Imaging and Physiologic Evaluation of Coronary Artery Disease: a Prospective Registry Study (IP-CAD)
Conditions: Ischemic Heart Disease, Atherosclerosis
Sponsor: Chonnam National University Hospital

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Imaging and Physiologic Evaluation of Coronary Artery 
Disease: a Prospective Registry Study  
 
(IP-CAD) 
 
 
 
 
 
Chonnam National University Hospital, 
Chonnam National University Medical School 
 
 
 
Principal Investigator: Young Joon Hong 
 
 

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Table of Contents 
Table of Contents 
……………………………………… 
2 
Protocol Summary 
……………………………………… 
4 
1. 
Title of Study 
……………………………………… 
6 
2. 
Clinical Research Center 
……………………………………… 
6 
3. 
Principal Investigator, Staff, Co-researchers 
……………………………………… 
6 
4. 
Background  
……………………………………… 
6 
5. 
Study Design 
……………………………………… 
7 
5.1 
Study Design 
 
 
5.2 
Patients Enrollment 
 
 
5.3 
Patient Follow-up 
 
 
6. 
End points 
……………………………………… 
7 
6.1 
Primary End point 
 
 
6.2 
Secondary End point 
 
 
6.3 
Study Timeline 
 
 
7. 
Patient Enrollment and Withdrawal 
……………………………………… 
8 
7.1 
Patient Population 
 
 
7.2 
Eligibility Criteria 
 
 
   7.2.1 Inclusion Criteria 
 
 
   7.2.2 Exclusion Criteria 
 
 
7.3 
Patient Discontinuation (Withdrawal Criteria) 
 
 
   7.3.1 Lost to Follow-up 
 
 
8. 
Protocol Procedures 
……………………………………… 
9 
8.1 
Schedule of Measurements 
 
 
9. 
Measurement of study outcome variables 
……………………………………… 
11 
9.1 
Visit 1 Screening & Baseline 
 
 
9.2 
Follow-up 
 
 
10. 
Ethical Considerations and Confidentiality 
……………………………………… 
12 
10.1 Institutional Review Board / Ethical Committee 
 
 
10.2 Participant Safety 
 
 
   10.2.1 Elements of Informed Consent 
 
 
   10.2.2 Potential Risks 
 
 
   10.2.3 Adequacy of Protection Against Risks 
 
 

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10.3 Confidentiality 
 
 
11. 
Study Organization 
……………………………………… 
14 
11.1 Steering committee and DSMB 
 
 
11.2 Clinical Event Adjudication Committee 
 
 
11.3 Data Coordination and Site Management 
 
 
12. 
Statistical Analysis 
……………………………………… 
14 
12.1 Primary End point Analysis 
 
 
12.2 Secondary End point Analysis 
 
 
12.3 Multivariable Analysis 
 
 
12.4 Survival Analysis 
 
 
13. 
Publication Policy 
……………………………………… 
16 
13.1 Data Analysis and Release of Results 
 
 
13.2 Review Process 
 
 
13.3 Authorship: Primary Outcome Paper 
 
 
13.4 Other Study Papers, Abstracts, and Presentations 
 
 
14. 
QA / QC / Clinical Monitoring 
……………………………………… 
16 
14.1 Protocol Adherence 
 
 
14.2 Data Collection : Electronic Case Report Forms (eCRF) 
 
15. 
Event Adjudication and Reporting 
……………………………………… 
18 
15.1 End point Adjudication 
 
 
16. 
Regulatory Responsibilities 
……………………………………… 
18 
16.1 Investigator Responsibilities 
 
 
16.2 IRB / EC Approval 
 
 
16.3 Informed Consent 
 
 
16.4 Study Coordinator 
 
 
17. 
Records Retention and Reports 
……………………………………… 
19 
17.1 Records 
 
 
17.2 Reports 
 
 
18. 
Investigational Agreement 
……………………………………… 
21 
19.   Appendix 
……………………………………… 
22 
   Appendix A: Definitions 
 
 
20.   References 
……………………………………… 
29 
 
 
 

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Research Summary 
Study Title 
Imaging and Physiologic Evaluation of Coronary Artery Disease: a Prospective 
Registry Study (IP-CAD) 
Principal  
Investigator 
Young Joon Hong, MD, PhD.  
 
Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju, 
Republic of Korea, 61469, 
Chonnam National University Hospital, 42 Jaebong-ro, Dong-gu, Gwangju, 
Republic of Korea, 61469, 
Telephone: 82-62-220-5778 
E-mail: hyj200@hanmail.net 
Countries 
Involved 
Republic of Korea 
Purpose / Objectives: 
To evaluate the long-term clinical outcomes and prognostic factors in patients with coronary artery 
disease (CAD) undergoing invasive coronary angiography (ICA), intravascular imaging, or invasive 
physiologic assessment.  
Study Design 
(1) Trial Design 
A prospective observational study 
 
(2) Cohorts 
Patients with CAD who undergoing ICA, intravascular imaging (including intravascular ultrasound 
[IVUS] or optical coherence tomography [OCT]), or invasive physiologic assessment (including 
fractional flow reserve [FFR], resting indexes, coronary flow reserve [CFR], or index of 
microcirculatory resistance [IMR]) 
 
(3) Study Population  
About 2,000 patients with suspected ischemic heart disease and underwent ICA, intravascular 
imaging, or invasive physiologic assessment 
 
(4) Entry criteria 
1) Inclusion criteria 
① Subject must be at least 18 years of age 
② Subjects who suspected ischemic heart disease and underwent ICA. 
③ Subjects who were performed intravascular imaging or invasive physiologic assessment 
 
2) Exclusion criteria 
① Subject with Age <18 years 
② Pregnant women 
 
(5) Outcome Measures 
1) Primary end point:  
A composite of all-cause death, myocardial infarction, or any revascularization 
 

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2) Secondary end points: 
① All-cause death at 3 years 
② Cardiac death at 3 years 
③ Myocardial infarction at 3 years 
④ Target lesion revascularization at 3 years 
⑤ Target vessel revascularization at 3 years 
⑥ Any revascularization at 3 years 
⑦ Stent thrombosis (definite or probable) at 3 years 
⑧ Cerebrovascular accident 3 years 
⑨ Bleeding (BARC type 2,3 or 5) at 3 years 
⑩ MACCE (major adverse cardiac and cerebrovascular accident), a composite of all-cause 
death, myocardial infarction, any revascularization, and cerebrovascular events 
 
 
 

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1. Title of Study 
Imaging and Physiologic Evaluation of Coronary Artery Disease: a Prospective Registry Study 
(IP-CAD) 
 
