Effect of PCSK9 Inhibitors on Calcific Aortic Valve Stenosis

Inclusion criteria

• Patients older than 18 years of age with mild or moderate calcific aortic stenosis (peak aortic jet velocity ≥ 2m/s and < 4m/s or mean transvalvular gradients ≥ 20mmHg and < 40mmHg), or asymptomatic severe aortic stenosis (peak aortic jet velocity ≥ 4m/s or mean transvalvular gradients ≥ 40mmHg and no symptoms and/or signs related to aortic stenosis and negative exercise treadmill test)
• Patients who are required to be treated with a stable statin (atorvastatin or rosuvastatin) dose for at least 4 weeks and to have an LDL-C level of 80 mg/dL or higher or between 60 and 80 mg/dL (to convert LDL-C values to mmol/L, multiply by 0.0259) with 1 major or 3 minor cardiovascular risk factors. Major risk factors include atherosclerotic cardiovascular disease, myocardial infarction or hospitalization for unstable angina in the preceding 2 years, or type 2 diabetes mellitus. Minor risk factors include current cigarette smoking, hypertension, low levels of high-density lipoprotein cholesterol, family history of premature coronary heart disease, high sensitivity C-reactive protein (hsCRP) level of 2 mg/L or higher (to convert hsCRP values to nmol/L, multiply by 9.524), or age 50 years or older for men and 55 years or older for women
• Patients agree to participate in the study by signing an informed consent form

Exclusion criteria

• Any previous treatment with PCSK9 inhibitors
• Patients who must be treated with long-term PCSK9 inhibitors
• Patients who cannot maintain statin and/or PCSK9 inhibitor use for 24 months
• Hypersensitivity to PCSK9 inhibitors and/or statin
• Fasting triglyceride (TG) levels > 400mg/dL (4.5 mmol/L) at screening
• Thyroid hypofunction
• Active or chronic liver disease
• Severe renal dysfunction (eGFR < 30 ml/min/1.73m2)
• History of cerebral hemorrhage
• History of alcohol or drug abuse
• Known active infection, or major hematological, metabolic, or endocrine dysfunction
• Patients who have been treated with systemic steroids or cyclosporine within the past 3 months
• Active malignant tumor
• Any life-threatening condition with life expectancy less than 12 months
• Severe mitral stenosis (valve area<1cm2)
• Severe mitral or aortic regurgitation
• Patients who are scheduled to undergo heart valve surgery
• Left ventricular ejection fraction < 30% or severe heart failure (NYHA class III or IV)
• The presence of a permanent pacemaker or defibrillator
• Arrhythmias that are not controlled by drugs
• Child-bearing potential without contraception