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Semin Thromb Hemost 2016; 42(03): 306-320
DOI: 10.1055/s-0035-1570083
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Platelet Function Testing in Patients on Antiplatelet Medications

Lisa Gross
1   Department of Cardiology, Ludwig-Maximilians-University, Munich, Germany
,
Dániel Aradi
2   Department of Cardiology, Heart Center Balatonfüred, Balatonfüred, Hungary
3   Heart and Vascular Center, Semmelweis University, Budapest, Hungary
,
Dirk Sibbing
1   Department of Cardiology, Ludwig-Maximilians-University, Munich, Germany
4   DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
17 February 2016 (online)

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Abstract

Guidelines provide a Class IA recommendation for the use of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI). However, there is interindividual variability in the pharmacodynamic response to antiplatelet medications. Some patients present with a status of high on-treatment platelet reactivity (HPR) during platelet function testing after standard doses of antiplatelet drugs, reflecting a failure to achieve adequate platelet inhibition. As an example, patients with HPR on clopidogrel are at increased risk for thrombotic events, particularly for stent thrombosis and myocardial infarction, but cardiovascular mortality is also elevated. On the contrary, low on-treatment platelet reactivity or an enhanced response to antiplatelet medications has been linked to a higher risk for bleeding. Although both thrombotic and bleeding events are multifactorial in origin, there is supportive evidence for the prognostic value of platelet function testing for risk prediction of both sides of the coin. However, although small studies have provided evidence that treatment adjustments based on platelet function testing results may improve clinical outcomes, the available randomized controlled trials showed no benefit of modifying antiplatelet treatment based on platelet function testing. This review presents the current evidence regarding platelet function testing in patients undergoing PCI. The prognostic value of platelet function testing regarding ischemic and bleeding events is highlighted. Furthermore, the value of platelet function testing for guiding treatment and possible explanations for the so-far negative trial results are presented. The possible future role of platelet function testing for individualized antiplatelet treatment regimens in high-risk patients will be also discussed.

Keywords

platelet function testing - high on-treatment platelet reactivity - low on-treatment platelet reactivity - stent thrombosis - risk prediction - tailored antiplatelet therapy - guidance of treatment
 

  • References

  • 1 Windecker S, Kolh P, Alfonso F , et al; Authors/Task Force members. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2014; 35 (37) 2541-2619
    CrossrefPubMedSearch in Google Scholar
  • 2 Mehta SR, Yusuf S, Peters RJ , et al; Clopidogrel in Unstable angina to prevent Recurrent Events trial (CURE) Investigators. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001; 358 (9281) 527-533
    CrossrefPubMedSearch in Google Scholar
  • 3 Bonello L, Tantry US, Marcucci R , et al; Working Group on High On-Treatment Platelet Reactivity. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 2010; 56 (12) 919-933
    CrossrefPubMedSearch in Google Scholar
  • 4 Angiolillo DJ, Fernandez-Ortiz A, Bernardo E , et al. Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol 2007; 49 (14) 1505-1516
    CrossrefPubMedSearch in Google Scholar
