Platelet function testing in acute cardiac care – is there a role for prediction or prevention of stent thrombosis and bleeding?

Dániel Aradi; Jean-Philippe Collet; Johannes Mair; Mario Plebani; Béla Merkely; Allan S. Jaffe; Martin Möckel; Evangelos Giannitsis; Kristian Thygesen; Jurrien M. ten Berg; Christian Mueller; Robert F. Storey; Bertil Lindahl; Kurt Huber

doi:10.1160/TH14-05-0449

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2015; 113(02): 221-230
DOI: 10.1160/TH14-05-0449

Current Opinion

Schattauer GmbH

Platelet function testing in acute cardiac care – is there a role for prediction or prevention of stent thrombosis and bleeding?

Dániel Aradi

¹Department of Cardiology, Heart Center Balatonfüred, Hungary

⁵Heart and Vascular Center, Semmelweis University, Budapest, Hungary

,

Jean-Philippe Collet

²ACTION Study Group-Institut de Cardiologie – INSERM UMRS-ICAN 1166 Groupe Hospitalier Pitié-Salpêtrière, Paris, France

,

Johannes Mair

³Department of Internal Medicine III – Cardiology and Angiology, Innsbruck Medical University, Innsbruck, Austria

,

Mario Plebani

⁴Department of Laboratory Medicine, University_Hospital, Padova, Italy

,

Béla Merkely

⁵Heart and Vascular Center, Semmelweis University, Budapest, Hungary

,

Allan S. Jaffe

⁶Division of Cardiovascular Diseases, Department of Medicine and Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA

,

Martin Möckel

⁷Emergency Medicine and Chest Pain Units, Campus Virchow-Klinikum und Campus Mitte Charité – Universittsmedizin Berlin, Germany

,

Evangelos Giannitsis

⁸8Department of Internal Medicine III – University of Heidelberg, Germany

,

Kristian Thygesen

⁹Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark

,

Jurrien M. ten Berg

¹⁰Department of Cardiology and Center of Platelet Function Research, St Antonius Hospital, Nieuwegein, the Netherlands;

,

Christian Mueller

¹¹Department of Cardiology and Cardiovascular Research Institute Basel, University Hospital Basel, Switzerland

,

Robert F. Storey

¹²Department of Cardiovascular Science, University of Sheffield, Sheffield, UK

,

Bertil Lindahl

¹³Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Sweden

,

Kurt Huber

¹⁴3^rd Department of Medicine, Cardiology and Intensive Care, Wilhelminenhospital, Vienna, Austria

› Author Affiliations

Abstract

Summary

The role of platelet function testing in acute coronary syndrome patients undergoing percutaneous coronary intervention remains controversial despite the fact that high platelet reactivity is an independent predictor of stent thrombosis and emerging evidence suggests also a link between low platelet reactivity and bleeding. In this expert opinion paper, the Study Group on Biomarkers in Cardiology of the Acute Cardiovascular Care Association and the Working Group on Thrombosis of the European Society of Cardiology aim to provide an overview of current evidence in this area and recommendations for practicing clinicians.

