CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY
Point-of-Care Measurement of Clopidogrel Responsiveness Predicts Clinical Outcome in Patients Undergoing Percutaneous Coronary InterventionResults of the ARMYDA-PRO (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity Predicts Outcome) Study
Giuseppe Patti, MD, FACC,
Annunziata Nusca, MD,
Fabio Mangiacapra, MD,
Laura Gatto, MD,
Andrea D'Ambrosio, MD and
Germano Di Sciascio, MD, FACC*
Department of Cardiovascular Sciences, Campus Bio-Medico University of Rome, Rome, Italy
Manuscript received March 25, 2008;
revised manuscript received June 5, 2008,
accepted June 9, 2008.
* Reprint requests and correspondence: Prof. Germano Di Sciascio, Department of Cardiovascular Sciences, Campus Bio-Medico University, Via Alvaro del Portillo, 200, 00128 Rome, Italy (Email: g.disciascio{at}unicampus.it).
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Abstract
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Objectives: The aim of this study was to evaluate the correlation of point-of-care measurement of platelet inhibition with clinical outcome in patients undergoing percutaneous coronary intervention (PCI).
Background: Individual variability of clopidogrel response might influence results of PCI.
Methods: A total of 160 patients receiving clopidogrel before PCI were prospectively enrolled. Platelet reactivity was measured by the VerifyNow P2Y12 assay (Accumetrics Inc., San Diego, California). Primary end point was 30-day occurrence of major adverse cardiac events (MACE) according to quartile distribution of P2Y12 reaction units (PRU).
Results: Primary end point occurred more frequently in patients with pre-procedural PRU levels in the fourth quartile versus those in the lowest quartile (20% vs. 3%; p = 0.034), and it was entirely due to periprocedural myocardial infarction (MI). Mean PRU absolute levels were higher in patients with periprocedural MI (258 ± 53 vs. 219 ± 69 in patients without; p = 0.030). On multivariable analysis pre-PCI PRU levels in the fourth quartile were associated with 6-fold increased risk of 30-day MACE (odds ratio: 6.1; 95% confidence interval: 1.1 to 18.3, p = 0.033). By receiver-operating characteristic curve analysis, the optimal cut-off for the primary end point was a pre-PCI PRU value  240 (area under the curve: 0.69; 95% confidence interval: 0.56 to 0.81, p = 0.016).
Conclusions: This study indicates that high pre-PCI platelet reactivity might predict 30-day events. Use of a rapid point-of-care assay for monitoring residual platelet reactivity after clopidogrel administration might help identify patients in whom individualized antiplatelet strategies might be indicated with coronary intervention.
Key Words: clopidogrel • percutaneous coronary intervention • platelet aggregometry
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Abbreviations and Acronyms
| | ACS = acute coronary syndromes | | ADP = adenosine diphosphate | | CK-MB = creatine kinase-myocardial band | | LTA = light transmittance aggregometry | | MACE = major adverse cardiac events | | MI = myocardial infarction | | PCI = percutaneous coronary intervention | | PRU = platelet (P2Y12) reaction units | | ROC = receiver-operating characteristic | | Tn = troponin |
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Optimal platelet inhibition plays a key role in the prevention of early myocardial ischemic complications during percutaneous coronary intervention (PCI) (1,2); accordingly, the association of aspirin and clopidogrel, a nonreversible P2Y12 platelet receptor inhibitor, represents the established antiplatelet therapy in this setting.
Because of inter-individual variability in clopidogrel responsiveness, platelet function monitoring assays are useful tools to identify patients with different drug responses who might potentially be at increased risk of recurrent cardiac events or bleeding. Adenosine diphosphate (ADP)-induced light transmittance aggregometry (LTA) is the standard test for evaluating platelet reactivity in patients receiving clopidogrel, but this is nonspecific and time-consuming (3); conversely, more rapid and specific tests measuring clopidogrel response in the individual patient might be widely applicable in clinical practice, thereby providing risk stratification and a guide to antithrombotic therapy. Thus, the ARMYDA study group (1,4–7) has designed the ARMYDA-PRO (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity Predicts Outcome) study to prospectively evaluate whether point-of-care measurements of platelet inhibition predict clinical outcome in patients undergoing PCI.
