PCSK 9 Inhibitor Added to High-Intensity Statin Therapy to Prevent Cardiovascular Events in Patients With ACS After PCI (SHAWN)

PCSK 9 Inhibitor Added to High-Intensity Statin Therapy to Prevent Cardiovascular Events in Patients With Acute Coronary Syndrome After Percutaneous Coronary Intervention: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study

The primary objective was to evaluate the effect of PCSK 9 Inhibitor (initiated within 4 h from PCI for the culprit lesion) with high-intensity statin treatment, compared to placebo with high-intensity statin treatment, on cardiovascular events (including cardiovascular death, myocardial infarction, stroke, re-hospitalization due to acute coronary syndromes or heart failure, or any ischemia-driven coronary revascularization) in patients with acute coronary syndrome and multiple lesions. Alirocumab was used before June 10, 2025; Tafolecimab has been used from June 10, 2025 onward.

Study Overview

• Status: Recruiting
• Conditions: Hyperlipidemias; Acute Coronary Syndrome; Percutaneous Coronary Intervention; Cardiovascular Events
• Intervention / Treatment: Drug: Placebo plus high-intensity statin; Drug: PCSK 9 Inhibitor plus high-intensity statin

Detailed Description

Patients with acute coronary syndrome (ACS) are at high-risk. ACS patients are commonly associated with multiple lesions or multivessel disease. Percutaneous coronary intervention (PCI) is an effective treatment for culprit lesions in ACS. Statin at high-intensity is recommended by current guidelines in order to prevent/slow the progression of non-culprit disease or restenosis. PCSK9 inhibitor serves as the most powerful medication in lowering LDL via promoting the expression of LDL receptors in the liver. However, if the combination of PCSK9 inhibitor with high-intensity statin treatment could significantly reduce the cardiovascular events in patients with ACS who underwent PCI remains unknown. Alirocumab was used before June 10, 2025; Tafolecimab has been used from June 10, 2025 onward.

• Study Type: Interventional
• Enrollment (Estimated): 1212
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shao-Liang Chen, MD, PhD; Phone Number: +86-25-52271351; Email: chmengx@126.com
• Study Contact Backup: Name: Jing Kan, MPH; Phone Number: +86-25-52271398; Email: kanjingok@126.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210006
      • Recruiting
      • Nanjing First Hospital
      • Contact: Shaoliang Chen, MD; Phone Number: +86 13605157029; Email: chmengx@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The subject, or their legal guardian, must have a clear understanding of the trial's design and treatment procedures. They must provide written informed consent before any trial-specific tests or procedures are conducted.
2. Both male and female subjects aged ≥18 years.
3. Subjects who have experienced an ACS and have undergone PCI for culprit lesions (either QFR or FFR < 0.8) are eligible. ACS is defined as:

(1) Unstable angina (characterized by rest pain lasting between 5 and 30 minutes or worsening exertional angina accompanied by either transient ST segment depression or elevation, or angiography revealing visually estimated diameter stenosis of 90% or greater, or a ruptured plaque or thrombotic lesion), or (2) Non-ST elevation myocardial infarction, indicated by positive troponin levels consistent with the clinical syndrome and non-ST segment elevation, or (3) ST elevation myocardial infarction, indicated by positive troponin levels consistent with the clinical syndrome and ST-segment elevation.

4. Low-density lipoprotein cholesterol levels must meet the following criteria:

1. Low-density lipoprotein cholesterol ≥70 mg/dL (≥1.8 mmol/L) in patients who have been on a stable high-intensity statin regimen for at least 4 weeks before enrollment.
2. Low-density lipoprotein cholesterol ≥90 mg/dL (≥2.3 mmol/L) in patients who have been on a moderate or low-intensity statin regimen before enrollment.
3. Low-density lipoprotein cholesterol ≥125 mg/dL (≥3.2 mmol/L) in patients who are statin-naïve or have not been on a stable statin regimen for at least 4 weeks before enrollment.

5. Subjects must have at least one culprit lesion for ACS in a major native coronary artery (diameter stenosis >70% with a QFR or FFR<0.8), and have at least one non-culprit vessel disease (diameter stenosis ≤70% with a QFR or FFR ≥0.8).

