Effect of Aficamten vs Metoprolol on Patient-Reported Health Status in Obstructive Hypertrophic Cardiomyopathy.

Summary

In a double-blind, randomized head-to-head trial of symptomatic obstructive HCM, aficamten improved KCCQ Overall Summary Scores by an adjusted +7.8 points versus metoprolol at 24 weeks, with more patients achieving very large (≥20-point) gains and fewer reporting worsening. SAQ Physical Limitation improved significantly with aficamten, supporting meaningful functional benefit.

Key Findings

• Adjusted between-group improvement in KCCQ-OSS was +7.8 points (95% CI 3.3–12.3; P<0.001) favoring aficamten at 24 weeks.
• Very large KCCQ-OSS improvement (≥20 points) occurred in 38.6% with aficamten vs 18.4% with metoprolol (NNT≈4.9).
• Fewer patients experienced worsening health status with aficamten (≤−5 points: 6.8% vs 18.4%).
• SAQ Physical Limitation improved by +10.1 points (95% CI 3.9–16.2; P=0.001) with aficamten.

Clinical Implications

For symptomatic obstructive HCM, aficamten can be considered as an initial monotherapy option to achieve greater symptom relief and quality-of-life gains than metoprolol. Shared decision-making should incorporate PRO benefits, while monitoring hemodynamics and LVOT gradients.

Limitations

• Modest sample size (n=175) and 24-week duration limit long-term generalizability
• Trial focused on monotherapy; combination strategies were not assessed

Future Directions

Evaluate long-term clinical outcomes, safety, and durability; compare against additional standard therapies; assess combination strategies and real-world effectiveness across diverse populations.