TY - JOUR
T1 - Impact of Aficamten on Disease and Symptom Burden in Obstructive Hypertrophic Cardiomyopathy
T2 - Results From SEQUOIA-HCM
AU - Maron, Martin S.
AU - Masri, Ahmad
AU - SEQUOIA‐HCM Investigators
AU - Nassif, Michael E.
AU - Barriales-Villa, Roberto
AU - Abraham, Theodore P.
AU - Arad, Michael
AU - Cardim, Nuno
AU - Choudhury, Lubna
AU - Claggett, Brian
AU - Coats, Caroline J.
AU - Düngen, Hans Dirk
AU - Garcia-Pavia, Pablo
AU - Hagège, Albert A.
AU - Januzzi, James L.
AU - Kulac, Ian
AU - Lee, Matthew M.Y.
AU - Lewis, Gregory D.
AU - Ma, Chang Sheng
AU - Michels, Michelle
AU - Oreziak, Artur
AU - Owens, Anjali T.
AU - Spertus, John A.
AU - Solomon, Scott D.
AU - Tfelt-Hansen, Jacob
AU - van Sinttruije, Marion
AU - Veselka, Josef
AU - Watkins, Hugh C.
AU - Jacoby, Daniel L.
AU - Heitner, Stephen B.
AU - Kupfer, Stuart
AU - Malik, Fady I.
AU - Meng, Lisa
AU - Wohltman, Amy
AU - Olivotto, Iacopo
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/11/5
Y1 - 2024/11/5
N2 - Background: Aficamten is a cardiac myosin inhibitor that mitigates left ventricular outflow gradients in obstructive hypertrophic cardiomyopathy (oHCM). The clinical efficacy of aficamten across multiple outcome domains in oHCM has not been fully defined. Objectives: This responder analysis from the SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM) trial characterizes the clinical impact of aficamten. Methods: Patients who were symptomatic of oHCM were randomized to aficamten (n = 142) or placebo (n = 140) daily for 24 weeks. Outcomes assessed included the proportion of patients with complete hemodynamic response (rest and Valsalva gradient <30 mm Hg and <50 mm Hg, respectively), relief in limiting symptoms (≥1 improvement in NYHA functional class and/or ≥10-point change in Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score), enhanced exercise capacity (≥1.5 mL/kg/min change in peak oxygen uptake), and ≥50% reduction in N-terminal pro–B-type natriuretic peptide. Eligibility for septal reduction therapy was also evaluated. Results: At 24 weeks, patients treated with aficamten vs placebo showed significant improvement in limiting symptoms (71% vs 42%), were more likely to have complete hemodynamic response (68% vs 7%), demonstrated enhanced exercise capacity (47% vs 24%), and showed a decrease ≥50% in N-terminal pro–B-type natriuretic peptide (84% vs 8%) (P ≤ 0.002 for all). An improvement in ≥1 of these outcome measures was achieved in 97% of patients treated with aficamten (vs 59% placebo), including 23% on aficamten who achieved all 4 outcomes compared with none in placebo. Among 32 patients receiving aficamten and 29 patients receiving placebo who were eligible for septal reduction therapy, 28 (88%) from the aficamten group were no longer eligible at 24 weeks compared with 15 (52%) from the placebo group (P = 0.002). Conclusions: Treatment with aficamten was associated with substantial improvements across a broad range of clinically relevant efficacy measures.
AB - Background: Aficamten is a cardiac myosin inhibitor that mitigates left ventricular outflow gradients in obstructive hypertrophic cardiomyopathy (oHCM). The clinical efficacy of aficamten across multiple outcome domains in oHCM has not been fully defined. Objectives: This responder analysis from the SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM) trial characterizes the clinical impact of aficamten. Methods: Patients who were symptomatic of oHCM were randomized to aficamten (n = 142) or placebo (n = 140) daily for 24 weeks. Outcomes assessed included the proportion of patients with complete hemodynamic response (rest and Valsalva gradient <30 mm Hg and <50 mm Hg, respectively), relief in limiting symptoms (≥1 improvement in NYHA functional class and/or ≥10-point change in Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score), enhanced exercise capacity (≥1.5 mL/kg/min change in peak oxygen uptake), and ≥50% reduction in N-terminal pro–B-type natriuretic peptide. Eligibility for septal reduction therapy was also evaluated. Results: At 24 weeks, patients treated with aficamten vs placebo showed significant improvement in limiting symptoms (71% vs 42%), were more likely to have complete hemodynamic response (68% vs 7%), demonstrated enhanced exercise capacity (47% vs 24%), and showed a decrease ≥50% in N-terminal pro–B-type natriuretic peptide (84% vs 8%) (P ≤ 0.002 for all). An improvement in ≥1 of these outcome measures was achieved in 97% of patients treated with aficamten (vs 59% placebo), including 23% on aficamten who achieved all 4 outcomes compared with none in placebo. Among 32 patients receiving aficamten and 29 patients receiving placebo who were eligible for septal reduction therapy, 28 (88%) from the aficamten group were no longer eligible at 24 weeks compared with 15 (52%) from the placebo group (P = 0.002). Conclusions: Treatment with aficamten was associated with substantial improvements across a broad range of clinically relevant efficacy measures.
UR - http://www.scopus.com/inward/record.url?scp=85206685901&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2024.09.003
DO - 10.1016/j.jacc.2024.09.003
M3 - Article
C2 - 39352339
AN - SCOPUS:85206685901
SN - 0735-1097
VL - 84
SP - 1821
EP - 1831
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 19
ER -