Exercise Performance With Aficamten vs Metoprolol in Obstructive Hypertrophic Cardiomyopathy: The MAPLE-HCM...

Area of Science:

• Cardiology
• Exercise Physiology
• Pharmacology

Background:

• Obstructive hypertrophic cardiomyopathy (oHCM) severely limits patients' exercise capacity.
• Current treatment guidelines for oHCM recommend beta-blockers based primarily on expert opinion, lacking robust comparative data.
• The MAPLE-HCM trial investigated the efficacy of aficamten versus metoprolol in patients with oHCM.

Purpose of the Study:

• To compare the effects of aficamten and metoprolol on comprehensive exercise response in patients with symptomatic oHCM.
• To evaluate 16 quantitative exercise measures across all exercise stages.
• To determine the potential of aficamten as a first-line therapy for oHCM.

Main Methods:

• A prespecified secondary analysis of the phase 3, randomized MAPLE-HCM trial.
• 175 patients with symptomatic oHCM and exercise intolerance were randomized 1:1 to aficamten or metoprolol for 24 weeks.
• Exercise response was assessed using 16 quantitative measures, including submaximal and peak exercise parameters, and oxygen recovery.

Main Results:

• Aficamten demonstrated superior improvements in multiple exercise stages compared to metoprolol, including submaximal VE/VCO2 slope and anaerobic threshold.
• Patients on aficamten showed greater improvements in peak workload and circulatory power.
• Large improvements in peak VO2 were significantly more common with aficamten, while large reductions were more frequent with metoprolol.

Conclusions:

• Aficamten monotherapy proved superior to metoprolol in enhancing exercise adaptation across multiple phases in patients with symptomatic oHCM.
• These findings support aficamten as a potential first-line therapy for obstructive hypertrophic cardiomyopathy.
• The study provides robust evidence for aficamten's efficacy in improving exercise capacity in oHCM patients.