V.S. Giri Prasad et al.

IRJP 2012, 3 (11)

INTERNATIONAL RESEARCH JOURNAL OF PHARMACY
www.irjponline.com ISSN 2230 – 8407
Research Article

CONTRAST ADVERSE EFFECT STUDY OF ASPIRIN AND CLOPIDOGREL IN STROKE PATIENTS USING
COMBINATION AND INDIVIDUAL MEDICATION
V.S. Giri Prasad1*, A.P. Ranjith kumar 2, Narender Karra3, P.Prathyusha4
1
Department of Clinical Pharmacy and Pharmacology, Bharat Institute of Technology, Hyderabad, Andhra Pradesh, India
2
Department of Pharmacology, Nalanda College of Pharmacy, Nalgonda, Andhra Pradesh, India
3
Department of Pharmaceutics, KLR College of Pharmacy, Khammam, Andhra Pradesh, India
4
Department of Pharmaceutics, SRM University, Kancheepuram, Tamilnadu, India
Article Received on: 16/09/12 Revised on: 20/10/12 Approved for publication: 10/11/12

*Email: vs.giriprasad@gmail.com
ABSTRACT
Ischemia and hemorrhage are the conditions which may lead to stroke. As stroke is a medical emergency, treated with medications such as aspirin, clopidogrel
and dipyridamole. In the present study the combination and individual adverse effects of aspirin and clopidogrel medication were studied. The study during
was around nine months in one of the private hospital at Hyderabad, Andhra Pradesh, India. Adverse effects evaluation was based on WHO guide lines and
Naranjo’s Algorithm. Total 69 stroke patients were taken in to studies. 46 (66.66%) were males and 23 (33.33%) were females. The number of ischemic stroke
patients was 39(56.5%) and hemorrhage stroke was 30(43.4%). Among 41 patients, 19 patients was on Aspirin (46.34%), 10 patients was on clopidogral
(24.34%) and 12 patients was on combinations medication (29.26%). Adverse effects reported among the antiplatelate users were 6 patients. Among these 6
patients 4 patients were observed with upper gastrointestinal bleeding (UGI) the overall percentage was 66.66% and 2 patients were observed with Vomiting,
the overall percentage was 33.33%. In this study, the relative risk reduction for secondary stroke prevention was 37% with use of a combination of extended-
release dipyridamole and aspirin. Importantly, the risk of major bleeding attributable to the combination therapy was no greater than that seen with aspirin
alone. The benefit of clopidogrel over aspirin for the prevention of vascular events was a relative risk reduction of 8.7%.In addition, there was less major
bleeding in the clopidogrel group, yielding a relative net benefit of about 10%. This study revels clopidogrel is the safe drug when compared with Aspirin and
as well as combination therapy.
Key words: Ischemia, hemorrhage, WHO guide lines and Naranjo’s Algorithm.

