For the long-term prevention of thromboembolic events in patients with atherosclerotic
vascular disease,
aspirin is the preferred
antiplatelet drug. Only
clopidogrel was shown to be more effective and at least as safe than medium-dose
aspirin in direct comparative large-scale trials.
Aspirin inhibits the
cyclooxygenase dependent pathway of platelet aggregation while
ticlopidine and
clopidogrel selectively bind to
adenosine diphosphate (
ADP) receptors on the platelet surface. Compounds which inhibit the synthesis of
thromboxane synthase, block the
thromboxane receptor or have the dual activity were effective in experimental
thrombosis models in animals but not predictive of results in humans. Activation of the
platelet glycoprotein (GPIIb/IIIa) receptor on the platelet surface is the final pathway of platelet aggregation, regardless of the initiating stimulus. Inhibitors of
GPIIb/IIIa receptors include
monoclonal antibodies (
abciximab) against this receptor and peptidic as well as non-peptidic synthetic specific receptor blockers.
Abciximab exchanges between and binds to platelets for as long as two weeks whereas synthetic GPIIb/IIIa inhibitors inhibit ex vivo platelet aggregation for only a few hours after the end of infusion but have the advantage of being also orally active. In the
secondary prevention of
atherothrombosis, large scale trials were successfully conducted with
aspirin,
dipyridamole and
clopidogrel. In the first large-scale trials with GPIIb/IIIa inhibitors with
abciximab was investigated. In aggregate, this class of
platelet inhibitors, combined with
aspirin and
heparin, was shown to reduce ischaemic events in patients with high- and low-risk coronary intervention,
stents,
unstable angina and non-Q-wave
infarction with long-term preservation of the initial benefit. With synthetic GPIIb/IIIa inhibitors there is no suppression of clinical evident restenosis 6 months after the end of treatment. With the doses presently used,
bleeding occurs more often with the synthetic GPIIb/IIIa inhibitors (used for 3 days) than with
abciximab (used for 12 hours) but there are no direct comparisons between these drugs.