Comparative safety and tolerability of clopidogrel and aspirin - Results from CAPRIE

Harker,Laurence A., Boissel, Jean-Pierre, Pilgrim, Alison J., Gent, Michael and CAPRIE Steering Committee and Investigators (1999) Comparative safety and tolerability of clopidogrel and aspirin - Results from CAPRIE. Drug Safety, 21 4: 325-335. doi:10.2165/00002018-199921040-00007


Author Harker,Laurence A.
Boissel, Jean-Pierre
Pilgrim, Alison J.
Gent, Michael
CAPRIE Steering Committee and Investigators
Title Comparative safety and tolerability of clopidogrel and aspirin - Results from CAPRIE
Journal name Drug Safety   Check publisher's open access policy
ISSN 0114-5916
1179-1942
Publication date 1999-10
Sub-type Article (original research)
DOI 10.2165/00002018-199921040-00007
Volume 21
Issue 4
Start page 325
End page 335
Total pages 11
Place of publication Auckland, New Zealand
Publisher Adis International
Language eng
Formatted abstract
Objective:
The objective of this study was to provide a comprehensive comparison of the long term safety and tolerability of clopidogrel, a new adenosine diphosphate (ADP) receptor antagonist that inhibits platelet activation induced by ADP, and aspirin (acetylsalicylic acid).

Patients and Methods:
The study population comprised 19,185 patients with symptomatic atherosclerosis manifested as recent ischaemic stroke, recent myocardial infarction or symptomatic peripheral arterial disease. Patients were randomised to receive clopidogrel 75 mg/day or aspirin 325 mg/day for a minimum of 1 year and a maximum of 3 years.

Results:
Compared with aspirin, clopidogrel reduced the combined risk of ischaemic stroke, myocardial infarction or vascuIar death by 8.7% (p = 0.043). The incidence of early permanent discontinuations of the study drug due to adverse events was almost identical in both treatment groups (11.94% for clopidogrel vs 11.92% for aspirin). Reported neutropenia was similar in the clopidogrel and aspirin groups (0.10 vs 0.17%, respectively) with corresponding rates (0.05 vs 0.04%, respectively) for severe neutropenia. Thrombocytopenia was identical in the clopidogrel and aspirin groups (0.26%), with the rates of seven thrombocytopenia being 0.19 vs 0.10%, respectively. None of these observed differences was statistically significant. The overall incidence of haemorrhagic events did not differ statistically significantly between treatment groups (9.27% for clopidogrel vs 9.28% for aspirin; p = 0.98). There was a trend towards a lower incidence of intracranial haemorrhage in the clopidogrel group (0.31%) compared with the aspirin group (0.42%). Any reported gastrointestinal haemorrhage was significantly less frequent with clopidogrel (1.99%) than with aspirin (2.66%) [p < 0.002]. The corresponding data for severe gastrointestinal bleeding were 0.49 vs 0.71%; p < 0.05. Overall, there were significantly fewer gastrointestinal adverse events with clopidogrel than with aspirin (27.1 vs 29.8%; p < 0.001), with less abdominal pain, dyspepsia, constipation. or peptic, gastric, or duodenal ulceration with clopidogrel. Diarrhoea was significantly more common in the clopidogrel group (4.46 vs 3.36%; p < 0.001), although the incidence of severe diarrhoea (0.23 vs 0.11%) was low and was not significantly different between groups. There were significantly more patients with rash in the clopidogrel group (6.0%) compared with the aspirin group (4.6%) [p < 0.001]. However, these events were generally mild and transient in nature.

Conclusion:
Given the favourable benefit/risk ratio, clopidogrel represents a clinically important advance in the treatment of patients with manifest atherosclerotic disease.
Keyword Secondary prevention
Stroke prevention
Ticlopidine
Mortality
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Tue, 07 Dec 2010, 10:01:12 EST