Keywords

Antiplatelet agents - platelet pharmacology - acute myocardial infarction

Full Text

References

References
1 Steg PG, James SK, Atar D. et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33: 2569-2619.
2 Hamm CW, Bassand JP, Agewall S. et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2011; 32: 2999-3054.
3 Aradi D, Storey RF, Komocsi A. et al. Expert position paper on the role of platelet function testing in patients undergoing percutaneous coronary intervention. Eur Heart J 2014; 35: 209-215.
4 Aradi D, Komócsi A, Vorobcsuk A. et al. Impact of clopidogrel and potent P2Y 12 -inhibitors on mortality and stroke in patients with acute coronary syndrome or undergoing percutaneous coronary intervention: a systematic review and meta-analysis. Thrombosis and haemostasis 2013; 109: 93-101.
5 Wiviott SD, Braunwald E, McCabe CH. et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001-2015.
6 Wallentin L, Becker RC, Budaj A. et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045-1057.
7 Mehta S, Yusuf S, Peters R. et al. 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: 527-533.
8 Steg PG, Bhatt DL, Hamm CW. et al. Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patientlevel data. Lancet 2013; 382: 1981-1992.
9 Tantry US, Bonello L, Aradi D. et al. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with is-chaemia and bleeding. J Am Coll Cardiol 2013; 62: 2261-2273.
10 Montalescot G, Sechtem U, Achenbach S. et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013; 34: 2949-3003.
11 Davi G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007; 357: 2482-2494.
12 Gurbel PA, Bliden KP, DiChiara J. et al. Evaluation of dose-related effects of aspirin on platelet function: results from the Aspirin-Induced Platelet Effect (ASPECT) study. Circulation 2007; 115: 3156-3164.
13 Kovacs 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: 320-324.
14 Kovacs EG, Katona E, Bereczky Z. et al. Evaluation of laboratory methods routinely used to detect the effect of aspirin against new reference methods. Thromb Res 2014; 133: 811-816.
15 Stone GW, Witzenbichler B, Weisz G. et al. Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study. Lancet 2013; 382: 614-623.
16 Mehta SR, Bassand JP, Chrolavicius S. et al. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med 2010; 363: 930-942.
17 Sumaya W, Daly RL, Mehra S. et al. Hirudin anticoagulation allows more rapid determination of P2Y(1)(2) inhibition by the VerifyNow P2Y12 assay. Thromb Haemost 2013; 109: 550-555.
18 Sumaya W, Joshi RR, Judge HM. et al. Stability of VerifyNow P2Y12 assay results with citrate anticoagulation as compared to hirudin anticoagulation over 20-min period. Platelets. 2014 Epub ahead of print.
19 Hubner U, Bockel-Frohnhofer N, Hummel B. et al. The effect of a pneumatic tube transport system on platelet aggregation using optical aggregometry and the PFA-100. Clin Lab 2010; 56: 59-64.
20 Johnston LR, Larsen PD, La Flamme AC. et al. Methodological considerations for the assessment of ADP induced platelet aggregation using the Multiplate(R) analyser. Platelets 2013; 24: 303-307.
21 Jeong YH, Bliden KP, Tantry US. et al. High on-treatment platelet reactivity assessed by various platelet function tests: is the consensus-defined cut-off of VASP-P platelet reactivity index too low?. J Thromb Haemost 2012; 10: 487-489.
22 Lordkipanidzé M, Pharand C, Nguyen T. et al. Comparison of four tests to assess inhibition of platelet function by clopidogrel in stable coronary artery disease patients. Eur Heart J 2008; 29: 2877-2885.
23 Breet NJ, van Werkum JW, Bouman HJ. et al. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. J Am Med Assoc 2010; 303: 754-762.
24 Siller-Matula JM, Delle-Karth G, Lang IM. et al. Phenotyping vs genotyping for prediction of clopidogrel efficacy and safety: the PEGASUS-PCI study. J Thromb Haemost 2012; 10: 529-542.
