ATORVASTATIN EFFECTIVENESS AND SAFETY IN CARDIOLOGY PATIENTS IN REAL WORLD SETTING: A REGISTRY STUDY IN CHINA
Conditions: Coronary Artery Disease, Hypercholesterolemia, Hypertension
Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

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NON-INTERVENTIONAL (NI) STUDY PROTOCOL 
Study information
Title
Atorvastatin Effectiveness and Safety in Cardiology 
patients in Real World Setting: A Registry Study in 
China
Protocol number
A2581197
Protocol version identifier
Version 3.0
Date of last version of protocol
21 September, 2017
Active substance
Atorvastatin
Medicinal product
Atorvastatin
Research question and objectives
Primary objective
To evaluate the effectiveness of atorvastatin in
Chinese cardiology patients in real world setting.
Secondary objectives:
•
To assess atorvastatin safety in cardiology 
patients in real world setting
•
To analyze patterns of atorvastatin prescription 
in cardiology patients. 
Author
, Medical Manager
, TA manager
PPD
PPD

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TABLE OF CONTENTS 
TABLE OF CONTENTS ...........................................................................................................2
1. LIST OF ABBREVIATIONS ................................................................................................4
2. RESPONSIBLE PARTIES ....................................................................................................6
3. ABSTRACT ...........................................................................................................................7
4. AMENDMENTS AND UPDATES .....................................................................................10
5. MILESTONES .....................................................................................................................12
6. RATIONALE AND BACKGROUND ................................................................................12
6.1. Clinical Pharmacology ............................................................................................13
6.2. Toxicology ..............................................................................................................14
7. RESEARCH QUESTION AND OBJECTIVES .................................................................14
7.1. Primary Objective: ..................................................................................................14
7.2. Secondary Objectives: .............................................................................................14
8. RESEARCH METHODS ....................................................................................................15
8.1. Study Design ...........................................................................................................15
8.1.1. Overall Design ............................................................................................15
8.1.2. Study Endpoint ...........................................................................................15
8.2. Setting ......................................................................................................................16
8.2.1. Study Population .........................................................................................16
8.2.2. Inclusion Criteria ........................................................................................16
8.2.3. Exclusion Criteria .......................................................................................16
8.2.4. Disease Diagnostic Basis ............................................................................17
8.2.5. Risk Stratification and LDL-C Therapy Target Value ...............................17
8.2.6. Study Period................................................................................................18
8.2.7. Study Procedures ........................................................................................18
8.2.8. Study Drug ..................................................................................................19
8.3. Variables ..................................................................................................................19
8.4. Data Sources ............................................................................................................20
8.5. Study Size ................................................................................................................20
8.6. Data Management ...................................................................................................20
8.7. Data Analysis ..........................................................................................................21

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8.8. Quality Control ........................................................................................................21
8.9. Strengths and Limitations of the Research Methods ...............................................21
8.10. Other Aspects ........................................................................................................21
9. PROTECTION OF HUMAN SUBJECTS ..........................................................................21
9.1. Patient Information and Consent .............................................................................21
9.2. Patient Withdrawal ..................................................................................................22
9.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ..............22
9.4. Ethical Conduct of the Study ..................................................................................22
10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ......................................................................................................................23
10.1. Single Reference Safety Document .......................................................................31
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS........31
12. REFERENCES ..................................................................................................................32
13. LIST OF TABLES .............................................................................................................32
14. LIST OF FIGURES ...........................................................................................................32
ANNEX 1. LIST OF STAND ALONE DOCUMENTS .........................................................32
ANNEX 2. ADDITIONAL INFORMATION .........................................................................32

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1. LIST OF ABBREVIATIONS 
Abbreviation
Definition
FPI
First Patient In
LPLV
Last Patient Last Visit
CK
Creatine Kinase
LDL-C
Low Density Lipoprotein-Cholesterol
LDL
Low Density Lipoprotein
ALT
Alanine Aminotransferase
AST
Aspartate Aminotransferase
ULN
Upper Limit of Normal
CHD
Coronary Heart Disease
ACC
American College of Cardiology
AHA
American Heart Association
HMG-CoA
3-hydroxy-3-methyl glutaryl coenzyme A
IDL
Intermediate-Density Lipoprotein
IDL-C
Intermediate-Density Lipoprotein Cholesterol
VLDL
Very-Low-Density Lipoprotein
VLDL-C
Very-Low-Density Lipoprotein Cholesterol
HDL
High-Density Lipoprotein
HDL-C
High-Density Lipoprotein Cholesterol
apo B
Apolipoprotein B
total-C
total Cholesterol
AUC
Area Under Curve
HGPRT
Hypoxanthine-Guanine Phosphoribosyl Transferase
ASCVD
Atherosclerotic Cardiovascular Disease
CVD
Cardiovascular Disease
GCP
Good Clinical Practice
eCRF
electronic Case Report Form
EDC
Electronic Data Collection
SAP
Statistical Analysis Plan
CRAs
Clinical Research Associates
IRB/IEC
Institutional 
Review 
Board/Independent 
Ethics 
committee
EDP
Exposure During Pregnancy

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AEM
Adverse Event Monitoring
AE
Adverse Events
SAE
Serious Adverse Events
FDA
Food and Drug Administration
NI
Non-Interventional
NIS
Non-Interventional Study 
SRSD
Single Reference Safety Document
CFDA
China Food and Drug Administration
PI
Package Insert
TBIL
Total Bilirubin
TG
Triglyceride
GPP
Good Pharmacoepidemiology Practices 
ISPE
International Society for Pharmacoepidemiology
GEP
Good Epidemiological Practice 
IEA
International Epidemiological Association 
ISPOR
International Society for Pharmacoeconomics and 
Outcomes Research
CIOMS
Council for International Organizations of Medical 
Sciences
EMA
European Medicines Agency 
ENCePP
European 
Network 
of 
Centres 
for 
Pharmacoepidemiology and Pharmacovigilance 
Cr
Creatinine
BUN
Blood urea nitrogen
UA
Uric acid
ACEI
Angiotensin converting enzyme inhibitors
ARB
Angiotensin receptor blockers

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2. RESPONSIBLE PARTIES 
Leading Principal Investigator 
Name, degree(s)
Title
Affiliation
Address
Dr.
Professor
Beijing
Coordinative Principal Investigator  
Name, degree(s)
Title
Affiliation
Address
Dr.
Professor
Beijing
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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3. ABSTRACT 
Study Title
Atorvastatin Effectiveness and Safety in Cardiology patients in Real 
World Setting: A Registry Study in China 
Sponsor 
Pfizer PharmaceuticalsLtd.
Principle 
Investigator
of 
the protocol
Professor
,