  • 5 Sibbing D, Koch W, Gebhard D , et al. Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation 2010; 121 (4) 512-518
    CrossrefPubMedSearch in Google Scholar
  • 6 Sibbing D, Steinhubl SR, Schulz S, Schömig A, Kastrati A. Platelet aggregation and its association with stent thrombosis and bleeding in clopidogrel-treated patients: initial evidence of a therapeutic window. J Am Coll Cardiol 2010; 56 (4) 317-318
    CrossrefPubMedSearch in Google Scholar
  • 7 Gurbel PA, Bliden KP. Platelet activation after stenting with heparin-coated versus noncoated stents. Am Heart J 2003; 146 (4) E10
    PubMedSearch in Google Scholar
  • 8 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 (2) 246-251
    CrossrefPubMedSearch in Google Scholar
  • 9 Holmes MV, Perel P, Shah T, Hingorani AD, Casas JP. CYP2C19 genotype, clopidogrel metabolism, platelet function, and cardiovascular events: a systematic review and meta-analysis. JAMA 2011; 306 (24) 2704-2714
    CrossrefPubMedSearch in Google Scholar
  • 10 Mega JL, Simon T, Collet JP , et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA 2010; 304 (16) 1821-1830
    CrossrefPubMedSearch in Google Scholar
  • 11 Geisler T, Anders N, Paterok M , et al. Platelet response to clopidogrel is attenuated in diabetic patients undergoing coronary stent implantation. Diabetes Care 2007; 30 (2) 372-374
    CrossrefPubMedSearch in Google Scholar
  • 12 Frelinger III AL, Bhatt DL, Lee RD , et al. Clopidogrel pharmacokinetics and pharmacodynamics vary widely despite exclusion or control of polymorphisms (CYP2C19, ABCB1, PON1), noncompliance, diet, smoking, co-medications (including proton pump inhibitors), and pre-existent variability in platelet function. J Am Coll Cardiol 2013; 61 (8) 872-879
    CrossrefPubMedSearch in Google Scholar
  • 13 Wiviott SD, Trenk D, Frelinger AL , et al; PRINCIPLE-TIMI 44 Investigators. Prasugrel compared with high loading- and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention: the Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial Infarction 44 trial. Circulation 2007; 116 (25) 2923-2932
    CrossrefPubMedSearch in Google Scholar
  • 14 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 (23) 2908-2913
    CrossrefPubMedSearch in Google Scholar
  • 15 Sibbing D, Braun S, Morath T , et al. Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol 2009; 53 (10) 849-856
    CrossrefPubMedSearch in Google Scholar
  • 16 Tantry US, Bonello L, Aradi D , et al; Working Group on On-Treatment Platelet Reactivity. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol 2013; 62 (24) 2261-2273
    CrossrefPubMedSearch in Google Scholar
  • 17 Aradi D, Kirtane A, Bonello L , et al. Bleeding and stent thrombosis on P2Y12-inhibitors: collaborative analysis on the role of platelet reactivity for risk stratification after percutaneous coronary intervention. Eur Heart J 2015; 36 (27) 1762-1771
    CrossrefPubMedSearch in Google Scholar
  • 18 Breet NJ, van Werkum JW, Bouman HJ , et al. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA 2010; 303 (8) 754-762
    CrossrefPubMedSearch in Google Scholar
  • 19 Serebruany VL, Aradi D, Kim MH, Sibbing D. Cangrelor infusion is associated with an increased risk for bleeding: meta-analysis of randomized trials. Int J Cardiol 2013; 169 (3) 225-228
    CrossrefPubMedSearch in Google Scholar
  • 20 Morrow DA, Braunwald E, Bonaca MP , et al; TRA 2P–TIMI 50 Steering Committee and Investigators. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med 2012; 366 (15) 1404-1413
    CrossrefPubMedSearch in Google Scholar
