Compare the Efficacy of Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Graft Surgery: Follow-up Extension
Conditions: Coronary Artery Bypass Grafting, Antiplatelet Therapy
Sponsor: Ruijin Hospital

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Study Number 
ESR-18-13658 
Version Number 
2.0 
Date 
10. Mar, 2021 
Compare the Efficacy of Different antiplatelet therapy strategy after 
Coronary Artery Bypass Graft Surgery: Follow-up Extension  
( DACAB Trial: Follow-up Extension, DACAB-FE) 
Principal Investigator: Qiang Zhao MD, Department of Cardiovascular Surgery, Ruijin Hospital Shanghai Jiao 
Tong University School of Medicine. 
Co-PI & Study Director: Yunpeng Zhu MD, Department of Cardiovascular Surgery, Ruijin Hospital Shanghai 
Jiao Tong University School of Medicine. 
Sponsor: Ruijin Hospital Shanghai Jiao Tong University School of Medicine 
Address：No. 197, Ruijin Er Road, Shanghai, China  
Telephone：86 21 6437 0045 
Post code：200025 
 
 
 

 
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TITLE PAGE ....................................................................................................... 1 
TABLE OF CONTENTS ..................................................................................... 2 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ........................... 4 
1. 
INTRODUCTION ............................................................................................... 5 
1.1 
Background .......................................................................................................... 5 
1.2 
Study Purpose ...................................................................................................... 7 
2. 
STUDY OBJECTIVES ........................................................................................ 7 
2.1 
Primary Observational Objective.......................................................................... 7 
2.2 
Secondary Observational Objectives .................................................................... 8 
3. 
STUDY PLAN AND PROCEDURES ................................................................. 8 
3.1 
Overall Study Design and Flow Chart .................................................................. 8 
3.2 
Rationale for Study Design, Doses and Control Groups ........................................ 9 
4. 
SUBJECT SELECTION CRITERIA.................................................................... 9 
4.1 
Inclusion / Exclusion Criteria ............................................................................... 9 
5. 
COLLECTION OF STUDY VARIABLES .......................................................... 9 
5.1 
Recording of Data ................................................................................................ 9 
5.2 
Data Collection at 5-year Visit ........................................................................... 10 
5.3 
Observation Endpoint......................................................................................... 10 
5.3.1 
Primary Observational Endpoint ........................................................................ 10 
5.3.2 
Secondary Observational Endpoints ................................................................... 10 
5.4 
Safety................................................................................................................. 12 
5.4.1 
Adverse Events .................................................................................................. 12 
6. 
ETHICAL AND REGULATORY REQUIREMENTS ....................................... 13 
6.1 
Ethical Conduct of The Study ............................................................................ 13 
6.2 
Ethics and Regulatory Review............................................................................ 13 
6.3 
Informed Consent............................................................................................... 13 
6.4 
Changes to The Protocol and Informed Consent Form........................................ 14 
6.5 
Audits and Inspections ....................................................................................... 15 
7. 
STUDY MANAGEMENT ................................................................................. 15 
7.1 
Training of Study Site Personnel ........................................................................ 15 
TABLE OF CONTENTS 
PAGE 

 
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7.2 
Study Monitoring ............................................................................................... 15 
7.2.1 
Source Data ....................................................................................................... 15 
7.2.2 
Use and Completion of CRF .............................................................................. 16 
7.2.3 
Record Retention in Study Sites ......................................................................... 16 
7.2.4 
Data Protection .................................................................................................. 16 
7.3 
Potential Biases Controlling ............................................................................... 16 
7.4 
Study Timetable and End of Study ..................................................................... 17 
8. 
EVALUATION AND CALCULATION OF ENDPOINTS ................................ 17 
8.1 
Calculation or Derivation of Observational Endpoints ........................................ 17 
9. 
STATISTICAL METHODS AND SAMPLE SIZE DETERMINATION ........... 18 
9.1 
Description of Analysis Sets .............................................................................. 18 
9.1.1 
Full Analysis Set ................................................................................................ 18 
9.1.2 
Per-protocol Set ................................................................................................. 18 
9.2 
Methods of Statistical Analyses.......................................................................... 18 
9.2.1 
General Method of Analysis ............................................................................... 18 
9.2.2 
Demographics and Baseline Characteristics ....................................................... 19 
9.2.3 
Primary Observational Endpoint ........................................................................ 19 
9.2.4 
Secondary Observational Endpoints ................................................................... 19 
9.3 
Determination of Sample Size ............................................................................ 19 
10. 
REFERENCES .................................................................................................. 20 
 