2. Clinical Research Center 
(1) Chonnam National University Hospital, Chonnam National University Medical School 
 
3. Principal Investigator, Staff, Co-researchers 
 
Name 
Center 
Position 
Principal 
investigator 
Young Joon Hong 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Professor 
Study Manager 
Seung Hun Lee 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Assistant 
Professor 
Co-researchers 
Myung Ho Jeong 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Professor 
Youngkeun Ahn 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Professor 
Ju Han Kim 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Professor 
Doo Sun Sim 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Associate 
Professor 
Min Chul Kim 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Associate 
Professor 
Seung Hun Lee 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Assistant 
Professor 
Kyung Hoon Cho 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Assistant 
Professor 
Jun Ho Ahn  
Chonnam National University Hospital, 
Chonnam National University Medical School 
Assistant 
Professor 
Dae Young Hyun 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Assistant 
Professor 
Seok Oh 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Clinical 
Professor 
Yongwhan Lim 
Chonnam National University Hospital, 
Chonnam National University Medical School 
Clinical 
Fellow 
 
4. Background 
The traditional standard method for evaluating coronary artery disease (CAD) is invasive 
coronary angiography (ICA). ICA enables the assessment of anatomic severity of the epicardial artery 
and the severity of diameter stenosis can be closely associated with myocardial ischemia. However, 
there remains concern that anatomical severity is not always identical with functional significance. 

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Actually, even the patients showed positive non-invasive tests including treadmill test, stress 
echocardiography, coronary computed tomography angiography, or nuclear imaging, less than half of 
the patients showed significant stenosis on ICA.1 Therefore, we need further investigation to overcome 
the limitations of ICA.  
In this regard, intravascular imaging, such as intravascular ultrasound (IVUS) and optical 
coherence tomography (OCT), is a useful tool for assessing the anatomical severity in more detail. 
Those imaging modalities produce cross-sectional images of CAD and they are allowing to assess 
lesion characteristics, plaque morphology, treatment planning, and optimization of the implanted stent.2 
Furthermore, imaging-guided percutaneous coronary intervention (PCI) has been shown favorable 
outcomes, compared with angiography only-guided PCI, especially in complex lesions.3–5 Meanwhile, 
there has been an ample body of evidence that invasive coronary physiology assessment, such as 
fractional flow reserve (FFR), also can be useful for assessing the functional significance.6,7 Therefore, 
the current guidelines have continuously recommended intracoronary imaging and invasive physiologic 
assessment for guiding the treatment of CAD.8–10 
The aim of the IP-CAD (Imaging and Physiologic Evaluation of Coronary Artery Disease: a 
Prospective Registry Study) is to evaluate the long-term clinical outcomes according to the imaging-
guided or physiology-guided PCI in real-world practice. 
 
 
5. Study design 
5.1 Study design 
A prospective observational study. 
 
5.2 Patients enrollment 
A total of 2,000 patients will be enrolled at single center in South Korea. Patients with CAD and 
underwent ICA with intravascular imaging or invasive physiologic assessment will be consecutive 
enrolled.  
 
5.3 Patient follow-up 
Clinical follow-up will occur at 1-month, 6-month and every 12-month after randomization. The 
investigator may conduct follow-up as telephone contacts or office visits. 
 
6. End points 
6.1. Primary end point 
A composite of all-cause death, myocardial infarction, or any revascularization 
 
6.2. Secondary end point 
① All-cause death at 3 years 
② Cardiac death at 3 years 

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③ Myocardial infarction at 3 years 
④ Target lesion revascularization at 3 years 
⑤ Target vessel revascularization at 3 years 
⑥ Any revascularization at 3 years 
⑦ Stent thrombosis (definite or probable) at 3 years 
⑧ Cerebrovascular accident 3 years 
⑨ Bleeding (BARC type 2,3 or 5) at 3 years 
⑩ MACCE (major adverse cardiac and cerebrovascular accident), a composite of all-cause death, 
myocardial infarction, any revascularization, and cerebrovascular events 
 
 
6.3 Study timeline 
Overall study will require 6~6.5 years to complete, including 3-year of recruitment and 3-year of 
follow-up followed by close out and reporting of final results. 
 
IRB approval date ~ 2027.12.31 
Subject enrollment: 2021.11.01 ~ 2024.12. (roughly 3 years of enrollment) 
End of follow-up period: 2027.12. (3 years after the end of recruitment) 
Analysis and report: ~2028.06.30 
 
7. Patient enrollment and withdrawal 
7.1 Patient population 
A total of 2,000 patients derived from a population of Korean patients with CAD and underwent ICA with 
intravascular imaging (IVUS or OCT) and invasive physiologic assessment (FFR, resting indexes, 
coronary flow reserve [CFR], or index of microcirculatory resistance [IMR]). 
 
7.2 Eligibility Criteria 
7.2.1 Inclusion Criteria 
① Subject must be at least 18 years of age 
② Subjects who suspected ischemic heart disease and underwent ICA. 
③ Subjects who were performed intravascular imaging or invasive physiologic assessment 
 
7.2.2 Exclusion criteria 
① Subject with Age <18 years 
② Pregnant women 
 
7.3 Patient discontinuation (Withdrawal criteria) 

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Once enrolled, each patient should remain in the study until the required follow-up period is complete. 
However, all patients have the right to withdraw at any point during the study without penalty or loss of 
benefit. The investigator may discontinue any patient at any time if medically necessary. Data obtained 
to the last follow-up will be used for the analysis. It will be documented whether or not each patient 
completed the clinical study. If the study treatment(s) or observations are discontinued in any patient, 
the reason will be recorded and the data coordinating center must be notified promptly.  
 
The following events will result in terminating the patient’s follow-up:  
• Patient voluntary withdrawal  
• Patient withdrawn by investigator as clinically indicated   
 
Every attempt should be made to collect follow-up information, except for those patients who specifically 
withdraw consent for release of such information. All procedures and laboratory specimens or tests 
requested for evaluation after enrollment in the study should be carried out when possible. Patients will 
not be replaced in this trial. 
 
7.3.1 Lost to follow up 
Patients that do not complete the scheduled follow-up visits and have not officially withdrawn from the 
study are considered lost to follow-up; this term does not apply to missed visits. Site personnel should 
make considerable effort to locate and communicate with the patient using all available methods (eg, 
telephone, emails, and postcards). The following contact procedure is recommended at each time point:  
 
• A minimum of 2 telephone calls on different days over the specified follow-up windows should be 
recorded in the source documentation including date, time, and site personnel initials for staff 
attempting to contact the patient.  
• If these attempts are unsuccessful, a certified letter should be sent to the patient.  
 
If the patient misses 2 consecutive scheduled contact time points and the above-mentioned attempts 
at communicating with the patient are unsuccessful, the patient will be considered lost to follow-up. 
 
8. Protocol procedures 
After the patient has been enrolled in the present study, the following procedures will take place. The 
schedule of events for this trial is located in section 8.1 Schedule of Events. The treatment strategy will 
be determined by the study-certified cardiologists. During the index procedure and appropriate medical 
follow up, it is recommended that enrolling investigators try to adhere to current ACC/AHA/SCAI or 
ESC/EACTS guidelines. 
 
