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

Impact of PCSK9 Inhibitors on Coronary Plaque Composition and Vulnerability in Patients With Coronary Artery Disease Assessed by Optical Coherence Tomography

Sponsors

Lead Sponsor: Beijing Anzhen Hospital

Source 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.

Overall Status Completed
Start Date 2019-03-02
Completion Date 2021-03-01
Primary Completion Date 2021-01-28
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
minimum fibrous-cap thickness 36 weeks
Secondary Outcome
Measure Time Frame
minimum lumen area and maximum lipid arc 36 weeks
Enrollment 60
Condition
Intervention

Intervention Type: Drug

Intervention Name: PCSK9 inhibitor plus statin

Description: Patients in the alirocumab arm will receive alirocumab 75 mg Q2W added to statin therapy (atorvastatin 20 mg/day or rosuvastatin 10mg/day).

Arm Group Label: alirocumab plus statin

Other Name: alirocumab

Intervention Type: Drug

Intervention Name: standard statin therapy

Description: Patients will continue to receive atorvastatin 20 mg/day or rosuvastatin 10 mg/day.

Arm Group Label: standard statin therapy

Intervention Type: Procedure

Intervention Name: Coronary imaging follow-up

Description: coronary angiography and OCT imaging at week 36 ± 2 weeks follow-up

Eligibility

Criteria:

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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

80 Years

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Yujie Zhou, MD Principal Investigator Beijing Anzhen Hospital
Location
Facility: Beijing Anzhen Hospital
Location Countries

China

Verification Date

2021-04-01

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Beijing Anzhen Hospital

Investigator Full Name: Yujie Zhou

Investigator Title: Vice president, professor

Has Expanded Access No
Number Of Arms 2
Arm Group

Label: alirocumab plus statin

Type: Experimental

Description: Patients in the alirocumab arm will receive alirocumab 75 mg Q2W added to statin therapy (atorvastatin 20 mg/day or rosuvastatin 10mg/day).

Label: standard statin therapy

Type: Active Comparator

Description: Patients 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.

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

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