Site Number/
Nationality
Approximately 65 sites/China
Objectives
Primary objective:
•
To measure effectiveness of atorvastatin in Chinese cardiology 
patients in real world setting.
Secondary objectives:
•
To assess atorvastatin safety in cardiology patients in real world 
setting
•
To analyze patterns of atorvastatin prescription in cardiology 
patients. 
Study 
Classification
Non-interventional study
Study Design
multiple centers, prospective, observational study 
Sample Size
Approximate 10,000 subjects
Inclusion 
Criteria
•
Men and women aged ≥18 years;
•
Cardiology patients# who has been prescribed atorvastatin by 
physician’s clinical judgment under normal clinical care. These 
patients will include those with established coronary heart disease, or 
having multiple risk factors and at risk for cardiovascular disease, or 
primary hypercholesterolemia.
•
Baseline laboratory reports* prior to starting atorvastatin therapy can 
be tracked, including lipid measurement, liver function, creatine 
kinase (CK) value and renal function
•
Evidence of a personally or his/her legally acceptable representative 
signed and dated informed consent document indicating that the 
patient has been informed of all pertinent aspects of the study and 
accept follow-up visit.
#The proportion of ward inpatients is not more than 20% of the total number of patients.
*The date of the baseline reports should be within 1 month before taking atorvastatin or 
PPD
PPD

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within 24hours (h) after starting atorvastatin therapy.
Exclusion 
Criteria
•
Patients who have regularly taken atorvastatin therapy more than 4 
weeks before enrollment 
•
Concomitant anyother lipid-lower medication at baseline, or during 
the study conduction on physician clinical judgment
Medicinal 
Product
Atorvastatin
Dosage 
Administration
Confirm refer to prescription
Primary 
Endpoint
•
Achievement rate of Low Density Lipoprotein-Cholesterol (LDL-C)
goals at 12 weeks of therapy of Atorvastatin according to Chinese 
Guideline on Dyslipidemia Prevention and Treatment in Adult (2007 
version). It will be presented with the proportion of patients who 
achieve the LDL-C goal value with the corresponding 95% 
confidence interval. (Please find the detailed description in the
section 8.1.2) 
 The time of 12-week will be calculated from the day when patient
start taking atorvastatin.
Secondary
Endpoints
•
Dosage distribution of Atorvastatin in cardiology patients with 
different risk categories at the end of 12-week follow-up
•
Safety and tolerability will be evaluated by recording the incidence 
and severity of adverse events, abnormal physical examination 
findings, and abnormal laboratory values through 12 weeks of 
treatment. Especially monitoring the proportion of patients who have 
any following events:
 Muscle symptoms such as myalgia, fatigue, weakness, creatine 
kinase values 10 times the upper limit of normal, and 
rhabdomyolysis
 Persistent elevations in Alanine Aminotransferase/ Aspartate 
Aminotransferase (ALT/AST) ˚ 3 Upper Limit of Normal 
(ULN).
 Major adverse cardiovascular events
•
Dropouts percentage and reason through 12 weeks of follow-up;
Observation 
Duration
12 weeks
Statistics
Sample size consideration:
•
The non-interventional
(NI)
study is designed to detect the 

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achievement rate of LDL-C value in cardiology patients with 
atorvastatin therapy in real world setting. The length of follow-up is
designed to be 12 weeks.
•
In the recently published DYSIS [1] study, the achievement rate of 
LDL-C value was about 60% among Chinese outpatients taking 3 
months lipid-lowering therapy. In this NI study, we assumed the 
achievement rate of LDL-C of 60%, allowable error rate of 1.1%, 
type I error of 0.05, we calculated a required sample size of 7600
patients. Considering 24% loss to follow-up in real-world setting, the 
sample size will be 10,000. This sample size will also allow for 
stratification by  sex, age (≥65 years), risk stratification ( very high 
risk, high risk, moderate risk and low risk) and baseline disease type 
(with established Coronary Heart Disease (CHD), having multiple 
risk factors, and primary hypercholesterolemia)
Statistics
•
Descriptive statistics including number (N), mean, median, standard 
deviation, minimum and maximum, will be produced for all 
continuous variables.  Frequency tables of number (N) and 
percentage of subjects will be produced for all categorical variables
•
All patients who received atorvastatin are included in the safety 
analysis, and safety data is summarized descriptively without 
statistical analysis.

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4. AMENDMENTS AND UPDATES
Amendm
ent 
number
Date
Substantial or 
administrative amendment
Protocol 
section(s) 
changed 
Summary of amendment(s)
Reason
1
9th June,
2015
Administrative amendment
3.abstract
5.
milestones
1. At Page 7:  modified the sponsor 
from “Pfizer Investment Co. Ltd” to 
“Pfizer Pharmaceuticals Ltd.”
2. At Page 7:  revised the study 
period as “14 August 2015 to 15 
November 2016”
3. At Page 11:  updated the planned 
date of milestones.
Sponsor name need to be
aligned with payment code 
2
16th July, 
2015
Administrative amendment
10.1. Single 
Reference 
Safety 
Document
At Page 29: modified the wording, 
changed “the detail version date” to 
“current local label”
There is no need to 
amendment when local 
label updates
3
6th August, 
2015
Administrative amendment
2.Responsi
ble Parties
8.3 
Variables
8.6 Data 
Manageme
nt
1. At Page 6: add Dr. 
as Principal Investigator of 
 
2. At Page 18: delete “occupation”
in Demographic information and 
“allergic history” in Medical history 
3. At Page 18: change database 
platform from “data-labs” to 
“OCRDC”
Add PI to facilitate the 
management and execution 
of the study
Reduce the variables which
is not related with study 
objectives
Alignment with the 
database change from 
Pfizer CRDC
4
20th
November,2
015
Administrative amendment
2.Responsi
ble Parties
1. At Page 6: change Dr. 
as Leading 
Principal Investigator; add Dr.
as Co-Principal Investigator
Change leading PI to 
facilitate the management 
and execution of the study
5
25th
January, 
2016
Substantial amendment
8.2.1 Study 
patients
8.5 Study 
size
8.1.1 
Overall 
design
8.3 
Variables
8.2.7 Study 
procedures
8.1.2 Study 
1. Change outpatients to patients
2. Change sample size from 15000 
to 10000
3. Change in site number from 75 to 
65
4. Add renal function variables
5.   Information on baseline and 
week 12 regular visit is required to 
record. Any other visits would be 
recorded as unplanned.
6. Change in how to calculate 12-
Make the study design 
closer to clinical practice
PPD
PPD
PPD
PPD
PPD

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endpoint
5.
MILESOT
NES
week
7. Several wording modifications
8. Updated the planned date of 
milestone per the latest progression
6
21st
September, 
2017
Substantial amendment
5.
MILESOT
NES
8.2.2 
Inclusion 
Criteria
8.2.7 Study 
Procedures
1. Update the planned date of all the 
milestones per the latest progression
2. Allow to collect the baseline lab 
reports within 24h after starting 
atorvastatin therapy
3. Change the time limit of 
unplanned visits to “any date during 
Week 4 to Week 16 (D29 to 
D115(f10 days))”
Change the Milestones
according to the actual 
execution
Make the study design 
closer to clinical practice