 
 
 

 
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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
The following abbreviations and special terms are used in this study Clinical Study Protocol. 
Abbreviation or special term 
Explanation 
ACS 
Acute Coronary Syndrome 
AE 
Adverse Event 
CABG 
Coronary Artery Bypass Graft 
CCS 
Canadian Cardiovascular Society 
DBL 
Database Lock 
ECG 
Electrocardiogram 
FAS 
Full Analysis Set 
IEC 
Independent Ethics Committee 
MedDRA 
Medical Dictionary for Regulatory Activities 
MSCTA 
Multi-slice Computed Tomography Angiography  
OPCAB 
Off-pump Coronary Artery Bypass 
PLATO 
Platelet Inhibition and Patient Outcomes Trial 
PI 
Principal Investigator 
PPS 
Per-Protocol Set  
SAE 
Serious Adverse Event 
UCG 
Ultrasonic Cardiogram 
TIMI 
Thrombolysis in Myocardial Infarction 
UCG 
Ultrasound Cardiogram 

 
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1. 
INTRODUCTION 
1.1 
Background 
In the last 30 years, antiplatelet agents were used to prevent vein graft thrombosis after CABG.1 
Aspirin, as the standard therapy, was recommended to be long-term use to reduce post-surgery 
adverse events2,3. 2012 STS guidelines4 and the 2016 AHA post-CABG secondary prevention 
guidelines5 recommended that dual antiplatelet therapy (DAPT) should be started or continued 
for ACS patients receiving CABG to reduce cardiovascular adverse events, meanwhile, improve 
the patency rate of vascular graft in the early postoperative period. The latest 2016 ACC/AHA6 
and 2017 ESC/EACTS7 DAPT guidelines made similar recommendations, but the level of 
evidence is Level C. On the other hand, for patients with stable coronary heart disease 
(SCAD/SIHD) receiving CABG, it is controversial on whether post-CABG DAPT can improve 
clinical outcomes or the patency rate of vascular graft. 
DACAB trial is an open label multi-center randomized clinical trial. The patients enrolled in 
DACAB trial were randomly assigned to the (1) ticagrelor+aspirin (T+A) group, (2) 
ticagrelor(T) group and (3) aspirin (A) group. Patients were treated and followed up for 12 
months. The primary endpoint was the patency rate of saphenous vein graft （SVG） after 1 
year of CABG. Secondary endpoint included MACEs within 1 year after CABG. There are 500 
patients were enrolled from July 2014 through November 2015 and follow-up was completed 
in January 2017, 168 patients in the T+A group, 166 in T group and 166 in A group. The results 
showed that the 1-year SVG patency rate (primary endpoint) of T+A group was 88.7% (432/487, 
T+A vs A, p=0.0006), the T group was 82.8% (371/485, T vs A, p=0.0962), and the A group 
was 76.5% (404/488). The incidence of MACE during 1 year of follow-up was 1.8% in T+A 
group, 2.4% in T group，and 5.4% in A group. The DACAB trial demonstrated that compared 
with aspirin monotherapy, the combination of ticagrelor and aspirin significantly improved 1-
year SVG patency after CABG. Meanwhile, the combination of ticagrelor and aspirin therapy 
or ticagrelor monotherapy showed a favor trend with reducing the MACEs compared with 
aspirin monotherapy. The results of DACAB trial were reported in the Late Breaking Clinical 
Trial at the American Heart Association Annual Meeting in November 2017 and published at 
JAMA journal (JAMA 2018, 319[16]:1677-1686）8,9. 

 
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Would the observed differences in SVG patency at 1 year post CAGB translate into long-term 
clinical benefit? This remain to be a great interest to follow up these patients. Previous studies 
showed that SVG patency might predict the long-term prognosis, however, results were 
inconsistent. Differences in sample sizes and study design might be the potential explanation 
for the discrepancies (Table 1). Therefore, in present study, we intend to collect and analyze the 
long-term data in patients who were enrolled and survived in DACAB trial. We would observe 
the cardiovascular outcomes in three groups at 5-year post-CABG, which would have great 
clinical implications. 
Table 1: Correlation between graft patency rate and long-term prognosis  
Author, Study Type 
Patient Group 
Result 
Comments 
Lytlel10  
Retrospective Study  
1296 patients with (723) and 
without (573) SVGs stenosis. At 
a mean follow-up of 6.9 years 
 
