Effect of Aficamten vs Metoprolol on Patient-Reported Health Status in Obstructive Hypertrophic Cardiomyopathy
Michael E. NassifPablo García‐PavíaAhmad MasriBéla MerkelyMaría Luisa Peña‐PeñaRoberto Barriales‐VillaOzlem BilenMelissa BurroughsBrian ClaggettJuan Pablo CostabelEdileide de Barros CorreiaAnne M. DybroPerry ElliottNeal K. LakdawalaGregory D. LewisAmy MannMartin S. MaronZi Michael MiaoAjith NairSteen Hvitfeldt PoulsenPatricia RéantP. Christian SchulzeScott D. SolomonAndrew Z. WangRegina SohnIndrias BerhaneStephen B. HeitnerDaniel JacobyStuart KupferFady I. MalikAmy WohltmanMichael A. FiferJohn A. Spertus
Key result
Aficamten improves KCCQ scores by ~8 points vs metoprolol in symptomatic oHCM.
- MD 7.8
- 95% CI 3.3-12.3
- P<0.001
- n=175
Why the study?
Given that improving health status is a primary treatment goal in oHCM, defining the incremental benefits of aficamten over metoprolol on symptoms, function, and quality of life was needed.
Does aficamten improve patient-reported health status compared to metoprolol in adults with symptomatic obstructive hypertrophic cardiomyopathy?
Key Points
- To compare the health status benefits of aficamten and metoprolol in patients with obstructive hypertrophic cardiomyopathy.
- Adults with symptomatic obstructive hypertrophic cardiomyopathy were randomly assigned to aficamten or metoprolol for 24 weeks
- Health status was measured using the Kansas City Cardiomyopathy Questionnaire and the Seattle Angina Questionnaire
- Changes in scores were statistically analyzed using linear regression.
- Aficamten led to a greater improvement in KCCQ-OSS by +7.8 points (95% CI: 3.3-12.3; P < 0.001) compared to metoprolol
- 38.6% of patients on aficamten had a very large improvement (≥20 points) in KCCQ-OSS vs 18.4% on metoprolol
- Smaller proportion of aficamten patients experienced worsening health status (6.8% vs 18.4%).
Study Design
Type
RCT (n=175)
Blinding
double-blind
Randomization
randomly assigned
Multicenter
Yes
Structured PICO
Does aficamten improve patient-reported health status compared to metoprolol in adults with symptomatic obstructive hypertrophic cardiomyopathy?
P
Population
175 adults with symptomatic obstructive hypertrophic cardiomyopathy, randomized to aficamten or metoprolol and followed for 24 weeks.
I
Intervention
Aficamten monotherapy for 24 weeks
C
Comparator
Metoprolol monotherapy for 24 weeks
O
Outcome
Change in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) at 24 weekspatient reported
Main Result
Mean Difference: 7.8 (95% CI 3.3–12.3)
p-value: p=< 0.001
Aficamten significantly improves patient-reported health status and physical limitation compared to metoprolol in patients with symptomatic obstructive hypertrophic cardiomyopathy.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“These additional analyses from MAPLE-HCM expand on the primary finding that aficamten is superior to metoprolol on exercise capacity, with new insights into the overall treatment effect of aficamten as well as its effect on symptoms and biomarkers in comparison to metoprolol. What's notable is patients treated with aficamten achieved a significantly greater number of clinical response categories compared with metoprolol, and that nearly 40% achieved significant improvements in patient reported symptoms.”
PGPablo Garcia-PaviaCardiologist, Hospital Universitario Puerta de Hierro, Madrid
“By directly comparing aficamten and metoprolol, the MAPLE-HCM trial expands our understanding of how aficamten may be optimally integrated into the management of patients with obstructive HCM. Currently, myosin inhibitor therapy is recommended as a second-line treatment for patients with persistent symptoms on beta-blockers. But here we show that aficamten—as monotherapy and as first-line therapy—demonstrated greater improvements in exercise capacity and symptoms than beta-blockers.”