  • 21 Chhatriwalla AK, Amin AP, Kennedy KF , et al; National Cardiovascular Data Registry. Association between bleeding events and in-hospital mortality after percutaneous coronary intervention. JAMA 2013; 309 (10) 1022-1029
    CrossrefPubMedSearch in Google Scholar
  • 22 Michelson AD, Frelinger III AL, Braunwald E , et al; TRITON-TIMI 38 Investigators. Pharmacodynamic assessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITON-TIMI 38 trial. Eur Heart J 2009; 30 (14) 1753-1763
    CrossrefPubMedSearch in Google Scholar
  • 23 Bonello L, Mancini J, Pansieri M , et al. Relationship between post-treatment platelet reactivity and ischemic and bleeding events at 1-year follow-up in patients receiving prasugrel. J Thromb Haemost 2012; 10 (10) 1999-2005
    CrossrefPubMedSearch in Google Scholar
  • 24 Cuisset T, Grosdidier C, Loundou AD , et al. Clinical implications of very low on-treatment platelet reactivity in patients treated with thienopyridine: the POBA study (predictor of bleedings with antiplatelet drugs). JACC Cardiovasc Interv 2013; 6 (8) 854-863
    CrossrefPubMedSearch in Google Scholar
  • 25 Parodi G, Bellandi B, Venditti F , et al. Residual platelet reactivity, bleedings, and adherence to treatment in patients having coronary stent implantation treated with prasugrel. Am J Cardiol 2012; 109 (2) 214-218
    CrossrefPubMedSearch in Google Scholar
  • 26 Bonaca MP, Bhatt DL, Cohen M , et al; PEGASUS-TIMI 54 Steering Committee and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015; 372 (19) 1791-1800
    CrossrefPubMedSearch in Google Scholar
  • 27 Kazi DS, Leong TK, Chang TI, Solomon MD, Hlatky MA, Go AS. Association of spontaneous bleeding and myocardial infarction with long-term mortality after percutaneous coronary intervention. J Am Coll Cardiol 2015; 65 (14) 1411-1420
    CrossrefPubMedSearch in Google Scholar
  • 28 Mayer K, Bernlochner I, Braun S , et al. Aspirin treatment and outcomes after percutaneous coronary intervention: results of the ISAR-ASPI registry. J Am Coll Cardiol 2014; 64 (9) 863-871
    CrossrefPubMedSearch in Google Scholar
  • 29 Kovács EG, Katona E, Bereczky Z , et al. New direct and indirect methods for the detection of cyclooxygenase 1 acetylation by aspirin; the lack of aspirin resistance among healthy individuals. Thromb Res 2013; 131 (4) 320-324
    CrossrefPubMedSearch in Google Scholar
  • 30 Kovács EG, Katona É, Bereczky Z , et al. Evaluation of laboratory methods routinely used to detect the effect of aspirin against new reference methods. Thromb Res 2014; 133 (5) 811-816
    CrossrefPubMedSearch in Google Scholar
  • 31 Paniccia R, Priora R, Liotta AA, Abbate R. Platelet function tests: a comparative review. Vasc Health Risk Manag 2015; 11: 133-148
    PubMedSearch in Google Scholar
  • 32 Siller-Matula JM, Trenk D, Schrör K , et al; EPA (European Platelet Academy). Response variability to P2Y12 receptor inhibitors: expectations and reality. JACC Cardiovasc Interv 2013; 6 (11) 1111-1128
    CrossrefPubMedSearch in Google Scholar
  • 33 Lordkipanidze M. Platelet function tests. Semin Thromb Hemost 2016;
    PubMedSearch in Google Scholar
  • 34 Aradi D, Storey RF, Komócsi A , et al; Working Group on Thrombosis of the European Society of Cardiology. Expert position paper on the role of platelet function testing in patients undergoing percutaneous coronary intervention. Eur Heart J 2014; 35 (4) 209-215
    CrossrefPubMedSearch in Google Scholar
  • 35 Breet NJ, van Werkum JW, Bouman HJ, Kelder JC, Ten Berg JM, Hackeng CM. High on-aspirin platelet reactivity as measured with aggregation-based, cyclooxygenase-1 inhibition sensitive platelet function tests is associated with the occurrence of atherothrombotic events. J Thromb Haemost 2010; 8 (10) 2140-2148
