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Antiplatelet therapy in the prevention of ischaemic stroke
M Verry1, E Panak, J P Cazenave
1Sanofi Pharma, Gentilly, France.
Insights
Antiplatelet therapy, particularly aspirin, significantly reduces the risk of stroke and other vascular events. Ticlopidine shows greater efficacy than aspirin for secondary stroke prevention, but optimal aspirin dosage and tolerability remain key considerations.
Area of Science:
- Cardiovascular Medicine
- Neurology
- Pharmacology
Background:
- Stroke is a leading cause of death and disability globally.
- Platelet aggregation plays a critical role in ischemic stroke pathogenesis.
- Antiplatelet agents are central to stroke prevention strategies.
Purpose of the Study:
- To review the efficacy of antiplatelet agents in preventing stroke and other vascular events.
- To compare the effectiveness of aspirin and ticlopidine in secondary stroke prevention.
- To discuss the optimal dosage and tolerability of aspirin.
Main Methods:
- Meta-analysis of 142 randomized trials involving over 100,000 vascular patients (Antiplatelet Trialists' Collaboration).
- Review of North American trials (TASS, CATS) evaluating ticlopidine efficacy.
- Analysis of controlled trials comparing different aspirin dosages (UK-TIA, SALT, Dutch TIA).
Main Results:
- Antiplatelet therapy reduces stroke, myocardial infarction, or vascular death by 27% in ischemic vascular events and 22% in TIA/stroke patients.
- Ticlopidine demonstrated superior efficacy over aspirin in reducing stroke and death in TIA/minor stroke patients (TASS).
- Ticlopidine showed a 30% risk reduction in stroke, myocardial infarction, and vascular death over placebo in recent stroke patients (CATS).
- Optimal aspirin dosage for vascular risk reduction in stroke precursors remains uncertain, with risks of gastrointestinal bleeding even at low doses.
Conclusions:
- Aspirin and ticlopidine are reference drugs for secondary cerebrovascular prevention.
- Ticlopidine offers significant benefits over aspirin for specific patient groups.
- Further research is needed to determine optimal aspirin dosing and manage its side effects.
Abstract:
Prevention of stroke is a crucial health care issue, as stroke is the third cause of death and the first cause of major disability in developed countries. The established role of platelet aggregation in TIA or minor and major ischaemic stroke has provided the rationale for many randomized trials of antiplatelet agents (aspirin, sulfinpyrazone, dipyridamole alone or in combination with aspirin, suloctidil, ticlopidine). The recent Antiplatelet Trialists' Collaboration (APT) meta-analysis (1994) based on 142 trials involving 100,000 vascular patients confirmed the data of the previous overview (1988). Aspirin, the only drug evaluated for primary prevention of ischaemic events, is not indicated for safety reasons in subjects at low risk of occlusive disease. Compared to control, antiplatelet therapy, notably aspirin which is by far the most widely used agent in trials, provides a 27% risk reduction of stroke, myocardial infarction or vascular death in patients suffering from ischaemic vascular events and a 22% risk reduction of these outcomes in patients having experienced a prior TIA/stroke. Aspirin (around 325 mg/day) and ticlopidine (500 mg/day) are currently the reference drugs for secondary prevention in cerebrovascular patients. The long term efficacy of ticlopidine, a specific antiaggregating agent, has been evaluated in two North American trials involving more than 4,000 patients. TASS showed ticlopidine to be significantly more effective in reducing the incidence of fatal or nonfatal stroke and death than aspirin in patients with TIA or minor stroke. The relative risk reductions over aspirin, the first year of greatest risk, were 41% for stroke and death and 46% for fatal or nonfatal stroke. CATS showed that ticlopidine compared with placebo induces a significant 30% relative risk reduction of stroke, myocardial infarction and vascular death over three years in patients who had suffered a recent thromboembolic stroke. The above results elicit two important issues: the optimal dose of aspirin and its tolerability compared to ticlopidine. The three controlled trials (UK-TIA, SALT, Dutch TIA) which have compared high (> or = 1 g/day) and low dose aspirin (< or = 300 mg/day) or various low doses of aspirin did not give a definite answer on the efficacy of low or very low (30 or 75 mg/day) doses of aspirin for reducing the risk of vascular outcomes in patients with stroke precursors. Even with low doses of aspirin there was still a risk of severe gastrointestinal bleeding, although minor side effects were less frequent.(ABSTRACT TRUNCATED AT 400 WORDS)