Nationwide Cohort Study of Antiplatelet Agents as Primary Prevention (NHIS)

Antiplatelet Agents in Patients With Intermediate Coronary Artery Stenosis and Negative Fractional Flow Reserve

There is no specific recommendation regarding pharmacologic treatment as primary prevention for patients with intermediate coronary artery stenosis whose revascularization was deferred based on negative fractional flow reserve (FFR).

Current nationwide cohort study conducted using Korean National Health Insurance Service database evaluated the safety and efficacy of antiplatelet therapy in patients with intermediate coronary artery stenosis with deferred revascularization based on negative FFR (FFR>0.80).

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Coronary Artery Stenosis
• Intervention / Treatment: Drug: Antiplatelet Agents

Detailed Description

This study was nationwide cohort study conducted using Korean National Health Insurance Service database. From 2013 to 2020, reimbursement criteria of FFR were patients with no previous evidence of myocardial ischemia and intermediate coronary artery stenosis (50-70%). Patients who were evaluated by coronary angiography and FFR but did not undergo revascularization were selected and classified according to the use of antiplatelet agents after index procedure. Patients with previous history of atherosclerotic cardiovascular disease were excluded. Eligible patients were matched using propensity score in a 1:1 ratio. Primary efficacy outcome was major adverse cardiac and cerebrovascular events a composite of all-cause death, myocardial infarction, unplanned revascularization, and stroke at 5-year. Primary safety outcome was gastrointestinal bleeding, regardless of the need of transfusion.

• Study Type: Observational
• Enrollment (Actual): 4657

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gwangju, Korea, Republic of
    • Chonnam National University Medical School

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

From 2013 to 2020, the use of FFR has been reimbursed by insurance criteria for patients with 50-70% intermediate stenosis by quantitative coronary angiography in a vessel greater than 2.5 mm in the absence of prior evidence of inducible myocardial ischemia by non-invasive tests. The current study included participants who underwent FFR but did not receive revascularization, meaning that they had 50-70% intermediate stenosis and revascularization was deferred based on negative FFR between 2013 and 2020.

Description

Inclusion Criteria:

• Patients with 50-70% intermediate stenosis by quantitative coronary angiography in a vessel greater than 2.5 mm
• Patients who underwent invasive coronary angiography and FFR measurement
• Patients whose revascularization was deferred based on FFR>0.80

Exclusion Criteria:

• Patients who underween FFR measurement after expansion of reimbursement criteria of FFR (since 2021)
• Patients with history of any bleeding with blood transfusion
• Patients with use of non-vitamin K antagonist oral anticoagulants (NOAC) or warfarin
• Patients with previous atherosclerotic cardiovascular disease
• Patients with already on antiplatelet agents including dual antiplatelet agents

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Antiplatelet agents; Among patients with intermediate coronary artery stenosis (50-70% diameter stenosis by quantitative coronary angiography) but who did not undergo PCI based on negative FFR, those who were taking antiplatelet agents (aspirin or clopidogrel) are classified into this group.	Drug: Antiplatelet Agents; Aspirin or clopidogrel; Other Names: aspirin; clopidogrel
No antiplatelet agents; Among patients with intermediate coronary artery stenosis (50-70% diameter stenosis by quantitative coronary angiography) but who did not undergo PCI based on negative FFR, those who were not taking antiplatelet agents (aspirin or clopidogrel) are classified into this group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiac and cerebrovascular events	Primaey efficacy ouotcome (MACCE, a composite of all-cause death, myocardial infarction, unplanned revascularization, and stroke)	at 5 years from index procedure
Gastrointestinal bleeding	Primary safety outcome (any gastrointestinal bleeding, regardless of the need of transfusion)	at 5 years from index procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause death	All-cause death which was obtained from death certification collected by Statistics Korea at the Ministry of Strategy and Finance of South Korea.	at 5 years from index procedure
Myocardial infarction	Myocardial infarction is defined as presence of the diagnostic codes (ICD-10 I21, I22) in the primary position during hospitalization	at 5 years from index procedure
Unplanned revascularization	Percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) after index hospitalization	at 5 years from index procedure
Stroke	Stroke is defined as ischemic stroke (ICD-10 I63, I64) or intracranial hemorrhage (ICD-10 I60-62), combined with the codes of diagnostic brain imaging.	at 5 years from index procedure
Major bleeding	Major bleeding is defined as a composite of intracranial bleeding or gastrointestinal bleeding with documented transfusion.	at 5 years from index procedure
Gastrointestinal bleeding necessitated hospitalization without documented transfusion	Gastrointestinal bleeding necessitated hospitalization without documented transfusion	at 5 years from index procedure
Intracranial hemorrhage	Intracranial hemorrhage	at 5 years from index procedure

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Collaborators: Chonnam National University
• Investigators: Principal Investigator: Joo Myung Lee, MD, MPH, PhD, Samsung Medical Center; Principal Investigator: Danbee Kang, PhD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2013
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: February 20, 2024
• First Submitted That Met QC Criteria: February 20, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 12, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Prognosis; Fractional flow reserve; Coronary artery stenosis; Antiplatelet agent
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Constriction, Pathologic; Coronary Artery Disease; Coronary Stenosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel; Platelet Aggregation Inhibitors
• Other Study ID Numbers: NHIS20240220

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is National Helath Insurance Data Analysis. therefore, sharing the original patient-level data is not possible under regulation by Korean Govenment.

Drug and device information, study documents

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