Identification of low responders to a 300-mg clopidogrel loading dose in patients undergoing coronary stenting

• Published in: Thrombosis research Vol. 115; no. 1; pp. 101 - 108
• Main Authors: Angiolillo, Dominick J., Fernandez-Ortiz, Antonio, Bernardo, Esther, Ramírez, Celia, Barrera-Ramirez, Carlos, Sabaté, Manel, Hernández, Rosana, Moreno, Raul, Escaned, Javier, Alfonso, Fernando, Bañuelos, Camino, Costa, Marco A., Bass, Theodore A., Macaya, Carlos
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Ltd 2005; Elsevier Science
• Subjects: Aged; Biological and medical sciences; Blood and lymphatic vessels; Blood. Blood coagulation. Reticuloendothelial system; Cardiology. Vascular system; Clopidogrel; Coronary heart disease; Coronary Vessels - surgery; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Heart; Humans; Male; Medical sciences; Middle Aged; P-Selectin - analysis; Pharmacology. Drug treatments; Platelet Activation - drug effects; Platelet Aggregation - drug effects; Platelet Function Tests; Platelet Glycoprotein GPIIb-IIIa Complex - metabolism; Platelets; Predictive Value of Tests; Risk Assessment; Stents; Stents - adverse effects; Thrombosis; Thrombosis - etiology; Ticlopidine - administration & dosage; Ticlopidine - analogs & derivatives; Ticlopidine - pharmacology; Clopidogrel; Platelets; Stents; Thrombosis; Human; Flow cytometry; Glycoprotein; Cardiovascular disease; ADP; Coronary heart disease; Stent; Antiplatelet agent; Blood flow; Vascular disease; Aggregation; P Selectin; Platelet; Treatment; Proportion; Risk factor; Platelet function; Hemodynamics; Thienopyridine derivative
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2004.07.007

Although patients undergoing coronary stenting routinely receive dual antiplatelet treatment to reduce the risk of stent thrombosis, this undesired event still occurs. A suboptimal response to clopidogrel treatment (low responders) has been suggested to contribute to stent thrombosis. In the present study, platelet function profiles were assessed in patients undergoing coronary stenting receiving a standard 300-mg clopidogrel loading dose with the aim to identify low clopidogrel responders. Platelet aggregation was assessed by light transmittance aggregometry following 6 μM ADP stimuli in 48 patients before and 10 min, 4 and 24 h after receiving clopidogrel front-loading. Patients having ≥40% inhibition of platelet aggregation 24 h after clopidogrel administration were defined as normal responders, whereas those having <40% inhibition were low responders. Glycoprotein (GP) IIb/IIIa activation and P-selectin expression were assessed by whole blood flow cytometry following 2 μM ADP stimuli at the same time points. Platelet function profiles were compared between normal and low clopidogrel responders. Twenty-seven patients (56%) were normal responders and 21 (44%) low responders. Baseline GP IIb/IIIa activation was higher in low responders (74.6±16.6% vs. 58.2±24.5%, p=0.03). Although GP IIb/IIIa activation reduced following clopidogrel front-loading in both groups, it remained increased among low responders at 24 h (58.6±21.3% vs. 40.2±28.7%, p=0.05) and during the overall study time course ( p=0.02). There were no differences in P-selectin expression. A considerable proportion of patients have an early suboptimal response to a 300-mg clopidogrel loading dose. An increased GP IIb/IIIa activation before intervention may identify this group of patients suggesting the use of a more aggressive antithrombotic treatment in these individuals.