A stenotic graft to the left 
anterior descending artery was a 
strong predictor of decreased 
survival (p <0.001), decreased 
reoperation-free 
survival 
(p 
<0.001), and decreased event-
free survival (p <0.001). 
Late vein graft stenosis are more 
dangerous 
than 
native 
coronary 
stenosis. Late stenosis in saphenous 
vein grafts to the left anterior 
descending coronary artery predict a 
high rate of death and cardiac events 
and are an indication for reoperation. 
Fitzgibbon GM11 
Retrospective Study 
A 
total 
of 
1,388 
patients 
underwent a first coronary 
artery bypass graft procedure, 
234 
had 
a 
second 
bypass 
procedure, and 15 had a third 
bypass procedure  
 
The presence of diseased but 
patent grafts, particularly those 
with high profile lesions (>50% 
graft 
stenosis), 
increased 
reoperation 
morbidity 
and 
mortality. 
Vein graft patency and occlusion were 
closely correlated with the need for 
reoperation and survival. 
 
Halabi AR12 
Retrospective Study 
1243 patients who underwent 
angiography after CABG 
 
Our primary outcome measure 
was the composite of death, 
myocardial infarction, or repeat 
revascularization. 
Of 
1,243 
patients included in the analysis, 
27.9% had no, 11.9% had 
noncritical, 20.8% had critical, 
and 39.3% had occlusive SVG 
disease. 
At 
10 
years, 
the 
corresponding 
adjusted 
composite event rates were 
41.2%, 56.2%, 81.2%, and 
67.1%, respectively (p <0.0001). 
Early vein graft failure was associated 
with death, MI, or revascularization. 
 
Lopes RD13 
Retrospective Study  
 
 
1829 patients who underwent 
coronary artery bypass graft 
surgery and had an angiogram 
performed up to 18 months after 
surgery 
 
The composite of death, 
myocardial infarction, or 
revascularization occurred more 
frequently among patients who 
had any VGF compared with 
those who had none (adjusted 
hazard ratio, 1.58; 95%CI, 
That SVG failure was associated with 
an increase in revascularization but 
not with death or myocardial 
infarction at long-term follow-up. 
 

 
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1.21–2.06; P=0.008). 
This was due mainly to more 
frequent revascularization with 
no differences in death 
(adjusted hazard ratio, 1.04; 
95% CI, 0.71–1.52; P=0.85) 
or death or myocardial 
infarction (adjusted hazard 
ratio, 1.08; 95% CI, 0.77–1.53; 
P≤0.65). 
Shavadia J14 
Retrospective Study 
5,276 patients undergoing 
CABG surgery 
 
A strong trend toward reduced 
patient survival was noted with 
“arterial graft failure” (arterial ± 
vein GF) compared to “vein 
graft failure only” (no arterial 
GF) (adjusted hazard ratio 2.2, 
95% CI 0.98-5.0, P = .056). 
LITA-to-LAD graft stenosis ≥70%, 
but SVG failure was associated with 
a worse long-term prognosis. 
 
Yamasaki M15 
Retrospective Study 
Two hundred thirty-four patients 
underwent late invasive 
angiography after coronary 
artery bypass operations. The 
study population consists of 163 
patients with thrombolysis in 
myocardial infarction (TIMI) 3 
flow of both the RA graft and 
study SVGs. 
 
MACE was higher in patients 
with significant graft stenosis 
than in patient without stenosis 
(10 of 28 [35.7%] versus 7 of 
135 [5.2%]; p < 0.0001). 
The incidence of adverse clinical 
events and need for revascularization 
were significantly higher in patients 
with graft stenosis. 
 
 
1.2 
Study Purpose 
This study is designed to compare the clinical outcomes of the subjects enrolled in the DACAB 
trial 5 years after CABG (randomization). 
2. 
STUDY OBJECTIVES 
2.1 
Primary Objective 
The primary objective is to compare the incidence of major adverse clinical events-4 (MACE-
4, a composite of all-cause death, myocardial infarction, stroke, and coronary revascularization) 
among 3 randomized regimens (T+A, T alone, A alone) in previous DACAB trial in the 
extended five-year follow-up after CABG.  

