Aficamten monotherapy was superior to metoprolol in promoting adaptation to multiple phases of exercise in patients with symptomatic obstructive HCM (oHCM), according to a prespecified analysis of the MAPLE-HCM trial published June 17 in JAMA Cardiology.

The MAPLE-HCM trial, conducted across 71 international sites, randomized 175 participants (58 years old, 42% women) with symptomatic oHCM 1:1 to either titrated aficamten 5-20 mg daily or metoprolol 50-200 mg daily for 24 weeks. The two groups were similar at the start of the study.

Among the 165 participants (94%) who had core laboratory-validated exercise tests at baseline and 24 weeks, results showed that aficamten, compared with metoprolol, improved several measures of exercise capacity: submaximal exercise VE/VCO₂ slope (−2.8; p<0.001), anaerobic threshold (76 mL/min; p<0.001), peak workload (8 watts; p=0.003), time required for VO₂ to recover by 12.5% postexercise (−11 seconds; p<0.001) and circulatory power (819 mm Hg x mL/min per kg; p<0.001).

Additionally, patients taking aficamten vs. metoprolol were nearly sevenfold more likely to have a large improvement in peak VO₂ increase of ≥3.0 mL/kg/min (21% vs. 4%; odds ratio [OR], 6.8; p<0.001). On the other hand, patients taking metoprolol vs. aficamten were nearly 11-times more likely to experience a large reduction in peak VO₂ of ≥3.0 mL/kg/min (2.4% vs. 20.7%; OR, 10.6; p<0.001).

“Exercise capacity is a critically important therapeutic target in oHCM,” where “cardiovascular event rates are infrequent but exercise intolerance is extremely common,” write study authors Gregory D. Lewis, MD, et al. “These findings provide compelling justification for aficamten treatment as an appropriate alternative to current first-line treatment with metoprolol, to treat exercise intolerance in oHCM.”