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5. MILESTONES 
Milestone
Planned date
Completion of feasibility assessment
January 2016
Start of data collection 
June 2016
End of data collection
October 2018
Data lock
January 2019
Final study report
April 2019
6. RATIONALE AND BACKGROUND 
Dyslipidemia is one of major risk factors leading to atherosclerotic origin cardiovascular 
disease (ASCVD). A large number of cohort studies indicated that serum total cholesterol or 
low density lipoprotein cholesterol is one of the independent risk factors resulting in 
atherosclerotic coronary heart disease and cerebrovascular disease [2-4]. At present, LDL-C is 
regarded as the primary targets of therapy for prevention and treatment for CHD in clinical 
guidelines. As the effective drug to lower plasma LDL-C effectively, atorvastatin is widely 
used in clinical practice [5-6]. 
2013 American College of Cardiology/ American Heart Association (ACC/AHA) Guideline
on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in 
Adult identified 4 statin benefit groups which focus efforts to reduce atherosclerotic 
cardiovascular disease events in secondary and primary prevention, and recommended high-
intensity and moderate-intensity statin therapy for use in secondary and primary prevention [7].
Due to fail to find randomized control trials evidence to support continued use of specific 
LDL-C treatment targets, the guideline recommended that the appropriate intensity of statin 
therapy should be used to reduce ASCVD risk in those most likely to benefit.  The new 
guidelines have already been the subject of controversy, with some observers arguing that 
some elements of the recommendations are not evidence-based. In China, many cardiology 
experts believe that the ACC/AHA guideline is not applicable for Chinese patients, e.g. high 
intensity statin (e.g. atorvastatin 40mg or greater) dosage and new perceptive on LDL-C
goals. Chinese experts think that Chinese population has lower LDL-C baseline compared 
with that of western population, moderate intensity statin (e.g. atorvastatin 10-20mg) maybe 
enough to control blood lipid level. Additionally, high intensity statin in Chinese population 
may also bring safety concerns. Atorvastatin have been demonstrated established benefits 
and well safety profiles in a wealth of high risk patients for primary and secondary 
prevention, however the data mainly came from western population. There is to date lack of 

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effectiveness and safety data in Chinese population, especially large-scale study in real world 
setting. Therefore, the study is to verify atorvastatin effectiveness and safety in Chinese 
population, and explore the optimal atorvastatin regimens in high-to-moderate risk for 
ASCVD. 
6.1. Clinical Pharmacology 
Atorvastatin is a selective, competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A 
(HMG-CoA) reductase, the rate-limiting enzyme that converts HMG-CoA to mevalonate, a 
precursor of sterols, including cholesterol. Cholesterol and triglycerides circulate in the 
bloodstream as part of lipoprotein complexes. With ultracentrifugation, these complexes 
separate into high-density lipoprotein (HDL), intermediate-density lipoprotein (IDL), low-
density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) fractions. Triglycerides 
(TG) and cholesterol in the liver are incorporated into VLDL and released into the plasma for 
delivery to peripheral tissues. LDL is formed from VLDL and is catabolized primarily 
through the high-affinity LDL receptor. Clinical and pathologic studies show that elevated 
plasma levels of total cholesterol (total-C), LDL-cholesterol (LDL-C), and apolipoprotein B 
(apo B) promote human atherosclerosis and are risk factors for developing cardiovascular 
disease, while increased levels of HDL-cholesterol (HDL-C) are associated with a decreased 
cardiovascular risk. 
In animal models, Atorvastatin lowers plasma cholesterol and lipoprotein levels by inhibiting 
HMG-CoA reductase and cholesterol synthesis in the liver and by increasing the number of 
hepatic LDL receptors on the cell surface to enhance uptake and catabolism of LDL; 
Atorvastatin also reduces LDL production and the number of LDL particles. Atorvastatin 
reduces LDL-C in some patients with homozygous familial hypercholesterolemia, a 
population that rarely responds to other lipid-lowering medication(s). 
A variety of clinical studies have demonstrated that elevated levels of total-C, LDL-C, and 
apo B (a membrane complex for LDL-C) promote human atherosclerosis. Similarly, 
decreased levels of HDL-C (and its transport complex, apo A) are associated with the 
development of atherosclerosis. Epidemiologic investigations have established that 
cardiovascular morbidity and mortality vary directly with the level of total-C and LDL-C, 
and inversely with the level of HDL-C.
Atorvastatin reduces total-C, LDL-C, and apo B in patients with homozygous and 
heterozygous familial hypercholesterolemia, non-familial forms of hypercholesterolemia, and 
mixed dyslipidemia. Atorvastatin also reduces Very-Low-Density Lipoprotein Cholesterol 
(VLDL-C) and TG and produces variable increases in HDL-C and apolipoprotein A-1. 
Atorvastatin reduces total-C, LDL-C, VLDL-C, apo B, TG, and non-HDL-C, and increases 
HDL-C in patients with isolated hypertriglyceridemia. Atorvastatin reduces intermediate 
density lipoprotein cholesterol (IDL-C) in patients with dysbetalipoproteinemia. 
Like LDL, cholesterol-enriched triglyceride-rich lipoproteins, including VLDL, intermediate 
density lipoprotein (IDL), and remnants, can also promote atherosclerosis. Elevated plasma 

