For Registration of Subject for Dissertation To

Synopsis

For Registration of subject for dissertation to

Rajiv Gandhi University of Health Sciences

Karnataka, Bangalore

In Partial Fulfilment of Regulations

In Regard for the award of

Masters Degree in medicine

In respect of

Dr v jayaprasad

Department of medicine

Command Hospital Air Force Bangalore-560007

Rajiv Gandhi University of Health Science

Karnataka, Bangalore

Annexure – II

Proforma for registration of subject for dissertation

1. / Name of the candidate and address / Dr v jayaprasad
Department of medicine
command hospital( air force)
Bangalore-07
2. / Name of the institution / command hospital (air force) Bangalore
3. / Course of study and subject / MD medicine
4. / Date of admission to the course / 1st May 2008
5. / Title of the topic / variability in platelet response to aspirin in high risk population
6. / Brief resume of intended work / 6.1 Need for study : As per Appendix – I
6.2 Review of literature : As per Appendix – II
6.3 Objectives of study : As per Appendix – III
7. / Material and methods / 7.1 Source of data : As per Appendix – IV
7.2 Method of collection of data : As per Appendix – IV
7.3 Does the study require any
investigation to be conducted
on patients if so, describe briefly : As per Appendix – IV
7.3 Has ethical clearance been
obtained from your institution
in case of 7.3 : Yes (copy enclosed)
8. / List of references / As per Appendix – V
9. / Signature of the candidate
10. / Remarks of the guide / .
11. / 11.1 Name and designation of the guide
11.2 Signature
11.3 Co-guide (1)
11.4 Signature
11.5 Co-guide (2)
11.6 Head of the department
Signature / wg cdr salil gupta md dm
neurologist
associate Professor
Department of
medicine
Chaf, Bangalore
wg cdr ds chadha md dm
cardiologist
associate PROFessor
department of medicine
chaf, bangalore
col r muralidhar md
Professor & HOD
Department of
medicine
Chaf, Bangalore
12. / 12.1 Remarks of the Principal
12. Signature

Appendix – I

NEED FOR STUDY

Aspirin is the cornerstone of antiplatelet therapy in cardiovascular medicine. Its role in the secondary prevention of vascular events has been proven beyond any doubt. A recent meta-analysis of 287 clinical trials on aspirin in the prevention of cardiovascular disease has provided firm evidence that antiplatelet therapy, mainly aspirin, can reduce approximately 25% the risk of non-fatal myocardial infarction (MI), non-fatal stroke, or vascular death in high-risk patients, regardless of sex, age, presence of arterial hypertension or diabetes.

However, a substantial proportion of patients manifest “breakthrough” events despite regular intake of aspirin. It is estimated that one in eight high-risk patients suffers from the recurrence of a vascular event within the next 2 years despite regular daily aspirin therapy. Based on the clinical and laboratory evidence of reduced or absent response to treatment with aspirin in some patients, the concept of “aspirin resistance” has emerged. Unfortunately, aspirin resistance remains a poorly defined term, and by using different methods of measuring platelet activity, several studies have demonstrated marked individual variations in the response to treatment with aspirin.

Not much work has been done in our country to assess the platelet resistance in the patients with coronary artery disease. In view of high incidence of premature coronary artery disease in our country it is worthwhile looking at the possibility of platelet resistance and its role in recurrence of disease.

There is therefore a pressing need to assess the platelet function in patients with acute and stable coronary artery disease.

Appendix – II

Review of Literature

Platelets play an important role in the development of atherosclerosis and the formation of coronary thrombi.Antiplatelet agents are used as a part of the treatment of patients with myocardial infarction. Aspirin is the most commonly used antiplatelet drug. Aspirin, via its antiplatelet effect, reduces the odds of an arterial thrombotic event in high-risk patients by_25%.However, 10% to 20% of patients with an arterial thrombotic event who are treated with aspirin have a recurrent arterial thrombotic event during long-term follow-up.The occurrence of arterial thrombotic events in patients receiving aspirin is often referred to as aspirin resistance or treatment failure.Patients demonstrate a marked variability in their laboratory responses to aspirin.True aspirin resistance has been suggested to be the insufficient inhibition of cyclooxygenase (COX)–dependent thromboxane A2 synthesis from arachidonic acid in subjects receiving aspirin.

Aspirin resistance may be defined as laboratory resistance and clinical resistance. Laboratory aspirin resistance is defined as the failure of aspirin to inhibit platelet thromboxane A2 production or inhibit tests of platelet function (eg, platelet aggregation) that are dependent on platelet thromboxane production.Clinical aspirin resistance is defined as the failure of aspirin to prevent clinical atherothromboembolic ischaemic events in patients prescribed aspirin

However aspirin resistance still remains a poorly defined term. There are conflicting reports on the incidence and clinical relevance of this phenomenon as platelet inhibition is not a uniform process. This mandates functional and biochemical in vitro tests to assess platelet function, and possibly identify the subgroup of patients at risk for future vascular events. There is paucity of data in our country on platelet resistance to aspirin . In view of high incidence of premature coronary artery disease it is prudent to assess this as it could be an important factor leading not only to primary coronary events but to a high incidence of their recurrence.