“Cardiac myosin inhibitors differ... in that they address the underlying pathophysiology of obstructive hypertrophic cardiomyopathy, which is a hypercontractile state that leads to left ventricular outflow tract obstruction. Aficamten, which is the second drug in the class, differs somewhat from mavacamten, which is the first drug in the class. It has a shorter half-life, which makes it faster to titrate to get the beneficial effects, and in case the drug needs to be withheld for one reason or another, it goes away faster after you stop it. Mavacamten has a number of drug-drug interactions, whereas aficamten does not.”
Implication
Aficamten may be preferred over metoprolol for health status gains in obstructive HCM; extends head-to-head RCT evidence for myosin inhibitors.
Abstract
BACKGROUND The cardiac myosin inhibitor aficamten was significantly more effective than metoprolol at improving exercise tolerance in MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM), a head-to-head, international, double-blind, randomized trial in patients with obstructive hypertrophic cardiomyopathy (oHCM). Given the primary treatment goal to improve patients' health status, defining the incremental benefits of aficamten over metoprolol on patients' symptoms, function, and quality of life is needed. OBJECTIVES In this study, the authors sought to compare patient-reported health status benefits of aficamten with metoprolol. METHODS Adults with symptomatic oHCM (Kansas City Cardiomyopathy Questionnaire [KCCQ] Clinical Summary Score [CSS] ≤90; left ventricular outflow tract obstruction ≥30 mm Hg at rest or ≥50 mm Hg with Valsalva) were randomly assigned to 24 weeks of aficamten or metoprolol as monotherapy. Changes in KCCQ Overall Summary Score (OSS) and Seattle Angina Questionnaire Summary Score (SAQ-SS), collected serially throughout the trial, were compared between treatment groups at 24 weeks using linear regression, adjusted for randomization strata and baseline scores. Individual participant experiences were described by comparing categories of clinically meaningful within-participant change: ≤-5 (worse), >-5 to <+5 (no change), +5 to <+10 (small improvement), +10 to <+15 (moderate improvement), +15 to <+20 (large improvement), and ≥+20 points (very large improvement). RESULTS Among 175 randomized patients, baseline health status scores were similar between treatment groups (n = 88 aficamten; n = 87 metoprolol). Aficamten, compared with metoprolol, resulted in a greater 24-week KCCQ-OSS improvement (adjusted between-group difference: +7.8 points; 95% CI: 3.3-12.3; P < 0.001), primarily driven by a greater proportion of aficamten-treated (38.6%) vs metoprolol-treated (18.4%) patients experiencing a very large (≥20 points) KCCQ-OSS improvement (number needed to treat = 4.9; 95% CI: 3.0-13.9), and a smaller proportion experiencing worsening health status (≤-5-point change: 6.8% vs 18.4%; number needed to harm = 8.6; 95% CI: 4.7-53.3). Nonsignificant SAQ-SS improvements with aficamten vs metoprolol (+4.6 points; 95% CI -0.3 to 9.5 points; P = 0.063) were driven by significantly larger improvements in the SAQ Physical Limitation scale (+10.1 points; 95% CI: 3.9-16.2 points; P = 0.001). CONCLUSIONS Aficamten improved the health status of patients with symptomatic oHCM significantly more than did metoprolol, highlighting its potential as an effective initial therapeutic option. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM (MAPLE-HCM; NCT05767346).
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Cite This Study
Nassif et al. (2025) conducted an RCT in obstructive hypertrophic cardiomyopathy (oHCM) (n=175). Aficamten vs. Metoprolol was evaluated on Change in KCCQ Overall Summary Score (OSS) at 24 weeks (MD 7.8, 95% CI 3.3-12.3, p=< 0.001). Aficamten significantly improved the 24-week KCCQ Overall Summary Score compared with metoprolol in adults with symptomatic obstructive hypertrophic cardiomyopathy (MD 7.8; 95% CI 3.3-12.3; P<0.001).