Antithrombotic agents stroke

Aspirin is maximally effective as an antithrombotic agent at the comparatively low dose of 81 to 325 mg per day. (The antipyretic dose of aspirin in adults is 325 to 650 mg every 4 h.) Higher doses of aspirin are actually contraindicated in patients prone to thromboembolism. At higher doses, aspirin also reduces synthesis of prostacyclin, another arachidonic acid metabolite. Prostacyclin normally inhibits platelet aggregation. The prophylactic administration of low-dose aspirin has been shown to increase survival following myocardial infarction, decrease incidence of stroke, and assist in maintenance of patency of coronary bypass grafts. 

Qureshi AI, Saad M, Zaidat OO, Suarez JI, Alexander MJ, Fareed M, Suri K, Ah Z, Hopkins LN. Intracerebral hemorrhages associated with neurointerventional procedures using a combination of antithrombotic agents including abciximab. Stroke 2002 33(7) 1916-19. 

The AHA/ASA guidelines recommend that antiplatelet therapy as the cornerstone of antithrombotic therapy for the secondary prevention of ischemic stroke and should be used in noncardioembolic strokes. Aspirin, dopidogrel, and extended-release dipyridamole plus aspirin are all considered first-line antiplatelet agents (see Table 13-1). The combination of aspirin and clopido-grel can only be recommended in patients with ischemic stroke and a recent history of myocardial infarction or coronary stent placement and then only with ultra-low-dose aspirin to minimize bleeding risk. 

Antiplatelet therapy reduces the risk of recurrent vascular events after TIA and ischemic stroke, although few trials have distinguished between different etiological subtypes (Antithrombotic Trialists Collaboration 2002). Most trial data concern aspirin, but other antiplatelet agents such as clopidogrel (CAPRIE Steering Committee 1996) or extended-release dipyridamole (Sivenius et al. 1991) have also been shown to be effective although mechanisms of action may differ (Table 24.2). 

All patients who have had an acute ischemic stroke or TEA should receive long-term antithrombotic therapy for secondary prevention. In patients with noncardioembolic stroke, this will be some form of antiplatelet therapy. In a recent meta-analysis, the overall benefit of antiplatelet therapy in patients with atherothrombotic disorders was estimated to be 22%. Aspirin is the best-studied of the available agents and, until recently, was considered the sole first-line agent. However, published literature has supported the use of clopidogrel and the aspirin plus extended-release dipyridamole combination product (ERDP + ASA) as additional first-line agents in secondary stroke prevention. 

Ticlopidine, a platelet aggregation inhibitor possessing antithrombotic effects (250 mg p.o. b.i.d.), is used to reduce the risk of thrombotic stroke in patients with a history of stroke or who have experienced stroke precursors (see also Figures 13 and 93). Ticlopidine, a thienopyridine derivative, and a new antiplatelet agent for secondary prevention of stroke, causes potent inhibition of adenosine diphosphate (ADP)-induced platelet aggregation and moderate inhibition... 

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