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triglycerides are frequently found in a triad with low HDL-C levels and small LDL particles, 
as well as in association with non-lipid metabolic risk factors for coronary heart disease. As 
such, total plasma TG has not consistently been shown to be an independent risk factor for 
CHD. Furthermore, the independent effect of raising HDL or lowering TG on the risk of 
coronary and cardiovascular morbidity and mortality has not been determined. 
6.2. Toxicology 
In a 2-year carcinogenicity study in rats at dose levels of 10, 30, and 100 mg/kg/day, 2 rare 
tumors were found in muscle in high-dose females: in one, there was a rhabdomyosarcoma 
and, in another, there was a fibrosarcoma. This dose represents a plasma area under curve 
˄AUC˅(0–24) value of approximately 16 times the mean human plasma drug exposure 
after an 80 mg oral dose.
A 2-year carcinogenicity study in mice given 100, 200, or 400 mg/kg/day resulted in a 
significant increase in liver adenomas in high-dose males and liver carcinomas in high-dose 
females. These findings occurred at plasma AUC (0–24) values of approximately 6 times the 
mean human plasma drug exposure after an 80 mg oral dose. 
In vitro, atorvastatin was not mutagenic or clastogenic in the following tests with and without 
metabolic activation: the Ames test with Salmonella typhimurium and Escherichia coli, the 
hypoxanthine-guanine phosphoribosyl transferase (HGPRT) forward mutation assay in 
Chinese hamster lung cells, and the chromosomal aberration assay in Chinese hamster lung 
cells. Atorvastatin was negative in the in vivo mouse micronucleus test. 
Studies in rats performed at doses up to 175 mg/kg (15 times the human exposure) produced 
no changes in fertility. There was aplasia and aspermia in the epididymis of 2 of 10 rats 
treated with 100 mg/kg/day of atorvastatin for 3 months (16 times the human AUC at the 80 
mg dose); testis weights were significantly lower at 30 and 100 mg/kg and epididymal weight 
was lower at 100 mg/kg. Male rats given 100 mg/kg/day for 11 weeks prior to mating had 
decreased sperm motility, spermatid head concentration, and increased abnormal sperm. 
Atorvastatin caused no adverse effects on semen parameters, or reproductive organ 
histopathology in dogs given doses of 10, 40, or 120 mg/kg for two years.  
7. RESEARCH QUESTION AND OBJECTIVES 
7.1. Primary Objective: 
•
To evaluate the effectiveness of atorvastatin in Chinese cardiology patients in real world 
setting. 
7.2. Secondary Objectives: 
•
To assess atorvastatin safety in cardiology patients in real world setting 
•
To analyze patterns of atorvastatin prescription in cardiology patients.  

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8. RESEARCH METHODS  
8.1. Study Design  
8.1.1. Overall Design 
This is a multi-center, prospective, observational study, which will be completed by Beijing 
Anzhen Hospital, Capital Medical University and approximately 64 other clinical sites. 
8.1.2. Study Endpoint 
•
Primary endpoint 
 Achievement rate of LDL-C goals at 12 weeks of therapy of Atorvastatin according 
to Chinese Guideline on Dyslipidemia Prevention and Treatment in Adult (2007 
version). It will be presented with the proportion of patients who achieve the LDL-C
goal value. LDL-C target value for the patients with different risk level is defined in 
the section 8.2.5 per guideline.
No. subjects who achieve LDL-C target value  
Achievement Rate =
No. subjects who complete 12-week follow up 
¾
The time of 12-week will be calculated from the day when each patient starts 
taking atorvastatin.  . 
¾
Achievement rate will be summarized overall, within each risk strata, and by 
dose within each risk strata. 95% confidence intervals will be provided. 
•
Secondary endpoint 
 Dosage distribution of Atorvastatin in cardiology patients with different risk 
stratification at the end of 12-week follow-up 
 Safety and tolerability will be evaluated by recording the incidence and severity of 
adverse events, abnormal physical examination findings, and abnormal laboratory 
values through 12 weeks of treatment. Especially monitoring the patients who have  
any the following events:
¾
Having muscle symptoms such as myalgia, fatigue, weakness, creatine kinase 
values 10 times the upper limit of normal, or rhabdomyolysis, 
¾
Having
persistent 
elevation 
in 
alanine 
aminotransferase, 
aspartate 
aminotransferase, or both (defined as two consecutive measurements obtained 4 
to 10 days apart that is more than three times the upper limit of the normal 
range).

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¾
Major adverse cardiovascular events will also be recorded as adverse events, 
including death, myocardial infarction, stroke, documented unstable angina 
requiring re-hospitalization, revascularization with either percutaneous coronary 
intervention or coronary-artery bypass grafting. 
Adverse events will be summarized overall and by dose within each risk strata.
 Dropout percentage and reason through 12 weeks of follow-up; 
8.2. Setting 
8.2.1. Study Population 
Judged by investigators, patients in cardiology department who are eligible for inclusion and 
exclusion criteria can be included into this study. Estimated total sample size is 10,000 and 
will be conducted in approximately 65 hospitals in China. 
8.2.2. Inclusion Criteria 
Patients must meet all of the following inclusion criteria to be eligible for inclusion in the 
study: 
•
Men and women aged ı18 years;
•
Cardiology patients# who has been prescribed atorvastatin by physician’s clinical 
judgment under normal clinical care. These patients will include those with established 
coronary heart disease, or having multiple risk factors and at risk for cardiovascular 
disease, or primary hypercholesterolemia.  
•
Baseline laboratory reports* prior to starting atorvastatin therapy can be tracked, 
including lipid measurement, liver function, creatine kinase (CK) value, and renal 
function.
•
Evidence of a personally or his/her legally acceptable representative signed and dated 
informed consent document indicating that the patient has been informed of all pertinent 
aspects of the study and accept follow-up visit. 
#The proportion of ward inpatients is not more than 20% of the total number of patients. 
*The date of the report should be within 1 month before taking atorvastatin or within 24h after starting atorvastatin 
therapy. 
8.2.3. Exclusion Criteria 
Patients meeting any of the following criteria will not be included in the study: 
•
Patients who have regularly taken atorvastatin therapy more than 4 weeks before 
enrollment  

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•
Concomitant any other lipid-lower medication at baseline, or during the study 
conduction on physician clinical judgment 
8.2.4. Disease Diagnostic Basis 
Refer to local clinical diagnosis and treatment guidelines listed below: 
•
Refer to chronic stable angina pectoris diagnosis and treatment guideline issued by 
Chinese Medical Association in 2007, Non-ST-segment elevation acute coronary 
syndrome diagnosis and treatment guideline issued by Chinese Medical Association in 
2012, ST-segment elevation acute myocardial infarction diagnosis and treatment 
guideline issued by Chinese Medical Association in 2015, respectively to diagnose 
coronary heart disease 
•
Refer to Chinese Hypertension Prevention Guideline 2010 to diagnose hypertension. 
•
Refer to Chinese Guideline on Dyslipidemia Prevention and Treatment in Adult 2007 to 
diagnose hyperlipidemia. 
8.2.5. Risk Stratification and LDL-C Therapy Target Value 
Referring to Chinese Guideline on Dyslipidemia Prevention and Treatment in Adult (2007), 
the cardiovascular disease (CVD) risk stratification and LDL-C therapy target value will be 
the following: 
Risk stratification
Beginning of drug therapy
Therapy target value
Low-risk: 10 years CV 
risk <5%
LDL-C≥4.92mmol/L
(190mg/dl)
LDL-C<4.14 mmol/L
(160mg/dl)
Medium-risk: 10 years 
CVD risk 5%~10%
LDL-C≥4.14 mmol/L
(160mg/dl)
LDL-C<3.37 mmol/L
(130mg/dl)
High risk: CHD or CHD
risk equivalents, or 10 
years 
CV 
risk 
10%~15%
LDL-C≥2.59 mmol/L
(100mg/dl)
LDL-C<2.59mmol/L
(100mg/dl)
Very high risk: acute 
coronary syndromes, or 
ischemic cardiovascular 
disease combined with 
diabetes
LDL-C≥2.07 mmol/L
(80mg/dl)
LDL-C<2.07mmol/L
(80mg/dl)

