Trial reportJournal of the American Heart Association2024
Dosing and Safety Profile of Aficamten in Symptomatic Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM.
Trial report in Journal of the American Heart Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05186818 (A Phase 3, Multi-Center, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of CK-3773274 in Adults With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction), which is not on this map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 3, Multi-Center, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of CK-3773274 in Adults With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Safety and Efficacy of Mavacamten and Aficamten in Patients With Hypertrophic Cardiomyopathy.Journal of the American Heart Association · 2025Pooled it
- Towards a Quantitative Understanding of Aficamten Clinical Pharmacology: Pharmacokinetic-Cardiodynamic Modeling to Support Safety and Efficacy.CPT: pharmacometrics & systems pharmacology · 2026Trial
- Efficacy and Safety of Aficamten in Children and Adolescents With Obstructive Hypertrophic Cardiomyopathy: Study Design and Rationale of CEDAR-HCM.Circulation. Heart failure · 2026Article
- Model-Based Economic Evaluation of the First-in-Class Myosin Inhibitor Mavacamten Versus Care as Usual in Obstructive Hypertrophic Cardiomyopathy Patients from a Dutch Societal Perspective.PharmacoEconomics · 2026Article
- Cardiac Myosin Inhibitors in the Treatment of Hypertrophic Cardiomyopathy: Clinical Trials and Future Challenges.Biomolecules · 2025Review
- Review
- Cardiac myosin inhibitors: Efficacy, safety and future directions of aficamten in hypertrophic obstructive cardiomyopathy.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2025Review
- Deep learning for electrocardiogram interpretation: Bench to bedside.European journal of clinical investigation · 2025Review
- Mavacamten maintenance dose determination: insights into individualised therapy for hypertrophic cardiomyopathy.Open heart · 2025Article
- Efficacy and safety of myosin inhibitors for symptomatic hypertrophic cardiomyopathy: systematic review and meta-analysis.Archives of medical sciences. Atherosclerotic diseases · 2025Review
- Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: Clinical Advances and Therapeutic Prospects.Drug design, development and therapy · 2025Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
37 authors.
Funding
Abstract
backgroundAficamten, a novel cardiac myosin inhibitor, reversibly reduces cardiac hypercontractility in obstructive hypertrophic cardiomyopathy. We present a prespecified analysis of the pharmacokinetics, pharmacodynamics, and safety of aficamten in SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM). METHODS AND
resultsA total of 282 patients with obstructive hypertrophic cardiomyopathy were randomized 1:1 to daily aficamten (5-20 mg) or placebo between February 1, 2022, and May 15, 2023. Aficamten dosing targeted the lowest effective dose for achieving site-interpreted Valsalva left ventricular outflow tract gradient <30 mm Hg with left ventricular ejection fraction (LVEF) ≥50%. End points were evaluated during titration (day 1 to week 8), maintenance (weeks 8-24), and washout (weeks 24-28), and included major adverse cardiac events, new-onset atrial fibrillation, implantable cardioverter-defibrillator discharges, LVEF <50%, and treatment-emergent adverse events. At week 8, 3.6%, 12.9%, 35%, and 48.6% of patients achieved 5-, 10-, 15-, and 20-mg doses, respectively. Baseline characteristics were similar across groups. Aficamten concentration increased by dose and remained stable during maintenance. During the treatment period, LVEF decreased by -0.9% (95% CI, -1.3 to -0.6) per 100 ng/mL aficamten exposure. Seven (4.9%) patients taking aficamten underwent per-protocol dose reduction for site-interpreted LVEF <50%. There were no treatment interruptions or heart failure worsening for LVEF <50%. No major adverse cardiovascular events were associated with aficamten, and treatment-emergent adverse events were similar between treatment groups, including atrial fibrillation.
conclusionsA site-based dosing algorithm targeting the lowest effective aficamten dose reduced left ventricular outflow tract gradient with a favorable safety profile throughout SEQUOIA-HCM. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05186818.
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