Further Lipid-Lowering With PCSK9 Inhibitors for Cardiovascular Outcomes in High-Risk Coronary Plaques Assessed by CT Angiography

NCT06863545 | Recruiting DMC

• 1 other identifier: 2025-0052
• Study Type: interventional
• Target: 3,596
• Locations: 2 countries
• Sites: 6

Brief Summary

The primary objective was to evaluate the effect of PCSK9 inhibitors in addition to the background lipid-modifying therapy (LMT), compared with standard LMT in terms of clinical outcomes in patients with coronary CT angiography (CCTA)-detected high-risk plaques.

Conditions

Coronary Artery Disease; CT Angiography; PCSK9; Cardiovascular Events

Keywords

PCSK9 inhibitors; Lipid-lowering therapy; High-Risk Coronary Plaques; Coronary CT angiography

Outcome Measures

Primary Outcomes (1)

• Major adverse cardiac and cerebrovascular events (MACCEs)

  A composite of death from any cause, myocardial infarction (MI), coronary revascularization, or stroke.

  24 months after the last patient's randomization

Secondary Outcomes (10)

• MACCEs

  60 months after the last patient's randomization

• Individual component of MACCEs.

  24 and 60 months after the last patient's randomization

• Major adverse cardiovascular events (MACEs)

  24 and 60 months after the last patient's randomization

• Target vessel failure (TVF)

  24 and 60 months after the last patient's randomization

• Cost-effectiveness analysis

  24 and 60 months after the last patient's randomization

Study Arms (2)

PCSK9 inhibitors plus background lipid-modifying therapy

EXPERIMENTAL

Patients will receive PCSK9 inhibitors treatment and background lipid-modifying therapy for the first 12 months after randomization, and then continue background lipid-modifying therapy for the remainder of the trial.

Standard lipid-modifying therapy

ACTIVE COMPARATOR

Patients will receive standard LMT commonly used in clinical practice.

Drug: Standard lipid-modifying therapy

Interventions

PCSK9 inhibitors and background lipid-modifying therapy DRUG

Patients will receive subcutaneous injections of PCSK9 inhibitors and oral administration of background LMT (including statins and/or cholesterol absorption inhibitors) for the first 12 months after randomization, with PCSK9 inhibitors administered every 2 weeks. After the first 12 months, patients will discontinue the PCSK9 inhibitors but continue background LMT for the remainder of the trial.

Standard lipid-modifying therapy DRUG

Patients will receive standard LMT commonly used in clinical practice.

Standard lipid-modifying therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be ≥ 18 years.
• Patients with at least one target lesion meet CCTA-detected plaque features of the following:
• Degree of stenosis ≥ 50% or plaque burden ≥ 70%
• At least 2 of the following high-risk plaque features:
• i. Low-attenuation plaque ii. Positive remodeling iii. Napkin-ring sign iv. Spotty calcium
• The target lesion is located at the proximal or mid segment of left anterior descending artery, left circumflex artery or right coronary artery.
• Subject is able to confirm his/her understanding of the risks, benefits, and treatment alternatives of receiving study-related treatment. He/she or his/her legally authorized representative provides written informed consent prior to any study-related procedure.

You may not qualify if:

• Target lesions underwent or planned to revascularization.
• Patients with acute coronary syndrome.
• New York Heart Association class III or IV, or last known left ventricular ejection fraction \< 30%.
• Uncontrolled or recurrent ventricular tachycardia.
• Homozygous familial hypercholesterolemia.
• Active liver disease or hepatic dysfunction.
• Failed CCTA plaque analysis.
• Non-cardiac co-morbid conditions with life expectancy \< 2 years.
• Pregnant and/or lactating women.
• Known hypersensitivity or contraindication to statin or PCSK9 inhibitors.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (6)

Zhejiang Provincial Hospital of Traditional Chinese Medicine

Hangzhou, Zhejiang, China

RECRUITING

Hangzhou Linping First People's Hospital

Hangzhou, China

RECRUITING

The Second Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, China

RECRUITING

Zhejiang Hospital

Hangzhou, China

RECRUITING

Jinhua Central Hospital

Jinhua, China

RECRUITING

Seoul National University Hospital

Seoul, South Korea

NOT YET RECRUITING

Related Publications (14)

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• Raber L, Ueki Y, Otsuka T, Losdat S, Haner JD, Lonborg J, Fahrni G, Iglesias JF, van Geuns RJ, Ondracek AS, Radu Juul Jensen MD, Zanchin C, Stortecky S, Spirk D, Siontis GCM, Saleh L, Matter CM, Daemen J, Mach F, Heg D, Windecker S, Engstrom T, Lang IM, Koskinas KC; PACMAN-AMI collaborators. Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial. JAMA. 2022 May 10;327(18):1771-1781. doi: 10.1001/jama.2022.5218.