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Methods
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Study population and design.
The ARMYDA-PRO is a prospective study including 160 patients receiving clopidogrel before PCI. Patients with a variety of coronary syndromes, including non–ST-segment elevation acute coronary syndromes (ACS) were enrolled. Exclusion criteria were: primary PCI; platelet count <70 x 109/l; high bleeding risk; and severe chronic renal failure (serum creatinine >2 mg/dl). All patients received 600 mg clopidogrel load approximately 6 h before intervention (n = 120) or were receiving chronic clopidogrel therapy (75 mg/day for 5 days, n = 40). Clopidogrel was continued for 1 month after PCI and for 12 months in patients with ACS or receiving drug-eluting stents. All patients received aspirin.
Platelet reactivity was evaluated in the catheterization laboratory before PCI and at 8 and 24 h after intervention by the VerifyNow P2Y12 assay (Accumetrics Inc., San Diego, California), which is a rapid cartridge-based assay specifically measuring direct effects of clopidogrel on the platelet P2Y12 receptor. Technical details were already described elsewhere (8). Results are expressed as P2Y12 reaction units (PRU)—the lower the PRU value, the greater the degree of P2Y12 receptor inhibition by clopidogrel and vice versa. Twenty randomly selected patients were analyzed to assess intra-assay variability, which was 2.1 ± 1.3% (coefficient of variation: 6%).
Blood samples were also drawn before and at 8 and 24 h in all patients for creatine kinase-myocardial band (CK-MB; mass) and troponin-I (Tn-I; mass) levels; further measurements were obtained if symptoms suggested myocardial ischemia. Measurements were performed by Access 2 Immunochemiluminometric assay (Beckman Coulter, Fullerton, California); normal limits were  4 ng/ml for CK-MB and 0.08 ng/ml for Tn-I. One-month and 6-month clinical follow-up were obtained by office visit in all patients. Each patient gave informed consent to the study. The study was not supported by external sources of funding.
End points.
Primary end point of the ARMYDA-PRO study was 30-day incidence of major adverse cardiac events (MACE): cardiac death, myocardial infarction (MI), target vessel revascularization, in relation to quartile distribution of platelet reactivity measured by PRU assay. Myocardial infarction was defined as post-procedural increase of cardiac biomarkers (Tn or CK-MB) >3 x 99th percentile of the upper reference limit (9). Target vessel revascularization included by-pass surgery or repeat PCI of the target vessel(s).
Secondary end points were: 1) evaluation of mean PRU absolute values in patients with or without post-PCI elevation of markers of myocardial damage (CK-MB, Tn-I); 2) distribution in PRU quartiles of patients with any post-procedural increase of cardiac markers above normal limits; 3) correlation of vascular/bleeding complications to PRU quartiles; and 4) clinical outcome at 6-month follow-up. Bleeding events were defined according to Thrombolysis In Myocardial Infarction criteria (10).
Statistics.
On the basis of patients' enrollment criteria, we assumed 8% overall incidence of 30-day MACE (1,11). We tested the hypothesis that incidence of 30-day MACE differed by PRU quartiles. We assumed as effect size for the power analysis a 7-fold increased risk of 30-day MACE in patients of the fourth quartile (12); thus, a study population of at least 153 patients would be needed to verify this hypothesis with alpha of 0.05 (2-tailed) and beta of 0.08.