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8.2.6. Study Period 
According to the overall timeline of the study, First Patient In (FPI) will start on 23 February,
2016, and Last Patient Last Visit (LPLV) will end on 30 December, 2016. Data collection 
will be finalized during this period. 
For each patient, the study period is from the time when patient signs informed consent form
to the time the study is closed. Patients’ information will be collected at baseline visit, week 
12 (D85, r10 days), and any unplanned visits (if occurrence). The study will be regarded as 
close when patient completes all the visits or withdraws from the study.  
For adverse events, the reporting period begins at the time of the patient’s first dose of 
atorvastatin or the time of the patient’s informed consent if s/he is already exposed to 
atorvastatin, and lasts through the end of the observation period of the study, which should 
include 28 calendar days following the last administration of a drug under study 
8.2.7. Study Procedures 
At baseline visit, patient inclusion/exclusion and demographic information, medical history, 
medication records, concomitant drugs and laboratory examination results prior to 
Atorvastatin therapy such as liver function, blood lipid parameter, creatine kinase value and 
renal function will be collected by investigators in the study. At week 12 visit and any 
unplanned visits, the laboratory examination results and medication records will be collected. 
Adverse events will be recorded at any time during the study period. 
Schedule of Activities is as follows: 
Visits
Protocol Activity
Visit 1
Visit 2
Any unplanned
Visits
Baseline
Day(D)1
Week 12
D85
(r10 days)
Any 
date 
during Week 4
to Week 16
D29~D115(f10 
days)
Signed Informed Consent Form
▲
Demographic information
▲
Medical history
▲
Laboratory examination
▲

▲
▲
Inclusion/exclusion criteria
▲

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Visits
Visit 1
Visit 2
Any unplanned
Visits
Adverse event records
Record at any time during the study period
Medication records 
▲
▲
▲
Notes: Each activity refers to section 8.3 Variables
 The date of the report should be within 1 month before taking atorvastatin or within 24h 
after starting atorvastatin therapy 
8.2.8. Study Drug 
The drug used in this study should be paid by patients themselves and administration method 
should be referred to the doctor’s prescription. 
8.3. Variables
This study will collect and analyze the effectiveness and safety data from approximately 
10,000 eligible subjects from the time of first subject first visit to the time the study is closed. 
Since this is primarily an observational study, patient subsequent visits are set according to 
the return dates in clinical practice, which are supposed to be week 12 and any unplanned 
visits during week 4 to week 16.  
•
Demographic information includes patients’ birth date, gender, body height and weight; 
•
Medical history includes information on current medical history, previous medical 
history, family history of premature cardiovascular disease and history of smoking ; 
•
Laboratory examination includes liver function [ ALT, AST, total bilirubin (TBil)],
serum lipid parameter (LDL-C, HDL-C, TG, Total-C), creatine kinase value (CK) and 
renal function [creatinine (Cr), blood urea nitrogen (BUN), uric acid (UA)];
•
Major adverse cardiovascular events including death, myocardial infarction, stroke, 
documented unstable angina requiring re-hospitalization, revascularization with either 
percutaneous coronary intervention or coronary-artery bypass grafting 
•
Other adverse events. (Details in Section 10 MANAGEMENT AND REPORTING OF
ADVERSE EVENTS/ADVERSE REACTIONS)
•
Medication record: dosage and duration of Atorvastatin, as well as any dose change 
including reasons will be recorded.  
•
Concomitant drugs: antiplatelet drugs, angiotensin converting enzyme inhibitors (ACEI)/ 
angiotensin receptor blockers (ARB), E-block, diuretics and calcium antagonist are 
concomitantly used or not. 

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8.4. Data Sources  
This NI study data will be recorded in the medical records by investigators, and then input to 
electronic Data Collection (EDC) system as the form of electronic Case Report Form (eCRF). 
8.5. Study Size 
•
The NI study is designed to detect the achievement rate of LDL-C value in cardiology 
patients with atorvastatin therapy in real world setting. The length of follow-up is 
designed to be 12 weeks.
•
In the recently published DYSIS [1] study, the achievement rate of LDL-C value was 
about 60% among Chinese patients taking 3 months lipid-lowering therapy. In this NI 
study, we assumed the achievement rate of LDL-C of 60%, allowable error rate of 1.1%, 
type I error of 0.05, we calculated a required sample size of 7600 patients. Considering 
24% loss to follow-up in real-world setting, the sample size will be 10,000. This sample 
size will also allow for stratification by  sex, age (≥65 years), risk stratification ( very 
high risk, high risk, moderate risk and low risk) and baseline disease type (with 
established CHD, having multiple risk factors, and primary hypercholesterolemia)Ǆ
8.6. Data Management  
OCRDC is the EDC system for the study. Discrepancy management is used to identify and 
manage potential problems with study data. OCRDC generates discrepancies during data 
entry and discrepancy management whenever there is a missing or inconsistency between the 
data entered and the validation specifications. OCRDC identifies a problem and creates a 
discrepancy entry in the database.  
The investigator is responsible to collect study data, including the eCRF data, laboratory 
data, via the EDC system in a timely manner and to ensure the integrity, accuracy, and 
completeness of the data.  
The investigator should keep accurate records of identity of all subjects (sufficient 
information to link the patients to the corresponding study data), serious adverse event forms, 
all related source documentation, details of treatment disposition, as well as relevant 
correspondence details (e.g. letters, emails, meeting minutes, telephone call reports). The 
investigator record retention period should comply with the local regulations, or as specified 
in the Clinical Study Agreement, whichever is longer.  
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (e.g., retirement, relocation), Pfizer should be notified. The study records 
must be transferred to a designee acceptable to Pfizer, such as another investigator, another 
institution, or to an independent third party arranged by Pfizer. The investigator must obtain 

