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

Summary

In this prespecified analysis of a phase 3 randomized, active-controlled trial (n=175 randomized; 165 with core-lab validated exercise tests), aficamten improved submaximal VE/VCO2 slope (−2.8), anaerobic threshold (+76 mL/min), peak workload (+8 W), faster VO2 recovery (−11 s), and higher circulatory power versus metoprolol. Large improvements in peak VO2 (≥3.0 mL/kg/min) were more frequent with aficamten (20.5% vs 3.7%), whereas large declines were more common with metoprolol.

Key Findings

• Aficamten reduced submaximal VE/VCO2 slope by −2.8 (95% CI, −4.0 to −1.5; P<.001) vs metoprolol.
• Anaerobic threshold increased by +76 mL/min (95% CI, 41 to 111; P<.001) with aficamten.
• Peak workload improved by +8 W (95% CI, 3 to 13; P=.003) and VO2 recovery was 11 s faster (P<.001).
• Large peak VO2 improvements (≥3.0 mL/kg/min) were more frequent with aficamten (20.5% vs 3.7%); large declines were less frequent (2.4% vs 20.7%).

Clinical Implications

Supports consideration of aficamten as first-line pharmacotherapy for symptomatic oHCM to improve exercise capacity; may alter guideline recommendations pending hard-outcome data.

Limitations

• Prespecified secondary analysis; trial not powered for clinical hard outcomes.
• 24-week duration; excluded atrial fibrillation and patients requiring continued β-blockers or CCBs, limiting generalizability.

Future Directions

Evaluate long-term clinical outcomes (HF hospitalization, mortality), safety, and comparative effectiveness versus other guideline-directed therapies; assess real-world first-line use.