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High Residual Platelet Reactivity After Clopidogrel

Extent of Coronary Atherosclerosis and Periprocedural Myocardial Infarction in Patients With Stable Angina Undergoing Percutaneous Coronary Intervention

Fabio Mangiacapra, MD^_*,, Bernard De Bruyne, MD, PhD^_*, Olivier Muller, MD, PhD^_*, Catalina Trana, MD^_*, Argyrios Ntalianis, MD, PhD^_*, Jozef Bartunek, MD, PhD^_*, Guy Heyndrickx, MD, PhD^_*, Germano Di Sciascio, MD, William Wijns, MD, PhD^_*, Emanuele Barbato, MD, PhD^_*,_*

^_* Cardiovascular Center, OLV Hospital, Aalst, Belgium
Department of Cardiovascular Sciences, Campus Bio-Medico University, Rome, Italy

^_* Reprint requests and correspondence: Dr. Emanuele Barbato, Cardiovascular Center OLV, Moorselbaan 164, B-9300 Aalst, Belgium (Email: emanuele.barbato{at}olvz-aalst.be).

Objectives: We tested the hypothesis that residual platelet reactivity after clopidogrel correlates with the extent and severity of coronary atherosclerosis in patients undergoing elective percutaneous coronary intervention (PCI).

Background: Platelets are actively involved in vascular atherosclerosis.

Methods: We prospectively enrolled 338 patients undergoing PCI for stable angina, loaded with 600-mg clopidogrel. Platelet reactivity was assessed 12 h later by measuring P2Y12 reactivity unit (PRU) with VerifyNow P2Y12 assay (Accumetrics, San Diego, California). High platelet reactivity (HPR) was defined as PRU value 240. Presence of multivessel disease (MVD) and total stent length (TSL) were used as surrogate markers of atherosclerosis severity and extension.

Results: Patients with MVD showed higher PRU compared with single-vessel disease (SVD) patients (222 ± 85 vs. 191 ± 73; p < 0.001). The PRU increased with the number of stenotic coronaries (1-vessel disease: 191 ± 73; 2-vessel disease: 220 ± 88; 3-vessel disease: 226 ± 80; p = 0.002). The PRU was higher in the third TSL tertile compared with first tertile (217 ± 83 vs. 191 ± 73; p = 0.048). The HPR was most frequently observed among MVD patients (40.5% vs. 21.6% in patients with SVD, respectively; p < 0.001) and those in the third TSL tertile (35.8% vs. 22.2% first tertile; p = 0.028). Higher incidence of periprocedural myocardial infarction was observed in patients with HPR (41.2% vs. 26.7% in patients without HPR; p = 0.008) and in those in the third tertile TSL (37.7% vs. 23.1% first tertile; p = 0.020). By multivariate analysis, HPR was the only independent predictor of periprocedural myocardial infarction (p = 0.034).

Conclusions: Patients with more extensive coronary atherosclerosis have a higher rate of HPR, which might partly account for higher risk of periprocedural MI.

Key Words: atherosclerosis • clopidogrel • PCI • platelets

Abbreviations and Acronyms   ANOVA = analysis of variance   CAD = coronary artery disease   CI = confidence interval   HPR = high platelet reactivity   MI = myocardial infarction   MVD = multivessel disease   OR = odds ratio   PCI = percutaneous coronary intervention   PRU = P2Y12 reactivity unit   SVD = single-vessel disease   TSL = total stent length