 
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2.2 
Secondary Objectives 
The secondary objectives are to compare the incidence of MACE-5 (a composite of all-cause 
death, myocardial infarction, stroke, coronary revascularization and hospitalization for unstable 
angina); MACE-3 (a composite of cardiovascular death, myocardial infarction and stroke); all-
cause death; cardiovascular death; myocardial infarction; stroke; coronary revascularization; 
hospitalization for unstable angina and graft failure among 3 randomized regimens in previous 
DACAB trial in the five-year follow-up after CABG. 
2.3 
Exploratory Objectives 
According to the imaging examination results of graft vessels at 1 year after surgery, all 
subjects were divided into two natural cohorts with or without graft failure. Similarly, all 
subjects were divided into two natural cohorts with or without vein graft failure.  
The exploratory objectives are to compare the incidence of MACE-4; MACE-5; MACE-3; all-
cause death; cardiovascular death; myocardial infarction; stroke; coronary revascularization 
and hospitalization for unstable angina between the two cohorts with or without graft/vein 
graft failure at one-year angiographic follow-up. 
Planned exploratory subgroup analysis consists of gender, age stratification, ACS 
presentation, hypertension, diabetes mellitus, history of high low-density lipoprotein 
cholesterol (LDL-C), history of high lipoprotein(a), prior myocardial infraction, stroke, 
peripheral vascular disease, COPD, history of CKD-3 or higher, smoking, left main coronary 
artery disease, SYNTAX Score stratification, EuroScore stratification at baseline, on-pump or 
off-pump, whether to use the internal thoracic artery, complete revascularization or not. 
3. 
STUDY PLAN AND PROCEDURES 
3.1 
Overall Study Design and Flow Chart 
This study will include the subjects who enrolled in DACAB trial to compare clinical outcomes 
5 years after CABG. After completing 12-month randomized treatment from DACAB trial, 
investigators would not make any interventions or impact on subjects’ therapeutic strategy. 

 
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Aspirin monotherapy would be given to most subjects according to the current guidelines. 
However, other antiplatelet regimens might be given for subjects by their attending physician 
based on the subject's individual condition. Subjects would spontaneously undergo regular 
laboratory test such as biochemical parameters, ECG, UCG, coronary computed tomography 
angiography imaging (CCTA) or coronary angiography (CAG) and clinical follow-up according 
to clinical need and their individual condition. At 5-year (± 3 month) after CABG, a face-to-
face visit is scheduled to be performed to collect the occurrence of clinical events, including 
types and time of events. The first 5-year visit would be performed around August 2019. 
 
Figure 1: Schematic Overview of the Study 
 
3.2 
Rationale for Study Design, Doses and Control Groups 
This study is a non-interventional, observational study. The follow-up data of subjects will be 
collected at 5-year after CABG.  
4. 
SUBJECT SELECTION CRITERIA 
4.1 
Inclusion / Exclusion Criteria 
All the subjects enrolled in the DACAB trial. 
5. 
COLLECTION OF STUDY VARIABLES 
5.1 
Recording of Data 
The investigator will ensure that the data is recorded on the paper form of Case Report Forms 
(CRF) as specified in the study protocol and in accordance with the instructions provided. 

 
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General information such as subject’s age and gender, medical history should be recorded.  
Medical record and laboratory test, such as biochemical parameters (cardiac troponin, brain 
natriuretic peptide, etc.), ECG, UCG, CT/MRI, coronary CTA or coronary angiography related 
to the end points of this study will be collected and recorded to assist in the determination of 
endpoint events. 
The investigator ensures the accuracy, completeness, and legibility of the data recorded and of 
the provision of answers to data queries according to the Clinical Study Agreement. The 
investigator will sign the completed paper CRF. A copy of the completed paper CRF will be 
archived at the study site. 
5.2 
Data Collection at 5-year Visit 
The data of subjects will be collected at the visit at 5-year (± 3 month) after CABG. The collected 
data includes: vital signs; current medications; types and time of events; original medical record 
and laboratory test results related to clinical events. For deceased patients, the death and cause 
of death will be determined by telephone interview with their relatives firstly. The related 
medical records would be acquired from their relatives to further determination the cause of 
death, if available. Electronic medical records would be approached under relatives’ permission.  
Determination of graft patency will be determined from medical records. Original images of 
coronary CTA or coronary angiography will be acquired and re-assessment. 
5.3 
Outcome Measures  
5.3.1 
Primary Outcome Measure 
The primary outcome is MACE-4, defined as a composite of all-cause death, myocardial 
infarction, stroke and coronary revascularization. The outcome measure is the time to the first 
occurrence of MACE-4 event from randomization to the last visit. 
5.3.2 
Secondary Outcome Measures 
Including: 