Continuous variables were compared by t test for normally distributed values; otherwise the Mann-Whitney U test was used. Proportions were compared by Fisher exact test when the expected frequency was <5; otherwise the chi-square test was applied. Event-free survival analysis was performed by Kaplan-Meier method with log-rank test group comparison. Odds ratios (ORs) and 95% confidence intervals (CIs) investigating the independent predictive role of PRU quartiles on the occurrence of the primary end point were assessed by logistic regression. The following parameters were first evaluated in a univariate model: comparison of PRU quartiles (fourth vs. first quartile, third vs. first, second vs. first); each of the variables indicated in Table 1; and procedural variables, such as stent length, direct stenting, inflations duration. Only variables with p value <0.15 were then entered into the final model of multivariable logistic regression analysis. Ability of the assay to discriminate between patients with and without MACE at 30 days was evaluated by receiver-operating characteristic (ROC) curve analysis. The optimal cut-off value was calculated by determining the PRU value providing the greatest sum of sensitivity and specificity. Results are expressed as mean ± SD. A p value <0.05 (2-tailed) was considered significant. Analysis was performed with SPSS 12.0 (SPSS Inc., Chicago, Illinois) software.
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Results
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Clinical and procedural characteristics according to pre-intervention PRU quartiles are indicated in Table 1.
Procedural success was obtained in 99% of patients. No vessel or side branch (2 mm) closure occurred. No patient required emergency coronary artery by-pass graft.
Primary end point.
Occurrence of composite primary end point was significantly more frequent in patients with pre-procedural PRU levels in the fourth quartile versus those in the first quartile (20% vs. 3%; p = 0.034) (Fig. 1); this was essentially due to periprocedural MI. No further event occurred during 1-month follow-up.
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Figure 1 The ARMYDA-PRO Study—Primary End Point
Incidence of primary end point (30-day major adverse cardiac events [MACE]) according to quartile distribution of pre-intervention platelet (P2Y12) reaction units (PRU) values. ARMYDA-PRO = Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity Predicts Outcome. Figure illustration by Rob Flewell.
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Secondary end points.
Higher PRU values before PCI (Fig. 2A) predicted periprocedural MI by CK-MB definition (258 ± 53 PRU in patients with MI vs. 219 ± 69 PRU in those without MI; p = 0.030) but not by Tn-I (Fig. 2B).
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Figure 2 The ARMYDA-PRO Study—Secondary End Points
Distribution of pre-intervention PRU levels according to post–percutaneous coronary intervention creatine kinase-myocardial band (CK-MB) (A) and troponin-I (Tn-I) (B) values. Abbreviations as in Figure 1. Figure illustration by Rob Flewell.
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Likewise, any post-procedural increase of CK-MB above upper normal limits was more frequently observed in patients in the fourth PRU quartile (48% vs. 23% in the first quartile; p = 0.035), but there was no difference in the proportion of patients with Tn-I elevation (65% in the fourth quartile vs. 45% in the first quartile; p = 0.12).
No relationship was found between MACE and PRU levels at 8 and 24 h after PCI (p 0.30).
No patient had major bleeding or required transfusions; minor bleeding occurred in 9 patients (6%): 1 patient had urethral bleeding from a Foley catheter and 8 had small entry-site hematomas, independent of baseline PRU quartiles. There were no side-effects in either group requiring discontinuation of clopidogrel. At 6-month follow-up, the cumulative incidence of MACE was 10% in the first quartile, 13% in the second, 17% in the third, and 30% in the fourth quartile (p = 0.05 first vs. fourth quartile).
Multivariable analysis.
Whereas the comparison of third and second quartiles versus first was not different (p = 0.68 and p = 0.71, respectively), multivariable analysis revealed that pre-PCI PRU levels in the fourth quartile were independent predictors of higher risk of adverse events at 30 days (OR: 6.1; 95% CI: 1.1 to 18.3; p = 0.033). Age >70 years, left ventricular dysfunction, and use of glycoprotein IIb/IIIa inhibitors were also associated with increased risk, whereas statin therapy at the time of PCI had a protective effect (OR: 0.21; CI: 0.10 to 0.91; p = 0.037) (4,7).
