PCSK9 Inhibitors in the Treatment of Calcific Aortic Stenosis

Inclusion Criteria: 1. 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; 2. 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; 3. 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 Criteria: 1. Any previous treatment with PCSK9 inhibitors; 2. Patients must be treated with PCSK9 inhibitors by physician's judgment; 3. Patients who cannot maintain PCSK9 inhibitor use for 24 months; 4. Contraindications or hypersensitivity to PCSK9 inhibitors; 5. Suspected or confirmed familial hypercholesterolemia; 6. Fasting triglycerides (TG) \>400 mg/dL (4.5 mmol/L) at baseline screening; 7. Thyroid hypofunction; 8. Active or chronic liver disease; 9. Severe renal insufficiency (eGFR \<30 mL/min/1.73 m²); 10. History of intracranial hemorrhage; 11. History of alcohol or drug abuse； 12. Known active infection, or severe hematologic, metabolic, or endocrine dysfunction; 13. Systemic corticosteroid or cyclosporine therapy within the past 3 months; 14. Active malignancy; 15. Any life-threatening condition with life expectancy less than 12 months; 16. Rheumatic aortic stenosis; 17. Severe mitral stenosis (mitral valve area \<1 cm²); 18. Severe mitral or aortic regurgitation; 19. Planned cardiac valve surgery; 20. Left ventricular ejection fraction \< 30% or severe heart failure (NYHA class III or IV); 21. Implanted permanent pacemaker or cardioverter-defibrillator; 22. Drug-refractory arrhythmias; 23. Pregnancy, lactation, or planned pregnancy.