Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement

Summary

Dual antiplatelet therapy with aspirin and clopidogrel decreases the rate of stent thrombosis in patients undergoing percutaneous coronary intervention (PCI). However, despite intensified antiplatelet treatment, up to 4.7% of the patients undergoing coronary stenting develop thrombotic stent occlusion, suggesting incomplete platelet inhibition due to clopidogrel resistance. We evaluated the percentage of clopidogrel nonresponders among 105 patients with coronary artery disease (CAD) undergoing elective PCI. All patients were treated regularly with aspirin 100 mg/d and received a loading dose of 600 mg clopidogrel followed by a maintenance dose of 75 mg/d before PCI. Clopidogrel non-responders were defined by an inhibition of ADP (5 and 20 μMol/L) induced platelet aggregation that was less than 10% when compared to baseline values 4 h after clopidogrel intake. Semi-responders were identified by an inhibition of 10 to 29%. Patients with an inhibition over 30% were regarded as responders. We found that 5 (ADP 5 μMol/L) to 11% (ADP 20 μMol/L) of the patients were non-responders and 9 to 26% were semi-responders. Among the group of nonresponders there were two incidents of subacute stent thrombosis after PCI. We conclude that a subgroup of patients undergoing PCI does not adequately respond to clopidogrel, which may correspond to the occurrence of thromboischemic complications. Point-of-care testing may help to identify these patients who may then benefit from an alternative antiplatelet therapy.

Keywords

Platelets - clopidogrel - non-responders - stenting - coronary artery disease

• References

• 1 Cutlip DE, Baim DS, Ho KK.. et al. Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials. Circulation 2001; 103: 1967-71.
• 2 Schomig A, Neumann FJ, Kastrati A.. et al. A randomised comparison of antiplatelet and anticoagulant therapy after the placement of coronary artery stents. N Engl J Med 1996; 334: 1084-9.
• 3 Bhatt DL, Bertrand ME, Berger PB.. et al. Meta-analysis of randomized and registry comparisons of ticlopidine with clopidogrel after stenting. J Am Coll Cardiol 2002; 39: 9-14.
• 4 Steinhubl SR, Berger PB, Mann JT.. 3rd et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002; 288: 2411-20.
• 5 Müller I, Seyfarth M, Rüdiger S, Wolf B, Pogatsa-Murray G, Schömig A.. Effect of a high loading dose of clopidogrel on platelet function in patients undergoing coronary stent placement. Heart 2001; 85: 92-3.
• 6 Gawaz M, Seyfarth M, Muller I.. et al. Comparison of effects of clopidogrel versus ticlopidine on platelet function in patients undergoing coronary stent placement. Am J Cardiol 2001; 87: 332-6.
• 7 Gawaz M, Ruf A, Pogatsa-Murray G.. et al. Incomplete inhibition of platelet aggregation and glycoprotein IIb-IIIa receptor blockade by abciximab: Importance of internal pool of glycoprotein IIb-IIIa receptors. Thromb Haemost 2000; 83: 915-22.
• 8 Helgason CM, Bolin KM, Hoff JA, Winkler SR, Mangat A, Tortorice KL, Brace LD.. Development of aspirin resistance in persons with previous ischemic stroke. Stroke 1994; 25: 2331-6.
• 9 Pappas JM, Westengard JC, Bull BS.. Population variability in the effect of aspirin on platelet function. Implications for clinical trials and therapy. Arch Pathol Lab Med 1994; 118: 801-4.
• 10 Grotemeyer KH, Scharafinski HW, Husstedt IW.. Two-year follow-up of aspirin responder and aspirin non responder. A pilot-study including 180 post-stroke patients. Thromb Res 1993; 71: 397-403.
• 11 Järemo P, Lindahl TL, Fransson SG, Richter A.. Individual variations of platelet inhibition after loading doses of clopidogrel. J Intern Med 2002; 252: 233-8.
• 12 Sokolova O, Schnurr A, Grossmann R, Kobsar A, Schwarz U, Barragan P, Bonz A, Walter U, Eigenthaler M.. Experiences with clopidogrel in patients with coronary heart disease: are all platelets inhibited?. Ann Hematol 2002; 81 suppl (01) A 320.
• 13 Dangas G, Mehran R, Abizaid AS.. et al. Combination therapy with aspirin plus clopidogrel versus aspirin plus ticlopidine for prevention of subacute thrombosis after successful native coronary stenting. Am J Cardiol 2001; 87: 470-2.
• 14 Duke magazine. 2001; 87 (06) 2001 http://www.dukemagazine.duke.edu