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Pfizer's written permission before disposing of any records, even if retention requirements 
have been met. 
8.7. Data Analysis  
•
Descriptive statistics including number (N), mean, median, standard deviation, minimum 
and maximum, will be produced for all continuous variables. Frequency tables of number 
(N) and percentage of subjects will be produced for all categorical variables
•
All patients who received atorvastatin are included in the safety analysis, and safety data 
is summarized descriptively without statistical analysis.
•
Detailed methodology for summary and statistical analyses of data collected in this study 
will be documented in a Statistical Analysis Plan (SAP), which will be dated, filed and 
maintained by the sponsor. The SAP may modify the plans outlined in the protocol; any 
major modifications of primary endpoint definitions or their analyses would be reflected 
in a protocol amendment.
8.8. Quality Control 
During study conduct, Clinical Research Associates (CRAs) or study manager will conduct 
periodic monitoring visits to ensure that the protocol and Good Clinical Practices (GCPs) are 
being followed. The monitors may review source documents to confirm that the data 
recorded on eCRF is accurate. The investigator and institution will allow CRAs or study 
manager monitors and appropriate regulatory authorities direct access to source documents to 
perform this verification. 
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process.
8.9. Strengths and Limitations of the Research Methods 
•
Strengths: Large simple size and enrolled patients come from most area of China. 
•
Limitations: study patient only representatives China cardiology patients, but not a 
general population. 
8.10. Other Aspects 
Not applicable. 
9. PROTECTION OF HUMAN SUBJECTS 
9.1. Patient Information and Consent 
•
All parties will ensure protection of patient personal data and will not include patient 
names on any sponsor forms, reports, publications, or in any other disclosures, except 

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where required by laws.  In case of data transfer, Pfizer will maintain high standards of 
confidentiality and protection of patient personal data. 
•
The informed consent form must be in compliance with local regulatory requirements 
and legal requirements.  
•
The informed consent form used in this study, and any changes made during the course 
of the study, must be prospectively approved by both the Institutional Review 
Board/Independent Ethics committee (IRB/IEC) and Pfizer before use. 
•
The investigator must ensure that each study patient, or his/her legally acceptable 
representative, is fully informed about the nature and objectives of the study and possible 
risks associated with participation.  The investigator, or a person designated by the 
investigator, will obtain written informed consent from each patient or the patient’s
legally acceptable representative before any study-specific activity is performed.  The 
investigator will retain the original of each patient's signed consent form. 
9.2. Patient Withdrawal 
•
Patients may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety, 
behavioral, or administrative reasons. In any circumstance, every effort should be made 
to document subject outcome, if possible. The investigator should inquire about the 
reason for withdrawal and follow-up with the subject regarding any unresolved adverse 
events.  
•
If the patient withdraws from the study, and also withdraws consent for disclosure of 
future information, no further evaluations should be performed, and no additional data 
should be collected. The sponsor may retain and continue to use any data collected 
before such withdrawal of consent. 
9.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, and informed consent forms, and other relevant documents, 
(e.g., recruitment advertisements), if applicable, from the IRB/IEC.  All correspondence with 
the IRB/IEC should be retained in the Investigator File.  Copies of IRB/IEC approvals should 
be forwarded to Pfizer.  
9.4. Ethical Conduct of the Study 
The study will be conducted in accordance with legal and regulatory requirements, as well as 
with scientific purpose, value and rigor and follow generally accepted research practices 
described in Guidelines for Good Pharmacoepidemiology Practices (GPP) issued by the 
International Society for Pharmacoepidemiology (ISPE), Good Epidemiological Practice 
(GEP) guidelines issued by the International Epidemiological Association (IEA), Good 

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Practices for Outcomes Research issued by the International Society for Pharmacoeconomics 
and Outcomes Research (ISPOR), International Ethical Guidelines for Epidemiological 
Research issued by the Council for International Organizations of Medical Sciences 
(CIOMS), European Medicines Agency (EMA) European Network of Centres for 
Pharmacoepidemiology and Pharmacovigilance (ENCePP) Guide on Methodological 
Standards in Pharmacoepidemiology, and Food and Drug Administration (FDA) Guidance 
for Industry: Good Pharmacovigilance and Pharmacoepidemiologic Assessment, FDA 
Guidance for Industry and FDA Staff: Best Practices for Conducting and Reporting of 
Pharmacoepidemiologic Safety Studies Using Electronic Healthcare Data Sets, Guidance for 
Industry: Patient-Reported Outcome Measures: Use in Medical Product Development to 
Support Labeling Claims and/or equivalent. 
10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS 
REQUIREMENTS 
The table below summarizes the requirements for recording safety events on the case report 
form and for reporting safety events on the non-interventional study (NIS) adverse event 
monitoring (AEM) Report Form to Pfizer Safety.  These requirements are delineated for 
three types of events: (1) serious adverse events (SAEs); (2) non-serious AEs (as applicable); 
and (3) scenarios involving drug exposure, including exposure during pregnancy, exposure 
during breast feeding, medication error, overdose,misuse, extravasation, lack of efficacy, and 
occupational exposure. These events are defined in the section “Definitions of safety events”.  
Safety event
Recorded on the case report 
form 
Reported on the NIS AEM 
Report Form to Pfizer Safety 
within 24 hours of awareness
SAE
All
All
Non-serious AE
All
None
Scenarios involving exposure to a 
drug 
under 
study
where 
applicable, including exposure 
during 
pregnancy, 
exposure 
during breast feeding, medication 
error, overdose, misuse, lack of 
efficacy, 
and 
occupational 
exposure;
All 
(regardless 
of 
whether 
associated with an AE), except 
occupational exposure
All (regardless of whether 
associated with an AE)
For each AE, the investigator must pursue and obtain information adequate both to determine 

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the outcome of the adverse event and to assess whether it meets the criteria for classification 
as a SAE (see section "Serious Adverse Events” below) 
Safety events listed in the table above must be reported to Pfizer within 24 hours of 
awareness of the event by the investigator regardless of whether the event is determined 
by the investigator to be related to a drug under study. In particular, if the SAE is fatal or 
life-threatening, notification to Pfizer must be made immediately, irrespective of the extent of 
available event information. This timeframe also applies to additional new (follow-up) 
information on previously forwarded safety event reports. In the rare situation that the 
investigator does not become immediately aware of the occurrence of a safety event, the 
investigator must report the event within 24 hours after learning of it and document the time 
of his/her first awareness of the events. 
For safety events that are considered serious or that are identified in the far right column of 
the table above that are reportable to Pfizer within 24 hours of awareness, the investigator is 
obligated to pursue and to provide any additional information to Pfizer in accordance with 
this 24-hour timeframe. In addition, an investigator may be requested by Pfizer to obtain 
specific follow-up information in an expedited fashion.  This information is more detailed 
than that recorded on the case report form. In general, this will include a description of the 
adverse event in sufficient detail to allow for a complete medical assessment of the case and 
independent determination of possible causality.  Any information relevant to the event, such 
as concomitant medications and illnesses must be provided.  In the case of a patient death, a 
summary of available autopsy findings must be submitted as soon as possible to Pfizer or its 
designated representative.
Reporting period 
For each patient, the safety event reporting period begins at the time of  the patient’s first 
dose of atorvastatin or the time of the patient’s informed consent if s/he is already exposed to 
atorvastatin, and lasts through the end of the observation period of the study, which must 
include at least 28 calendar days following the last administration of a drug under study; a 
report must be submitted to Pfizer Safety (or its designated representative) for any of the 
applicable types of safety events listed in the table above occurring during this period.  If a 
patient was administered a drug under study on the last day of the observation period, then 
the reporting period should be extended for 28 calendar days following the end of 
observation. Most often, the date of informed consent is the same as the date of enrollment. 
In some situations, there may be a lag between the dates of informed consent and enrollment.  
In these instances, if a patient provides informed consent but is never enrolled in the study 
(e.g., patient changes his/her mind about participation), the reporting period ends on the date 
of the decision to not enroll the patient.   
If the investigator becomes aware of a SAE occurring at any time after completion of the 
study and s/he considers the SAE to be related to atorvastatin, the SAE also must be reported 
to Pfizer Safety.  

