Clinical applications of antiplatelet therapy

Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Reviews in cardiovascular medicine (Impact Factor: 0.56). 02/2006; 7(3):130-46; quiz 148-9.
Source: PubMed


Dual antiplatelet therapy with aspirin and a thienopyridine has become the standard of care for patients undergoing percutaneous intervention with stenting, regardless of indication. This article will examine the evidence for and against the use of aspirin and thienopyridines, with emphasis on platelet resistance and nonresponsiveness. Data suggest that in some patients, clopidogrel plus aspirin is not superior to aspirin alone. Resistance to aspirin and clopidogrel has been reported. Patients exhibiting aspirin resistance, as measured by an elevated platelet aggregate ratio, have a 10-fold increase in the risk of recurrent vascular events as compared to aspirin-sensitive patients. Clopidogrel nonresponsiveness has been a consistently observed phenomenon in studies utilizing various P2Y12 receptor-specific assays. Nonresponsiveness to clopidogrel treatment has been suggested as a risk factor for the occurrence of ischemic events and stent thrombosis.

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    ABSTRACT: The antiplatelet effect of aspirin is attributed to platelet cyclooxygenase-1 inhibition. Controversy exists on the prevalence of platelet resistance to aspirin in patients with coronary artery disease and effects of aspirin dose on inhibition. Our primary aim was to determine the degree of platelet aspirin responsiveness in patients, as measured by commonly used methods, and to study the relation of aspirin dose to platelet inhibition. We prospectively studied the effect of aspirin dosing on platelet function in 125 stable outpatients with coronary artery disease randomized in a double-blind, double-crossover investigation (81, 162, and 325 mg/d for 4 weeks each over a 12-week period). At all doses of aspirin, platelet function was low as indicated by arachidonic acid (AA)-induced light transmittance aggregation, thrombelastography, and VerifyNow. At any 1 dose, resistance to aspirin was 0% to 6% in the overall group when AA was used as the agonist, whereas it was 1% to 27% by other methods [collagen and ADP-induced light transmittance aggregation, platelet function analyzer (PFA-100)]. Platelet response to aspirin as measured by collagen-induced light transmittance aggregation, ADP-induced light transmittance aggregation, PFA-100 (81 mg versus 162 mg, P < or = 0.05), and urinary 11-dehydrothromboxane B2 was dose-related (81 mg versus 325 mg, P = 0.003). No carryover effects were observed. The assessment of aspirin resistance is highly assay-dependent; aspirin is an effective blocker of AA-induced platelet function at all doses, whereas higher estimates of resistance were observed with methods that do not use AA as the stimulus. The observation of dose-dependent effects despite nearly complete inhibition of AA-induced aggregation suggests that aspirin may exert antiplatelet properties through non-cyclooxygenase-1 pathways and deserves further investigation.
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