    CrossrefPubMedSearch in Google Scholar
  • 36 Stone GW, Witzenbichler B, Weisz G , et al; ADAPT-DES Investigators. Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study. Lancet 2013; 382 (9892) 614-623
    CrossrefPubMedSearch in Google Scholar
  • 37 Pettersen AA, Seljeflot I, Abdelnoor M, Arnesen H. High on-aspirin platelet reactivity and clinical outcome in patients with stable coronary artery disease: results from ASCET (Aspirin Nonresponsiveness and Clopidogrel Endpoint Trial). J Am Heart Assoc 2012; 1 (3) e000703
    PubMedSearch in Google Scholar
  • 38 Mehta SR, Tanguay JF, Eikelboom JW , et al; CURRENT-OASIS 7 trial investigators. Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet 2010; 376 (9748) 1233-1243
    CrossrefPubMedSearch in Google Scholar
  • 39 Cuisset T, Frere C, Quilici J , et al. Predictive values of post-treatment adenosine diphosphate-induced aggregation and vasodilator-stimulated phosphoprotein index for stent thrombosis after acute coronary syndrome in clopidogrel-treated patients. Am J Cardiol 2009; 104 (8) 1078-1082
    CrossrefPubMedSearch in Google Scholar
  • 40 Parodi G, Marcucci R, Valenti R , et al. High residual platelet reactivity after clopidogrel loading and long-term cardiovascular events among patients with acute coronary syndromes undergoing PCI. JAMA 2011; 306 (11) 1215-1223
    CrossrefPubMedSearch in Google Scholar
  • 41 Geisler T, Langer H, Wydymus M , et al. Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation. Eur Heart J 2006; 27 (20) 2420-2425
    CrossrefPubMedSearch in Google Scholar
  • 42 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 (9) 1742-1750
    CrossrefPubMedSearch in Google Scholar
  • 43 Angiolillo DJ, Bernardo E, Sabaté M , et al. Impact of platelet reactivity on cardiovascular outcomes in patients with type 2 diabetes mellitus and coronary artery disease. J Am Coll Cardiol 2007; 50 (16) 1541-1547
    CrossrefPubMedSearch in Google Scholar
  • 44 Aradi D, Komócsi A, Vorobcsuk A , et al. Prognostic significance of high on-clopidogrel platelet reactivity after percutaneous coronary intervention: systematic review and meta-analysis. Am Heart J 2010; 160 (3) 543-551
    CrossrefPubMedSearch in Google Scholar
  • 45 Combescure C, Fontana P, Mallouk N , et al; CLOpidogrel and Vascular ISchemic Events Meta-analysis Study Group. Clinical implications of clopidogrel non-response in cardiovascular patients: a systematic review and meta-analysis. J Thromb Haemost 2010; 8 (5) 923-933
    PubMedSearch in Google Scholar
  • 46 Sofi F, Marcucci R, Gori AM, Giusti B, Abbate R, Gensini GF. Clopidogrel non-responsiveness and risk of cardiovascular morbidity. An updated meta-analysis. Thromb Haemost 2010; 103 (4) 841-848
    Thieme ConnectPubMedSearch in Google Scholar
  • 47 Brar SS, ten Berg J, Marcucci R , et al. Impact of platelet reactivity on clinical outcomes after percutaneous coronary intervention. A collaborative meta-analysis of individual participant data. J Am Coll Cardiol 2011; 58 (19) 1945-1954
    CrossrefPubMedSearch in Google Scholar
  • 48 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 (2) 221-231
    CrossrefPubMedSearch in Google Scholar
  • 49 Alexopoulos D, Galati A, Xanthopoulou I , et al. Ticagrelor versus prasugrel in acute coronary syndrome patients with high on-clopidogrel platelet reactivity following percutaneous coronary intervention: a pharmacodynamic study. J Am Coll Cardiol 2012; 60 (3) 193-199
    CrossrefPubMedSearch in Google Scholar