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Causality assessment 
The investigator is required to assess and record the causal relationship.  For all AEs, 
sufficient information should be obtained by the investigator to determine the causality of 
each adverse event.  For AEs with a causal relationship to atorvastatin, follow-up by the 
investigator is required until the event and/or its sequelae resolve or stabilize at a level 
acceptable to the investigator, and Pfizer concurs with that assessment.   
An investigator’s causality assessment is the determination of whether there exists a 
reasonable possibility that atorvastatin caused or contributed to an adverse event. If the 
investigator’s final determination of causality is “unknown” and s/he cannot determine 
whether atorvastatin caused the event, the safety event must be reported within 24 hours.   
If the investigator cannot determine the etiology of the event but s/he determines that 
atorvastatin did not cause the event, this should be clearly documented on the case report 
form and the NIS AEM Report Form.  
DEFINITIONS OF SAFETY EVENTS 
Adverse events 
An AE is any untoward medical occurrence in a patient administered a medicinal product.  
The event need not necessarily have a causal relationship with the product treatment or usage.
Examples of adverse events include but are not limited to:   
x
Abnormal test findings (see below for circumstances in which an abnormal test finding 
constitutes an adverse event); 
x
Clinically significant symptoms and signs; 
x
Changes in physical examination findings; 
x
Hypersensitivity; 
x
Progression/worsening of underlying disease;  
x
Lack of efficacy;  
x
Drug abuse;  
x
Drug dependency. 
Additionally, for medicinal products, they may include the signs or symptoms resulting from: 

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x
Drug overdose; 
x
Drug withdrawal; 
x
Drug misuse;  
x
Off-label use;  
x
Drug interactions; 
x
Exposure during pregnancy; 
x
Exposure during breast feeding; 
x
Medication error 
x
Occupational exposure. 
; 
Abnormal test findings 
The criteria for determining whether an abnormal objective test finding should be reported as 
an adverse event are as follows:  
x
Test result is associated with accompanying symptoms, and/or 
x
Test result requires additional diagnostic testing or medical/surgical intervention, and/or 
x
Test result leads to a change in study dosing or discontinuation from the study, significant 
additional concomitant drug treatment, or other therapy, and/or 
x
Test result is considered to be an adverse event by the investigator or sponsor. 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an adverse event.  Any abnormal test result that is determined to be an error does 
not require reporting as an adverse event. 
Serious adverse events 
A serious adverse event is any untoward medical occurrence in a patient administered a 
medicinal or nutritional product (including pediatric formulas) at any dose that: 
•
Results in death; 
•
Is life-threatening; 

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•
Requires inpatient hospitalization or prolongation of hospitalization (see below for 
circumstances that do not constitute adverse events); 
•
Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions); 
•
Results in congenital anomaly/birth defect. 
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the patient or may require intervention to prevent one of the other outcomes listed in the 
definition above, the important medical event should be reported as serious. 
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse. 
Additionally, any suspected transmission via a Pfizer product of an infectious agent, 
pathogenic or non-pathogenic, is considered serious.  The event may be suspected from 
clinical symptoms or laboratory findings indicating an infection in a patient exposed to a 
Pfizer product.  The terms “suspected transmission” and “transmission” is considered 
synonymous.  These cases are considered unexpected and handled as serious expedited cases 
by Pharmacovigilance (PV) personnel.  Such cases are also considered for reporting as 
product defects, if appropriate. 
Hospitalization 
Hospitalization is defined as any initial admission (even if less than 24 hours) to a hospital or 
equivalent healthcare facility or any prolongation to an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (e.g., from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, neurological floor to a 
tuberculosis unit). An emergency room visit does not necessarily constitute a hospitalization; 
however, an event leading to an emergency room visit should be assessed for medical 
importance.  
Hospitalization in the absence of a medical AE is not in itself an AE and is not reportable. 
For example, the following reports of hospitalization without a medical AE are not to be 
reported.  
•
Social admission (e.g., patient has no place to sleep) 
•
Administrative admission (e.g., for yearly exam) 
•
Optional admission not associated with a precipitating medical AE (e.g., for elective 
cosmetic surgery) 

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•
Hospitalization for observation without a medical AE 
•
Admission for treatment of a pre-existing condition not associated with the development 
of a new AE or with a worsening of the pre-existing condition (e.g., for work-up of 
persistent pre-treatment lab abnormality) 
•
Protocol-specified admission during clinical study (e.g., for a procedure required by the 
study protocol) 
Scenarios necessitating reporting to Pfizer Safety within 24 hours  
Scenarios involving exposure during pregnancy, exposure during breastfeeding, medication 
error, overdose, misuse, extravasation, lack of efficacy, and occupational exposure are 
described below.
Exposure during pregnancy 
An exposure during pregnancy (EDP) occurs if: 
1. A female becomes, or is found to be, pregnant either while receiving or having been  
exposed to (e.g., environmental) atorvastatin, or the female becomes, or is found to be, 
pregnant after discontinuing and/or being exposed to atorvastatin (maternal exposure). 
An example of environmental exposure would be a case involving direct contact with a 
Pfizer product in a pregnant woman (e.g., a nurse reports that she is pregnant and has 
been exposed to chemotherapeutic products). 
2. A male has been exposed, either due to treatment or environmental exposure to 
atorvastatin prior to or around the time of conception and/or is exposed during the partner 
pregnancy (paternal exposure). 
As a general rule, prospective and retrospective exposure during pregnancy reports from any 
source are reportable irrespective of the presence of an associated AE and  the procedures for 
SAE reporting should be followed. 
If a study participant or study participant’s partner becomes, or is found to be, pregnant 
during the study participant’s treatment with atorvastatin, this information must be submitted 
to Pfizer, irrespective of whether an adverse event has occurred using the NIS AEM Report 
Form and the EDP Supplemental Form.  
In addition, the information regarding environmental exposure to atorvastatin in a pregnant 
woman (e.g., a subject reports that she is pregnant and has been exposed to a cytotoxic 

