V.S. Giri Prasad et al. IRJP 2012, 3 (11)
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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 kumar2, 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
Cerebrovascular disease (CVD) is strongly connected to lifestyle, especially the use of tobacco, unhealthy diet habits, physical inactivity, and psychosocial stress1.Cerebrovascular disease includes all disorders in which an area of the brain is transiently or permanently affected by ischemia or bleeding and one or more of the cerebral blood vessels are involved in the pathological process2. A stroke is the rapidly developing
loss of brain functions due to disturbance in the blood supply to the brain3. This can be due to ischemia (lack of glucose & oxygen supply) caused by thrombosis or embolism or due to a hemorrhage4. A stroke is a medical emergency and can cause permanent neurological damage, complications, and death. 95% of strokes occur in people age 45 and older, and two-thirds of strokes occur in those over the age of six5. Recently, several large-scale randomized controlled trials investigating the use of aspirin combined with clopidogrel therapy have been performed thus Clinical efficacy of these drugs for reducing serious vascular events and mortality in patients with high harm has been shown in several large-scale clinical trials6. The combination of clopidogrel and aspirin in patients with acute coronary syndrome (ACS) reduces the risk of reinfarction, stroke, and death by 20% compared with aspirin alone7.
MATERIALS AND METHODS
(1) The main purpose of this study is to analyze the occurrence of adverse effects of Anti-platelet drugs used in stroke disease. (2)To monitor the inappropriate drug prescribing patterns. (3)To identify the main therapeutic class drugs used in treatment of conditions. (4)Discuss epidemiology and Discus basic methods to detect, evaluate, and document ADRs. (5) Adverse effects were calculated based on Naranjo’s Algorithm.
Methodology: This work was held in one of the eminent
hospital in Hyderabad Andhra Pradesh, India. The adverse Effects of anti-platelet Agents we intended to studied on 69 stroke patients who were admitted in medical intensive care unit (MICU) , between September -2009 and AUG- 2010.All patients, clinical Encounters and medication changes were under close monitoring by neurophysicians. This data represents patients presenting to the emergency department with neurological stroke disease. Adverse Effects noted in in-patients to medications administered while in the hospital.
Inclusion Criteria: (1) Prescription for stroke disease. (2) In-patient prescription during the period of 2009-2010.
(3) Prescriptions collected from medical intensive care unit. (4) Prescription meant for stroke disease (cerobrovascular disease).Age >20years.
Exclusion criteria: (1) Age<20yrs. (2) Prescription from outside hospitals. (3) Prescription from other than stroke disease.
Table 1: Classification of stroke patients
Patients category Number of patients % of patients No.of ischemic stroke patients 39 56.53 No.of hemorrhagic stroke patients 30 43.47
Total no.of patients 69 100
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 Non-antipaltelet users 28 40.57 Total no.of patients 69 100
Table 3: Total number of male and female stroke patients
Type of patients No.of patients Percentage
No.of males 46 66.66
No.of females 23 33.34
V.S. Giri Prasad et al. IRJP 2012, 3 (11)
Page 132 Table 4: Total and type of anti-platelet usage stroke patients
Drug users No.of patients Percentage Total antiplatelet users 41 100
Aspirin users 19 46.34
Clopidogrel users 10 24.40 Combination users 12 29.26
Table 5: ADRs reported patients among anti-platelet users
Category No.of patients Percentage Total antiplatelet users 41 100
ADRs reported 6 14.63
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
administered?
+2 - -
Did the AR improve when the drug was discontinued or a specific antagonist was administered?
+1 - -
Did the AR reappear when drug was readministered? +2 - - Are there alternate causes [other than the drug] that could
solely have caused the reaction?
- - 0
Did the reaction reappear when a placebo was given? - - 0 Was the drug detected in the blood [or other fluids] in a
concentration known to be toxic?
- - 0
Was the reaction more severe when the dose was increased, or less severe when the dose was decreased?
+1 - -
Did the patient have a similar reaction to the same or similar drugs in any previous exposure?
- - 0
Was the adverse event confirmed by objective evidence? +1 - -
ASPIRIN&CLOPIDOGREL SCORING FOR NARANJO's ALGORITHM
V.S. Giri Prasad et al. IRJP 2012, 3 (11)
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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.
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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Source of support: Nil, Conflict of interest: None Declared
