Effect of Aficamten Compared with Metoprolol on Cardiac Structure and Function in Symptomatic Obstructive Hypertrophic Cardiomyopathy:
A prespecified analysis of MAPLE-HCM
Sheila M. Hegde, MD MPH1,2, Xiaowen Wang, MD, MPH, Pablo Garcia-Pavia, MD, PhD, Stoyan Getchevski, MD, Ahmad Masri, MD, Bela Merkely, MD, Michael E. Nassif, MD, Maria Luisa Peña-Peña, MD, Roberto Barriales-Villa, MD, PhD, Ozlem Bilen, MD,
Melissa Burroughs, MD, Brian Claggett, PhD, Juan Pablo Costabel, MD, Edileide de Barros Correia, MD, Anne M. Dybro, MD, PhD, Perry Elliott, MBBS, MD, Neal K. Lakdawala, MD, Amy Mann, BA, Martin S. Maron, MD, Ajith Nair, MD, Steen H. Poulsen, MD, Patricia Reant, MD, PhD, P. Christian Schulze, MD; Andrew Wang, MD, Regina Sohn, MD, PhD, Indrias Berhane, PhD,
Stephen B. Heitner, MD, Daniel L. Jacoby, MD, Stuart Kupfer, MD, Fady I. Malik, MD, PhD, Amy Wohltman, ME, Michael A. Fifer, MD, Scott D. Solomon, MD, on behalf of the MAPLE-HCM Investigators
1Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
2University of Texas Southwestern Medical Center, Dallas, TX, USA.
AUGUST 31, 2025
Background
-
Beta-blockers have served as the first-line therapy for symptomatic obstructive HCM (oHCM) for decades
-
Aficamten is an investigational, next-in-class CMI, a small-molecule selective inhibitor of the cardiac myosin ATPase, that targets and reduces hypercontractility
-
MAPLE-HCM is a phase 3 head-to-head comparative efficacy and safety study of monotherapy with aficamten vs metoprolol in adults with symptomatic oHCM
Baseline Characteristics
-
175 participants
-
Mean age: 58 ± 13 years
-
42% Female
-
80% White, 14% Asian
-
70% prior B-blocker use
-
13% CCB use
Primary Endpoint (peak VO )
Aficamten 5‒20 mg + placebo for metoprolol (n=88)
Metroprolol 50‒200 mg + placebo
for aficamten (n=87)
Adults (aged 18‒85 years) with:
-
Diagnosis of oHCM
-
NYHA class II or III
-
Resting LVOT-G ≥30 mmHg and/or post-Valsalva ≥50 mmHg
-
LVEF ≥60% at screening
-
pVO2 <100%
Randomization 1:1
End of Study
Dose adjustment based on echo and vital signs*
2
Mean Change from Baseline to Week 24
Mean (95% CI) pVO2(mL/kg/min)
22
LSM difference (SE) vs metoprolol
2.3 mL/kg/min (0.39)
P<0.0001
21
20
|
2-4 weeks (2-week SoC washout) |
Study Visits
Screening D1 W2*W4* W6* W8 W12 W16 W20 W24 W28
19
18
17
BL Week 24
*Metoprolol doses were uptitrated in 50 mg increments from 50 to 200 mg. Aficamten doses were uptitrated in 5 mg increments from 5 to 20 mg.
CCB, calcium channel blocker; CMI, cardiac myosin inhibitor; D, day; echo, echocardiogram; KCCQ, Kansas City Cardiomyopathy Questionnaire; LSM, least squared mean; LVEF, left ventricular ejection fraction; LVOT, left ventricular outflow tract;; NT-proBNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; oHCM, obstructive hypertrophic cardiomyopathy; pVO2, peak oxygen uptake; SoC, standard of care; W, week.
