SEQUOIA-HCM (substudy)
Trial question
What is the role of aficamten in patients with symptomatic obstructive HCM?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
41.0% female
59.0% male
N = 282
282 patients (115 female, 167 male).
Inclusion criteria: patients with symptomatic obstructive HCM.
Key exclusion criteria: Noonan syndrome; Fabry disease; amyloidosis; significant valvular heart disease; history of LV systolic dysfunction or stress cardiomyopathy; inability to exercise on a treadmill or bicycle; previous treatment with septal reduction therapy; paroxysmal AF during the screening period.
Interventions
N=142 aficamten (at a starting dose 5 mg, maximum dose 20 mg, for 24 weeks).
N=140 placebo (matching placebo for 24 weeks).
Primary outcome
Mean improvement in integrated composite Z score for exercise performance at week 24
0.17 points
-0.19 points
0.2 points
0.1 points
0.1 points
0.0 points
0.0 points
-0.0 points
-0.1 points
-0.1 points
-0.2 points
Aficamten
Placebo
Significant
increase ▲
Significantly greater improvement in mean integrated composite Z score for exercise performance at week 24 (0.17 points vs. -0.19 points; AD 0.35 points, 95% CI 0.25 to 0.46).
Secondary outcomes
Significant increase in peak oxygen uptake at week 24 (1.8 mL/kg/min vs. 0 mL/kg/min; AD 1.7 mL/kg/min, 95% CI 1 to 2.4).
Significant increase in peak workload at week 24 (14 W vs. 1 W; AD 12 W, 95% CI 6 to 18).
Significant increase in exercise duration at week 24 (1.2 min vs. 0.1 min; AD 1 min, 95% CI 0.5 to 1.4).
Conclusion
In patients with symptomatic obstructive HCM, aficamten was superior to placebo with respect to mean improvement in integrated composite Z score for exercise performance at week 24.
Reference
Matthew M Y Lee, Ahmad Masri, Michael E Nassif et al. Aficamten and Cardiopulmonary Exercise Test Performance: A Substudy of the SEQUOIA-HCM Randomized Clinical Trial. JAMA Cardiol. 2024 Nov 1;9(11):990-1000.
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