Exercise performance in obstructive HCM better with aficamten vs metoprolol

In the treatment of patients with obstructive hypertrophic cardiomyopathy (HCM), aficamten exerts superior effects on a broad array of exercise measures compared with metoprolol, according to a secondary analysis of the phase III MAPLE-HCM trial.

The analysis included patients with symptomatic obstructive HCM with objective evidence of exercise intolerance (peak oxygen uptake [pVO2] <100 percent of predicted). Exclusion criteria were a history of atrial fibrillation (paroxysmal or persistent), medical indication for β-blockers or calcium channel blockers prohibiting drug discontinuation, or intolerance or medical contraindication to β-blockers.

A total of 175 participants (mean age 57.7 years, 41.7 percent female) were randomly assigned to receive titrated aficamten (5–20 mg daily) or matching titrated metoprolol (50–200 mg daily) for 24 weeks. Of these, 165 participants (94 percent) had core laboratory–validated exercise tests at baseline and week 24.

Outcomes included submaximal exercise minute ventilation (VE)/carbon dioxide output (VCO2) slope and anaerobic threshold; peak exercise duration, workload, heart rate, and heart rate reserve; postexercise oxygen recovery rates; and composite variables, such as circulatory power.

Compared with metoprolol, aficamten treatment was associated with improvements in multiple stages of exercise. These included submaximal exercise VE/VCO2 slope (−2.8; p<0.001) and anaerobic threshold (76 mL/min; p<0.001), peak workload (8 watts; p=0.003), the time required for VO2 to recover by 12.5 percent postexercise (−11 seconds; p<0.001), and circulatory power (819 mm Hg × mL/min per kg; p<0.001).

More aficamten-treated participants had large improvements (≥3.0 mL/kg/min) in peak VO2 compared with those who received metoprolol (20.5 percent vs 3.7 percent; odds ratio, 6.8; p<0.001). In contrast, more metoprolol-treated participants had large reductions in peak VO2 (≥3.0 mL/kg/min) (20.7 percent vs 2.4 percent; odds ratio, 10.6; p<0.001).