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Blocking platelets more: are we skating on thin ice?
  1. Service de Cardiologie,
  2. Centre Hospitalier Universitaire Pitié-Salpêtrière,
  3. 47 Boulevard de l’Hôpital,
  4. 75013 Paris, France

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Past: the era of aspirin and ticlopidine

Over the past century, the enormous success of aspirin was mainly due to its analgesic and anti-inflammatory properties. However, aspirin has triumphed during the past decade in the prevention and treatment of platelet mediated arterial events. The modern history of aspirin may have started with the ISIS-2 trial and antiplatelet treatment in vascular diseases has rapidly become a monopoly for aspirin as no other drug compares favourably in terms of both risk:benefit and cost-effectiveness analyses.1 Indeed, only one study compared ticlopidine and aspirin head to head showing a borderline superiority for ticlopidine in a high risk population with cerebrovascular disease.2 The other studies conducted with either drug were placebo controlled and demonstrated relative risk reductions for the composite outcome of stroke, myocardial infarction or vascular death of 33% with ticlopidine and 25% with aspirin. This difference of efficacy was used to calculate the sample size of the second major trial comparing two oral antiplatelet drugs, aspirin and clopidogrel (a ticlopidine derivative), to prevent thrombotic complications in patients with atherosclerotic disease manifest as either recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease.3

Present: the era of clopidogrel

The evaluation of clopidogrel in vitro is impossible because, like ticlopidine, it requires hepatic metabolisation for its anti-aggregating effect. Clopidogrel interferes with ADP binding sites thereby affecting ADP dependent activation of the glycoprotein IIb/IIIa receptors. Clopidogrel is 100 times more potent than ticlopidine and both drugs affect platelets irreversibly, as does aspirin. The final difference observed in the CAPRIE trial for the risk reduction of stroke, myocardial infarction or vascular death significantly favoured clopidogrel over aspirin. The risk reduction was small but it was close to the difference …

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