underscore the program's ongoing nature. Involving a pharmacist in discussions helps mitigate risks and enhance education for patients and clinicians alike.

Monitoring for drug-drug interactions, especially with cytochrome P450 inhibitors, is essential to manage potential complications. The REMS program emphasizes collaborative decision-making and close follow-up to optimize patient outcomes while minimizing risks associated with mavacamten therapy in obstructive HCM.

James L. Januzzi, MD, comments on mavacamten as the first approved cardiac myosin inhibitor for oHCM, balancing the increased risk of heart failure with the medication, and the role of the REMS program.

An expert in cardiology shares clinical trial findings of emerging and approved cardiac myosin inhibitors for the treatment of oHCM.

Clinical Trial Outcomes for Cardiac Myosin Inhibitors in oHCM Treatment

This is a video synopsis of a discussion involving James L. Januzzi, MD, providing insights from clinical trials investigating cardiac myosin inhibitors in obstructive hypertrophic cardiomyopathy (HCM). These trials have shown profound effects on left ventricular outflow tract (LVOT) gradient, a key mechanism contributing to symptoms in HCM patients.

The landmark EXPLORER-HCM trial examined mavacamten, the first cardiac myosin inhibitor approved for obstructive HCM. In this trial, individuals with an LVOT gradient ≥50 and heart failure symptoms (NYHA class II-III) were randomized to receive either mavacamten or placebo for 30 weeks. Mavacamten demonstrated significant improvements in peak oxygen consumption (a marker of exercise capacity), LVOT gradient reduction, symptom severity, and health status compared to placebo. Notably, safety profiles were favorable, with no exaggerated drop in ejection fraction observed.

The VALOR-HCM study further explored the benefits of mavacamten in patients referred for septal reduction therapy. Those treated with mavacamten showed a marked reduction in the perceived need for septal reduction therapy compared to placebo, emphasizing its potential as an alternative therapeutic option.

Additionally, the newer cardiac myosin inhibitor, aficamten, showed promising results in the Redwood trial, reducing LVOT gradients and improving symptoms without significant safety concerns. Its shorter half-life and lack of drug interactions may offer additional advantages for patients with obstructive HCM.

Overall, these trials underscore the efficacy and safety of cardiac myosin inhibitors in managing obstructive HCM, providing hope for improved outcomes and quality of life for affected individuals.

Dr James L. Januzzi reviews the use of cardiac myosin inhibitors for the management of oHCM.

Using Cardiac Myosin Inhibitors for the Treatment of oHCM

This is a video synopsis of a discussion involving James L. Januzzi, MD, focusing on the development of cardiac myosin inhibitors and other therapies for the treatment of hypertrophic cardiomyopathy (HCM). Currently, the spotlight is on two cardiac myosin inhibitors: mavacamten (MYK-461) and aficamten. Mavacamten, the first approved cardiac myosin inhibitor for obstructive HCM, boasts a longer half-life of six to nine days, requiring time to interpret dose changes. However, it interacts with drugs inhibiting cytochrome P450 2C19 and 3A4 pathways, potentially increasing its concentrations when co-administered with common medications like omeprazole and certain antibiotics.

On the horizon is aficamten, with a shorter half-life of approximately three days, making dose adjustments more rapidly discernible compared to mavacamten. Notably, aficamten currently appears to have no issues with drug interactions via the P450 system, widening its therapeutic window. The advent of aficamten presents an additional therapeutic option for patients with HCM, offering benefits such as a shorter half-life and reduced susceptibility to drug interactions.

Understanding the benefits and risks of these medications is crucial for effective treatment. While cardiac myosin inhibitors hold promise for managing HCM, careful consideration of pharmacology and potential drug interactions is essential for optimizing patient outcomes. With both mavacamten and aficamten in the treatment arsenal, clinicians have more options to tailor therapies to individual patient needs, ultimately improving the management of HCM.

James Januzzi, MD

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