Systolic Function and Gradients
Resting LVOT Gradient
Valsalva LVOT Gradient
Resting LVOT Gradient (mmHg)
Valsalva LVOT Gradient (mmHg)
|
80 P < 0.001 70 60 50 40 30 20 10 0 Washout 0 2 4 6 8 12 16 20 24 28 Weeks |
80 P < 0.001 70 60 50 40 30 20 10 0 Washout 0 2 4 6 8 12 16 20 24 28 Weeks |
|
−30 mmHg (−37, −23) |
−35 mmHg (−44, −26) |
Resting LVOT-G Valsalva LVOT-G
Metoprolol Aficamten
LV Ejection Fraction (%)
Absolute LV Global Circumferental Strain (%)
Absolute LV Global Longitudinal Strain (%)
LV Ejection Fraction
Absolute LV GCS
Absolute LV GLS
−5% (−5, −3)
Treatment-corrected difference (95% CI) is adjusted for baseline echo measure, treatment, exercise mode (bicycle vs treadmill) and stratification by time of diagnosis (recent [Group 1] vs chronic [Group 2]) with corresponding P values at 24 weeks.
Horizontal dashed lines represent thresholds for gradients and normal values for LVEF.
GCS, global circumferential strain; GLS, global longitudinal strain; LV, left ventricular; LVEF, left ventricular ejection fraction; LVOT-G, left ventricular outflow tract gradient.
−1.8% (−1.8, −0.5)
−2.5% (−3.7, −1.3)
70
P < 0.001
60
55
45
35
34
33
32
31
30
29
28
P < 0.001
P < 0.001
18
65
17
16
50
15
Washout
Washout
14
Washout
0 2 4 6 8
12 16
Weeks
20 24 28
0
12
24 28
0
12
24 28
Weeks
Weeks
LVEF
Absolute LV GCS Absolute LV GLS
Cardiac Structure
22
16
P = 0.04
16
P < 0.001
21
20
19
18
17
16
15
15
14
14
13
13
12
12
Washout
11
Washout
11
Washout
0 2 4 6 8 12 16 20 24 28 0 2 4 6 8 12 16 20 24 28 0 2 4 6 8 12 16 20 24 28
Weeks Weeks Weeks
+1.6 mL/m2 (0.7, 2.5)
−0.8 mm (−1.5 −0.0)
−1.0 mm (−1.8, −0.20)
0.02
P =
Maximum Wall Thickness (mm)
Inferolateral Wall Thickness (mm)
LV End Systolic Volume Index (ml/m2)
Maximal Wall Thickness Inferolateral Wall Thickness LV ESVi
Metoprolol Aficamten
Not Shown: Interventricular Septal Wall LV Mass Index
Maximal Wall Thickness
LV ESVi
Treatment-corrected difference (95% CI) is adjusted for baseline echo measure, treatment, exercise mode (bicycle vs treadmill) and stratification by time of diagnosis (recent [Group 1] vs chronic [Group 2]) with corresponding P values at 24 weeks.
LV, left ventricular; LV; ESVi, left ventricular end systolic volume index.
Diastolic Function
LAVi Lateral E/e Septal E/e
P < 0.001
P < 0.001
P < 0.001
45
20
20
18
18
40
16
16
35
14
14
12
12
30
Washout
10
Washout
10
Washout
0
12
Weeks
24 28
0
12
Weeks
24 28
0
12
Weeks
24 28
−3.1 (−4.5, −1.7)
−2.8 (−4.0, −1.6)
−7.0 mL/m2 (−9.1, −4.8)
Left Atrial Volume Index (mm2)
LAVi
Lateral E/e'
Septal E/e'
Lateral e Septal e Lateral E/e Septal E/e
Metoprolol Aficamten
Treatment-corrected difference (95% CI) is adjusted for baseline echo measure, treatment, exercise mode (bicycle vs treadmill) and stratification by time of diagnosis (recent [Group 1] vs chronic [Group 2]) with corresponding P values at 24 weeks.
Horizontal dashed lines represent normal values left atrial volume index, lateral E/e′ , and septal E/e′.
LAVi, left atrial volume index; e', mitral annular early diastolic velocity; E/e', ratio between early mitral inflow velocity and septal and lateral mitral annular early diastolic velocity
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Disclaimer
Cytokinetics Incorporated published this content on August 31, 2025, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on August 31, 2025 at 18:06 UTC.