8.1 Schedule of measurements 

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Visit 
Screening 
& Baseline 
Follow-Up 
1-month 
±14days 
6-month 
±30days 
12-month 
±30days 
24-month 
±30days 
36-month 
±30days 
Medical/Clinical/History 
(age, sex, risk factors, 
clinical Dx, angina status) 
× 
 
 
 
 
 
Informed Consent 
× 
 
 
 
 
 
Inclusion/Exclusion Criteria 
× 
 
 
 
 
 
Brief Physical Examination 
× 
 
 
 
 
 
Vital status 
× 
× 
× 
× 
× 
× 
Weight, height 
× 
 
 
 
 
 
12 lead ECG 
× 
×6) 
×6) 
×6) 
×6) 
×6) 
Coronary angiography2) 
× 
 
 
 
 
 
IVUS/OCT 
× 
 
 
 
 
 
Invasive physiologic 
assessment 
× 
 
 
 
 
 
CBC 
× 
 
 
 
 
 
Electrolytes, LFT 
× 
 
 
 
 
 
Creatinine, BUN 
× 
 
 
 
 
 
Fasting plasma TG, LDL, 
HDL, total cholesterol 
× 
 
 
 
 
 
Fasting glucose level 
× 
 
 
 
 
 
HbA1C 
× 
 
 
 
 
 
Medications3) 
× 
× 
× 
× 
× 
× 
Echocardiography4) 
× 
 
 
 
 
 
Clinical event5) 
 
× 
× 
× 
× 
× 
 
* Follow-up visits will allow telephone contact if clinic visits are unavailable. 
* Because all test results are collected only when performed with clinical requirements, it will not be 
recorded as a protocol violence whether or not the tests are done. 
* The last visit will be conducted within 1 month from the time when the participating center declares 
the end of follow-up. 
 
1) The subject identification code will be assigned consecutively from CNUH-0001 by the interactive 
web response system of e-CRF. Stratified randomization according to participating center, clinical 
diagnosis, and complex lesion PCI will be performed. 
2) The data of pre- and post-PCI angiography will be collected including lesion location, the number of 
diseased vessels, and the type, number, length, and diameter of DESs.  
3) Medication data included medication at baseline (before admission) and post-discharge 

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4) Echocardiography will be recorded with the closest result from the enrollment among the tests 
performed before and after the enrollment. 
5) Only end point-related clinical events (all-cause death, cardiac death, myocardial infarction, stent 
thrombosis, TLR, RVR, any revascularization, stroke, systemic embolism, bleeding [ISTH major or 
clinically relevant non-major bleeding]) will be collected. 
6) Electrocardiogram at follow up visits will only be obtained when clinically indicated such as recurrent 
chest pain, ischemia, significant arrhythmias, heart failure or other signs or symptoms of clinical 
instability.  
 
9. Measurement of study outcome variables 
9.1 Visit 1 Screening & Baseline 
① Informed consent 
Before any examination, they will be informed about the study aims, procedures, and possible risks 
and the Investigator will ensure that the patient or the patient’s legally acceptable representative has 
provided written informed consent. Written consent should include signature and date of legally 
authorized representatives and investigator. 
A copy of the signed consent form will be given to the subject or legal representative of the subject and 
the original will be maintained with the subject’s records.  
② Inclusion/Exclusion Criteria 
Review of subject eligibility 
③ Medical/Clinical/ History  
Demographic information (age, sex, risk factors, angina status, cardiac history, and cardio-cerebral 
event) will be recorded at Screening& Baseline. 
Relevant medical history, including history of current disease, other pertinent cardiac history, and 
information regarding underlying diseases will be recorded at Screening & Baseline. 
④ Brief Physical Examination, Height and Weight, Vital signs 
Height, weight, blood pressure and pulse will be measured 
⑤ 12 lead electrocardiogram, angiogram 
Angiographic data will be obtained at Screening & baseline visits. Electrocardiogram at follow up 
visits will only be obtained when clinically indicated such as recurrent chest pain, ischemia, significant 
arrhythmias, heart failure or other signs or symptoms of clinical instability 
⑥ Intravascular imaging (IVUS/OCT), invasive physiologic assessment 
IVUS, OCT, or invasive physiologic assessment data will be obtained at Screening & baseline visits.  
⑦ Laboratory data 
Complete blood count, liver function test, renal function test, electrolytes, fasting plasma glucose, and 
lipid profile will be obtained. 
⑧ Concomitant Medication 
Concomitant medication will be documented at Baseline/Screening and at follow-up. Dose, route, unit 
frequency of administration, and indication for administration and dates of medication will be 
captured. 
 
9.2 Follow-up 

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Follow-up will occur at 1-month, 6-month, 12-month, 24-month, and 36-month. Investigator or 
designee may conduct follow-up as office visits. 
① Vital signs 
Blood pressure and pulse will be performed 
② 12 lead electrocardiogram 
Electrocardiogram at follow up visits will only be obtained when clinically indicated such as recurrent 
chest pain, ischemia, significant arrhythmias, heart failure or other signs or symptoms of clinical 
instability 
③ Concomitant medications 
④ Clinical Event 
Information regarding occurrence of clinical events (any death, any myocardial infarction or any 
revascularization etc.) will be captured throughout the study.  
 
10. Ethical Considerations and Confidentiality 
10.1 Institutional Review Board (IRB) / Ethical Committee Approval 
Institutional Review Board / Ethical Committee approval for the protocol and informed consent form will 
be obtained by the investigator prior to study participation. The approval letter must be signed by the 
IRB Chairperson or authorized representative prior to beginning the present study. No changes will be 
made to the protocol or informed consent form without appropriate approval from the IRB. According to 
IRB requirements, the investigator will report study progress until it is completed. Further, any protocol 
amendments as well as associated informed consent changes will be submitted to the IRB and written 
approval must be obtained prior to implementation. 
 
10.2 Participant Safety 
10.2.1 Elements of Informed Consent 
This study will involve patients with CAD and underwent ICA with intravascular imaging or invasive 
physiologic assessment. We anticipate enrolling 2,000 patients with a mean age in the 60s. Patients 
under the age of 18 will be excluded from the study for ethical and safety concerns. Women of child-
bearing potential must have a negative serum/urine pregnancy test prior to enrollment and sexually-
active females must use contraception for up to 1-year following the index procedure. 
Prior to collecting study data, the details of the study will be explained to the participant including: (1) 
that the study represents a prospective observational study, (2) that participation is voluntary, and there 
is no penalty for withdrawal, (3) anticipated costs to the patient for participation, (4) potential risks and 
benefits for participation, and (5) contact information for additional concerns. Patients are informed of 
the purpose of the study, the treatment alternative, the need to be available for telephone follow-up and 
return clinic visits at regular intervals for questionnaires and/or medical tests, and of their options to 
accept or refuse entry into the study without affecting their clinical care. 
All patients or legally authorized patient representatives must sign the current IRB approved informed 
consent form prior to any study-related activities and the index procedure. Failure to obtain signed 
informed consent will render the patient ineligible for the study. The signed informed consent will be 
kept in the patient’s medical records and a copy given to the patient or legally authorized patient 
representative.  

