Volume 9, Number 8, November 2002

Issues relating to clopidogrel use in hospital practice
R Andrew Archbold, Nicholas P Curzen

The spectrum of clinical applications for clopidogrel, either with or without aspirin, has expanded rapidly. Evidence about the use of clopidogrel in stable coronary artery disease comes from the CAPRIE trial. The annual rate of the combined primary end point of ischaemic stroke, myocardial infarction or vascular death was significantly reduced in clopidogrel-compared with aspirin-treated patients.
In CURE, the primary end point (cardiovascular death, myocardial infarction or stroke) occurred in 11.4% of the aspirin-treated patients compared with 9.3% of patients treated with aspirin plus clopidogrel during a mean follow-up period of nine months. This was predominantly due to a significant reduction in non-fatal myocardial infarction in clopidogrel-treated patients.
The PCI-CURE study, an observational study of the 2,658 patients in CURE who underwent percutaneous coronary intervention, showed a significantly lower primary outcome in the clopidogrel group than in the placebo group: this probably reflects a treatment advantage for clopidogrel in the pre-procedure phase.
More up-to-date information on risk analysis is provided by application of the TIMI risk score to the CURE data. The new ACC/AHA and ESC guidelines on management of patients with unstable angina and non-ST segment elevation MI are briefly discussed.
Cost-effectiveness is one issue relevant to the use of clopidogrel in the UK. Formal cost-effectiveness analyses from the CURE investigators are awaited.
There is evidence of a small improvement in gastrointestinal tolerability for clopidogrel over aspirin, and a decreased frequency of gastrointestinal haemorrhage.
The use of a loading dose of clopidogrel in non-ST segment elevation ACS patients prior to angiography prolongs their bleeding time. If they are then found to need coronary surgery, the timing of surgery poses a dilemma for the cardiac surgeons.
The most appropriate duration of treatment after acute coronary syndrome (with and without PCI) and the degree of additional benefit of clopidogrel when added to other cardioactive agents remain to be defined. Many questions about the extent of the potential clinical applicability of clopidogrel in patients with coronary disease still remain to be answered.

Br J Cardiol 2002;9:S13-S19.

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