Evolocumab in Patients With Multivessel Coronary Disease After Acute Myocardial Infarction: A Target Trial Emulation (EVEREST)

Effect of Evolocumab on Non-culprit Coronary Lesions in Patients With Multivessel Disease Following Acute Myocardial Infarction: A Target Trial Emulation

The goal of this Target Trial Emulation (TTE) study is to evaluate the effect of evolocumab on clinical prognosis in patients with multivessel disease (MVD) following acute myocardial infarction (AMI) who have deferred non-culprit vessel. The main question it aims to answer is:

Does evolocumab lower risks of major adverse cardiovascular events (MACE) in patients with deferred non-culprit vessel after AMI?

Study Overview

• Status: Completed
• Conditions: Multivessel Coronary Artery Disease; Acute Myocardial Infarction (AMI)
• Intervention / Treatment: Drug: Evolocumab; Drug: Lipid Lowering Medication

Detailed Description

This study aims to investigate the potential prognostic benefits of evolocumab in patients with MVD after AMI at 2-year follow-up. The primary endpoint is MACE, defined as a composite of cardiac death, myocardial infarction, stroke, angina-driven coronary revascularization, and rehospitalization for heart failure. This is a multicentre, cohort-based TTE study and the target RCT is the FOURIER trial.

• Study Type: Observational
• Enrollment (Actual): 1862

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Zhongshan Hospital, Fudan University

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

This is a TTE study based on a multicentered, consecutive cohort of AMI patients from 2021 to 2022 at five 3rd-tier hospital in Shanghai. Patients who were diagnosed as AMI and refferred to primary invasive coronary angiography are consecutively enrolled in this cohort, regardless of revascularization treatment and lipid lowering strategy. The five hospitals are Zhongshan Hospital, Renji Hospital, Tongji Hospital, Shanghai General Hospital, and Shanghai Tenth People's Hospital.

Description

Inclusion Criteria:

• Age ≥18 years old;
• Acute myocardial infarction diagnosed at hospital admission;
• Multivessel coronary artery disease diagnosed at primary invasive coronary angiography;
• Culprit vessel successfully revascularized;
• At lease 1 non-culprit vessel with ≥50% stenosis and deferred at the opinion of the operator, and no staged revascularization within 6 months.

Exclusion Criteria:

• Cardiac shock, hemodynamically unstable, or severe heart failure (Killip IV)
• Any cardiac surgery within 6 weeks prior to screening;
• Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73m^2 at screening;
• Contraindication or allergy to iodinated contrast agent;
• Malignancy except non-melanoma skin cancers, cervical, or breast ductal carcinoma in situ within the last 5 years;
• Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed in short term.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
TTE cohort; The TTE cohort is the finally anlyzed population. The participates are enrolled upon meeting the inclusion/exclusion criteria.	Drug: Evolocumab; Evolocumab 140mg every two weeks; Drug: Lipid Lowering Medication; Any lipid lowering medication, including statin, ezetimibe, fibrates and etc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MACE	A composite of cardiac death, myocardial infarction, and rehospitalization for heart failure.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death	All-cause death	2 years
Myocardial infarction	Myocardial infarction denotes the presence of acute myocardial injury detected by abnormal cardiac biomarkers in the setting of evidence of acute myocardial ischemia, according to the Fourth Universal Definition of Myocardial Infarction (2018).	2 years
Rehospitalization for heart failure	Readmissions due to symptoms from clinically diagnosed heart failure with or without reduced left ventricular ejection fraction.	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Landmark analysis at 30 days	MACE at 30 days	30 days

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Collaborators: RenJi Hospital; Tongji Hospital; Shanghai 10th People's Hospital; Shanghai Shenkang Hospital Development Center; Shanghai General Hospital, China

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): October 31, 2025

Study Registration Dates

• First Submitted: December 15, 2024
• First Submitted That Met QC Criteria: December 15, 2024
• First Posted (Actual): December 18, 2024

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: outcome; acute myocardial infarction; multivessel coronary artery disease; target trial emulation; evelocumab; non-culprit vessel
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Necrosis; Arteriosclerosis; Arterial Occlusive Diseases; Ischemia; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; 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: SHDC2024CRI050

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD is under protection and surveilliance of Shanghai Hospital Development Ceter.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes