Using PCSK9 inhibitors to treat calcific aortic valve stenosis

A Randomized Trial of PCSK9 Inhibitors in Calcific Aortic Valve Stenosis

This study is testing if adding a new type of cholesterol-lowering medication to the treatment of adults with calcific aortic stenosis can help slow down the disease compared to just using standard statins.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 160 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Beijing Anzhen Hospital (other)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT04968509 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effect of PCSK9 inhibitors on patients with calcific aortic stenosis (CAS), a condition that can lead to severe cardiac events. The study aims to determine whether these inhibitors, which significantly lower LDL-C and Lp(a) levels, can prevent or delay the progression of CAS compared to standard statin therapy. Participants will include adults with varying degrees of aortic stenosis who are already on stable statin therapy. The trial will assess the efficacy of adding PCSK9 inhibitors to their treatment regimen.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with mild to moderate calcific aortic stenosis or asymptomatic severe aortic stenosis who are on stable statin therapy.

Not a fit: Patients with severe symptomatic aortic stenosis requiring immediate surgical intervention may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option to slow the progression of calcific aortic stenosis and reduce the need for surgical interventions.

How similar studies have performed: While observational studies suggest a link between lipid-lowering therapies and reduced incidence of CAS, this approach using PCSK9 inhibitors is novel and has not been extensively tested in randomized controlled trials.

Eligibility criteria

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

Where this trial is running

Beijing, Beijing Municipality

• Beijing Anzhen Hospital, Capital Medical University — Beijing, Beijing Municipality, China (RECRUITING)

Study contacts

• Principal investigator: Zhijian Wang — Beijing Anzhen Hospital
• Study coordinator: Zhijian Wang

Conditions: Aortic Stenosis, PCSK9 Inhibitors, Calcific Aortic Stenosis