Comparative Safety and Tolerability of Clopidogrel and Aspirin
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.
Compared with aspirin, clopidogrel reduced the combined risk of ischaemic stroke, myocardial infarction or vascular 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 severe 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.
Given the favourable benefit/risk ratio, clopidogrel represents a clinically important advance in the treatment of patients with manifest atherosclerotic disease.
Unable to display preview. Download preview PDF.
- 6.ASPECT Research Group. Effect of long-term oral anticoagulant treatment on mortality and cardiovascular morbidity after myocardial infarction. Lancet 1994; 343: 499–503Google Scholar
- 7.Sixty Plus Reinfarction Study Research Group. Risks of long-term oral anticoagulant therapy in elderly patients after myocardial infarction. Lancet 1982; I: 64–8Google Scholar
- 12.Bennet CL, Weinberg PD, Rozenberg-Ben-Dror K, et al. Thrombotic thrombocytopenic purpura associated with ticlopidine: a review of 60 cases. Ann Intern Med 1998; 128: 541–4Google Scholar
- 20.Cappelleri JC, Lau J, Kupelnick B, et al. Efficacy and safety of different aspirin dosages on vascular diseases in high-risk patients: a metaregression analysis. Online J Curr Clin Trials 1995; Doc. No. 174Google Scholar