25 Freynhofer MK, Brozovic I, Bruno V. et al. Multiple electrode aggregometry and vasodilator stimulated phosphoprotein-phosphorylation assay in clinical routine for prediction of postprocedural major adverse cardiovascular events. Thromb Haemost 2011; 106: 230-239.
26 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: 1078-1082.
27 Keller T, Zeller T, Peetz D. et al. Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med 2009; 361: 868-877.
28 Hijazi Z, Oldgren J, Siegbahn A. et al. Biomarkers in atrial fibrillation: a clinical review. Eur Heart J 2013; 34: 1475-1480.
29 Dahlen JR, Price MJ, Parise H. et al. Evaluating the clinical usefulness of platelet function testing: Considerations for the proper application and interpretation of performance measures. Thromb Haemost 2013; 109: 808-816.
30 Airoldi F, Colombo A, Morici N. et al. Incidence and predictors of drug-eluting stent thrombosis during and after discontinuation of thienopyridine treatment. Circulation 2007; 116: 745-754.
31 Brodie B, Pokharel Y, Garg A. et al. Predictors of early, late, and very late stent thrombosis after primary percutaneous coronary intervention with bare-metal and drug-eluting stents for ST-segment elevation myocardial infarction. JACC Cardiovasc Interv 2012; 05: 1043-1051.
32 Cayla G, Hulot JS, O’Connor SA. et al. Clinical, angiographic, and genetic factors associated with early coronary stent thrombosis. . J Am Med Assoc 2011; 306: 1765-1774.
33 Aradi D, Komocsi 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: 543-551.
34 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: 1945-1954.
35 Combescure C, Fontana P, Mallouk N. et al. Clinical implications of clopidogrel non-response in cardiovascular patients: a systematic review and meta-analysis. J Thromb Haemost 2010; 08: 923-933.
36 Sofi F, Marcucci R, Gori AM. et al. Clopidogrel non-responsiveness and risk of cardiovascular morbidity. An updated meta-analysis. Thromb Haemost 2010; 103: 841-848.
37 Kirtane AJ, Rinaldi M, Parise H. et al. Impact of Point-of-Care Platelet Function Testing among Patients with and without Acute Coronary Syndromes Undergoing Pci with Drug-Eluting Stents: An Adapt-Des Substudy. J Am Coll Cardiol 2012; 59: E291.
38 Gurbel P, Erlinge D, Ohman E. et al. Platelet function during extended prasugrel and clopidogrel therapy for patients with ACS treated without revascularisation: the TRILOGY ACS platelet function substudy. . J Am Med Assoc 2012; 308: 1785-1794.
39 Gurbel P, Bliden K, Butler K. et al. Response to ticagrelor in clopidogrel nonre-sponders and responders and effect of switching therapies: the RESPOND study. Circulation 2010; 121: 1188-1199.
40 Wiviott S, Trenk D, Frelinger A. et al. 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: 2923-2932.
41 Bonello L, Pansieri M, Mancini J. et al. High on-treatment platelet reactivity after prasugrel loading dose and cardiovascular events after percutaneous coronary intervention in acute coronary syndromes. J Am Coll Cardiol 2011; 58: 467-473.
42 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.
43 Price M, Angiolillo D, Teirstein P. 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: 1132-1137.
44 Schulz S, Sibbing D, Braun S. et al. Platelet response to clopidogrel and restenosis in patients treated predominantly with drug-eluting stents. Am Heart J 2010; 160: 355-361.
45 Aradi D, Tornyos A, Pinter T. et al. Optimizing P2Y-receptor inhibition in acute coronary syndrome patients based on platelet function testing: impact of prasu-grel and high-dose clopidogrel. J Am Coll Cardiol. 2014 Epub ahead of print.
46 Blindt R, Stellbrink K, de Taeye A. et al. The significance of vasodilator-stimulated phosphoprotein for risk stratification of stent thrombosis. Thromb Hae-most 2007; 98: 1329-1334.
47 Bonello L, Paganelli F, Arpin-Bornet M. et al. Vasodilator-stimulated phospho-protein phosphorylation analysis prior to percutaneous coronary intervention for exclusion of postprocedural major adverse cardiovascular events. J Thromb Haemost 2007; 05: 1630-1636.