ROC curve analysis.
The ROC curve analysis showed that PRU levels significantly discriminate between patients with and without 30-day MACE with an area under the curve of 0.69 (95% CI: 0.56 to 0.81; p = 0.016). A PRU value 240 was identified as the optimal cutoff point to predict 30-day outcome, with sensitivity of 81% and specificity of 53%.
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Discussion
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This prospective study indicates that high residual platelet reactivity after clopidogrel administration, measured by a point-of-care assay at the time of intervention, is associated with higher incidence of 30-day MACE after PCI; this outcome is mainly driven by increased risk of periprocedural MI.
Evaluation of individual clopidogrel responsiveness is an emerging issue in interventional cardiology. Wide variability is reported (13), ascribed in turn to differences in drug absorption, variations in biotransformation rate into active metabolite (due to drug–drug interactions at the site of cytochrome P or genetic CYP3A polymorphisms) (14), P2Y12 receptor polymorphisms affecting receptor number and activity (15), and even noncompliance (16). The prevalence of reduced clopidogrel responsiveness varies from 4% to 30% (2,13,17), depending on the assay used, definitions empirically applied, and presence of potential confounders.
Several methods have been used to evaluate clopidogrel response in patients undergoing PCI, with the aim of identifying those at higher risk of adverse events (18), with optical aggregometry after ADP stimulation being the most widely used in previous studies. A low platelet response to clopidogrel measured with LTA was associated with increased incidence of periprocedural myocardial injury (19), cardiovascular events at short- (12,20) and midterm (2,21), and stent thrombosis (22). Nevertheless, this test has a number of limitations, such as need for highly trained personnel, repeated centrifugations, large sample volume, length of assay time, and suboptimal reproducibility (3). Furthermore, it is nonspecific, because it also measures aggregation due to binding of ADP to P2Y1 platelet receptor, which is not inhibited by clopidogrel.
Vasodilator-stimulated phosphoprotein phosphorylation by flow cytometry is more specific, because it directly measures effects of the drug on the target receptor; in observational studies, a lower platelet inhibition assessed by vasodilatator-stimulated phosphoprotein was observed in patients with stent thrombosis (22). Cost and need for long sample preparation and skilled personnel limit a widespread use of this test (3).
Platelet reactivity by VerifyNow can be rapidly measured without sample preparation by moderately experienced personnel with low sample volumes; the test specifically reflects the extent of ADP-induced inhibition of adenylyl cyclase, which is mediated uniquely by action of clopidogrel on the P2Y12 receptor. The assay allows detection of absolute PRU values and percent P2Y12 receptor inhibition, which might be calculated as a percent change from baseline platelet aggregation (8,23). A close correlation was described between results of ADP-induced optical aggregometry and absolute PRU values by VerifyNow assay in patients undergoing PCI (24). This method was also tested and clinically validated in a multicenter prospective study (VERITAS [VERIfy Thrombosis risk Assessment]) (23).
In this study we demonstrate the correlation between clopidogrel response and clinical outcome after coronary intervention. Although multivariable analysis might be overfitted, given the number of end point events included, the predictive value for adverse events of the fourth quartile of platelet reactivity was independent of possible confounding factors, with a 6-fold increased risk of periprocedural MI versus the first quartile. An ROC analysis indicated that this assay can predict outcome at 30 days, with optimal cutoff point to discriminate patients at higher risk of events of 240 PRU, and a positive predictive value of 81%. The threshold identified in our study coincides with that observed by Price et al. (25) in an observational study in which a cutoff 235 PRU correlated with 6-month events, including stent thrombosis, in patients receiving sirolimus-eluting stents. In ARMYDA-PRO, the negative predictive value of PRU in the first quartile was 98%, with minimal probability of early adverse events with PRU levels <178. Interestingly, higher PRU values correlated with CK-MB elevation but not with Tn-I elevation, suggesting that platelet-unrelated events (i.e., distal embolization) might be also responsible for Tn raise after PCI (12). No cut-off value for events was described in a recent study (26) on stable patients treated with drug-eluting stents after variable loading doses of clopidogrel (300 or 600 mg) that also used VerifyNow.
