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Effect of Aficamten on Health Status Outcomes in Patients With Obstructive Hypertrophic Cardiomyopathy
TAKE-HOME MESSAGE
- This prespecified analysis of the SEQUOIA-HCM trial evaluated the effects of aficamten on health status in 282 patients with symptomatic obstructive hypertrophic cardiomyopathy, focusing on symptoms and quality of life. Aficamten significantly improved patient-reported outcomes, with higher mean improvements observed in the Kansas City Cardiomyopathy Questionnaire and Seattle Angina Questionnaire 7-item scores and more patients experiencing substantial benefits. These improvements emerged within 4 weeks and included reductions in chest pain, fatigue, and physical and social limitations. Upon treatment cessation, health status worsened more in the aficamten group.
- These findings suggest that aficamten can significantly enhance symptom relief and quality-of-life measures, offering a promising option for managing health status in patients with obstructive hypertrophic cardiomyopathy.
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
A primary goal in treating obstructive hypertrophic cardiomyopathy (oHCM) is to improve patients' health status: their symptoms, function, and quality of life. The health status benefits of aficamten, a novel cardiac myosin inhibitor, have not been comprehensively described.
OBJECTIVES
This study sought to determine the effect of aficamten on patient-reported health status, including symptoms of fatigue, shortness of breath, chest pain, physical and social limitations, and quality of life.
METHODS
SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM) randomized symptomatic adults with oHCM to 24 weeks of aficamten (n = 142) or placebo (n = 140), followed by a 4-week washout. The Kansas City Cardiomyopathy Questionnaire (KCCQ) and Seattle Angina Questionnaire 7-item (SAQ7) were serially administered. Changes in mean KCCQ-Overall Summary Score (KCCQ-OSS) and SAQ7-Summary Score (SAQ7-SS) from baseline to 24 weeks and following treatment withdrawal were compared using linear regression adjusted for baseline scores and randomization strata. Proportions of patients with clinically important changes were compared.
RESULTS
Among 282 participants, the mean age was 59 ± 13 years, 115 (41%) were female, and 223 (79%) were White. Baseline KCCQ-OSS (69.3 ± 20.1 vs 67.3 ± 18.8) and SAQ7-SS (72.0 ± 21.0 vs 72.4 ± 18.3) were similar between aficamten and placebo groups. Treatment with aficamten, compared with placebo, improved both the mean KCCQ-OSS (13.3 ± 16.3 vs 6.1 ± 12.6; mean difference: 7.9; 95% CI: 4.8-11.0; P < 0.001) and SAQ7-SS (11.6 ± 17.4 vs 3.8 ± 14.4; mean difference: 7.8; 95% CI: 4.7-11.0; P < 0.001) at 24 weeks, with benefits emerging within 4 weeks. No heterogeneity in treatment effect was found across subgroups. A much larger proportion of participants experienced a very large health status improvement (≥20 points) with aficamten vs placebo (KCCQ-OSS: 29.7% vs 12.4%, number needed to treat: 5.8; SAQ7-SS: 31.2% vs 13.9%, number needed to treat: 5.8). Participants' health status worsened significantly more after withdrawal from aficamten than placebo (KCCQ-OSS: -16.2 ± 19.0 vs -3.0 ± 9.6; P < 0.001; SAQ7-SS: -17.4 ± 21.4 vs -2.5 ± 13.3), further confirming a causal effect of aficamten.
CONCLUSIONS
In patients with symptomatic oHCM, treatment with aficamten resulted in markedly improved health status, including significant improvement in chest pain-related health status, than placebo. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM [SEQUOIA-HCM]; NCT05186818).
Additional Info
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Effect of Aficamten on Health Status Outcomes in Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM
J Am Coll Cardiol 2024 Nov 05;84(19)1773-1785, CF Sherrod, S Saberi, ME Nassif, BL Claggett, CJ Coats, P Garcia-Pavia, JL Januzzi, GD Lewis, C Ma, MS Maron, ZM Miao, I Olivotto, J Veselka, M Butzner, DL Jacoby, SB Heitner, S Kupfer, FI Malik, L Meng, A Wohltman, JA SpertusFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
A primary goal in the management of obstructive hypertrophic cardiomyopathy (oHCM) is to enhance patients’ symptoms, functional capacity, and quality of life.1 In the SEQUOIA-HCM study, patients with oHCM were randomized to aficamten, a second-generation cardiac myosin inhibitor, or placebo. Aficamten demonstrated significant improvements in peak exercise capacity.2 This prespecified analysis further evaluated the effects of aficamten on patient-reported health status using the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Seattle Angina Questionnaire (SAQ).3 These tools were chosen for their relevance in capturing the overlap between oHCM symptoms and those of heart failure and coronary disease.4,5
Patients randomized to 24 weeks of aficamten therapy showed clinically and statistically significant improvements in both KCCQ and SAQ scores. These improvements emerged shortly after the titration period and diminished following treatment withdrawal. Aficamten therapy resulted in a 7.9-point greater improvement in KCCQ Overall Summary Scores and a 7.8-point greater improvement in SAQ Summary Scores compared with placebo (P < .001). Notably, the improvements were substantial, with a number needed to treat of fewer than six patients to achieve a large clinical benefit (≥20-point improvement).3
While cardiac myosin inhibitors such as aficamten improve cardiac structure and function, these benefits are most effective when evaluated alongside enhancements in patients’ perceived health and functional status. Aficamten, as a next-generation agent, significantly improved the health status of patients living with oHCM. Future research should focus on optimizing the implementation of this promising therapy.
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