 
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1) MACE-5, defined as a composite of all-cause death, myocardial infarction, stroke, coronary 
revascularization and hospitalization for unstable angina. The outcome measure is the time 
to the first occurrence of MACE-5 event from randomization to the last visit. 
2) MACE-3, defined as a composite of cardiovascular death, myocardial infarction and stroke. 
The outcome measure is the time to the first occurrence of MACE-3 event from 
randomization to the last visit.  
3) All-cause death. The outcome measure is the time to the first occurrence of all-cause death 
from randomization to the last visit. 
4) Cardiovascular death. All “undetermined death” will be assumed as “cardiovascular death”. 
The outcome measure is the time to the first occurrence of cardiovascular death from 
randomization to the last visit. 
5) Myocardial infarction, including STEMI, NSTEMI, or silent/unrecognized MI (eg. new 
pathological Q waves detected by ECG, or new reduced ventricular wall motion detected 
by UCG during follow-up).The outcome measure is the time to the first myocardial 
infarction from randomization to the last visit. 
6) Stroke, including ischemic, hemorrhagic, or unknown type. The outcome measure is the 
time to the first stroke from randomization to the last visit. 
7) Coronary revascularization, any repeated PCI or CABG, no matter ischemic driven or not. 
The outcome measure is the time to the first coronary revascularization from randomization 
to the last visit. 
8) Hospitalization for unstable angina. The outcome measure is the time to the first 
hospitalization for unstable angina from randomization to the last visit. 
9) Graft failure/vein graft failure at the last visit (Fitzgibbon Grade B/O assessed by CCTA or 
CAG). The outcome measure is the incidence of graft failure/vein graft failure. 

 
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5.4 
Safety 
The primary and secondary efficacy outcomes and measures serve as the primary and secondary 
safety outcomes and measures. Other safety outcome measures include other serious adverse 
events resulting in hospitalization or emergency visits. 
5.4.1 
Adverse Events Collection Reports 
The present study is a non-interventional, observational study without specific Astrazeneca drug 
during 1 to 5 year after CABG. Actively collection of all AEs is not required. However, ADR 
related to Astrazeneca drugs will be spontaneously reported to Astrazeneca Patient Safety 
according to local regulation-Order 81. Astrazeneca Patient Safety contact information: Fax: 
+86 21 38683551; E-mail: China.AZDrugSafety@astrazeneca.com; Tel: +86 21 52929866，
+86 21 58385073 (Emergency). 
5.4.2 
Severe Adverse Events Collection Reports 
In addition to the primary and secondary outcome events, the present study also collect other 
severe adverse events resulting in hospitalization or emergency visits, which includes cardiac 
insufficiency, heart failure; arrhythmias, such as atrial fibrillation, atrial flutter, and 
supraventricular tachycardia; other thrombotic events, such as pulmonary embolism, deep 
venous thrombosis; neurological diseases, such as Alzheimer's disease, dizziness and vertigo 
(excluding stroke), tumors; respiratory system diseases, such as pulmonary infection, acute 
onset of COPD; digestive system diseases, such as gastrointestinal bleeding, tumors; urinary 
system diseases, such as renal insufficiency, hemodialysis, urinary tract infections, tumors; 
endocrine system diseases, such as diabetes, tumors; hematological system diseases, such as 
anemia, tumors; musculoskeletal system diseases, such as fractures, cervical and lumbar 
diseases, tumors; other unclassified reasons, such as social factors. Physical examination 
needs do not fall into this category. 

 
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6. 
ETHICAL AND REGULATORY REQUIREMENTS 
6.1 
Ethical Conduct of The Study 
The final study of this study will be implemented after and under the supervision of the ethics 
committee/institutional review board (IRB)/independent ethics committee (IEC). 
6.2 
Ethics and Regulatory Review 
This trial will be initiated only after all required legal documentation has been reviewed and 
approved by the respective Institutional Review Board (IRB) / Independent Ethics Committee 
(IEC) and competent authority (CA) according to national and international regulations. The 
same applies for the implementation of changes introduced by amendments. 
Prior to subject participation in the trial, written informed consent must be obtained from each 
subject (or the subject’s legally accepted representative) according to ICH GCP, Chinese GCP 
and to the regulatory and legal requirements of the participating country. The informed consent 
and any additional subject information form retained by the investigator as part of the trial 
records. A signed copy of the informed consent and any additional subject information must be 
given to each subject or the subject’s legally accepted representative. 
The subject must be informed that his/her personal trial-related data will be used by principle 
investigator in accordance with the local data protection law. The level of disclosure must also 
be explained to the subject. 
The subject must be informed that his / her medical records may be examined by authorized 
monitors (CRA) or Clinical Quality Assurance auditors, by appropriate IRB / IEC members, 
and by inspectors from regulatory authorities. 
6.3 
Informed Consent 
The Principal Investigator(s) at each center will: 
• Ensure each subject is given full and adequate oral and written information about the 
nature, purpose, possible risk and benefit of the study 

