Antiplatelet therapy in cardiovascular disease.(Cardiology Update)

Postgrad Med J 2004;80:155-164. doi: 10.1136/pgmj.2003.007062

Platelet activation and aggregation are considered to be central to arterial thrombus formation. Antiplatelet therapy is therefore important for both the treatment and prevention of cardiovascular disease. Aspirin, the most widely used antiplatelet agent, inhibits platelet cyclo-oxygenase and the conversion of arachidonic acid to the potent platelet agonist thromboxane [A.sub.2] but does not prevent platelet activation occurring via various signalling pathways that are independent of thromboxane [A.sub.2] release. Therefore a number of other compounds have been developed to complement aspirin's beneficial effect. These include the thienopyridines (clopidogrel and ticlopidine), dipyridamole, and the [[alpha].sub.IIb][[beta].sub.3] (glycoprotein IIb/IIIa) receptor inhibitors.

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The leading cause of morbidity and mortality in the Western world is cardiovascular disease. (1) Thrombotic and thromboembolic occlusions of atherosclerotic blood vessels are the main cause of ischaemic events. (2 3) Since the observation that thrombi occluding coronary arteries were platelet-rich in content, antiplatelet agents have been extensively researched and developed as potential therapies in the prevention and management of arterial thrombosis. (4)

Platelet activation and aggregation is considered to be central to arterial thrombus production. (5 6) This review discusses currently available antiplatelet agents and their mechanisms of action (fig 1). There are four main groups: aspirin, the thienopyridines (ticlopidine and clopidogrel), dipyridamole, and the platelet [[alpha].sub.IIb][[beta].sub.3] (glycoprotein IIb/IIIa) receptors antagonists.

Aspirin has been regarded as the prototype antiplatelet drug and is still the most widely used agent. It inhibits irreversibly the enzyme cyclo-oxygenase, thereby blocking conversion of arachidonic acid to endoperoxides such as thromboxane [A.sub.2] in platelets and prostaglandin [I.sub.2] in vascular endothelium. However, platelet activation occurs via several pathways that do not rely on amplification by released thromboxane [A.sub.2]. A number of other compounds have been developed to complement the therapeutic effect of aspirin.

PATHOGENESIS OF THROMBOSIS