  • 50 Parodi G, Valenti R, Bellandi B , et al. Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation myocardial infarction patients: RAPID (Rapid Activity of Platelet Inhibitor Drugs) primary PCI study. J Am Coll Cardiol 2013; 61 (15) 1601-1606
    CrossrefPubMedSearch in Google Scholar
  • 51 Wallentin L, Varenhorst C, James S , et al. Prasugrel achieves greater and faster P2Y12receptor-mediated platelet inhibition than clopidogrel due to more efficient generation of its active metabolite in aspirin-treated patients with coronary artery disease. Eur Heart J 2008; 29 (1) 21-30
    CrossrefPubMedSearch in Google Scholar
  • 52 Collet JP, Cuisset T, Rangé G , et al; ARCTIC Investigators. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 2012; 367 (22) 2100-2109
    CrossrefPubMedSearch in Google Scholar
  • 53 Price MJ, Berger PB, Teirstein PS , et al; GRAVITAS Investigators. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 2011; 305 (11) 1097-1105
    CrossrefPubMedSearch in Google Scholar
  • 54 Serebruany V, Rao SV, Silva MA , et al. Correlation of inhibition of platelet aggregation after clopidogrel with post discharge bleeding events: assessment by different bleeding classifications. Eur Heart J 2010; 31 (2) 227-235
    CrossrefPubMedSearch in Google Scholar
  • 55 Cayla G, Cuisset T, Silvain J , et al. Prasugrel monitoring and bleeding in real world patients. Am J Cardiol 2013; 111 (1) 38-44
    CrossrefPubMedSearch in Google Scholar
  • 56 Patti G, Pasceri V, Vizzi V, Ricottini E, Di Sciascio G. Usefulness of platelet response to clopidogrel by point-of-care testing to predict bleeding outcomes in patients undergoing percutaneous coronary intervention (from the Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty-Bleeding Study). Am J Cardiol 2011; 107 (7) 995-1000
    CrossrefPubMedSearch in Google Scholar
  • 57 Mokhtar OA, Lemesle G, Armero S , et al. Relationship between platelet reactivity inhibition and non-CABG related major bleeding in patients undergoing percutaneous coronary intervention. Thromb Res 2010; 126 (2) e147-e149
    CrossrefPubMedSearch in Google Scholar
  • 58 Grosdidier C, Quilici J, Loosveld M , et al. Effect of CYP2C19*2 and *17 genetic variants on platelet response to clopidogrel and prasugrel maintenance dose and relation to bleeding complications. Am J Cardiol 2013; 111 (7) 985-990
    CrossrefPubMedSearch in Google Scholar
  • 59 Sibbing D, Schulz S, Braun S , et al. Antiplatelet effects of clopidogrel and bleeding in patients undergoing coronary stent placement. J Thromb Haemost 2010; 8 (2) 250-256
    CrossrefPubMedSearch in Google Scholar
  • 60 Campo G, Parrinello G, Ferraresi P , et al. Prospective evaluation of on-clopidogrel platelet reactivity over time in patients treated with percutaneous coronary intervention relationship with gene polymorphisms and clinical outcome. J Am Coll Cardiol 2011; 57 (25) 2474-2483
    CrossrefPubMedSearch in Google Scholar
  • 61 Mangiacapra F, Patti G, Barbato E , et al. A therapeutic window for platelet reactivity for patients undergoing elective percutaneous coronary intervention: results of the ARMYDA-PROVE (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity for Outcome Validation Effort) study. JACC Cardiovasc Interv 2012; 5 (3) 281-289
    CrossrefPubMedSearch in Google Scholar
  • 62 Gurbel PA, Bliden KP, Navickas IA , et al. Adenosine diphosphate-induced platelet-fibrin clot strength: a new thrombelastographic indicator of long-term poststenting ischemic events. Am Heart J 2010; 160 (2) 346-354
    CrossrefPubMedSearch in Google Scholar
