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Platelets have a central role in cardiovascular atherothrombosis; antiplatelet agents are proven to be beneficial in this setting by blocking pathways involved in platelet activation and aggregation. However, these functions also cause bleeding, a major side effect of antiplatelet therapy.
Aspirin is the most widely studied antiplatelet drug, and the most widely used on the basis of proven benefit and low cost.
On the basis of 100 randomized trials in high-risk patients, aspirin reduces vascular death by about 15% and nonfatal vascular events by about 30%. Long-term aspirin therapy reduces the risk of subsequent MI, stroke, or vascular death among subjects with a high risk of vascular complications.
Aspirin-induced impairment of primary hemostasis cannot be separated from its antithrombotic efficacy, and is similar at doses > 75 mg. Bleeding risk and potential benefit of preventing thrombotic events depends on the thrombotic vs hemorrhagic risk of the patient.
Ticlopidine, clopidogrel, and prasugrel are the three generations of oral thienopyridines that selectively
inhibit ADP-induced platelet aggregation. These are prodrugs that must undergo metabolic activation through the hepatic CYP450 system to generate the active metabolites that inhibit the platelet P2Y12 receptor.
Ticlopidine is limited by bone marrow toxicity and its clinical role is limited.
Clopidogrel is widely used in patients with ACS and in those undergoing percutaneous coronary intervention (PCI). However, clopidogrel has a delayed onset of action, and assays reveal interpatient response variability.
Prasugrel has a more rapid onset of action, has a different metabolism (less dependence on CYP enzymes), is more potent than clopidogrel, and produces more consistent platelet inhibition.
Dipyridamole is a pyrimidopyrimidine derivative that has both antiplatelet and vasodilator properties. The combination of aspirin plus dipyridamole has been shown to be superior to aspirin alone for secondary prevention of vascular events in patients with a history of TIA or stroke.
Aggrenox is a modified release formulation of 200 mg dipyridamole with 25 mg of aspirin and is FDA approved for stroke prevention.
Cilostazol (Pletal) is a selective nucleotide PDE3 inhibitor with antiplatelet, vasodilatory and anti- proliferative effects. It is FDA approved for intermittent claudication, and has been studied in stroke prevention and use in ercutaneous coronary intervention. However, side effects are frequent leading to a high rate of discontinuation.
View a table of FDA-approved antiplatelet agents from The American Society of Hematology Education Program Book 2011.
Antiplatelet Drugs : Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: Evidence-Based Clinical Practice Guidelines. Chest 2012;141;e89S-e119S
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