Antiplatelet drugs have been shown to prevent a range of atherothrombotic events, including transient ischaemic attack (TIA) and
ischaemic stroke.
Clopidogrel and
ticlopidine are
adenosine diphosphate (
ADP)-receptor antagonists that inhibit
ADP-induced
fibrinogen binding to platelets, a necessary step in the platelet aggregation process. The Antithrombotic Trialists' Collaboration recently published a major meta-analysis that assessed the effect of antiplatelet
therapy in patients with various manifestations of
atherosclerosis. In total, this analysis included 135,000 patients in comparisons of
antiplatelet agents versus control and 77,000 patients in comparisons of different antiplatelet regimens. This meta-analysis found that overall, antiplatelet
therapy reduces the combined odds of
stroke,
myocardial infarction (MI) or vascular death by 22%, and that
antiplatelet agents reduce the odds of a non-fatal
stroke by 25% over a wide range of patients with or without a history of
cerebrovascular disease. In the CAPRIE trial of
clopidogrel versus
acetylsalicylic acid (ASA), there was
a 10% odds reduction for
stroke, MI or vascular death in favour of
clopidogrel (p = 0.03). In a meta-analysis performed by the Cochrane
Stroke Group,
ADP-receptor antagonist therapy significantly reduced the odds of a serious vascular event (
stroke, MI or vascular death) by 9% (2p = 0.01) and of any
stroke by 12%. The safety/tolerability profile of
clopidogrel was superior to that of
ticlopidine, and at least as good as that of ASA. In CURE, a long-term benefit was observed with the use of
clopidogrel on top of standard
therapy (including ASA in all patients), with a 20% relative risk reduction for the primary endpoint of cardiovascular death, MI or
stroke (p < 0.001) in patients with
unstable angina and non-Q-wave MI. A consistent benefit was seen across all patient subgroups, including patients with a previous history of
stroke. More recently, CREDO has demonstrated the incremental benefit of prolonged use of
clopidogrel on top of ASA in patients undergoing elective PCI, with a 27% reduction in the combined risk of death, MI or
stroke after 12 months of
therapy (p = 0.02) and a 25% reduction in
stroke over the same time period. The MATCH trial is currently being conducted to test the hypothesis that long-term administration of
clopidogrel on top of ASA is superior to
clopidogrel alone for the reduction of major ischaemic events in patients with recent TIA or
ischaemic stroke who are at high risk of atherothrombotic recurrence. Further trials of
clopidogrel on top of standard
therapy (including ASA) are planned in neurology; these include SPS3, in patients with small subcortical
strokes, and ATARI, in patients who have recently recovered from a TIA.