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product by inhalation or spillage) must be submitted using the NIS AEM Report Form and 
the EDP supplemental form. This must be done irrespective of whether an AE has occurred.   
Information submitted should include the anticipated date of delivery (see below for 
information related to termination of pregnancy). 
Follow-up is conducted to obtain general information on the pregnancy; in addition, follow-
up is conducted to obtain information on EDP outcome for all EDP reports with pregnancy 
outcome unknown.  A pregnancy is followed until completion or until pregnancy termination 
(e.g., induced abortion) and Pfizer is notified of the outcome.  This information is provided 
as a follow up to the initial EDP report.  In the case of a live birth, the structural integrity of 
the neonate can be assessed at the time of birth.  In the event of a termination, the reason(s) 
for termination should be specified and, if clinically possible, the structural integrity of the 
terminated fetus should be assessed by gross visual inspection (unless pre-procedure test 
findings are conclusive for a congenital anomaly and the findings are reported). 
If the outcome of the pregnancy meets the criteria for an SAE (e.g., ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live born, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
procedures for reporting SAEs should be followed. 
Additional information about pregnancy outcomes that are reported as SAEs follows:  
x
Spontaneous abortion includes miscarriage and missed abortion; 
x
Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs.  In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure 
to investigational product 
Additional information regarding the exposure during pregnancy may be requested.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (e.g., follow-up on 
preterm infants to identify developmental delays).   
In the case of paternal exposure, the study participant will be provided with the Pregnant 
Partner Release of Information Form to deliver to his partner.  It must be documented that the 
study participant was given this letter to provide to his partner. 
Exposure during breastfeeding 
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated AE. An exposure during breastfeeding report is not created when a Pfizer drug 
specifically approved for use in breastfeeding women (e.g., vitamins) is administered in 

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accord with authorized use.  However, if the infant experiences an AE associated with such a 
drug’s administration, the AE is reported together with the exposure during breastfeeding.
Medication error 
A medication error is any unintentional error in the prescribing, dispensing or administration 
of a medicinal product that may cause or lead to inappropriate medication use or patient harm 
while in the control of the health care professional, patient, or consumer.  Such events may 
be related to professional practice, health care products, procedures, and systems including: 
prescribing; order communication; product labeling, packaging, and nomenclature; 
compounding; dispensing; distribution; administration; education; monitoring; and use.   
Medication errors include: 
x
Near misses, involving or not involving a patient directly (e.g., inadvertent/erroneous 
administration, which is the accidental use of a product outside of labeling or prescription 
on the part of the healthcare provider or the patient/consumer); 
x
Confusion with regard to invented name (e.g., trade name, brand name). 
The investigator must submit the following medication errors to Pfizer, irrespective of the 
presence of an associated AE/SAE: 
x
Medication errors involving patient exposure to the product, whether or not the 
medication error is accompanied by an AE. 
x
Medication errors that do not involve a patient directly (e.g., potential medication errors 
or near misses).  When a medication error does not involve patient exposure to the 
product the following minimum criteria constitute a medication error report: 
1. An identifiable reporter; 
2. A suspect product; 
3. The event medication error. 
Overdose, Misuse 
Reports of overdose and misuse, associated with the use of a Pfizer product  are reported to 
Pfizer by the investigator, irrespective of the presence of an associated AE/SAE.  
Lack of Efficacy 

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Reports of lack of efficacy to a Pfizer product are reported to Pfizer by the investigator, 
irrespective of the presence of an associated AE/SAE or the indication for use of the Pfizer 
product. 
Occupational Exposure 
Reports of occupational exposure to a Pfizer product are reported to Pfizer by the investigator, 
irrespective of the presence of an associated AE/SAE. 
10.1. Single Reference Safety Document 
The current Lipitor local label [package insert, (PI)] approved by China Food and Drug 
Administration (CFDA), will serve as the single reference safety document during the course 
of the study, which will be used by Pfizer safety to assess any safety events reported to Pfizer 
Safety by the investigator during the course of this study.  
The single reference safety document (SRSD) should be used by the investigator for 
prescribing purposes and guidance  
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS 
COMMUNICATION OF ISSUES 
The first publication will be the result analysis based on the primary end points of all the 
research units. 
Investigators must inform the sponsor in advance about the publication plan of articles or 
reports of any study data analysis. The investigator or his/her representative must obtain 
review and written approval from sponsor when dealing with anything about publication or 
result report (magazine, abstract of newspaper or oral report, etc.), no matter in whole or in 
part. 
The sponsor will not suppress or veto publication, but will reserve the right to delay 
publication for the protection of intellectual property right. 
COMMUNICATION OF IISUES 
In the event of any prohibition or restriction imposed (e.g., clinical hold) by an applicable 
Competent Authority in any area of the world, or if the investigator is aware of any new 
information which might influence the evaluation of the benefits and risks of a Pfizer product, 
Pfizer should be informed immediately.   

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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study patients against any immediate hazard, and of 
any serious breaches of this NI study protocol that the investigator becomes aware of. 
12. REFERENCES 
[1] Zhao Shuiping,  Wang Yongjun, Mu Yiming, etc. Prevalence of dyslipidaemia in patients 
treated with lipid-lowering agents in China: Results of the DYSlipidemia International Study 
(DYSIS). Atherosclerosis. 2014, 235:463-469 
[2] Zhao Dong,Wu Zhaosu,Wang Wei,etc. Trend analyses of the incidence of atherosclerotic 
events of acute coronary heart disease from 1984 to 1997 in Beijing (China MONICA).
Chinese Journal of Cardiologyˈ2000ˈ28(1)˖l4-l7ˊ
[3]Wang Wenhua, Zhao Dong, Wu Guixian,etc.Trend analyses of the incidence of stroke 
from1984 to 1999 in Beijing. Chinese Journal of Epidemiology, 2001ˈ22(4)˖269-272ˊ
[4] Wang Wenhua, Zhao Dong, Wu Guixian,etc. Trend analyses of the incidence of acute 
cerebral hemorrhage and cerebral thrombosis in Beijing. Chinese Journal of Epidemiologyˈ
2002ˈ23(5)˖352-355. 
[5] Chen Haozhu. Status of blood lipid level and treatment of hyperlipidemia in Chinese 
populationChinese Journal of integrated traditional Chinese and Western Medicine, 

[6] Zhao Shuiping. Effects of statin in the overall prevention and control of atherosclerotic 
coronary heart disease. Chinese Journal of Cardiology
[7]Stone NJ, Robinson JG, Lichtenstein AH, etc. 2013 ACC/AHA Guideline on the 
Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. 
Journal of the American College of Cardiology. 2014 Jul 1;63(25 Pt B):2889-934. doi: 
10.1016/j.jacc.2013.11.002. Epub 2013 Nov 12. 
13. LIST OF TABLES  
None 
14. LIST OF FIGURES 
None 
ANNEX 1. LIST OF STAND ALONE DOCUMENTS 
None  
ANNEX 2. ADDITIONAL INFORMATION 
Not applicable