INTRODUCTION hospital in Hyderabad Andhra Pradesh, India. The adverse

Cerebrovascular disease (CVD) is strongly connected to Effects of anti-platelet Agents we intended to studied on 69
lifestyle, especially the use of tobacco, unhealthy diet habits, stroke patients who were admitted in medical intensive care
physical inactivity, and psychosocial stress1. Cerebrovascular unit (MICU) , between September -2009 and AUG- 2010.All
disease includes all disorders in which an area of the brain is patients, clinical Encounters and medication changes were
transiently or permanently affected by ischemia or bleeding under close monitoring by neurophysicians. This data
and one or more of the cerebral blood vessels are involved in represents patients presenting to the emergency department
the pathological process2. A stroke is the rapidly developing with neurological stroke disease. Adverse Effects noted in in-
loss of brain functions due to disturbance in the blood supply patients to medications administered while in the hospital.
to the brain3. This can be due to ischemia (lack of glucose & Inclusion Criteria: (1) Prescription for stroke disease. (2) In-
oxygen supply) caused by thrombosis or embolism or due to patient prescription during the period of 2009-2010.
a hemorrhage4. A stroke is a medical emergency and can (3) Prescriptions collected from medical intensive care unit.
cause permanent neurological damage, complications, and (4) Prescription meant for stroke disease (cerobrovascular
death. 95% of strokes occur in people age 45 and older, and disease). Age >20years.
two-thirds of strokes occur in those over the age of six5. Exclusion criteria: (1) Age<20yrs. (2) Prescription from
Recently, several large-scale randomized controlled trials outside hospitals. (3) Prescription from other than stroke
investigating the use of aspirin combined with clopidogrel disease.
therapy have been performed thus Clinical efficacy of these
drugs for reducing serious vascular events and mortality in Table 1: Classification of stroke patients
patients with high harm has been shown in several large-scale Patients category Number of patients % of patients
No.of ischemic stroke patients 39 56.53
clinical trials6. The combination of clopidogrel and aspirin in No.of hemorrhagic stroke patients 30 43.47
patients with acute coronary syndrome (ACS) reduces the Total no.of patients 69 100
risk of reinfarction, stroke, and death by 20% compared with
aspirin alone7. Table 2: Total number of anti-platelet and non-antiplatelet users
Category of users No.of patients % of users
Anti-platelet users 41 59.43
MATERIALS AND METHODS Non-antipaltelet users 28 40.57
(1) The main purpose of this study is to analyze the Total no.of patients 69 100
occurrence of adverse effects of Anti-platelet drugs used in
stroke disease. (2)To monitor the inappropriate drug Table 3: Total number of male and female stroke patients
prescribing patterns. (3)To identify the main therapeutic class Type of patients No.of patients Percentage
No.of males 46 66.66
drugs used in treatment of conditions. (4)Discuss No.of females 23 33.34
epidemiology and Discus basic methods to detect, evaluate, Total no.of patients 69 100
and document ADRs. (5) Adverse effects were calculated
based on Naranjo’s Algorithm.
Methodology: This work was held in one of the eminent

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Table 4: Total and type of anti-platelet usage stroke patients Table 5: ADRs reported patients among anti-platelet users
Drug users No.of patients Percentage Category No.of patients Percentage
Total antiplatelet users 41 100 Total antiplatelet users 41 100
Aspirin users 19 46.34 ADRs reported 6 14.63
Clopidogrel users 10 24.40
Combination users 12 29.26 Table 6: Classification of reported ADRs
Category No.of patients Percentage
ADRs reported 6 100
GI bleeding cases 4 66.66
Vomiting 2 33.33

NARANJO's ALGORITHM FOR ASPIRIN&CLOPIDOGREL

question Yes No Don't know
Are there previous conclusion reports on this reaction? +1 - -
Did the adverse event appear after the suspect drug was +2 - -
administered?
Did the AR improve when the drug was discontinued or a +1 - -
specific antagonist was administered?
Did the AR reappear when drug was readministered? +2 - -
Are there alternate causes [other than the drug] that could - - 0
solely have caused the reaction?
Did the reaction reappear when a placebo was given? - - 0
Was the drug detected in the blood [or other fluids] in a - - 0
concentration known to be toxic?
Was the reaction more severe when the dose was increased, +1 - -
or less severe when the dose was decreased?
Did the patient have a similar reaction to the same or - - 0
similar drugs in any previous exposure?
Was the adverse event confirmed by objective evidence? +1 - -

