Preventing Arterial Thrombosis

Patients with atherosclerotic plaque in extracranial or intracranial cerebral arteries have an increased risk for arterial thrombus formation. They are frequently treated with platelet aggregation inhibitors. These drugs prevent the sticking of platelets to each other, and therefore limit the growth of platelet-rich, relatively fibrin-poor thrombus on the surface of a damaged atherosclerotic plaque.

Patients with carotid stenosis, either symptomatic (causing TIA or stroke) or asymptomatic, have a reduced incidence of stroke when they are placed on platelet aggregation inhibitors. Stenosis indicates the presence of atherosclerotic plaque that could become thrombogenic. Presumably antiplatelet drugs reduce the chance of thrombus formation leading to complete vascular occlusion as well as embolization. There are several choices:

• Aspirin prevents the aggregation of platelets through its irreversible action on an enzyme of prostaglandin metabolism (prostaglandin G/H synthase).Its effects are rapid. This is the first line (and lowest cost) therapy for patients with TIA and ischemic stroke.
• Clopidogrel (Plavix®) also irreversibly prevents platelet aggregation, but does so by action on the cyclic-AMP pathway. It takes a few days to become maximally effective.
• Ticlopidine (Ticlid®) acts similarly to clopidogrel. It has more side effects, and must be taken twice a day.

Aspirin-Extended Release Dipyridamole (Aggrenox®) is a combination of aspirin with another platelet aggregation inhibitor that appears to have an advantage over aspirin alone in controlled trials.
Antiplatelet agents are also used when atherosclerosis in intracranial arteries has been demonstrated by imaging or is suspected from the medical history.