Exclusion Criteria:

1. Fasting serum triglyceride levels exceeding 400 mg/dL (exceeding 4.52 mmol/L) before randomization.
2. Coronary artery disease is located within a saphenous vein graft or an arterial graft.
3. Residual diameter stenosis greater than 50% as determined by visual examination after percutaneous coronary intervention of the culprit lesion.
4. TIMI (Thrombolysis in Myocardial Infarction) flow less than 3 in the culprit vessel after PCI.
5. Unstable clinical status, characterized by hemodynamic (including cardiogenic shock) or electrical instability.
6. Uncontrolled hypertension, indicated by multiple readings with systolic blood pressure (SBP) exceeding 180 mmHg or diastolic blood pressure (DBP) exceeding 110 mmHg.
7. New York Heart Association (NYHA) Class III or IV, and an already known left ventricular ejection fraction (LVEF) below 30%.
8. Known history of hemorrhagic stroke in last 180 days before randomization.
9. Uncontrolled cardiac arrhythmia, defined as recurrent and symptomatic ventricular tachycardia or atrial fibrillation with rapid ventricular response that has not been controlled by medications in the past 3 months before screening.
10. Severe renal dysfunction, defined by an estimated glomerular filtration rate (eGFR) below 30 ml/min/1.73m².
11. Active liver disease or hepatic dysfunction.
12. Known intolerance to rosuvastatin or any statin.
13. Known allergy to contrast medium, heparin, aspirin, ticagrelor, prasugrel, or clopidogrel.
14. Subjects who have previously received PCSK9 inhibitors.
15. Subjects who have received cholesterol ester transfer protein inhibitors within the past 12 months before enrollment.
16. Treatment with systemic steroids or systemic cyclosporine within the past 3 months.
17. Known active infection or major hematologic, metabolic, or endocrine dysfunction, as determined by the Investigator.
18. Planned non-cardiac surgery within the next 12 months.
19. Subjects who will not be able to attend the required study visits, as determined by the Investigator.
20. Currently enrolled in another investigational device or drug study.
21. History of cancer within the past 5 years, unless adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer.
22. Estimated life expectancy of less than 12 months.
23. Female of childbearing potential (age <50 years and last menstruation within the last 12 months), who did not undergo tubal ligation, ovariectomy, or hysterectomy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo plus high-intensity statin; Participants received placebo subcutaneous injections once every 2 weeks (Q2W) plus high-intensity statin treatment (Rosuvastatin, 20 mg, once daily)	Drug: Placebo plus high-intensity statin; Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen, Q2W, and oral administration of rosuvastatin (20 mg, once daily).
Active Comparator: PCSK 9 Inhibitor plus high-intensity statin; Participants received PCSK 9 Inhibitor Q2W subcutaneous injections	Drug: PCSK 9 Inhibitor plus high-intensity statin; Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen, Q2W, and oral administration of rosuvastatin (20 mg, once daily).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular events	Cardiovascular events defined as the composite of cardiovascular death, myocardial infarction, stroke or transit ischemic attack, re-hospitalization due to unstable angina or heart failure, or any ischemia-driven coronary revascularization.	12 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular death	It will be adjudicated by an independent external CEC according to protocol defined definition.	12 months after randomization
All cause death	It is defined as any death from randomization to the last visit.	12 months after randomization
Myocardial infarction	It will be adjudicated by an independent external CEC.	12 months after randomization
Ischemia-driven coronary revascularization	It will be adjudicated by an independent external CEC.	12 months after randomization
Re-hospitalization due to unstable angina or heart failure	It will be adjudicated by an independent external CEC.	12 months after randomization
Diagnostic malignant tumor	It will be adjudicated by an independent external CEC.	12 months after randomization
PCSK9 inhibitors or statin intolerance	It will be adjudicated by an independent external CEC.	12 months after randomization
Stroke	stroke will be adjudicated by an independent external CEC.	12 months after randomization

Collaborators and Investigators

• Sponsor: Nanjing First Hospital, Nanjing Medical University
• Collaborators: National Natural Science Foundation of China; Nanjing Medical University
• Investigators: Study Chair: Shao-Liang Chen, MD, PhD, Nanjing First Hospital, Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2030

Study Registration Dates

• First Submitted: July 7, 2022
• First Submitted That Met QC Criteria: July 12, 2022
• First Posted (Actual): July 14, 2022

Study Record Updates

• Last Update Posted (Actual): June 13, 2025
• Last Update Submitted That Met QC Criteria: June 10, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Metabolic Diseases; Disease; Dyslipidemias; Lipid Metabolism Disorders; Myocardial Ischemia; Syndrome; Acute Coronary Syndrome; Hyperlipidemias; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Antimetabolites; Serine Proteinase Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; PCSK9 Inhibitors; Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Other Study ID Numbers: NMU20220701

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No