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All sources of research materials will be in the form of medical records, coronary angiograms, 
electrocardiograms and routine blood work. This material will be obtained both for routine medical care 
as well as for research purposes. 
 
10.2.2 Potential Risks 
Risks of PCI with Stent Implantation 
Stents are metallic foreign bodies, which remain in the artery indefinitely. Complications that may be 
associated with stenting include but are not limited to thrombosis with reinfarction and even death, 
intramural hematoma, side branch occlusion, stroke, stent migration, arterial rupture/perforation, 
dissection, embolization, and stent deformability. The risk of stent thrombosis is amplified by early 
discontinuation of antiplatelet therapy post procedure. Evidence suggests that the incidence of these 
complications after coronary stenting is low. Stent thrombosis is a complication that is well described in 
the coronary and peripheral interventional literature. Several causes of stent thrombosis have been 
documented and there are effective strategies for minimizing this complication. Stent delivery by the 
operator to the target site is an important determinant of thrombosis. Proper apposition of the stent to 
the arterial wall with minimal residual narrowing reduces the risk of thrombosis. Treatment with aspirin 
and P2Y12 inhibitor also reduces the incidence of stent thrombosis. As a result, thrombosis is distinctly 
uncommon with proper operator technique and use of antiplatelet medication. Stent migration may 
occur but is uncommon. Endovascular snares have been developed to deal with this problem. In the 
majority of cases, experienced operators can retrieve stents that have migrated, without permanent 
complications. Arterial rupture is rare. Proper device selection as well as the choice of inflation pressure 
effectively minimizes this complication. Stenting has been successfully performed for over 20 years. 
 
Pharmacological Risks 
Patients treated with stents will be given aspirin and P2Y12 inhibitor to minimize the likelihood of 
thrombus formation at the stent site. Aspirin, however, may increase the likelihood of gastrointestinal 
adverse effects and bleeding. Clopidogrel is uncommonly associated with rash, headache, dizziness, 
stomach pain, nausea, diarrhea, indigestion, increase in cholesterol levels, leucopenia, or 
thrombocytopenia. The anticoagulation medication used also involves additional risks.  
 
10.2.3 Adequacy of Protection against Risks  
The Data Coordinating Center (DCC), CEAC, and the DSMB play key roles in detecting any hazards 
the study may pose for its participants. Data are routinely collected and regularly monitored to document 
morbidity or mortality associated with study-related procedures. Timely reports will be made to the 
DSMB. In addition, the DCC is responsible for calling the Board’s attention to significant interim safety 
concerns.  
The DSMB is responsible for advising early termination of the trial in the event if there are non-rectifiable, 
serious safety concerns in any groups. It will be the responsibility of the DSMB to review the data and 
establish limits of safety for the trial, as well as its termination, however, the final decision on the early 
termination of the study will be made by the executive committee upon the recommendations of the 
DSMB.  
 

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10.3 Confidentiality 
The confidentiality of protected health information shall be maintained by all parties involved at all times 
throughout the clinical trial. All data should be secured against unauthorized access. Study patients will 
be assigned a unique coded identifier on eCRFs. Patient data will be protected by the use of locked 
cabinets at the Clinical Centers and use of passwords, data encryption and secure, limited access 
storage of electronic data. The DCC has programs, policies and procedures in use at all times to ensure 
the security and confidentiality of the data. The explicit issue of privacy and confidentiality is outlined in 
the Informed Consent Form.  
 
11. Study Organization 
11.1 Steering Committee and Data Safety Monitoring Board (DSMB) 
The executive steering committee comprised of the chairperson and the principal investigator 
approved the study design, protocol, and amendments issued to the DSMB and the participating 
centers. An independent DSMB will review the safety data from the study and construct 
recommendations for adverse events/serious adverse events, protocol deviation, and follow-up case 
reports. Scheduled DSMB meetings will discuss safety or compliance issues and will provide advice 
on modifying or stopping the study as needed. However, the final decisions regarding changes in the 
study protocol remain in the hands of the executive steering committee. In addition, the DSMB will 
help to conduct the trial appropriately by reviewing and reporting the cumulative investigational data 
for accuracy and completeness, ensuring protocol compliance. The DSMB will develop a consensus 
understanding of all trial end points and definitions used in the event adjudication process. 
 
11.2 Clinical Event Adjudication Committee (CEAC) 
CEAC is comprised of interventional and non-interventional cardiologists who are not participants in the 
study. The CEAC is charged with the development of specific criteria used for the categorization of 
clinical events and clinical end points in the study which are based on protocol. At the onset of the trial, 
the CEAC will establish explicit rules outlining the minimum amount of date required, and the algorithm 
followed in order to classify a clinical event. All members of the CEAC will be blinded to the primary 
results of the trial. 
The CEAC will meet regularly to review and adjudicate all clinical events. The Committee will also 
review and rule on all deaths that occur throughout the trial. 
 
11.3 Data Coordination and Site Management 
Data coordination and site management services will be performed at the Heart Center and Biomedical 
Research Institute of Chonnam National University Hospital. 
 
12. Statistical Analysis 
12.1. Primary End point Analysis 
Primary end points (the composite rate of all-cause death, myocardial infarction, or any 

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revascularization) will be analyzed with Kaplan-Meier survival with log-rank test.  
 
12.2. Secondary End point Analysis 
The individual components of ischemic and bleeding events will be with Kaplan-Meier survival with log-
rank test at 3 years after enrollment. 
 
Primary End point 
Statistical methods 
Time point of analysis 
MACE (a composite of death, any MI, or 
any revascularization) 
Kaplan-Meier survival esti
mates and log-rank tests 
3 year after enrollment 
 
Secondary End point 
Statistical methods 
Time point of analysis 
All-cause and cardiac death 
χ2-test 
Kaplan-Meier survival esti
mates and log-rank tests 
3 year after enrollment 
Any myocardial infarction  
χ2-test 
Kaplan-Meier survival esti
mates and log-rank tests 
3 year after enrollment 
Target-lesion revascularization (clinically 
driven revascularization) 
χ2-test 
Kaplan-Meier survival esti
mates and log-rank tests 
3 year after enrollment 
Target-vessel revascularization 
(clinically driven revascularization) 
χ2-test 
Kaplan-Meier survival esti
mates and log-rank tests 
3 year after enrollment 
Any revascularization (clinically driven 
revascularization) 
χ2-test 
Kaplan-Meier survival esti
mates and log-rank tests 
3 year after enrollment 
Stent thrombosis 
χ2-test 
Kaplan-Meier survival esti
mates and log-rank tests 
3 year after enrollment 
Cerebrovascular accident (CVA) 
χ2-test 
Kaplan-Meier survival esti
mates and log-rank tests 
3 year after enrollment 
Bleeding (BARC type 2, 3 or 5) 
χ2-test 
Kaplan-Meier survival esti
mates and log-rank tests 
3 year after enrollment 
 
 
12.3. Multivariable Analyses 
Multivariable predictors of all primary and secondary end points will be determined using multiv
ariable regression models, using either binary or Cox’s proportional hazard method. Forward or 
backward stepwise selection algorithms will be used to select predictors as needed. Baseline de
mographic and clinical variables that are predictive at the 0.1 level will be included in the mod
els. The purpose of this is two-fold: to do a covariate adjusted analysis of treatment for all pri
mary and secondary end points and to identify the risk factors which are associated with the s
tudy end points.  
 
