Patients with acute stroke or transient ischemic attack (TIA) should be admitted to a hospital for initial care and assessment; however, a substantial number of these patients will never be seen by a neurologist because of the limited number of physicians in this specialty area. Currently there is only one neurologist per 26,000 people in the United States, and most neurologists prefer to practice in the outpatient setting.1 According to one study, only 11.3% of stroke patients are attended exclusively by a neurologist.2 Hospitalists play a vital role in overcoming this lack of specialized care for stroke patients.
A significant body of evidence supports secondary prevention as a critical intervention strategy in reducing stroke risk. Identifying specific risk factors remains pivotal to successful secondary prevention. Managing hypertension, diabetes, and hyperlipidemia serves as an effective preventive role; however, preventive management with antithrombotic agents is an important part of the drug regimen for secondary prevention of recurrent ischemic stroke (IS).3
The choice of pharmacologic agents is based on stroke etiology. Anticoagulants such as warfarin are restricted to patients with stroke due to a cardioembolic source, whereas antiplatelet agents are mainly used to treat noncardioembolic and lacunar strokes.4 Currently, four oral antiplatelet agents may be used as therapy to prevent secondary IS: aspirin (acetylsalicylic acid or ASA), ticlopidine, clopidogrel, and ASA plus extended-release dipyridamole.
ASA is the most widely used and cost-effective antiplatelet agent. A salicylate, it blocks platelet activation by inhibiting the cyclo-oxygenase enzymes (COX-1 and COX-2). In several primary prevention trials ASA was associated with a statistically significant reduction in risk of first myocardial infarction (MI). Neither overall cardiovascular mortality nor total number of strokes was reduced by long-term ASA prophylaxis, however.5
ASA was shown to be effective in secondary prevention of noncardioembolic stroke (offering equivalent or better efficacy compared with warfarin) in the Stroke Prevention in Reversible Ischemia Trial and the Warfarin-Aspirin Recurrent Stroke Study.6 The Swedish Aspirin Low-Dose Trial, Dutch TIA Trial, and United Kingdom Transient Ischaemic Attack Aspirin Trial consistently demonstrated the efficacy and reduced gastric toxicity of low-dose ASA.7 A meta-analysis of 197 randomized trials versus control and 90 randomized comparisons between antiplatelet regimens show risk reduction with ASA of approximately 23% in combined vascular events (MI, stroke, and vascular death).8
Ticlopidine hydrochloride (thienopyridine) blocks platelet activation by inhibiting adenosine diphosphate-induced fibrinogen binding.7 Ticlopidine was superior to placebo and high-dose ASA in reducing the occurrence of stroke, MI, or vascular death in patients of both genders who had recent cerebral ischemia. This was demonstrated in two major phase 3 multicenter trials: the Ticlopidine Aspirin Stroke Study and the Canadian American Ticlopidine Study.9 Despite ticlopidine’s efficacy in these trials, the drug has been associated with severe adverse effects, including life-threatening neutropenia (1%) and thrombocytopenic purpura (one per 1,600 to 5,000 patients treated).3
The ticlopidine analogue clopidogrel is a potent inhibitor of platelet aggregation induced by adenosine diphosphate.7 The efficacy and safety of clopidogrel was evaluated in a randomized, double-blind, multicenter study—the Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events trial, the largest clinical study of clopidogrel—of 19,000 patients with stroke, MI, or peripheral arterial disease.10
In this study, clopidogrel showed a more favorable safety and tolerability profile than ticlopidine; however, compared with ASA clopidogrel offered only a modest benefit of 8.7% for all cardiovascular events and showed no significant benefit over ASA for recurrent stroke.