Article Impact Level: HIGH Data Quality: STRONG Summary of JAMA Cardiology, 8(10), 968. https://doi.org/10.1001/jamacardio.2023.3342 Dr. Milind Y. Desai et al.
Points
- The research paper investigated the impact of mavacamten on the need for septal reduction therapy (SRT) in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM).
- The study was a double-blind, placebo-controlled, multicenter, randomized clinical trial conducted from July 2020 to November 2022.
- At week 56, 8.9% of patients in the mavacamten group and 19.2% in the placebo crossover group met the composite endpoint, indicating a reduced need for SRT in the mavacamten group.
- In both groups, there was a sustained reduction in resting and Valsalva left ventricular outflow tract (LVOT) gradients, along with an improvement in the New York Heart Association class.
- Close monitoring is necessary due to the potential risk of left ventricular systolic dysfunction in some patients.
Summary
A recent research paper investigated the impact of mavacamten on the requirement for septal reduction therapy (SRT) in patients with severely symptomatic obstructive hypertrophic cardiomyopathy (HCM). The study aimed to assess the sustained effects of mavacamten on the need for SRT up to week 56.
The study was a double-blind, placebo-controlled, multicenter, randomized clinical trial conducted from July 2020 to November 2022. Participants were recruited from 19 HCM centers in the US and included patients with obstructive HCM referred for SRT. The data analysis was performed from April to August 2023.
Patients initially assigned to mavacamten continued the drug for 56 weeks, while patients on placebo crossed over to mavacamten from week 16 to week 56. Dose titrations were conducted based on echocardiographic measurements of left ventricular outflow tract (LVOT) gradient and left ventricular ejection fraction (LVEF).
The primary outcome measured was the proportion of patients undergoing SRT or remaining in a guideline-eligible or unevaluable SRT status at week 56. The results showed that at week 56, 8.9% of patients in the original mavacamten group (5 out of 56 patients) met the composite endpoint, with 3 undergoing SRT, 1 being SRT eligible, and 1 being not SRT evaluable. In the placebo crossover group, 19.2% of patients (10 out of 52) met the composite endpoint, with 3 undergoing SRT, 4 being SRT eligible, and 3 not SRT evaluable. 89% of patients (96 out of 108) continued mavacamten long term.
Furthermore, the study found that after 56 weeks, there was a sustained reduction in resting LVOT gradients of -34.0 mm Hg (95% CI, -43.5 to -24.5 mm Hg) and -33.2 mm Hg (95% CI, -41.9 to -24.5 mm Hg) in the mavacamten and placebo-to-mavacamten groups, respectively. Similarly, there was a sustained reduction in Valsalva LVOT gradients of -45.6 mm Hg (95% CI, -56.5 to -34.6 mm Hg) and -54.6 mm Hg (95% CI, -66.0 to -43.3 mm Hg) in the mavacamten and placebo-to-mavacamten groups, respectively. Additionally, an improvement in the New York Heart Association class of 1 or higher was observed in 93% of patients (51 out of 55) in the original mavacamten group and 73% of patients (37 out of 51) in the placebo crossover group.
In conclusion, the randomized clinical trial demonstrated that mavacamten reduced the need for SRT in patients with symptomatic obstructive HCM at week 56. The treatment showed sustained improvements in LVOT gradients and symptoms. However, it is essential to note that 11.1% of patients (12 out of 108) had an LVEF of less than 50%, indicating a potential risk of LV systolic dysfunction. Therefore, close monitoring is necessary when considering mavacamten as a therapeutic option for patients with obstructive HCM.
Link to the article: https://jamanetwork.com/journals/jamacardiology/article-abstract/2809050
References Desai, M. Y., Owens, A., Wolski, K., Geske, J. B., Saberi, S., Wang, A., Sherrid, M., Cremer, P. C., Lakdawala, N. K., Tower-Rader, A., Fermin, D., Naidu, S. S., Smedira, N. G., Schaff, H., McErlean, E., Sewell, C., Mudarris, L., Gong, Z., Lampl, K., … Nissen, S. E. (2023). Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 56 Results From the VALOR-HCM Randomized Clinical Trial. JAMA Cardiology, 8(10), 968. https://doi.org/10.1001/jamacardio.2023.3342
