Effect of PCSK9 Inhibitors on Coronary Atherosclerotic Plaques Derived From Optical Coherence Tomography

NCT06520904 | Recruiting Phase 4 DMC

• 1 other identifier: EPCAP-OCT
• Study Type: interventional
• Target: 396
• Locations: 1 country
• Sites: 1

Brief Summary

The presence of coronary atherosclerotic vulnerable plaque significantly impacts the clinical outcomes of patients diagnosed with coronary artery disease (CAD). However, the influence of PCSK9 inhibitors on stabilizing coronary atherosclerotic plaques in individuals with early-onset CAD, evaluated through optical coherence tomography (OCT), remains inadequately understood. Moreover, there is a notable absence of relevant randomized controlled trials investigating this phenomenon. This current study represents a single-center, randomized, controlled, open-label trial conducted among Asian patients with early-onset CAD. Its principal objective was to explore the effects of PCSK9 inhibitors on coronary atherosclerotic plaque morphology as assessed by OCT.

Conditions

Coronary Artery Disease; Optical Coherence Tomography

Keywords

Coronary Artery Disease; Lipid-lowering Therapy; PCSK9; Optical Coherence Tomography

Outcome Measures

Primary Outcomes (6)

• mFCT

  minimum fibrous cap thickness

  Immediate and 1 year after PCI

• MLA

  maximum lipid arc

  Immediate and 1 year after PCI

• Calcification

  calcification

  Immediate and 1 year after PCI

• Fibrosis

  fibrosis

  Immediate and 1 year after PCI

• Fibrolipid deposition

  fibrolipid deposition

  Immediate and 1 year after PCI

• Necrosis

  necrosis

  Immediate and 1 year after PCI

Study Arms (2)

PCSK9 inhibitor group

EXPERIMENTAL

PCSK9 Inhibitors Combined with Moderate-Intensity Statin Therapy

Drug: PCSK9 inhibitor

Intensive statin group

OTHER

Intensive statin therapy

Drug: Statin

Interventions

PCSK9 inhibitor DRUG

PCSK9 inhibitors combined with moderate-intensity statin therapy

PCSK9 inhibitor group

Statin DRUG

Intensive statin therapy

Intensive statin group

Eligibility Criteria

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

You may qualify if:

• Men aged 18-55 years and women aged 18-65 years;
• CAD patients with coronary angiographically confirmed lesions in ≥2 vessels; at least one vessel was critically diseased (50-70% stenosis level);
• LDL-C \>3.4 mmol/L without regular statin therapy or LDL-C \>1.8 mmol/L after 4 weeks of statin lipid-lowering therapy.

You may not qualify if:

• Known allergies or contraindications to PCSK9 inhibitors and/or statin therapy;
• Prior use of PCSK9 inhibitors;
• Prior history of hemorrhagic stroke;
• Prior coronary artery bypass grafting or coronary intervention;
• Inability to perform OCT imaging or unclear imaging;
• Severe renal insufficiency (creatinine clearance \< 30 mL/min);
• Severe hepatic dysfunction;
• Baseline triglycerides \> 5.6 mmol/L;
• Pregnant or lactating women;
• Life expectancy not exceeding 1 year;
• In the judgment of the investigator, unsuitable for this study for any reason.

Sponsors & Collaborators

• First Affiliated Hospital of Xinjiang Medical University: lead

Study Sites (1)

First Affiliated Hospital of Xinjiang Medical University

Ürümqi, Xinjiang, 830011, China

RECRUITING

Related Publications (14)

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  PMID: 33865792 BACKGROUND

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  PMID: 26655874 BACKGROUND

• Prati F, Romagnoli E, Gatto L, La Manna A, Burzotta F, Ozaki Y, Marco V, Boi A, Fineschi M, Fabbiocchi F, Taglieri N, Niccoli G, Trani C, Versaci F, Calligaris G, Ruscica G, Di Giorgio A, Vergallo R, Albertucci M, Biondi-Zoccai G, Tamburino C, Crea F, Alfonso F, Arbustini E. Relationship between coronary plaque morphology of the left anterior descending artery and 12 months clinical outcome: the CLIMA study. Eur Heart J. 2020 Jan 14;41(3):383-391. doi: 10.1093/eurheartj/ehz520.