  PMID: 35368058 BACKGROUND

• Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, Sever PS, Pedersen TR; FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017 May 4;376(18):1713-1722. doi: 10.1056/NEJMoa1615664. Epub 2017 Mar 17.

  PMID: 28304224 BACKGROUND

• Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, Edelberg JM, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Lecorps G, Mahaffey KW, Moryusef A, Pordy R, Quintero K, Roe MT, Sasiela WJ, Tamby JF, Tricoci P, White HD, Zeiher AM; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018 Nov 29;379(22):2097-2107. doi: 10.1056/NEJMoa1801174. Epub 2018 Nov 7.

  PMID: 30403574 BACKGROUND

• Vrints C, Andreotti F, Koskinas KC, Rossello X, Adamo M, Ainslie J, Banning AP, Budaj A, Buechel RR, Chiariello GA, Chieffo A, Christodorescu RM, Deaton C, Doenst T, Jones HW, Kunadian V, Mehilli J, Milojevic M, Piek JJ, Pugliese F, Rubboli A, Semb AG, Senior R, Ten Berg JM, Van Belle E, Van Craenenbroeck EM, Vidal-Perez R, Winther S; ESC Scientific Document Group. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J. 2024 Sep 29;45(36):3415-3537. doi: 10.1093/eurheartj/ehae177. No abstract available.

  PMID: 39210710 BACKGROUND

• Virani SS, Newby LK, Arnold SV, Bittner V, Brewer LC, Demeter SH, Dixon DL, Fearon WF, Hess B, Johnson HM, Kazi DS, Kolte D, Kumbhani DJ, LoFaso J, Mahtta D, Mark DB, Minissian M, Navar AM, Patel AR, Piano MR, Rodriguez F, Talbot AW, Taqueti VR, Thomas RJ, van Diepen S, Wiggins B, Williams MS; Peer Review Committee Members. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2023 Aug 29;148(9):e9-e119. doi: 10.1161/CIR.0000000000001168. Epub 2023 Jul 20.

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• Yang S, Hoshino M, Yonetsu T, Zhang J, Hwang D, Shin ES, Doh JH, Nam CW, Wang J, Chen S, Tanaka N, Matsuo H, Kubo T, Chang HJ, Kakuta T, Koo BK. Outcomes of non-ischaemic coronary lesions with high-risk plaque characteristics on coronary CT angiography. EuroIntervention. 2023 Jan 23;18(12):1011-1021. doi: 10.4244/EIJ-D-22-00562.

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• Lee JM, Choi KH, Koo BK, Park J, Kim J, Hwang D, Rhee TM, Kim HY, Jung HW, Kim KJ, Yoshiaki K, Shin ES, Doh JH, Chang HJ, Cho YK, Yoon HJ, Nam CW, Hur SH, Wang J, Chen S, Kuramitsu S, Tanaka N, Matsuo H, Akasaka T. Prognostic Implications of Plaque Characteristics and Stenosis Severity in Patients With Coronary Artery Disease. J Am Coll Cardiol. 2019 May 21;73(19):2413-2424. doi: 10.1016/j.jacc.2019.02.060.

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MeSH Terms

Conditions

Coronary Artery Disease

Interventions

PCSK9 Inhibitors

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses

Study Officials

• Xinyang Hu

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  PRINCIPAL INVESTIGATOR

• Bon-Kwon Koo

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xinyang Hu

CONTACT

+86 0571 87784808; hxy0507@126.com

Jian'an Wang

CONTACT

+86 0571 87784808; wangjianan111@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2025
• First Posted: March 7, 2025
• Study Start: April 22, 2025
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2033
• Last Updated: February 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be available within 12 months of study completion.
• Access Criteria: Data access requests will be reviewed by an external Independent Review Panel. Requestors will be required to sign a Data Access Agreement.

Locations

KR (1); CN (5)