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Published on: September 5, 2016
What have we learned from recent antiplatelet trials?
1Department of Clinical Neurosciences, Brown University School of Medicine, Rhode Island Hospital, Providence 02903, USA.
Insights
Aspirin modestly prevents vascular events like stroke and heart attack. Combination antiplatelet therapies offer enhanced protection against ischemic events and improve acute stroke outcomes.
Area of Science:
- Cardiology
- Neurology
- Pharmacology
Background:
- Aspirin is a well-established agent for preventing vascular outcomes, reducing risk by approximately 25% compared to placebo.
- Ticlopidine and clopidogrel have demonstrated greater efficacy than aspirin in preventing stroke or death, though ticlopidine carries significant adverse effects.
- Dipyridamole, alone or in combination with aspirin, also shows promise in stroke prevention, with the combination being more effective than aspirin alone.
Purpose of the Study:
- To evaluate the comparative effectiveness and safety of aspirin, ticlopidine, clopidogrel, and dipyridamole in preventing vascular events.
- To assess the role of aspirin in the acute treatment of ischemic stroke.
- To explore the potential of combination antiplatelet therapy for maximizing therapeutic benefits.
Main Methods:
- Review of major clinical trials including CAPRIE, ESPS-2, CAST, and IST.
- Comparative analysis of relative risk reductions for vascular outcomes (stroke, myocardial infarction, vascular death).
- Evaluation of safety profiles and cost-effectiveness of different antiplatelet agents.
Main Results:
- Aspirin reduces vascular risk by about 25%; however, ticlopidine and clopidogrel offer a greater risk reduction (around 12%).
- Clopidogrel is as safe as aspirin, while ticlopidine has notable adverse effects.
- Aspirin in acute ischemic stroke reduces early death, recurrence, and dependence, with modest but definite benefits.
- Combination therapy with aspirin and dipyridamole showed a 13% relative risk reduction for stroke or death compared to aspirin alone.
Conclusions:
- Aspirin provides definite but modest benefits in both acute stroke treatment and prevention.
- Clopidogrel and dipyridamole are safe alternatives or adjuncts to aspirin, albeit at a higher cost.
- Combination antiplatelet therapy, utilizing agents with different mechanisms, represents a promising strategy to enhance prevention of vascular events and improve stroke outcomes.
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.
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