12.4. Survival Analyses 
All time-to-event outcomes will be summarized using Kaplan-Meier survival estimates and comp

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ared between groups using log-rank tests. 
 
13. Publication Policy  
Study derived data are the property of the participating investigators. However, individual investigators 
will not use study related data for any purpose other than study completion or for generating publication 
material as stated in the study site agreement without prior consent from the executive committee.  
 
13.1 Data Analysis and Release of Results 
No results will be released publicly before completion of the final analysis regarding the primary end 
point of this study. The statistical analysis will be performed according to the pre-specified analysis plan 
as described in this protocol. Any decisions on release of results will be undertaken by the Executive 
Committee after the approval of the DSMB. 
 
13.2 Review Process 
The Executive Committee will review the primary outcome data according to the pre-specified statistical 
analysis plan, and then will (i) decide on the early dissemination of the information at national and 
international scientific meetings (ii) provide the data to the publications committee which will in turn (a) 
first prepare a formal presentation to the Steering Committee members and (b) after taking under 
account the input and comments of the Steering Committee will proceed with submitting the manuscript 
to the Executive Committee. No study results will be released to the scientific or lay community without 
the approval of the Executive Committee. 
 
13.3 Authorship: Primary Outcome Paper 
Authorship of the primary outcome paper will be credited collectively to the “Investigators”. 
 
13.4 Other Study Papers, Abstracts and Presentations 
Manuscripts on Ancillary Studies or Subset Analyses should be approved by the Executive Committee. 
The investigators significantly contributing to the study, considering both the number of patients enrolled 
by the specific investigators and their contribution to the study design will have the priority in the 
authorships of the ancillary studies or subset analysis. Each presentation of results on behalf of the 
investigators should have the approval of the Executive Committee.  
 
14. Quality Assurances, Quality Control and Clinical Monitoring 
The purposes are: 
• To ensure accuracy of study data; 
• To provide constructive feedback to site and core laboratory staff to improve and/or maintain high 
performance; 

IP-CAD_CNUH-2021-314_November 04, 2021 
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• To document data quality for the study record. 
This section addresses of issues with respect to protocol adherence, data collection at the clinical 
centers, and interpreter variability at the core laboratories. 
 
14.1 Protocol Adherence 
There are three key components, each of which is pre-specified. The DATABASE will be programmed 
to monitor: eligibility criteria, correct treatment administration, and completion in a timely manner of all 
required data collection (no missed visits, missed studies or specimens). Eligibility criteria are also 
checked for all or a random sample of patients at every clinic site visit by auditing the patient’s 
record/worksheet. 
It is the Investigator's responsibility to ensure that there are no deviations from the protocol except in 
cases of medical emergencies, when the deviation is necessary to protect the life or physical well-being 
of the patient. The DCC will monitor these aspects of protocol adherence continually. In addition, clinic 
site personnel will have clearly specified timeframes for entry of all data and for resolution of any edit 
queries. All of these aspects of protocol can be monitored at the DCC via real-time reporting, in 
aggregate and by clinic site. 
Any of the protocol violations listed below will be reviewed immediately by the DCC and communicated 
to the principal investigator. All remedial actions will be jointly decided and, in general, implemented by 
the DCC. Any clinical site being considered for temporary or permanent termination of patient 
recruitment may be visited administratively by the monitoring group. The major protocol violations for 
this study consist of, but are not limited to, the following:  
 
Protocol Violations: 
• Eligibility not confirmed, or subject found to be ineligible; 
• Informed consent not obtained (or not obtained in a timely manner); 
• Failure to conduct protocol required clinical follow-ups and within time windows; 
 
In the event of any deviation from the protocol, the Investigator will be notified of the site’s non-
compliance. Corrective actions will be required if necessary. After any one violation, the DCC will work 
closely with the site PI to ensure further violations are avoided. Any clinic investigator, certified for the 
trial, who commits any two of the above violations will be immediately considered for suspension from 
participation in the trial and the clinic site principal investigator will also be given notice that further 
violations by investigators at that site may result in site suspension (after an administrative site visit). If 
a site is suspended early in the trial, all patient recruitment and follow-up (except for vital status and 
safety) may be terminated. A site suspended later in the trial may still be required to complete follow-
up on those subjects already randomized, assuming that the site’s adherence to the follow-up protocol 
is satisfactory or can be remediated.  
 
14.2 Data Collection: Electronic Case Report Forms (eCRF) 
DCC personnel will determine form content, considering (1) Identify the minimal set of measurements 
for the specified variables; (2) Choose those measurements (if more than one candidate) which are 
valid and reliable and, other considerations being equal, are least burdensome to the subject; and (3) 

IP-CAD_CNUH-2021-314_November 04, 2021 
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Develop, test and assess reliability of new measures as required. Experienced DCC staff will then order 
and format items to ensure clarity, smooth flow and to minimize missing information, using clear skip 
patterns, consistent coding for all close-ended items, and standard "footers" to identify form name, 
version date, and page number. Standard, modular data forms will be identified and developed to be 
used in both the Trial and Registry as needed.  
Case report forms will be developed by the Clinical Research Center as an online electronic form where 
investigators from individual site can access and input the data via the internet 
 
15. Event Adjudication and Reporting 
15.1 End point Adjudication. 
With the exception of all-cause mortality, most end points will require clear, prespecified criteria, and 
centralized review. These end points will be captured during patient interview, supplemented by death 
certificates; hospital record abstracts and related reports (autopsy, biopsy, diagnostic output).  
From extensive experience, the following approach is proposed. First, all required documents, reports, 
hospital records will be identified, made anonymous, and copied to the DCC by clinical staff. Second, 
the DCC will check to ensure confidentiality and, if required, have the records centrally abstracted onto 
standard forms by trained DCC staff. Central abstraction in large (>30) batches is recommended to 
reduce variability and secular drift and maintain adequate accuracy and completeness. Third, centrally 
prepared forms and documents will be circulated to CEAC members for assessment. 
 