  • 63 Gurbel PA, Becker RC, Mann KG, Steinhubl SR, Michelson AD. Platelet function monitoring in patients with coronary artery disease. J Am Coll Cardiol 2007; 50 (19) 1822-1834
    CrossrefPubMedSearch in Google Scholar
  • 64 Palmerini T, Calabrò P, Piscione F , et al. Impact of gene polymorphisms, platelet reactivity, and the SYNTAX score on 1-year clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention: the GEPRESS study. JACC Cardiovasc Interv 2014; 7 (10) 1117-1127
    CrossrefPubMedSearch in Google Scholar
  • 65 Mangiacapra F, Ricottini E, Barbato E , et al. Incremental value of platelet reactivity over a risk score of clinical and procedural variables in predicting bleeding after percutaneous coronary intervention via the femoral approach: development and validation of a new bleeding risk score. Circ Cardiovasc Interv 2015; 8 (5) 8
    PubMedSearch in Google Scholar
  • 66 Trenk D, Stone GW, Gawaz M , et al. A randomized trial of prasugrel versus clopidogrel in patients with high platelet reactivity on clopidogrel after elective percutaneous coronary intervention with implantation of drug-eluting stents: results of the TRIGGER-PCI (Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel) study. J Am Coll Cardiol 2012; 59 (24) 2159-2164
    CrossrefPubMedSearch in Google Scholar
  • 67 Price MJ, Angiolillo DJ, Teirstein PS , et al. Platelet reactivity and cardiovascular outcomes after percutaneous coronary intervention: a time-dependent analysis of the Gauging Responsiveness with a VerifyNow P2Y12 assay: Impact on Thrombosis and Safety (GRAVITAS) trial. Circulation 2011; 124 (10) 1132-1137
    CrossrefPubMedSearch in Google Scholar
  • 68 Mayer K, Schulz S, Bernlochner I , et al. A comparative cohort study on personalised antiplatelet therapy in PCI-treated patients with high on-clopidogrel platelet reactivity. Results of the ISAR-HPR registry. Thromb Haemost 2014; 112 (2) 342-351
    Thieme ConnectPubMedSearch in Google Scholar
  • 69 Aradi D, Tornyos A, Pintér T , et al. Optimizing P2Y12 receptor inhibition in patients with acute coronary syndrome on the basis of platelet function testing: impact of prasugrel and high-dose clopidogrel. J Am Coll Cardiol 2014; 63 (11) 1061-1070
    CrossrefPubMedSearch in Google Scholar
  • 70 Siller-Matula JM, Francesconi M, Dechant C , et al. Personalized antiplatelet treatment after percutaneous coronary intervention: the MADONNA study. Int J Cardiol 2013; 167 (5) 2018-2023
    CrossrefPubMedSearch in Google Scholar
  • 71 Antman EM, Wiviott SD, Murphy SA , et al. Early and late benefits of prasugrel in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis. J Am Coll Cardiol 2008; 51 (21) 2028-2033
    CrossrefPubMedSearch in Google Scholar
  • 72 Roffi M, Patrono C, Collet JP , et al; Authors/Task Force M. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 2016; 14;37 (3) 267-315
    PubMedSearch in Google Scholar
  • 73 Bonello L, Paganelli F, Arpin-Bornet M , et al. Vasodilator-stimulated phosphoprotein phosphorylation analysis prior to percutaneous coronary intervention for exclusion of postprocedural major adverse cardiovascular events. J Thromb Haemost 2007; 5 (8) 1630-1636
    CrossrefPubMedSearch in Google Scholar
  • 74 Campo G, Fileti L, de Cesare N , et al; 3T/2R Investigators. Long-term clinical outcome based on aspirin and clopidogrel responsiveness status after elective percutaneous coronary intervention: a 3T/2R (tailoring treatment with tirofiban in patients showing resistance to aspirin and/or resistance to clopidogrel) trial substudy. J Am Coll Cardiol 2010; 56 (18) 1447-1455
    CrossrefPubMedSearch in Google Scholar