 
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• Ensure each subject is notified that they are free to discontinue from the study at any 
time 
• Ensure that each subject is given the opportunity to ask questions and allowed time to 
consider the information provided 
• Ensure each subject provides signed and dated informed consent before conducting any 
procedure specifically for the study 
• Ensure the original, signed Informed Consent Form(s) is/are stored in the Investigator’s 
Study File 
• Ensure a copy of the signed Informed Consent Form is given to the subject 
• Ensure that any incentives for subjects who participate in the study as well as any 
provisions for subjects harmed as a consequence of study participation are described in 
the informed consent form that is approved by an Ethics Committee. 
6.4 
Changes to The Protocol and Informed Consent Form 
Study procedures will not be changed without the mutual agreement of the National Co-
ordinating Investigator and Sponsor. 
If there are any substantial changes to the study protocol, then these changes will be documented 
in a study protocol amendment and where required in a new version of the study protocol 
(Revised Clinical Study Protocol). 
The amendment should be approved by each Ethics Committee before implementation. Local 
requirements should be followed for revised protocols. 
Sponsor will distribute any subsequent amendments and new versions of the protocol to each 
Principal Investigator(s).  

 
15(21) 
If a protocol amendment requires a change to a center’s Informed Consent Form, Sponsor and 
the center’s Ethics Committee should approve the revised Informed Consent Form before the 
revised form is used. 
If local regulations require, any administrative change will be communicated to or approved by 
each Ethics Committee. 
6.5 
Audits and Inspections 
Authorized representatives of Ruijin Hospital, a regulatory authority, or an Ethics Committee 
may perform audits or inspections at the center, including source data verification.  The purpose 
of an audit or inspection is to systematically and independently examine all study-related 
activities and documents, to determine whether these activities were conducted, and data were 
recorded, analyzed, and accurately reported according to the protocol, Good Clinical Practice 
(GCP), guidelines of the International Conference on Harmonization (ICH), and any applicable 
regulatory requirements. 
7. 
STUDY MANAGEMENT 
7.1 
Training of Study Site Personnel 
The PI should ensure adequate training and updated information or notifications have been 
delivered to study relevant personnel including physicians and nurses. 
7.2 
Study Monitoring 
7.2.1 
Source Data 
Source documents provide evidence for the existence of the subject and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
Data entered in the CRFs that are transcribed from source documents must be consistent with 
the source documents or the discrepancies must be explained. The investigator may need to 
request previous medical records or transfer records, depending on the trial; also current medical 
records must be available. 

 
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For CRFs, all data must be derived from source documents. 
7.2.2 
Use and Completion of CRF 
It is the responsibility of the Investigator to maintain adequate and accurate CRF designed by 
the study team to record all study data in a timely manner. All CRFs should be completed in 
their entirety in a neat, legible manner to ensure accurate interpretation of data. 
Should a correction be made, the corrected information will be entered in the CRF overwriting 
the initial information. An audit trail allows identifying the modification. 
Data are available within the system to study team as soon as they are entered in the CRF. 
7.2.3 
Record Retention in Study Sites 
The Investigator must maintain confidential all study documentation and take measures to 
prevent accidental or premature destruction of these documents. 
7.2.4 
Data Protection 
The subject's personal data, which are included in the study database shall be treated in 
compliance with all applicable laws and regulations. Sponsor shall take all appropriate measures 
to safeguard and prevent access to this data by any unauthorized third party when archiving or 
processing personal data pertaining to the subjects. 
 
7.3 
Potential Biases Controlling 
The 5-year after CABG visit (on site) will be in person by a trained site coordinator and CRC.  
Original materials such as medical record and laboratory test results would be asked to provide 
for endpoint assessment. All potential endpoint events （including all-cause death, 
cardiovascular death, non-fatal MI, non-fatal stroke, repeated coronary revascularization）will 
be adjudicated by an independent Clinical Endpoint Committee (CEC) according to the 2014 
ACC/AHA Cardiovascular Endpoints Data Standards. Original coronary artery imagine would 

