SEQUOIA-HCM (original research)
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 peak oxygen uptake by cardiopulmonary exercise testing at week 24
1.8
0
1.8 mL/kg/...
1.4 mL/kg/...
0.9 mL/kg/...
0.5 mL/kg/...
0.0 mL/kg/...
Aficamten
Placebo
Significant
increase ▲
Significantly greater improvement in mean the peak oxygen uptake by cardiopulmonary exercise testing at week 24 (1.8 mL/kg/min vs. 0 mL/kg/min; MD 1.7, 95% CI 1 to 2.4).
Secondary outcomes
Significantly greater improvement in Kansas City Cardiomyopathy Questionnaire clinical summary score at week 24 (11 points vs. 5 points; MD 7, 95% CI 5 to 10).
Significantly greater improvement of ≥ 1 in NYHA functional class at week 24 (58.5% vs. 24.3%; AD 34.2%, 95% CI 23.4 to 45).
Significantly greater improvement in LVOT gradient of < 30 mmHg after Valsalva maneuver at week 24 (49.3% vs. 3.6%; AD 45.7%, 95% CI 36.9 to 54.5).
Safety outcomes
No significant difference in any serious adverse event.
Conclusion
In patients with symptomatic obstructive HCM, aficamten was superior to placebo with respect to mean improvement in the peak oxygen uptake by cardiopulmonary exercise testing at week 24.
Reference
Martin S Maron, Ahmad Masri, Michael E Nassif et al. Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy. N Engl J Med. 2024 May 30;390(20):1849-1861.
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