16. Regulatory Responsibilities 
16.1 Investigator Responsibilities  
The investigator is responsible for ensuring that the trial is conducted according to all signed 
agreements, the study protocol and good clinical practice (GCP) requirements. Also, each investigator 
must complete and sign the Investigator's Agreement. In signing, the investigator agrees to: 
• Sign and adhere to the Investigator Agreement 
• Participate in Investigator meetings and training sessions as scheduled by Sponsor 
• Maintain up-to-date angiographic and intravascular ultrasound equipment (if applicable) 
• Be willing to provide original cine films/CD ROMs/intravascular ultrasound videotape for analysis 
• Have access to cardiac surgery 
• Be willing to perform and be capable of performing treatment procedures as outlined in this protocol 
• Comply with all required elements of this protocol (e.g., perform testing and follow-up as specified, 
especially during personnel transitions) and supply angiographic material suitable for quantitative 
analysis 
• Obtain written Informed Consent from each study participant before any study specific procedures 
are performed in accordance with GCP 
• Complete all electronic case report forms for completed patients visits and/or applicable events prior 
to scheduled monitoring visits 
• Adhere to all relevant Core Laboratory requirements and, 
 
 
16.2 Institutional Review Board (IRB) or Ethics Committee Approval 

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The investigator must submit the study protocol to IRB or Ethics Committee and obtain their written 
approval before being allowed to conduct and participate in the study. The investigator is also 
responsible for fulfilling any conditions of approval imposed by the IRB, such as regular reporting, study 
timing, etc. The investigator will provide the Sponsor with copies of such approvals and reports. 
 
16.3 Informed Consent 
Part of the IRB/Ethics Committee approval must include approval of an Informed Consent text specific 
to the study. The investigator must administer this approved Informed Consent text to each prospective 
study patient and obtain the patient's signature on the text prior to enrollment in the study. This may be 
modified to suit the requirements of the individual site. The investigator will provide the Sponsor with a 
copy of the approved Informed Consent for his/her site. 
 
16.4 Study Coordinator 
To assure proper execution of the study protocol, each investigator must identify at least one study 
coordinator. Working with and under the authority of the investigator, the study coordinator assures that 
all study requirements are fulfilled and is the contact person at the site for all aspects of study 
administration. 
 
17. Records Retention and Reports  
To comply with ICH guidelines, the Primary Investigator will maintain all records relevant to this study 
for 2 years following study completion, unless the records are archived by an external vendor. The 
investigator shall take responsibility for maintaining adequate and accurate hard copy source 
documents of all observations and data generated as required during this study. Such documentation 
may be subject to inspection by appropriate regulatory agencies.  
 
17.1 Records 
investigator must maintain the following accurate, complete, and current records relating to the conduct 
of the investigation. (The data for some of these records may be available in computerized form from 
the Data Coordinating Center; however the final responsibility for maintaining remains with the 
investigator.)   
• All correspondence with another investigator, an IRB, a Core Laboratory, the Sponsor, a monitor, 
Data Coordinating Center, including required reports. 
 
• Records of each subject's case history, including study-required Case Report Forms, evidence of 
informed consent, the condition of each subject upon entering and during the course of the 
investigation, relevant medical history, the results of all diagnostic testing, and the date of each 
study treatment. 
 
17.2 Reports 
Below is a list of the reports which are the investigator's responsibility to generate. The table also 
shows to whom the report is to be sent and with what frequency or within what time constraints. While 

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some of these reports will be developed by or with the assistance of the Data Coordinating Center, 
the final responsibility for them rests with the investigator.  
 
Reports Required from Clinical Investigators: 
Type of Report 
Prepared by Investigator For: 
Time Constraints of 
Notification 
Patient withdrawal 
DCC 
Notify within 7 days 
Annual progress report 
EC/Principal investigator 
Submitted per 1 year 
Deviations from investigational plan 
IRB 
Per local standard. 
EC/Principal investigator 
Notify within 7 days. 
Informed consent not obtained 
DCC/IRB 
Notify within 7 days. 
Final summary report 
EC/Principal investigator 
Within 1 month. 
* DCC: Data Coordinating Center; DSMB; Data Safety Monitoring Board; EC: Executive Committee 
(Co-researchers) 
 
 

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18. Investigational Agreement  
I have read and understand the protocol (including the Investigator’s Brochure) and agree that it 
contains all the ethical, legal and scientific information necessary to conduct this trial. I will personally 
conduct the study as described and agree to adhere strictly to the attached protocol.  
I will provide copies of the protocol to all physicians, nurses and other professional personnel, who 
under my responsibility will participate in this study. I will discuss the protocol with them to assure that 
they are sufficiently informed regarding the drugs used in the study, the concurrent medications, the 
efficacy and safety parameters, and the overall execution of the study in general. I am aware that this 
protocol must be approved by the Institutional Review Board (IRB) or Ethics Committee (EC) 
responsible for such matters in the clinical study facility where the drug will be tested, prior to 
commencement of this study. I agree that clinical data entered on case report forms by the staff and I, 
can be utilized in various ways including, but not limited to, publication in peer journals, submission as 
abstracts, submission to governmental regulatory authorities and/or in combination with clinical data 
gathered from other research sites, whenever applicable. I agree to allow monitors and auditors as well 
as inspectors from regulatory authorities, full access to all medical records at the research facility for 
patients screened in the study. 
I agree to provide all patients with informed consent forms, as required by government and ICH 
regulations. I further agree to report to the DCC any adverse experiences in accordance with the terms 
of this protocol, KFDA regulation, and ICH guideline. 
 
 
 
 
 
 
 
 
 
Principal Investigator 
(print) 
 
 
Principal Investigator (signature) 
 
Date 
Institution Name/Location 
 

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19. Appendix. Definitions 
Angina  
Canadian Cardiovascular Society Classification of Stable Angina 
I. Ordinary physical activity does not cause angina, such as walking or climbing stairs. Angina occurs with 
strenuous, rapid or prolonged exertion at work or recreation.  
II. Slight. Slight limitation of ordinary activity. Angina occurs on walking or climbing stairs rapidly, walking 
uphill, walking or stair climbing after meals, or in cold, in wind, under emotional stress or only during the few 
hours after awakening. Angina occurs on walking more than two blocks on the level and climbing more than one 
flight of ordinary stairs at a normal pace and in normal condition.  
III. Marked. Marked limitation of ordinary physical activity. Angina occurs on walking one to two blocks on the 
level and climbing one flight of stairs in normal conditions and at a normal pace.  
IV. Inability. Inability to carry on any physical activity without discomfort. angina symptoms may be present at 
rest.  
 
Braunwald Classification of Unstable Angina 
I. New onset of severe or accelerated angina: Patients with new onset (< 2 months in duration) exertional angina 
pectoris that is severe or frequent (> 3 episodes/day) or patients with chronic stable angina who develop 
accelerated angina (that is, angina distinctly more frequent, severe, longer in duration, or precipitated by distinctly 
less exertion than previously) but who have not experienced pain at rest during the preceding 2 months.  
II. Angina at rest, subacute: Patients with 1 or more episodes of angina at rest during the preceding month but not 
within the preceding 48 hours.  
III. Angina at rest, acute: Patients with 1 or more episodes of angina at rest within the preceding 48 hours.  
 