 
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be acquired if available. All grafts outcomes will be adjudicated by an independent Image Data 
Review Committee (IDRC) according to the DACAB protocol. 
7.4 
Study Timetable and End of Study 
• Protocol Approved: Dec2018 
• First 5-year Visit: Aug2019 
• Last 5-year Visit: Dec2020 
• DBL: Jun2021 
• CSR: Sep2021 
• Publication: Dec2021 
The first 5-year visit in this study is expected in Aug 2019, while the last is in Dec 2020. 
Database Lock will be about 6 months after the last 5-year visit. Clinical study report is planned 
to be finalized in Sep 2021. 
8. 
EVALUATION AND CALCULATION OF ENDPOINTS 
8.1 
Calculation or Derivation of Clinical Outcomes 
The primary outcome is the time to the first occurrence of any MACE-4, which is a composite 
of all-cause death, myocardial infarction, stroke, and coronary revascularization and measured 
in days since the date of randomization. Subjects who had not experienced any major adverse 
clinical events from randomization to the last visit will be right-censored. For those subjects 
who lost to follow-up at 5-year visit, the date of the last contact and the most updated clinical 
outcomes available in medical record or other source will be used in primary analysis. If there’s 
no major adverse clinical events recorded for those subjects who lost to follow-up at 5-year visit, 
then these subjects will be right-censored at the date of their last contact. The survival curves 
will be estimated using Kaplan-Meier method. 

 
18(21) 
The secondary outcomes (time to event) will be analyzed similarly with the primary 
observational endpoint. 
Graft failure after CABG is in accordance with Fitzgibbon classification criteria by using 
MSCTA or CAG, there were a total of 3 categories, grade A, B and O, where grade B/O 
accounted for the graft failure. 
9. 
STATISTICAL 
METHODS 
AND 
SAMPLE 
SIZE 
DETERMINATION 
9.1 
Description of Analysis Sets 
Subjects will be analyzed per the randomized treatment groups they were assigned to in the 
previous DACAB study. 
9.1.1 
Full Analysis Set 
The Full Analysis Set (FAS) in current study is same as FAS in DACAB trial.  
9.1.2 
Per-protocol Set 
Per-protocol set (PPS) is defined as all subjects in the FAS with exclusion of the following 
subjects:  
• Subject discontinued the application of study drug longer than 60 days during the 
treatment phase in the previous DACAB study 
PPS will only be used in the analysis of primary observational endpoint. The analysis using the 
FAS will be regarded as primary while the analysis based on PPS will act as supportive. 
9.2 
Methods of Statistical Analyses 
9.2.1 
General Method of Analysis 
Descriptive summary statistics, such as number of subjects, mean, SD, median, IQR, minimum, 
and maximum for continuous variables, and counts and percentages for discrete variables will 
be used to summarize data. Summary statistics will be provided for each group in previous 
DACAB study. 

 
19(21) 
The correlations between the observational endpoints (both primary and secondary) and the 
characteristics of subjects will be explored, the characteristics of subject include age, gender, 
medical history, etc. 
The missing data will be assumed missing at random, no imputation will be applied unless 
specified otherwise. 
The detailed statistical methods applied in analyses will be provided in Statistical Analysis Plan. 
9.2.2 
Demographics and Baseline Characteristics 
Demographic and baseline characteristic variables will be descriptively summarized by the 
group in previous DACAB study. 
9.2.3 
Primary Outcome Measure 
Kaplan-Meier method will be applied to analyze the primary outcome (MACE-4), and the rate 
of subjects who has the first MACE-4 occurred within 1, or 2, or 3, or 4, or 5 years after CABG 
will be provided. 
9.2.4 
Secondary Outcome Measures 
The time to event variables in the secondary outcomes will be analyzed similarly with the 
primary outcome. 
As 1-4 vessels were generally measured in each subject, the vein graft patency at 5 years after 
CABG is a categorical data measured repeatedly in subjects. The number and the percentage of 
the grafts in Fitzgibbon grade B/O will be summarized by the group in previous DACAB study.  
9.3 
Determination of Sample Size 
A total of 500 subjects were randomized in DACAB study (ticagrelor + aspirin, 168; ticagrelor 
alone, 166; aspirin alone, 166). There are 5 subjects died before 12-month visit, of these, 2 died 
in ticagrelor + aspirin group, and 3 died in aspirin alone group. Therefore, 495 patients would 
be scheduled for 5-year on-site visit.  
 