  • 75 Frere C, Cuisset T, Quilici J , et al. ADP-induced platelet aggregation and platelet reactivity index VASP are good predictive markers for clinical outcomes in non-ST elevation acute coronary syndrome. Thromb Haemost 2007; 98 (4) 838-843
    PubMedSearch in Google Scholar
  • 76 Gurbel PA, Antonino MJ, Bliden KP , et al. Platelet reactivity to adenosine diphosphate and long-term ischemic event occurrence following percutaneous coronary intervention: a potential antiplatelet therapeutic target. Platelets 2008; 19 (8) 595-604
    CrossrefPubMedSearch in Google Scholar
  • 77 Marcucci R, Gori AM, Paniccia R , et al. Cardiovascular death and nonfatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting are predicted by residual platelet reactivity to ADP detected by a point-of-care assay: a 12-month follow-up. Circulation 2009; 119 (2) 237-242
    CrossrefPubMedSearch in Google Scholar
  • 78 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 (8) 992-1000
    CrossrefPubMedSearch in Google Scholar
  • 79 Sibbing D, Bernlochner I, Schulz S , et al. Prognostic value of a high on-clopidogrel treatment platelet reactivity in bivalirudin versus abciximab treated non-ST-segment elevation myocardial infarction patients. ISAR-REACT 4 (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment-4) platelet substudy. J Am Coll Cardiol 2012; 60 (5) 369-377
    CrossrefPubMedSearch in Google Scholar
  • 80 Yamaguchi Y, Abe T, Sato Y, Matsubara Y, Moriki T, Murata M. Effects of VerifyNow P2Y12 test and CYP2C19*2 testing on clinical outcomes of patients with cardiovascular disease: a systematic review and meta-analysis. Platelets 2013; 24 (5) 352-361
    CrossrefPubMedSearch in Google Scholar
  • 81 Cuisset T, Cayla G, Frere C , et al. Predictive value of post-treatment platelet reactivity for occurrence of post-discharge bleeding after non-ST elevation acute coronary syndrome. Shifting from antiplatelet resistance to bleeding risk assessment?. EuroIntervention 2009; 5 (3) 325-329
    CrossrefPubMedSearch in Google Scholar
  • 82 Tsukahara K, Kimura K, Morita S , et al. Impact of high-responsiveness to dual antiplatelet therapy on bleeding complications in patients receiving drug-eluting stents. Circ J 2010; 74 (4) 679-685
    CrossrefPubMedSearch in Google Scholar
  • 83 Bonello L, Camoin-Jau L, Armero S , et al. Tailored clopidogrel loading dose according to platelet reactivity monitoring to prevent acute and subacute stent thrombosis. Am J Cardiol 2009; 103 (1) 5-10
    CrossrefPubMedSearch in Google Scholar
  • 84 Wang XD, Zhang DF, Zhuang SW, Lai Y. Modifying clopidogrel maintenance doses according to vasodilator-stimulated phosphoprotein phosphorylation index improves clinical outcome in patients with clopidogrel resistance. Clin Cardiol 2011; 34 (5) 332-338
    CrossrefPubMedSearch in Google Scholar
  • 85 Ari H, Ozkan H, Karacinar A, Ari S, Koca V, Bozat T. The EFFect of hIgh-dose ClopIdogrel treatmENT in patients with clopidogrel resistance (the EFFICIENT trial). Int J Cardiol 2012; 157 (3) 374-380
    CrossrefPubMedSearch in Google Scholar
  • 86 Hazarbasanov D, Velchev V, Finkov B , et al. Tailoring clopidogrel dose according to multiple electrode aggregometry decreases the rate of ischemic complications after percutaneous coronary intervention. J Thromb Thrombolysis 2012; 34 (1) 85-90
    CrossrefPubMedSearch in Google Scholar
  • 87 Mrdovic I, Savic L, Krljanac G , et al. Rationale and design of the on-treatment PLAtelet Reactivity-Guided Therapy Modification FOR ST-Segment Elevation Myocardial Infarction (PLATFORM) randomized trial. J Interv Cardiol 2013; 26 (3) 221-227
    CrossrefPubMedSearch in Google Scholar