ASPIRIN&CLOPIDOGREL SCORING FOR NARANJO's ALGORITHM

8 = probable ADR

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 V.S. Giri Prasad et al. IRJP 2012, 3 (11)
RESULTS
A total of 69 patients were studied; 46 (66.66%) were males
and 23 (33.33%) were females. the number of ischemic
stroke patients were 39(56.5%) and haemorrhage stroke were
30(43.4%). The number of patients on antiplatelates were 41
(59.42%) and non-antiplatelate patients were 28(40.57).
Among 41 patients, Aspirin users were 19 (46.34%),
clopidogrel users were 10(24.34%) and combinations of both
drugs were 12(29.26%).
Adverse Effects reported among the antiplatelate users were
6 patients. Among these 6 patients 4 patients were observed
with upper gastrointestinal bleeding (UGI) the overall
percentage was 66.66% and 2 patients were observed with
Vomiting, the overall percentage was 33.33%.
In this trial, the benefit of clopidogrel over aspirin for the
prevention of vascular events was a relative risk reduction of
8.7%.In addition, there was less major bleeding in the
clopidogrel group, yielding a relative net benefit of about
10%. It has been assumed by many physicians that the
combination of Clopidogrel with aspirin may be substantially
more effective than either agent alone. In fact, many patients
with CVD this are currently treated with this combination
despite the absence of any substantial safety or efficacy data
regarding the use of this combination in TIA (transient
ischaemic attack) patients.
DISCUSSION
Virtually, 80-85% of strokes have an ischemic aetiology8 .
Stroke can have many effects, some of which may end up
being long-term. They can include things like difficulty
moving one side of the body and trouble speaking ect9.
Secondary prevention of ischemic stroke with different drugs
mechanisms of action is available. When used as a solitary
drug, the efficacy of antiplatelet therapy is temperate. Widely
used antiplatelet agent for stroke prevention is aspirin.
Despite, it provides only an approximately 15% relative risk
reduction for secondary prevention of stroke or other major
vascular events. Combining dual antiplatelet drugs with
different mechanisms of action was demonstrated to provide
a substantial increase in efficacy in the ESPS-2 study10. In
current study, the risk of major bleeding attributable to the
combination therapy was no greater than that seen with
aspirin alone. CAPRIE study reviles Clopidogrel is safe and
efficacious medication for secondary prevention of vascular
diseases11. In this trial, the benefit of clopidogrel over aspirin
for the prevention of vascular events was a relative risk
reduction of 8.7%. In addition, there was less major bleeding
in the clopidogrel group, yielding a relative net benefit of
about 10%. It has been assumed by many physicians that, the
combination of Clopidogrel with aspirin may be substantially
more effective than alone. In fact, many patients with CVD
this are currently treated with this combination despite the
absence of any substantial safety or efficacy data regarding
the use of this combination in TIAs patients.
The study was carried out in the one of private eminent
Hospital located at Hyderabad, Andhra pardesh, India.
Around eight months the work was conducted. Patients
admitted under stroke case were considered as MICU cases.
Under this study 69 stroke patients were considered.
Source of support: Nil, Conflict of interest: None Declared
IRJP is an official publication of Moksha Publishing House. Website: www.mokshaph.com. All rights reserved.
Neuroprotective drugs, Hyoplipidemic agents, anti-
hypertensives, antiplatelates, proton pump inhibitors and
antibiotics were used in the stroke patients. Among them
antiplatelates drugs are very frequently used. In our study
drugs Aspirin and clopidogrel were under taken.
Aspirin was the most widely studied anti-platelet. Based on
this review, the evidence "supports daily doses of aspirin in
the range of 75-150 mg for the long-term prevention of
serious vascular events in high risk patients. However the
risks and benefits of aspirin therapy vary for each person.
While the benefits may be significant for people who are at
higher risk, healthy individuals should weigh the pros and
cons of aspirin therapy carefully, in my opinion.
CONCLUSION
According to my thesis work, antiplatelets are more
frequently used drug in ischemic stroke patients. (Clinically
Aspirin & clopidogrel are the drugs which commonly used).
Usual Adverse Effects of Aspirin are gastro intestinal
discomfort, nausea, vomiting where as for clopidogrel
neutropenia, thrombotic thrombocytopenia, purpura, diarrhea,
rash pruritus and abdominal discomfort.
In my studies Aspirin was found with more upper
gastrointestinal bleeding (3 cases), then clopidogrel
(1case).In combination vomiting severity was more (2 cases).
Hence, according to Narinjo’s scale, I conclude that, the
clopidogrel is the safe drug when compared with Aspirin and
as well as in combination therapy.
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