 
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10. 
REFERENCES 
1. 
Chesebro JH, Clements IP, Fuster V, et al. A platelet-inhibitor-drug trialin coronary-artery bypass 
operations: benefit of perioperative dipyridamoleand aspirin therapy on early postoperative vein-graft 
patency.NEnglJ Med 1982;307:73-8. 
2. 
Eagle KA, Guyton RA, Davidoff R, et al. ACC/AHA 2004 guidelineupdate for coronary artery bypass 
graft surgery: a report of the AmericanCollege of Cardiology/American Heart Association Task Force 
on PracticeGuidelines (Committee to Update the 1999 Guidelines for CoronaryArtery Bypass Graft 
Surgery). Circulation 2004;110:e340-437. 
3. 
Becker RC, Meade TW, Berger PB, et al. The primary and secondaryprevention of coronary artery 
disease: American College of Chest PhysiciansEvidence-Based Clinical Practice Guidelines (8th 
Edition). Chest2008;133:776S-814S. 
4. 
Victor A. Ferraris，2012 Update to The Society of Thoracic Surgeons Guideline on Use of 
Antiplatelet Drugs in Patients Having Cardiac and Noncardiac Operations.Ann Thorac Surg 
2012;94:1761–81 
5. 
Alexander Kulik, MD, MPH, FAHA, Chair; Secondary Prevention After Coronary Artery Bypass 
Graft Surgery A Scientific Statement From the American Heart Association. Circulation. 2015;131:00-
00. DOI: 10.1161/CIR.0000000000000182 
6. 
Glenn N. Levine, 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet 
Therapy. Journal of the American College of Cardiology (2016), doi: 10.1016/j.jacc.2016.03.513. 
7. 
Marco Valgimigli, 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease 
developed in collaboration with EACTS. European Heart Journal (2017) 0, 1–48 ESC GUIDELINES 
doi:10.1093/eurheartj/ehx419 
8. 
Qiang Zhao, Yunpeng Zhu, Zhiyun Xu, et al. Effect of Ticagrelor Plus Aspirin, Ticagrelor Alone, or 
Aspirin Alone on Saphenous Vein Graft Patency 1 Year After Coronary Artery Bypass Grafting：A 
Randomized Clinical Trial. JAMA. 2018;319(16):1677-1686. doi:10.1001/jama.2018.3197. 
9. 
Yunpeng Zhu, Qiang Zhao. Antiplatelet Therapy After Coronary Artery Bypass Grafting-Reply. 
JAMA. 2018 Sep 11;320(10):1036-1037. doi: 10.1001/jama.2018.10446. 
10. Lytle BW, Loop FD, Taylor PC, Simpfendorfer C, Kramer JR, Ratliff NB,Goormastic M, Cosgrove 
DM. Vein graft disease: the clinical impact of stenoses in saphenous vein bypass grafts to coronary 
arteries. J Thorac Cardiovasc Surg. 1992;103:831–840 
11. Fitzgibbon GM, Kafka HP, Leach AJ, Keon WJ, Hooper GD, Burton JR. Coronary bypass graft fate 
and patient outcome: angiographic follow-up of 5,065 grafts related to survival and reoperation in 
1,388 patients during 25 years. J Am Coll Cardiol. 1996;28:616–626. 

 
21(21) 
12. Halabi AR, Alexander JH, Shaw LK, Lorenz TJ, Liao L, Kong DF, Milano CA, Harrington RA, Smith 
PK. Relation of early saphenous vein graft failure to outcomes following coronary artery bypass 
surgery. Am J Cardiol. 2005;96:1254–1259. doi: 10.1016/j.amjcard.2005.06.067. 
13. Lopes RD, Mehta RH, Hafley GE, Williams JB, Mack MJ, Peterson ED, Allen KB, Harrington RA, 
Gibson CM, Califf RM, Kouchoukos NT, Ferguson TB. Alexander JH; Project of Ex Vivo Vein Graft 
Engineering via Transfection IV (PREVENT IV) Investigators. Relationship between vein graft failure 
and subsequent clinical outcomes after coronary artery bypass surgery. Circulation. 2012;125:749–
756. doi: 10.1161/CIRCULATIONAHA.111.040311. 
14. Shavadia J, Norris CM, Graham MM, Verma S, Ali I, Bainey KR. Symptomatic graft failure and 
impact on clinical outcome after coronary arDownloaded tery bypass grafting surgery: results from the 
Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry. Am Heart J. 
2015;169:833–840. doi: 10.1016/j.ahj.2015.02.022. 
15. Yamasaki M, Deb S, Tsubota H, Moussa F, Kiss A, Cohen EA, Radhakrishnan S, Dubbin J, Ko D, 
Schwartz L, Fremes SE; Radial Artery Patency Study Investigators. Comparison of radial artery and 
saphenous vein graft stenosis more than 5 years after coronary artery bypass grafting. Ann Thorac 
Surg. 2016;102:712–719. doi: 10.1016/j.athoracsur.2016.02.107.