What have we learned from recent antiplatelet trials?

Abstract

Aspirin's benefit in preventing vascular outcomes is well established. It reduces the relative risk for stroke, myocardial infarction, and vascular death by about 25% compared with placebo. Almost 10 years ago we learned that ticlopidine is more effective than aspirin (about 12% relative risk reduction for stroke or death). However, ticlopidine has important adverse effects. In 1996, the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial showed that clopidogrel, a new thienopyridine similar to ticlopidine, is also more effective than aspirin (by a similar amount) and is as safe as aspirin. Also in 1996, the European Stroke Prevention Study 2 (ESPS-2) showed that dipyridamole alone prevents stroke and that when combined with aspirin it is more effective, probably comparable to ticlopidine and clopidogrel. Dipyridamole combined with aspirin reduced the relative risk for stroke or death by about 13% compared with aspirin alone. Both clopidogrel and dipyridamole are safe but will cost more than aspirin. Aspirin also appears beneficial for acute stroke treatment. The Chinese Acute Stroke Trial (CAST) and the International Stroke Trial (IST) demonstrated that aspirin given at the time of an acute ischemic stroke reduces the risk for early death (about 5 less/1,000 treated), recurrence or death (about 10 less/1,000 treated), and dependence (about 5 less/1,000 treated). Overall, the benefits of aspirin in acute stroke treatment and stroke prevention are definite but modest. Combination therapy with antiplatelet agents that act through different mechanisms is a promising way to maximize the benefits of antiplatelet treatment.

Secondary Prevention Strategies in Ischemic Stroke: Identification and Optimal Management of Modifiable Risk Factors

“…Antiplatelet agents, including aspirin, ticlopidine, clopidogrel, and extended-release dipyridamole and aspirin have proved valuable in the secondary prevention of ischemic stroke. [15][16][17] Also, randomized trial evidence supports secondary prevention strategies for the treatment of hypertension, 18,19 hyperlipidemia, 20,21 symptomatic carotid disease, 22 and atrial fibrillation, 14,23 as well as use of coordinated acute stroke units. 24 Observational data suggest that control of diabetes 13 and smoking cessation reduce the risk of second stroke or cardiac disease.…”

Protective Effects of Cilostazol against Transient Focal Cerebral ischemia and Chronic Cerebral Hypoperfusion Injury

“…This therapy is a key component of secondary preventive strategies in ischemic stroke (Majid et al 2001). The secondary prevention strategies rely largely on the risk factor reduction, carotid endarterectomy, anticoagulation for cardioembolic stroke, and antiplatelet agents for atherothrombotic stroke (Easton 1998). In line with these reports, cilostazol was suggested for treatment of cerebral ischemic events caused by thrombus formation in the carotid artery (Kohda et al 1999).…”

Cilostazol: Therapeutic Potential Against Focal Cerebral Ischemic Damage

“…Primary strategies to minimize the acute ischemic brain injury included anti-platelet agents, anti-coagulants, and thrombolytics [5], since anti-platelet therapy modestly improved the outcome in both acute stroke (with aspirin) and in secondary stroke prevention (aspirin with or without dipyridamole, an adenosine uptake inhibitor) [6]. Secondary prevention strategies have relied largely on the risk factor reduction, carotid end-arterectomy, anti-coagulation for cardioembolic strokes, and anti-platelet agents for atherothrombotic strokes [7]. Cilostazol significantly inhibited the occlusive thrombus formation in a porcine model, which was considered due to its anti-platelet effect [8].…”