  PMID: 31504405 BACKGROUND

• Erlinge D, Maehara A, Ben-Yehuda O, Botker HE, Maeng M, Kjoller-Hansen L, Engstrom T, Matsumura M, Crowley A, Dressler O, Mintz GS, Frobert O, Persson J, Wiseth R, Larsen AI, Okkels Jensen L, Nordrehaug JE, Bleie O, Omerovic E, Held C, James SK, Ali ZA, Muller JE, Stone GW; PROSPECT II Investigators. Identification of vulnerable plaques and patients by intracoronary near-infrared spectroscopy and ultrasound (PROSPECT II): a prospective natural history study. Lancet. 2021 Mar 13;397(10278):985-995. doi: 10.1016/S0140-6736(21)00249-X.

  PMID: 33714389 BACKGROUND

• Raber L, Koskinas KC, Yamaji K, Taniwaki M, Roffi M, Holmvang L, Garcia Garcia HM, Zanchin T, Maldonado R, Moschovitis A, Pedrazzini G, Zaugg S, Dijkstra J, Matter CM, Serruys PW, Luscher TF, Kelbaek H, Karagiannis A, Radu MD, Windecker S. Changes in Coronary Plaque Composition in Patients With Acute Myocardial Infarction Treated With High-Intensity Statin Therapy (IBIS-4): A Serial Optical Coherence Tomography Study. JACC Cardiovasc Imaging. 2019 Aug;12(8 Pt 1):1518-1528. doi: 10.1016/j.jcmg.2018.08.024. Epub 2018 Dec 12.

  PMID: 30553686 BACKGROUND

• Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, Graham IM, Halliday A, Landmesser U, Mihaylova B, Pedersen TR, Riccardi G, Richter DJ, Sabatine MS, Taskinen MR, Tokgozoglu L, Wiklund O; ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020 Jan 1;41(1):111-188. doi: 10.1093/eurheartj/ehz455. No abstract available.

  PMID: 31504418 BACKGROUND

• Koskinas KC, Gencer B, Nanchen D, Branca M, Carballo D, Klingenberg R, Blum MR, Carballo S, Muller O, Matter CM, Luscher TF, Rodondi N, Heg D, Wilhelm M, Raber L, Mach F, Windecker S. Eligibility for PCSK9 inhibitors based on the 2019 ESC/EAS and 2018 ACC/AHA guidelines. Eur J Prev Cardiol. 2021 Mar 23;28(1):59-65. doi: 10.1177/2047487320940102. Epub 2020 Jul 20.

  PMID: 33755142 BACKGROUND

• Nicholls SJ, Puri R, Anderson T, Ballantyne CM, Cho L, Kastelein JJ, Koenig W, Somaratne R, Kassahun H, Yang J, Wasserman SM, Scott R, Ungi I, Podolec J, Ophuis AO, Cornel JH, Borgman M, Brennan DM, Nissen SE. Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial. JAMA. 2016 Dec 13;316(22):2373-2384. doi: 10.1001/jama.2016.16951.

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• Nicholls SJ, Kataoka Y, Nissen SE, Prati F, Windecker S, Puri R, Hucko T, Aradi D, Herrman JR, Hermanides RS, Wang B, Wang H, Butters J, Di Giovanni G, Jones S, Pompili G, Psaltis PJ. Effect of Evolocumab on Coronary Plaque Phenotype and Burden in Statin-Treated Patients Following Myocardial Infarction. JACC Cardiovasc Imaging. 2022 Jul;15(7):1308-1321. doi: 10.1016/j.jcmg.2022.03.002. Epub 2022 Mar 16.

  PMID: 35431172 BACKGROUND

• 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

• Gao F, Wang ZJ, Ma XT, Shen H, Yang LX, Zhou YJ. Effect of alirocumab on coronary plaque in patients with coronary artery disease assessed by optical coherence tomography. Lipids Health Dis. 2021 Sep 12;20(1):106. doi: 10.1186/s12944-021-01528-3.

  PMID: 34511134 BACKGROUND

• Liu S, Wang P, Liu C, Jin M, Wan J, Hou J, Yang Y, Wang D, Liu Z, Fu Z. Effect of PCSK9 antibodies on coronary plaque regression and stabilization derived from intravascular imaging in patients with coronary artery disease: A meta-analysis. Int J Cardiol. 2023 Dec 1;392:131330. doi: 10.1016/j.ijcard.2023.131330. Epub 2023 Sep 4.

  PMID: 37666281 RESULT

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Hydroxymethylglutaryl-CoA Reductase 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; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses

Study Officials

• Zhenyan Fu, PhD

  First Affiliated Hospital of Xinjiang Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sen Liu, MD

CONTACT

09914366872; 463387160@qq.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: July 20, 2024
• First Posted: July 25, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: August 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)