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Impact of PCSK9 Inhibitors on Coronary Plaque Composition and Vulnerability Assessed by Optical Coherence Tomography

Phase 4
Completed
Conditions
Randomized Controlled Trials
Interventions
Drug: PCSK9 inhibitor plus statin
Drug: standard statin therapy
Procedure: Coronary imaging follow-up
Registration Number
NCT04851769
Lead Sponsor
Beijing Anzhen Hospital
Brief Summary

The study is a prospective, open-label, randomized, single-center study involving patients with intermediate coronary lesions (50%-70% diameter stenosis) and who have elevated LDL-C values (LDL-C≥100 mg/dL) despite stable statin therapy.

Eligible patients are randomized to receive either alirocumab or standard-of-care (1:1). The last dose of alirocumab will be given at week 34. Patients in the alirocumab arm will receive alirocumab 75 mg Q2W added to statin therapy (atorvastatin 20 mg/day or rosuvastatin 10mg/day). Patients in the standard-of-care arm will continue to receive atorvastatin 20 mg/day or rosuvastatin 10 mg/day. OCT images will be acquired at the baseline and at week 36 ± 2 weeks follow-up.

Detailed Description

The study is a prospective, open-label, randomized, single-center study involving patients with intermediate coronary lesions (50%-70% diameter stenosis) and who have elevated LDL-C values (LDL-C≥100 mg/dL) despite stable statin therapy.

Eligible patients included those who are (I) at least 18 years of age, (II) diagnosed as stable coronary artery disease or acute coronary syndrome during admission (III) undergoing clinically indicated coronary angiography and identified with at least one intermediate lesion (50%-70% diameter stenosis) on de novo coronary arteries, (IV) have an elevated LDL-C values (LDL-C≥100 mg/dL) despite taken rosuvastatin 10 mg/day or atorvastatin 20 mg/day for 2-4 weeks after initiation or with maximally tolerated statin therapy, (V) able to provide written, informed consent.

The study included a 36-week open-label treatment period (including post-treatment OCT imaging), starting within 4 weeks of baseline coronary angiogram. During the open-label treatment period, patients are randomized to receive either alirocumab or standard-of-care (1:1). The last dose of alirocumab will be given at week 34.

Patients in the alirocumab arm will receive alirocumab 75 mg Q2W added to statin therapy (atorvastatin 20 mg/day or rosuvastatin 10mg/day). Patients in the standard-of-care arm will continue to receive atorvastatin 20 mg/day or rosuvastatin 10 mg/day. Statin dose escalation or adding concomitant non-statin lipid-lowering therapy would be considered by their responsible physician to achieve an LDL-C target \<100 mg/dL. Antithrombotic therapy and other concomitant medications are exclusively decided by the responsible physicians. Follow-up coronary angiograms and OCT imaging analyses of the same vessels will be carried out at the end of treatment period (at week 36 ± 2 weeks, depending on patient availability) in both study arms. Regular medical examination and laboratory tests will be conducted at weeks 4, 12, 24, and 36. All enrolled patients are monitored and evaluated for safety and any other adverse events during the study period.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
Inclusion Criteria

(I) 18 - 80 years of age, (II) diagnosed as stable coronary artery disease or acute coronary syndrome during admission (III) undergoing clinically indicated coronary angiography and identified with at least one intermediate lesion (50%-70% diameter stenosis) on de novo coronary arteries, (IV) have an elevated LDL-C values (LDL-C≥100 mg/dL) despite taken rosuvastatin 10 mg/day or atorvastatin 20 mg/day for 2-4 weeks after initiation or with maximally tolerated statin therapy, (V) able to provide written, informed consent.

Exclusion Criteria
  1. Patients who have been treated previously with at least one dose of any anti-PCSK9 monoclonal antibody
  2. received target vessel revascularization
  3. Known hypersensitivity or have contraindications to any anti-PCSK9 monoclonal antibody or statins
  4. Unable to receive OCT imaging tests
  5. Known history of hemorrhagic stroke
  6. Currently under treatment for cancer
  7. Baseline triglyceride > 400 mg/dl
  8. Patients with severe liver or renal dysfunction
  9. Pregnant or breast-feeding women
  10. Considered by the investigator as inappropriate for this study for any reason

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
alirocumab plus statinCoronary imaging follow-upPatients in the alirocumab arm will receive alirocumab 75 mg Q2W added to statin therapy (atorvastatin 20 mg/day or rosuvastatin 10mg/day).
standard statin therapyCoronary imaging follow-upPatients in the standard statin arm will continue to receive atorvastatin 20 mg/day or rosuvastatin 10 mg/day. Statin dose escalation or adding concomitant non-statin lipid-lowering therapy could be considered by their responsible physician to achieve an LDL-C target \<100 mg/dL.
alirocumab plus statinPCSK9 inhibitor plus statinPatients in the alirocumab arm will receive alirocumab 75 mg Q2W added to statin therapy (atorvastatin 20 mg/day or rosuvastatin 10mg/day).
standard statin therapystandard statin therapyPatients in the standard statin arm will continue to receive atorvastatin 20 mg/day or rosuvastatin 10 mg/day. Statin dose escalation or adding concomitant non-statin lipid-lowering therapy could be considered by their responsible physician to achieve an LDL-C target \<100 mg/dL.
Primary Outcome Measures
NameTimeMethod
minimum fibrous-cap thickness36 weeks

The primary endpoint of the study is the OCT derived changes in minimum fibrous-cap thickness between baseline and follow-up.

Secondary Outcome Measures
NameTimeMethod
minimum lumen area and maximum lipid arc36 weeks

Secondary endpoints include minimum lumen area between baseline and follow-up, as well as the absolute changes in maximum lipid arc.

Trial Locations

Locations (1)

Beijing Anzhen Hospital

🇨🇳

Beijing, Beijing, China

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