We used quartile distribution, because clopidogrel responsiveness is multifactorial and it should be considered as a continuum; accordingly, a progressively increasing incidence of events was observed across PRU quartiles (Fig. 1), with a similar pattern of correlation between PRU values and peak levels of myocardial markers (Fig. 2).
Unlike the Price et al. study (25), ARMYDA-PRO was not powered to evaluate relationship between degree of clopidogrel inhibition and occurrence of bleeding complications or late thrombotic events; larger prospective studies with longer follow-up are needed to address this issue.
Clopidogrel responsiveness variability, within the enhanced thrombotic milieu of PCI, requires careful evaluation. The ARMYDA-PRO study supports the use of a rapid point-of-care assay for monitoring residual platelet reactivity after clopidogrel administration: VerifyNow can be a useful and easily applicable method that might help establish a clinically driven threshold of platelet reactivity that would identify patients at higher risk of periprocedural events; in those, individualized antithrombotic strategies (i.e., restricted use of drug-eluting stents, more extensive use of glycoprotein IIb/IIIa inhibitors, higher clopidogrel maintenance dose, or use of newer P2Y12 receptor antagonists) might be indicated to improve clinical outcome after coronary intervention.
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References
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|---|
1. Patti G, Colonna G, Pasceri V, Lassandro Pepe L, Montinaro A, Di Sciascio G. Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention: results from the ARMYDA-2 study Circulation 2005;111:2099-2106.[Abstract/Free Full Text]2. Gurbel PA, Bliden KP, Guyer K, et al. Platelet reactivity in patients and recurrent events post-stenting: results of the PREPARE POST-STENTING Study J Am Coll Cardiol 2005;46:1820-1826.[Abstract/Free Full Text] 3. Michelson AD. Platelet function testing in cardiovascular diseases Circulation 2004;110:489-493.[Abstract/Free Full Text] 4. Pasceri V, Patti G, Nusca A, Pristipino C, Richichi G, Di Sciascio G. Randomized trial of atorvastatin for reduction of myocardial damage during coronary intervention: results from the ARMYDA study Circulation 2004;110:674-678.[Abstract/Free Full Text] 5. Patti G, Chello M, Candura D, et al. Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in patients undergoing cardiac surgery: results of the ARMYDA-3 study Circulation 2006;114:1455-1461.[Abstract/Free Full Text] 6. Patti G, Chello M, Pasceri V, et al. Protection from procedural myocardial injury by atorvastatin is associated with lower levels of adhesion molecules after percutaneous coronary intervention: results from the ARMYDA-CAMs substudy J Am Coll Cardiol 2006;48:1560-1566.[Abstract/Free Full Text] 7. Patti G, Pasceri V, Colonna G, et al. Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial J Am Coll Cardiol 2007;49:1272-1278.[Abstract/Free Full Text] 8. Malinin A, Pokov A, Swaim L, Kotob M, Serebruany V. Validation of a VerifyNow-P2Y12 cartridge for monitoring platelet inhibition with clopidogrel Methods Find Exp Clin Pharmacol 2006;28:315-322.[CrossRef][Web of Science][Medline] 9. Thygesen K, Alpert JS, White HD, Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction Universal definition of myocardial infarction J Am Coll Cardiol 2007;50:2173-2195.[Free Full Text] 10. Rao AK, Pratt C, Berke A, et al. Thrombolysis in Myocardial Infarction (TIMI) Trial-phase I: hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase J Am Coll Cardiol 1988;11:1-11.[Abstract] 11. Kastrati A, Mehilli J, Neumann FJ, et al. