Evolocumab in STEMI (EVO-STEMI)

The Effect of Evolocumab on Infarct Size in Patients With ST-segment Elevation Myocardial Infarction; Prospective, Randomized, Open Label, Controlled Trial

The goal of this clinical trial is to compare the size of myocardial infarct between evolocumab and control groups in patients with ST segment elevation myocardial infarction who undergoing primary percutaneous coronary intervention(PCI). All study participants will undergo a cardiac MRI 4 weeks after primary reperfusion. The evolocumab group will receive 420 mg before PCI via subcutaneous injection.

Study Overview

• Status: Active, not recruiting
• Conditions: ST Elevation Myocardial Infarction
• Intervention / Treatment: Drug: Repatha®

Detailed Description

The gold standard for the treatment of ST-segment elevation myocardial infarction (STEMI) is to rapidly restore myocardial blood flow through primary percutaneous coronary intervention (primary PCI) as soon as possible. While primary PCI achieves successful reperfusion of the infarct-related epicardial coronary artery in over 90% of these patients, only approximately 35% achieve ideal reperfusion to the myocardium level. This condition is termed myocardial no-reflow or microvascular obstruction (MVO). The primary pathophysiology of MVO includes severe inflammatory reactions within the ischemic vessel, distal embolization of thrombi, microthrombi formation in the microvasculature, and microvascular spasm, tissue peri-infarct edema, and intramyocardial hemorrhage. Previous studies has reported that the use of atorvastatin 80mg before PCI can reduce myocardial injury occurring during PCI in patients with acute coronary syndrome (ACS), and can improve microvascular blood flow in STEMI patients undergoing primary PCI. Furthermore, it has been reported to improve microvascular functional impairment evaluated by microvascular resistance index in non-ST-segment elevation acute coronary syndrome patients and exhibit anti-inflammatory effects. However, Two randomized trials atorvastatin 80mg did not reduce infarct size, which was primary endpoint in STEMI patients.

Recently, strong LDL cholesterol-lowering agent, PCSK9 inhibitors, have been developed and used in clinical practice, and they seem to have pleiotropic effects similar to high-intensity statins, including anti-inflammatory and antithrombotic effects. In-vitro and vivo models have shown that the introduction of human PCSK9 increases platelet aggregation in normal adult plasma and that mice without PCSK9 exhibit decreased arterial thrombosis and thrombus stability when induced . Patients with higher levels of serum PCSK9 had higher platelet reactivity after antiplatelet therapy and an increased incidence of ischemic events following coronary intervention in ACS setting. This suggests that circulating PCSK9 contributes to arterial thrombus formation, and PCSK9 inhibition may improve this. Additionally, evolocumab is known to reduce Lp(a), which is well-known for its pro-atherosclerotic and pro-inflammatory effects, by approximately 30%.

Also, Pharmaceutically, evolocumab exhibits maximum inhibitory effect against PCSK9 within just 4 hours of injection, potentially beneficial for patients with acute myocardial infarction who need a rapid effect before the infarction fully develops.

In this clinical trial, we hypothesize that administering evolocumab before primary PCI in patients with acute STEMI may reduce MVO through its antiplatelet and anti-inflammatory effects and subsequently decrease the size of the myocardial infarction.

• Study Type: Interventional
• Enrollment (Estimated): 166
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Bucheon, Korea, Republic of, 14574
    • Sejong General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Typical ischemic chest pain persists for more than 30 minutes
• An elevation of an ST segment greater than 1 mm in two consecutive leads or new-onset left bundle branch block
• Presenting more than 12 hours after the onset of symptoms

Exclusion Criteria:

• Previous history of myocardial infarction
• Previous history of coronary bypass surgery
• Cardiogenic shock that lasts more than 10 minutes or cardiac arrest
• Occlusion of the left main coronary artery
• Pregnant or have a plan of pregnancy
• Serum creatinine level is >2.5mg/dL or dialysis is required

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Evolocumab group; Evolocumab 420mg subcutaneous injection before primary PCI	Drug: Repatha®; Repatha® 140mg x 3 pens subcutaneous injection
No Intervention: Control group; without Evolocumab 420mg before primary PCI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial infarct size	assessed by cardiac MRI	1 month after primary reperfusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of MVO	assessed by cardiac MRI	1 month after primary reperfusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ST segment resolution	assessed by 12-leads ECG	1 hour after primary reperfusion
Area under the curve of enzymatic infarct size		within 48 hours after primary reperfusion
Myocardial blush grade	assessed by coronary angiography	Immediate after primary reperfusion
Corrected TIMI frame count	assessed by coronary angiography	Immediate after primary reperfusion
TIMI myocardial perfusion grade	assessed by coronary angiography	Immediate after primary reperfusion
The change of LDL-Cholesterol from baseline		1 month after primary reperfusion
The change of Lipoprotein (a) from baseline		1 month after primary reperfusion
Platelet reactivity on treatment	Assessed by Verifynow	1 month after primary reperfusion
Hs-CRP level		1 month after primary reperfusion

Collaborators and Investigators

• Sponsor: Sejong General Hospital
• Collaborators: Samsung Medical Center; Chonnam National University Hospital; Daegu Catholic University Medical Center; National Health Insurance Service Ilsan Hospital; Catholic University of Korea Eunpyeong St. Mary's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2020
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: September 30, 2023
• First Submitted That Met QC Criteria: October 10, 2023
• First Posted (Actual): October 13, 2023

Study Record Updates

• Last Update Posted (Actual): June 19, 2025
• Last Update Submitted That Met QC Criteria: June 16, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: percutaneous coronary intervention; PCSK9; Infarct size
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Necrosis; Myocardial Ischemia; Ischemia; ST Elevation Myocardial Infarction; Myocardial Infarction; Infarction; PCSK9 Inhibitors; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Antimetabolites; Serine Proteinase Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Evolocumab
• Other Study ID Numbers: EVO-STEMI_version 4.1

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
• product manufactured in and exported from the U.S.: No