Add-on Mavacamten reduces the need to reduce the septum of obstructive HCM

Washington – Researchers reported that treatment with Mabacamten during clinical trials was able to avoid septal reduction therapy (SRT) in patients with progressive obstructive hypertrophic cardiomyopathy (oHCM).

Additions to maximally acceptable medical treatment In a VALOR-HCM study of 56 patients with documented oHCM who received placebo camten, 17.9% met the composite endpoint (16). (Decision to move to SRT by week or 2011 American Heart Association / American Heart Association) Guidelines are eligible for week 16 while receiving placebo and maximally acceptable medical treatment 76.8% Reported Milind Y. Desai, MD, MBA of Cleveland Clinic.

The difference in treatment was 58.93% (P<0.0001), he said in a presentation at American Heart Association (ACC) Meeting.

“Mavacamten, a targeted inhibitor of cardiac myosin, reduces the number of myosin-actin crossbridges and reduces the excessive contractility characteristic of HCM,” the authors say. In addition, in oHCM, they said the drug improves the left ventricular outflow tract (LVOT). November 2021, FDA has extended new drug application review Use of Mabacamten for the treatment of symptomatic oHCM until April 28, 2022.

“VALOR-HCM is based on Phase III results EXPLORER-HCM trialAnd it shows that Mabacamten is an effective potential treatment option for patients with severe symptomatic oHCM who meet the SRT guideline criteria, “Desai said. [at ACC] It is clinically meaningful and has shown the potential to affect parameters that lead to SRT eligibility. “

Mortality from SRT (surgical septal resection or alcohol ablation) can be less than 1% in the hands of a Center of Excellence doctor, Desai said. Today’s MedPage, However, overall statistics suggest a general mortality rate in the range of 5% to 6%. “If you have little experience with surgical treatment, the mortality rate can be as high as 16%,” he said.

Joseph Cleveland Jr., MD, Ph.D., Anschutz Medical Campus, University of Colorado, Aurora, Today’s MedPage “Septal reduction surgery is a big deal. Patients need to go to a heart-lung machine while cutting the muscles that block the heart valves.”

He also said, “Unfortunately, I inherited. [SRT] “Patients of inexperienced surgeons” have too few or too many muscle resections requiring a second surgery, leading to more intensive orthodontic surgery.

In the placebo-controlled VALOR-HCM study, patients with a family history of HCM and recorded oHCM with a septal thickness of 15 mm or more or 13 mm or more (about 60 years, about half of women, 85% in both study groups) White) has been registered. Other registration criteria are as follows:

• Severe symptoms (NYHA functional class III / IV or exertional syncope or near syncope class II) despite maximally acceptable treatment
• Dynamic LVOT gradient at rest or with provocation of 50 mmHg (Valsalva maneuver or exercise)
• Documented LV ejection fraction (LVEF) 60%
• Introducing SRT within the last 12 months
• Actively consider SRT scheduling

The authors report that nearly half of patients receive beta-blocker monotherapy, and more than 92% are NYHA class ≥ III, “patients can choose to proceed to SRT at any time after randomization.” did. For 20% of patients taking disopyramide, the study results provide “first evidence of concomitant use with disopyramide,” Desai and colleagues pointed out.

They reported the following among patients who received SRT or maintained the guidelines covered by SRT, and those who improved one or more, one or more, or two or more NYHA classes:

• Mavacamten: The 18% guideline is eligible, while the 82% guideline is ineligible. None 36%, ≥163%, ≥227%
• Placebo: 77% vs. 23%; 77%, 21%, 2%, respectively

Desai reported that patients treated with Mabacamten achieved a 10-point improvement over baseline for a 3-point reduction in placebo patients (3 points reduction).P<0.001) Kansas City Cardiomyopathy Questionnaire.

Regarding adverse events (AEs) in the safety population (n = 56 mavacamten; n = 55 placebo), the authors reported:

• Non-persistent ventricular tachycardia: 0% with mabacamten vs. 9.1% with placebo
• Nausea: 7.1% vs. 1.8%
• Rash: 7.1% vs. 0%

However, no patient experienced severe AE with congestive heart failure, syncope, or sudden cardiac death. Also, there was no permanent discontinuation of treatment due to LVEF ≤ 30%.

The limits of the study included the fact that the primary endpoint was caused by a decline in SRT guideline eligibility. The period of randomization is short. “Uncertainty about whether patients can avoid SRT during long-term administration by inhibiting myosin,” the authors said. In addition, long-term safety remains unclear, and the study population was predominantly Caucasian and was treated in large numbers of HCM centers with established SRT programs.

Cleveland, who was not involved in the trial, said that if Mabacamten is FDA-approved and the patient is recommended for SRT, they will ask if the patient tried the add-on Mabacamten before moving on to invasive treatment. rice field.