PCSK9 Inhibitors in the Treatment of Calcific Aortic Stenosis

Trial details

Who runs it

Beijing Anzhen Hospital

Trial code

NCT07256197

Record updated

2 April 2026

Original description

Calcific aortic stenosis (CAS) can cause severe adverse cardiac events, but there are currently no effective drugs that can prevent or delay the progression of the disease. Our trial aims to investigate the effect of PCSK9 inhibitors on preventing or delaying the progression of CAS.Read full original descriptionShow less

Effect and Safety of PCSK9 Inhibitors on the Progression of Mild/Middle Calcific Aortic Stenosis: A Randomized Controlled Clinical Trial

Calcific aortic stenosis (CAS) can cause severe adverse cardiac events, but there are currently no effective drugs that can prevent or delay the progression of the disease. Our trial aims to investigate the effect of PCSK9 inhibitors on preventing or delaying the progression of CAS.

Inclusion: Aged 18-85 years old, clinically diagnosed with mild or moderate CAVS (echocardiography shows ejection fraction > 50%; valve orifice area > 1.0 cm²; left ventricular stroke volume index > 35 ml/m²; flow velocity ≥ 2 m/s and < 4 m/s, or mean transvalvular pressure gradient < 40 mmHg) and currently not requiring valve replacement therapy; LDL-C ≥ 2.6 and < 4.9 mmol/L, or Lp(a) ≥ 30 mg/dL, or receiving statin therapy due to a clinical diagnosis of hypercholesterolemia/hyperlipidemia; Patients who can understand the purpose of the trial, voluntarily participate, sign the informed consent form, and are willing to undergo clinical follow-up in accordance with the trial requirements; The position and method of measurement have been further clarified in ultrasonic measurement to ensure comparability among all enrolled patients, as follows: Aortic valve peak flow velocity, aortic valve mean pressure gradient, and valve orifice area (select images of at least 3 consecutive cardiac cycles with stable heart rate; for atrial fibrillation, select images of more than 5 consecutive cardiac cycles; obtain the peak blood flow velocity of the aortic valve orifice using continuous wave Doppler in the apical 5-chamber view; calculate the instantaneous aortic valve pressure gradient using the simplified Bernoulli equation, and calculate the standardized aortic valve orifice area using the continuity equation; all participating sonographers will receive unified training, perform measurements in fixed views and retain images, which will then be reviewed by two experienced sonographers who are blinded to the trial in the core laboratory).

Exclusion: Any previous treatment with PCSK9 inhibitors; Patients must be treated with PCSK9 inhibitors by physician's judgment; Patients who cannot maintain PCSK9 inhibitor use for 24 months; Systemic corticosteroid or cyclosporine therapy within the past 3 months; Contraindications or hypersensitivity to PCSK9 inhibitors; Active or chronic liver disease; History of intracranial hemorrhage; History of alcohol or drug abuse；; Known active infection, or severe hematologic, metabolic, or endocrine dysfunction; Active malignancy; Any life-threatening condition with life expectancy less than 12 months; Planned cardiac valve surgery; Drug-refractory arrhythmias; Fasting triglycerides (TG) >400 mg/dL (4.5 mmol/L) at baseline screening; Severe renal insufficiency (eGFR <30 mL/min/1.73 m²); Left ventricular ejection fraction < 30% or severe heart failure (NYHA class III or IV); Suspected or confirmed familial hypercholesterolemia; Thyroid hypofunction; Rheumatic aortic stenosis; Severe mitral stenosis (mitral valve area <1 cm²); Severe mitral or aortic regurgitation; Implanted permanent pacemaker or cardioverter-defibrillator; Pregnancy, lactation, or planned pregnancy.

ClinicalTrials.gov NCT07256197