Complex lesions 
Defined as 
1. 
True bifurcation lesion (Medina 1,1,1/1,0,1/0,1,1) with side branch ≥2.5mm size 
2. 
Chronic total occlusion (≥3 months) as target lesion  
3. 
Unprotected LM disease PCI (LM ostium, body, distal LM bifurcation including non-true bifurcation) 
4. 
Lesion needed ≥2 more overlapping stents or lesion length ≥30mm by visual estimation 
5. 
Multivessel PCI (≥2 vessels treated at one PCI session) 
6. 
Multiple stent needed (≥3 more stent per patient) 
7. 
In-stent restenosis lesion as target lesion  
8. 
Severely calcified lesion (encircling calcium in angiography) 
 
Cerebrovascular accident (CVA) or Stroke 

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Sudden onset of vertigo, numbness, dysphasia, dysarthria or central neurologic deficit secondary to vascular 
lesions of the brain such as hemorrhage, embolism, thrombosis, or rupturing aneurysm, that persists for > 72 hours 
 
* CVA type 
1. 
Hemorrhagic: A stroke with documentation on imaging (e.g., CT scan or MRI of hemorrhage in the 
cerebral parenchyma, or a subdural or subarachnoid hemorrhage). Evidence of hemorrhagic stroke 
obtained from lumbar puncture, neurosurgery, or autopsy can also confirm the diagnosis. 
2. 
Nonhemorrhagic: A focal neurological deficit that results from a thrombus or embolus (and not due to 
hemorrhage) that appears and is still partially evident for more than 24 hours 
3. 
Unknown/no imaging performed: if the type of stroke could not be determined by imaging or other 
means (from lumbar puncture, neurosurgery, or autopsy) 
 
Death  
Death defined by the Academic Research Consortium is as follows:  
All death is considered to be cardiac death unless an unequivocal noncardiac cause can be established. Specifically, 
any unexpected death even in patients with coexisting potentially fatal noncardiac disease (eg, cancer, infection) 
should be classified as cardiac. The cause of death (cardiac vs. non-cardiac) will be adjudicated by an independent 
clinical event adjudication committee 
Cardiac death: Any death due to proximate cardiac cause (eg, myocardial infarction, low-output failure, fatal 
arrhythmia), unwitnessed death and death of unknown cause, and all procedure-related deaths, including those 
related to concomitant treatment, will be classified as cardiac death.  
Vascular death: Death caused by noncoronary vascular causes, such as cerebrovascular disease, pulmonary 
embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular diseases.  
Non-cardiovascular death: Any death not covered by the above definitions, such as death caused by infection, 
malignancy, sepsis, pulmonary causes, accident, suicide, or trauma.  
 
Diabetes 
Defined as 
1. 
History of diabetes, regardless of duration of disease, need for antidiabetic agents, or  
2. 
a fasting blood glucose > 126 mg/dl. 
The type of diabetic control should be noted: 
① None 
② Diet: Diet treatment 
③ Oral: Oral agent treatment 
④ Insulin: Insulin treatment (includes any combination of insulin) 
 
Enrolled Patient  
The point of enrollment occurs when a patient or patient’s legally authorized representative has provided written 
informed consent to participate in the trial 
 

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Myocardial Infarction (MI)  
Myocardial Infarction Classification and Criteria for Diagnosis is defined by the Fourth Universal Definition of 
Myocardial Infarction 23 as follows: 
Type  
Biomarker criteria 
Time frame 
Necessary additional criteria 
Type 1: 
Spontaneous 
Rise and/or fall of cTn values 
with at least one value above 99th 
percentile URL 
None 
Requiring at least one of the following:  
- Symptoms of acute myocardial ischemia 
- New ischemic ECG changes 
- Development of pathological Q waves 
- Imaging evidence of new loss of viable myocardium or 
new regional wall motion abnormality in a pattern 
consistent with an ischemic etiology 
- Identification of a coronary thrombus by angiography 
including intracoronary imaging or by autopsy 
Type 2: 
Ischemic 
imbalance 
Rise and/or fall of cTn values 
with at least one value above 99th 
percentile URL 
None 
Requiring at least one of the following:  
- Symptoms of acute myocardial ischemia 
- New ischemic ECG changes 
- Development of pathological Q waves 
- Imaging evidence of new loss of viable myocardium or 
new regional wall motion abnormality in a pattern 
consistent with an ischemic etiology 
Type 3: 
Cardiac death 
before biomarkers 
drawn 
None 
None 
- Symptoms suggestive of myocardial ischemia accompanied 
by presumed new ischemic ECG changes or ventricular 
fibrillation 
- Myocardial infarction is detected by autopsy 
Type 4a: 
After 
percutaneous 
coronary 
intervention (PCI) 
One of the following: 
Elevation of cTn values >5 times 
the 99th percentile URL in 
patients with normal baseline 
values 
Rise of postprocedural cTn values 
>20% in patients with cTn level 
are stable or falling 
Within 48 
hours after 
PCI 
Requiring at least one of the following:  
- New ischemic ECG changes 
- Development of new pathological Q waves 
- Imaging evidence of new loss of viable myocardium or 
new regional wall motion abnormality in a pattern 
consistent with an ischemic etiology 
- Angiographic findings consistent with a procedural flow-
limiting complication such as coronary dissection, 
occlusion of a major epicardial artery or a side branch 
occlusion/thrombus, disruption of collateral flow, or distal 
embolization 
Type 4b: 
Stent thrombosis 
Rise and/or fall of cTn values 
with at least one value above 99th 
percentile URL 
Acute, 0~24 
hours; 
Subacute, 
>1~30 days; 
Late, >30 
days~1 year; 
Very late, 
> 1 year 
Documented by angiography or autopsy using the same 
criteria utilized for type 1 myocardial infarction  
Type 4c: 
PCI restenosis 
Focal or diffuse restenosis, or a 
complex lesion associated with a 
rise and/or fall of cTn values 
above the 99th percentile URL 
None 
Same criteria utilized for type 1 myocardial infarction 
Type 5: 
After coronary 
artery bypass 
grafting (CABG) 
Elevation of cTn values >10 
times the 99th percentile URL in 
patients with normal baseline cTn 
values.  
In patients with elevated 
preprocedure cTn in whom cTn 
levels are stable (≤20% variation) 
or falling, the postprocedure cTn 
must rise by >20%.  
Within 48 
hours after 
CABG 
Requiring at least one of the following: 
- Development of new pathological Q waves 
- Angiographic documented new graft occlusion or new 
native coronary artery occlusion 
- Imaging evidence of new loss of viable myocardium or 
new regional wall motion abnormality in a pattern 
consistent with an ischemic etiology. 

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cTn = cardiac troponin; ECG = electrocardiogram; URL = Upper Reference Limit (defined 99th percentile of 
normal reference range).  
 