Appendix - III

Objective of Study

To assess the platelet resistance in patients with Vascular disease .

Appendix – IV

Materials and Methods

Aspirin resistance will be defined as a mean aggregation of ≥ 70% with 10 µm ADP and a mean aggregation of ≥ 20% with 0.5 mg/ml (AA). Aspirin semi responders were defined as those meeting only one of the criteria. Laboratory standards will be established by screening 25 age- and sex-matched healthy controls without any history or family history suggestive of CAD and who are not on any drugs for the past 7 days.

1 Source of data

Cases of Coronary artery disease, Cerebro vascular accidents,Peripheral vascular disease reporting to

MEDICAL OPD of COMMAND HOSPITAL

AIR FORCE BANGALORE

2 Method of collection

A) Duration of study: From 01 NOV 2008 TO NOV 2009

B) Sample size: 100

C) Inclusion criteria:

Patients with established coronary artery disease (CAD)

or stroke or transient ischemic attack (TIA) or peripheral vascular disease or with multiple atherothrombotic

risk factors like diabetes plus one of the following - hypertension, dyslipidemia, cigarette smoking or family history of CAD.

D) Exclusion criteria

Exclusion criteria included use

of clopidogrel, dipyridamole, non-steroidal antiinflammatory

drugs (NSAIDs), administration of heparin/

other antithrombotics in last 48 hours, family or personal

history of bleeding disorders, platelet count < 150 × 103/μl

or > 450 × 103/μl, hemoglobin <8 gm/dl, history of blood

dyscrasias, heparin-induced thrombocytopenia and major

surgical procedure within one week before enrolment.

3 Investigation method

Platelet resistance will be assessed by checking the agonist induced platelet aggregation. This will be done using either light or optical transmission aggregometry.

Light or optical transmission aggregometry measures the increase in light transmission through a platelet suspension when platelets are aggregated (and forms clumps) by an agonist such as arachidonic acid, ADP, or collagen.

4 Interpretation of results

5 Research Hypothesis

Variability in the response of platelets to aspirin therapy in high risk population leading to recurrence of coronary or cardiovascular events will be studied.

6 Statistical Methods

Data obtained will be subjected to statistical analysis using a computer based statistical programme (SPSS-15 / STATA).

proforma

NAME: CLINIC/OPD NO:

AGE/SEX: DATE:

ADDRESS:

TELEPHONE NO:

CARDIAC RISK FACTORS:

SMOKING: YES/NO

HYPERTENSION: YES/NO

DIABETES MELLITUS: YES/NO

DYSLIPIDEMIA: YES/NO

FAMILY H/O CAD: YES/NO

OBESITY: YES/NO

PHYSICAL INACTIVITY: YES/NO

BRIEF HISTORY:

PAST HISTORY:

ON EXAMINATION:

HEIGHT: WEIGHT:

BMI:

PR: (BIL SYMM – YES/NO)

BP:

TYPE OF OBESITY APPLE \PEAR\OVOID

EAR LOBE CREASE ACANTHOSIS NIGRICANS

SYSTEMIC EXAMINATION

INVESTIGATIONS:

HB:

TLC:

DLC:

PLATELETS:

FBS:

PPBS:

BUN:

S.CREATININE:

S.CHOLESTEROL:

LDL:

TG:

HDL:

VLDL:

S.BILIRUBIN:

SGOT:

SGPT:

SAP:

URINE RE:

CXR PA VIEW:

ECG:

AMI AWMI IWMI LWMI PWMI

CORONARY ANATOMY:

NORMAL SVD DVD TVD

PVD

CVA MCA ACA PCA

PLATELET RESPONSE

RESPONDER SEMI RESPONDER NONRESPONDER

APPENDIX - V

references

1. Cattaneo M. Aspirin and clopidogrel: efficacy, safety and the issue of drug resistance. Arterioscler Thromb Vasc Biol. 2004;24:1980 –1987.

2. Michelson AD. Platelet function testing in cardiovascular diseases. Circulation. 2004;110:e489–e493.

3. Armen Yuri Gasparyan, MD, PHD, Timothy Watson, MRCP, Gregory Y. H. Lip, MD, FRCP Role of Aspirin in Cardiovascular prevention JAAC 2008 51_19

4. Hankey GJ, Eikelboom JW. Aspirin resistance. Lancet 2006; 376:606-617

5.. Bhatt D, Topol EJ. Scientific and therapeutic advances in antiplatelet therapy. Nature Rev 2003; 2: 15–28

6. Rocca B, Patrono C. Determinants of the interindividual variability in response

to antiplatelet drugsJ Thromb Haemost 2005; 3:1597–602.

7. Sadiq PA, Puri A, Dixit M, Ghatak A, Dwivedi SK,
Narain VS, Saran RK, Puri VK Profile and Prevalence of Aspirin Resistance in Indian Patients with Coronary Artery Disease. Indian Heart J 2005; 57: 658-661