MINISTRY OF EDUCATION
AND TRAINING
MINISTRY OF NATIONAL
DEFENSE
VIETNAM MILITARY MEDICAL UNIVERSITY
DO DUC THUAN
A STUDY ON THE EFFECTS OF ALLELE CYP2C19*2,
CYP2C19*3
AND SOME FACTORS RELATED TO CLOPIDOGREL
RESPONSIVENESS IN PATIENTS WITH CEREBRAL
INFARCTION
Major: Neuroscience
Code: 9720159
SUMMARY OF DOCTORAL THESIS
WORKS ARE COMPLETED AT VIETNAM MILITARY
MEDICAL UNIVERSITY
SUPERVISORS:
1. Assoc. Prof. PHAM DINH TAI
2. Assoc. Prof. TRAN VAN KHOA
Reviewer 1: Prof. NGUYEN VAN THONG
Reviewer 2: Assoc. Prof. TRAN VAN KHANH
Reviewer 3: Assoc. Prof. NGUYEN TRONG HUNG
The thesis will be upheld at the thesis evaluation council
at Vietnam Military Medical University
at: …….
The thesis can be found at:
1. National Library
2. Library of Vietnam Military Medical University
1
INTRODUCTION
1. The necessity for the topic.
A cerebral infarction is caused by a narrowed artery for a variety
of causes but the most common is arterial thrombosis in which
platelets play a central role in the formation of blood clots.
Clopidogrel is an antiplatelet drug approved by the World Stroke
Organization to use thromboprophylaxis in patients with cerebral
infarction. However, some patients still have recurrent cerebral
infarction while being treated with clopidogrel. Research in the world
show that there are a number of factors affecting the responsiveness,
causing clopidogrel resistance with the rate from 4% to 30%. The
reason is that patients carry alleles CYP2C19*2, CYP2C19*3
containing genetic coding information of CYP2C19 enzyme (the
enzyme that metabolize clopidogrel from precursor to active
substance). Some non-gene CYP2C19 factors related to clopidogrel
responsiveness, such as: age, gender, accompanying drugs, diabetes,
obesity, increased HbA1C or increased plasma protein C also
decreased the response of clopidogrel. In Vietnam, research on the
effects of these alleles and factors related to clopidogrel
responsiveness in patients with cerebral infarction has not been
published. Therefore, we conducted research on the topic " A study
on the effect of alleles CYP2C19*2, CYP2C19*3 and some factors
related to clopidogrel responsiveness in patients with cerebral
infarction".
2. The objectives of the topic
- To identify some non- gene CYP2C19 factors related to
clopidogrel responsiveness in patients with cerebral infarction.
2
- To assess the effect of alleles CYP2C19*2, CYP2C19*3 on
the response of clopidogrel in patients with cerebral infarction.
3. Practical significance and contribution of the topic
The topic gives information about the rate of clopidogrel
resistance in cerebral infarction, the rate of alleles CYP2C19*2,
CYP2C19*3 and their effects on the responsiveness of clopidogrel.
The topic provides information on the relation between age,
gender, BMI, co-morbidities (such as hypertension, diabetes,
atherosclerosis, blood biochemical indices (increased CRP; albumin
reduction, drugs used together with insulin or metformin)) and
clopidogrel responsiveness and since then improves the use of
clopidogrel in the prevention on cerebral infarction.
4.The structure of the thesis
The thesis is presented in 127 pages (excluding references and
appendix)
The thesis is divided: Introduction 2 pages, chapter 1: Literature
Review 31 pages, chapter 2: Objects and Methodology 23 pages,
chapter 3: Results 36 pages, chapter 4: Discussion 32 pages,
Conclusions 2-page and Recommendations 1-page
The thesis includes 48 tables, 19 figures, 1 diagram. Among 176
references there are 23 Vietnamese documents, 153 English
documents, 31 documents in the last 5 years. The appendix includes a
studying medical record, an application for voluntary participation in
the study, ACR / EULAR 2015 diagnostic gout criteria.
3
CHAPTER 1: LITERATURE REVEIW
1.1. Cerebral infarction
1.1.1. Definition
1.1.2. Pathogenesis of cerebral infarction and the role of platelets
in cerebral infarction
Cerebral infarction is caused by a blocked brain artery that
reduces blood flow to the brain area supplied by that artery. The most
common cause is due to arterial thrombosis. The process of
thrombosis occurs gradually over many years and goes through two
stages: Vascular phase, hematology and the chemical change phase
of the cell. Platelets are mainly involved in blood vessel and
hematologic stages, play an important role in the formation and
development of thrombosis-atherosclerosis of brain arteries and
increased the activation of platelet after cerebral blood vessel is
blocked, platelets are aggregated at the micro vessels in the anemia
region, releasing substances acting on blood vessels.
1.1.3. Classification of cerebral infarction
Classify cerebral infarction according to TOAST.
1.1.4. Epidemiology of cerebral infarction
The rate of cerebral infarction accounts for 85% of the total
number of strokes, including 17% from infarction caused by heart,
4% from carotid atherosclerosis, 64% from other reasons. Recurrent
cerebral strokes account for about 25% of all types of the brain
strokes. Using anti-platelet aggregation medication is an important
therapy to prevent recurrent cerebral infarction.
1.1.5. Clopidogrel in the treatment and prevention on cerebral
infarction