OR WAIT null SECS
Findings from VALOR-HCM suggest more data is needed to assess the durability of improvement in septal reduction therapy eligibility over longer time periods.
New findings from the VALOR-HCM trial suggested the administration of mavacamten significantly reduced eligibility for invasive septal reduction therapy (SRT) at 16 weeks in patients with obstructive hypertrophic cardiomyopathy (oHCM).
Additional treatment benefits from mavacamten occurred within key secondary endpoints of the study (P < .0001), including a reduction of post-exercise dynamic LV outflow tract (LVOT) gradient, ≥1 class improvement in New York Heart Association (NYHA) class, improvement in KCCQ-clinical summary score, reduction in NT ProBNP, and reduction in troponin I.
Led by Milind Y Desai, MD, Director, Hypertrophic Cardiomyopathy Center, Cleveland Clinic, the study was presented in a session at The American College of Cardiology (ACC) 2022 Scientific Sessions in Washington, DC.
Although SRT has been known to improve long-term survival, symptoms, and quality of life, there is currently an unmet need for noninvasive alternatives for patients with oHCM who are highly symptomatic.
The primary objective of the VALOR-HCM trial aimed to determine if mavacamten added to maximally-tolerated medical therapy would allow severely symptomatic oHCM patients to improve sufficiently if they no longer met criteria for SRT or chose not to undergo the procedure for 16 weeks.
In double-blind, placebo-controlled treatment for 16 weeks, a total of 56 patients were randomized to mavacamten and a total of 56 patients were randomized to placebo. Titration occurred at weeks 8 (10 mg, 5 mg, 2.5 mg) and weeks 12 (15 mg, 10 mg, 5 mg, 2.5 mg).
Patients were 18 years and older and had documented HCM with maximum septal wall thickness ≥15 mm or ≥13mm and family history of HCM. Additionally, inclusion criteria included NYHA functional Class III/IV or Class II with exertional syncope or near syncope, dynamic LVOT gradient at rest or with provocation ≥50 mmHg, and documented LV ejection fraction ≥60%.
Patients were required to be referred within the past 12 months for SRT and actively considering scheduling the procedure.
Patient characteristics showed a mean age of 59.8 years in the mavacamten group, with 48.2% of patients being female and 30.4% had family history of HCM. In comparison, the placebo group had a mean age of 60.9 years, 50.0% of patients were female, and 26.8% had a family history of HCM.
Data show 10 of 56 patients (17.9%) in the mavacamten group and 43 of 56 patients (76.8%) in the placebo group made the decision to proceed with SRT by Week 16 or were guideline eligible at Week 16 (58.93; 95% CI, 43.99 - 73.87; P <.0001).
Regarding the primary endpoint, 18% of patients in the mavacamten group remained guideline eligible for SRT, compared to 77% of patients in the placebo group. Additionally, in the mavacamten group, 63% of patients improved by ≥1 NYHA class, compared to 21% in the placebo group. Data show 77% of those in the placebo group did not improve NYHA class.
The study noted there were no permanent treatment discontinuations due to LVEF ≤30%, with no subjects experiencing severe adverse events of congestive heart failure, syncope, or sudden cardiac death.
The discussed limitations of the study included the duration of 16 week randomization, uncertainties regarding whether myosin inhibitors can allow patients to avoid SRT during long-term administration, and long-term safety.
Moreover, the effect of mavacamten on life threatening arrhythmias and sudden death was not assessed and the current study consisted of predominantly white patients treated at HCM centers with established SRT programs.
“Additional data is needed to assess the durability of improvement in SRT eligibility over longer time periods,” Desai wrote.
The study, “Myosin Inhibition to Defer Surgical Myectomy or Alcohol Septal Ablation in Obstructive Hypertrophic Cardiomyopathy Results of the VALOR-HCM Trial,” was presented at ACC 2022.