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial JAMA 2006;295:1531-1538.[Abstract/Free Full Text] 12. Hochholzer W, Trenk D, Bestehorn HP, et al. Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement J Am Coll Cardiol 2006;48:1742-1750.[Abstract/Free Full Text] 13. Gurbel PA, Bliden KP, Hiatt BL, O'Connor CM. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity Circulation 2003;107:2908-2913.[Abstract/Free Full Text] 14. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Contribution of gene sequence variations of the hepatic cytochrome P450 3A4 enzyme to variability in individual responsiveness to clopidogrel Arterioscler Thromb Vasc Biol 2006;26:1895-1900.[CrossRef][Web of Science][Medline] 15. Fontana P, Dupont A, Gandrille S, et al. Adenosine diphosphate-induced platelet aggregation is associated with P2Y12 gene sequence variations in healthy subjects Circulation 2003;108:989-995.[Abstract/Free Full Text] 16. Serebruany VL. The "clopidogrel resistance" trap Am J Cardiol 2007;100:1044-1046.[CrossRef][Medline] 17. Serebruany VL, Steinhubl SR, Berger PB, Malinin AI, Bhatt DL, Topol EJ. Variability in platelet responsiveness to clopidogrel among 544 individuals J Am Coll Cardiol 2005;45:246-251.[Abstract/Free Full Text] 18. Snoep JD, Hovens MM, Eikenboom JC, van der Bom JG, Jukema JW, Huisman MV. Clopidogrel nonresponsiveness in patients undergoing percutaneous coronary intervention with stenting: a systematic review and meta-analysis Am Heart J 2007;154:221-231.[CrossRef][Web of Science][Medline] 19. Gurbel PA, Bliden KP, Zaman KA, Yoho JA, Hayes KM, Tantry US. Clopidogrel loading with eptifibatide to arrest the reactivity of platelets: results of the CLEAR PLATELETS study Circulation 2005;111:1153-1159.[Abstract/Free Full Text] 20. Cuisset T, Frere C, Quilici J, et al. Benefit of a 600-mg loading dose of clopidogrel on platelet reactivity and clinical outcomes in patients with non–ST-segment elevation acute coronary syndrome undergoing coronary stenting J Am Coll Cardiol 2006;48:1339-1345.[Abstract/Free Full Text] 21. Bliden KP, DiChiara J, Tantry US, Bassi AK, Chaganti SK, Gurbel PA. Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention: is the current antiplatelet therapy adequate? J Am Coll Cardiol 2007;49:657-666.[Abstract/Free Full Text] 22. Gurbel PA, Bliden KP, Samara W, et al. Clopidogrel effect on platelet reactivity in patients with stent thrombosis: results of the CREST study J Am Coll Cardiol 2005;46:1827-1832.[Abstract/Free Full Text] 23. Malinin A, Pokov A, Spergling M, et al. Monitoring platelet inhibition after clopidogrel with the VerifyNow-P2Y12 rapid analyzer: the VERIfy Thrombosis risk ASsessment (VERITAS) study Thromb Res 2007;119:277-284.[CrossRef][Web of Science][Medline] 24. Van Werkum JW, Van der Stelt CA, Seesing TH, Hackeng CM, Ten Berg JM. A head-to-head comparison between the VerifyNow P2Y12 assay and light transmittance aggregometry for monitoring the individual platelet response to clopidogrel in patients undergoing elective percutaneous coronary intervention J Thromb Haemost 2006;4:2516-2518.[CrossRef][Web of Science][Medline] 25. Price MJ, Endemann S, Gollapudi RR, et al. Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation Eur Heart J 2008;29:992-1000.[Abstract/Free Full Text] 26. Buch AN, Singh S, Roy P, et al. Measuring aspirin resistance, clopidogrel responsiveness, and postprocedural markers of myonecrosis in patients undergoing percutaneous coronary intervention Am J Cardiol 2007;99:1518-1522.[CrossRef][Web of Science][Medline]
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Abstract
Methods