NCT07256197

PCSK9 Inhibitors in the Treatment of Calcific Aortic Stenosis

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

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 160 (estimated)
• Sponsor: Beijing Anzhen Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed 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. In fact, aortic valve replacement remains the only treatment option. CAS has been shown to be associated with Lp(a), LDL-C and PCSK9. Several observational studies indicated that the use of statins to decrease LDL-C levels was associated with the reduced incidence of CAS, but no randomized controlled trials (RCTs) showd that statins had any benefit on the progression of CAS. This may be related to the limited reduction of LDL-C by statin therapy. The PCSK9 inhibitors have emerged as a new lipid-lowering drug. On the basis of statin therapy, PCSK9 inhibitors can further reduce LDL-C and Lp(a) levels by 50% to 60% and 20% to 30%, respectively. Some studies reported that elevated plasma PCSK9 levels were related to CAS and PCSK9 R46L loss-of-function mutation was associated with lower rates of CAS, and importantly, some observational studies found that PCSK9 inhibitors could reduce the incidence of CAS. Our trial aims to investigate the effect of PCSK9 inhibitors on preventing or delaying the progression of CAS. A total of 160 patients with mild or moderate CAS not currently requiring valve replacement therapy will be enrolled and randomized (stratified by center) in a 1:1 ratio to two groups, the PCSK9 inhibitor treatment group (test group) or the no PCSK9 inhibitor group (control group). All patients will be followed for at least 2 years after randomization. After enrollment, telephone follow-ups will be conducted in the first month and every three months to collect data including medication use, quality-of-life scores, and clinical endpoint events. Doppler echocardiography will be collected at baseline, the 1-year visit, the 2-year visit, and before study withdrawal. Blood samples and aortic computed tomography angiography (CTA) will be collected at baseline, the 2-year visit, and before study withdrawal. The primary endpoint is the annualized mean change in peak aortic jet velocity over the 24-month follow-up period. Secondary endpoints include the annualized mean change in aortic valve area by echocardiography, the annualized mean change in aortic valve calcium score by aortic CTA, the incidence of cardiac valve surgery, and changes in quality-of-life scores. The safety endpoint is a composite of all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke. The results of this trial will provide new insights into the treatment of CAS patients. Blood samples should be tested for serological indicators, including blood routine, C-reactive protein (CRP), biochemical, coagulation function, brain natriuretic peptide (BNP), markers of myocardial injury, glycosylated hemoglobin, erythrocyte sedimentation rate, cytokines (12 items).

Conditions

• Aortic Stenosis, Calcific

Interventions

Type	Name	Description
DRUG	Treatment with PCSK9 inhibitors	Patients in experimental group are treated with PCSK9 inhibitors (Tafolecimab subcutaneously every two weeks) plus guideline-directed management in cardiovascular primary or secondary prevention.
OTHER	Treatment without PCSK9 inhibitors	Patients in control group only receive guideline-directed management in cardiovascular primary or secondary prevention without PCSK9 inhibitor treatment.

Timeline

• Start date: 2026-04-01
• Primary completion: 2028-12-31
• Completion: 2029-01-31
• First posted: 2025-12-01
• Last updated: 2026-04-02

Locations

1 site across 1 country: China