Principal Investigator  
A physician-specialist responsible for overseeing trial conduct at all sites, protocol compliance, and relevant 
KFDA regulations  
 
Repeat coronary revascularization 
See revascularization 
 
Restenosis  
Re-narrowing of the artery following the removal or reduction of a previous narrowing. 
 
Binary restenosis: Percent diameter stenosis > 50% at angiographic follow-up 
 
Revascularization  
Revascularization is defined by the Academic Research Consortium as follows:  
 
Target lesion revascularization: TLR is defined as any repeat percutaneous intervention of the target lesion or 
bypass surgery of the target vessel performed for restenosis or other complication of the target lesion. All TLRs 
should be classified prospectively as clinically indicated* or not clinically indicated by the investigator prior to 
repeat angiography. An independent angiographic core laboratory should verify that the severity of percent 
diameter stenosis meets requirements for clinical indication and will overrule in cases where investigator reports 
are not in agreement. The target lesion is defined as the treated segment from 5 mm proximal to the stent and to 
5 mm distal to the stent. 
Target vessel Revascularization: TVR is defined as any repeat percutaneous intervention or surgical bypass of 
any segment of the target vessel. The target vessel is defined as the entire major coronary vessel proximal and 
distal to the target lesion, which includes upstream and downstream branches and the target lesion itself. 
Non Target Lesion Revascularization (non-TLR): Any revascularization in a lesion other than the target lesion is 
considered a non-target lesion revascularization.  
Non Target Vessel Revascularization (non-TVR): Any revascularization in a vessel other than the target vessel is 
considered a non-target vessel revascularization.  
 
*Clinically indicated revascularization: A revascularization is considered clinically indicated if angiography at 
follow-up shows a percent diameter stenosis ≥ 50% (core laboratory quantitative coronary angiography 
assessment) and if one of the following occurs:  
(1) A positive history of recurrent angina pectoris, presumably related to the target vessel;  

IP-CAD_CNUH-2021-314_November 04, 2021 
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(2) Objective signs of ischemia at rest (ECG changes) or during exercise test (or equivalent), presumably related 
to the target vessel;  
(3) Abnormal results of any invasive functional diagnostic test (eg, Doppler flow velocity reserve, fractional flow 
reserve);  
(4) A TLR or TVR with a diameter stenosis ≥ 70% even in the absence of the above-mentioned ischemic signs or 
symptoms.  
 
Stent Thrombosis  
Stent thrombosis is defined and discussed by the Academic Research Consortium as follows: 
 
Stent thrombosis should be reported as a cumulative value at the different time points and with the different 
separate time points. Time 0 is defined as the time point after the guiding catheter has been removed and the 
subject left the catheterization laboratory.  
 
Timing 
Acute stent thrombosis* 
0-24 hours post stent implantation  
Subacute stent thrombosis*: 
> 24 hours-30 days post stent implantation  
Late stent thrombosis†: 
> 30 days-1 year post stent implantation  
Very late stent thrombosis†: 
> 1 year post stent implantation  
* Acute/subacute can also be replaced by early stent thrombosis. Early stent thrombosis (0-30 days) is currently used in the community. 
† Including “primary” as well as “secondary” late stent thrombosis; “secondary” late stent thrombosis is a stent thrombosis after a target segment 
revascularization.  
 
Stent Thrombosis Categories: a) Definite b) Probable, and c) Possible  
 
a) Definite stent thrombosis: Definite stent thrombosis is considered to have occurred by either angiographic or 
pathologic confirmation.  
Angiographic confirmation of stent thrombosis [*The incidental angiographic documentation of stent occlusion in the absence 
of clinical signs or symptoms is not considered a confirmed stent thrombosis (silent occlusion).]: The presence of a thrombus 
[†Intracoronary thrombus] that originates in the stent or in the segment 5 mm proximal or distal to the stent and 
presence of at least 1 of the following criteria within a 48-hour time window: 
. Acute onset of ischemic symptoms at rest  
. New ischemic ECG changes that suggest acute ischemia  
. Typical rise and fall in cardiac biomarkers (refer to definition of spontaneous MI)  
. Nonocclusive thrombus: Intracoronary thrombus is defined as a (spheric, ovoid, or irregular) noncalcified 

IP-CAD_CNUH-2021-314_November 04, 2021 
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filling defect or lucency surrounded by contrast material (on 3 sides or within a coronary stenosis) seen in 
multiple projections, or persistence of contrast material within the lumen, or a visible embolization of 
intraluminal material downstream.  
. Occlusive thrombus: TIMI 0 or TIMI 1 intrastent or proximal to a stent up to the most adjacent proximal 
side branch or main branch (if originates from the side branch).  
Pathological confirmation of stent thrombosis: Evidence of recent thrombus within the stent determined at 
autopsy or via examination of tissue retrieved following thrombectomy.  
b) Probable stent thrombosis: Clinical definition of probable stent thrombosis is considered to have occurred after 
intracoronary stenting in the following cases:  
. Any unexplained death within the first 30 days [‡ For studies with ST-elevation MI population, one may consider the exclusion 
of unexplained death within 30 days as evidence of probable stent thrombosis.] 
. Irrespective of the time after the index procedure, any MI that is related to documented acute ischemia in the 
territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any 
other obvious cause  
c) Possible stent thrombosis: Clinical definition of possible stent thrombosis is considered to have occurred with 
any unexplained death from 30 days after intracoronary stenting until end of trial follow-up.  
 
Target Lesion  
A lesion to be treated during the index procedure  
 
Target Vessel  
The entire epicardial vessel containing the treated lesion  
 
Thrombosis in Myocardial Infarction (TIMI) Flow Grades 
Definitions of perfusion in the TIMI Trial 
Grade 0 (no perfusion): There is no antegrade flow beyond the point of occlusion. 
Grade 1 (penetration with minimal perfusion): The contrast material passes beyond the area of obstruction, but 
"hangs up" and fails to opacify the entire coronary bed distal to the obstruction for duration of the cine run. 
Grade 2 (partial perfusion): The contrast material passes across the obstruction and opacifies the coronary bed 
distal to the obstruction. However, the rate of entry of contrast material into the vessel distal to the obstruction or 
its rate of clearance from the distal bed (or both) are perceptibly slower than its entry into or clearance from 
comparable areas not perfused by the previously occluded vessel, e.g., the opposite coronary artery or the coronary 
bed proximal to the obstruction. 
Grade 3 (complete perfusion): Antegrade flow into the bed distal to the obstruction occurs as promptly as 
antegrade flow into the bed proximal to the obstruction, and clearance of contrast material from the involved bed 
is as rapid as clearance from an uninvolved bed in the same vessel or the opposite artery. 
 
Transient Ischemic Neurological Attack (TIA)  

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A sudden onset of reversible focal neurological deficits due to vascular lesions of the brain that lasts ≤ 24 hours  
 
 

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