48 El Ghannudi S, Ohlmann P, Meyer N. et al. Impact of P2Y12 inhibition by clopi-dogrel on cardiovascular mortality in unselected patients treated by percutaneous coronary angioplasty: a prospective registry. JACC Cardiovasc Interv 2010; 03: 648-656.
49 Steg PG, Huber K, Andreotti F. et al. Bleeding in acute coronary syndromes and percutaneous coronary interventions: position paper by the Working Group on Thrombosis of the European Society of Cardiology. Eur Heart J 2011; 32: 1854-1864.
50 Sibbing D, Schulz S, Braun S. et al. Antiplatelet effects of clopidogrel and bleeding in patients undergoing coronary stent placement. J Thromb Haemost 2010; 08: 250-256.
51 Campo G, Parrinello G, Ferraresi P. et al. Prospective evaluation of on-clopido-grel platelet reactivity over time in patients treated with percutaneous coronary intervention relationship with gene polymorphisms and clinical outcome. J Am Coll Cardiol 2011; 57: 2474-2483.
52 Cuisset T, Grosdidier C, Loundou AD. et al. Clinical Implications of Very Low On-Treatment Platelet Reactivity in Patients Treated With Thienopyridine. JACC: Cardiovasc Interv 2013; 06: 854-863.
53 Bonello L, Mancini J, Pansieri M. et al. Relationship between post-treatment platelet reactivity and ischaemic and bleeding events at 1-year follow-up in patients receiving prasugrel. J Thromb Haemost 2012; 10: 1999-2005.
54 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; 05: 281-289.
55 Park DW, Lee SW, Yun SC. et al. A point-of-care platelet function assay and C-reactive protein for prediction of major cardiovascular events after drug-elut-ing stent implantation. J Am Coll Cardiol 2011; 58: 2630-2639.
56 Alexopoulos D, Xanthopoulou I, Gkizas V. et al. Randomized assessment of ti-cagrelor versus prasugrel antiplatelet effects in patients with ST-segment-elev-ation myocardial infarction. JACC Cardiovasc Interv 2012; 05: 797-804.
57 Kirtane AJ, Stuckey T, Xu K. et al. Is There a Therapeutic Window For Platelet Responsiveness Among PCI Patients? Analysis from the ADAPT-DES Study. J Am Coll Cardiol 2013; 62: B48-49..
58 Kerneis M, Silvain J, Abtan J. et al. Switching acute coronary syndrome patients from prasugrel to clopidogrel. JACC Cardiovasc Interv 2013; 06: 158-165.
59 Price MJ, Berger PB, Teirstein PS. et al. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. J Am Med Assoc 2011; 305: 1097-1105.
60 Collet JP, Cuisset T, Range G. et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 2012; 367: 2100-2109.
61 Aradi D, Komocsi A, Price MJ. et al. Efficacy and safety of intensified antipla-telet therapy on the basis of platelet reactivity testing in patients after percutaneous coronary intervention: systematic review and meta-analysis. Int J Car-diol 2013; 167: 2140-2148.
62 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: 2159-2164.
63 Siller-Matula JM, Francesconi M, Dechant C. et al. Personalized antiplatelet treatment after percutaneous coronary intervention: the MADONNA study. Int J Cardiol 2013; 167: 2018-2023.
64 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: 342-351.
65 Mahla E, Suarez TA, Bliden KP. et al. Platelet function measurement-based strategy to reduce bleeding and waiting time in clopidogrel-treated patients undergoing coronary artery bypass graft surgery: the timing based on platelet function strategy to reduce clopidogrel-associated bleeding related to CABG (TARGET-CABG) study. JACC Cardiovasc Interv 2012; 05: 261-269.
66 Ferraris VA, Saha SP, Oestreich JH. et al. 2012 update to the Society of Thoracic Surgeons guideline on use of antiplatelet drugs in patients having cardiac and noncardiac operations. Ann Thoracic Surg 2012; 94: 1761-1781.
67 Sousa-Uva M, Storey R, Huber K. et al. Expert position paper on the management of antiplatelet therapy in patients undergoing coronary artery bypass graft surgery. Eur Heart J 2014; 35: 1510-1514.
68 Straub N, Beivers A, Lenk E. et al. A model-based analysis of the clinical and economic impact of personalising P2Y12-receptor inhibition with platelet function testing in acute coronary syndrome patients. Thromb Haemost 2014; 111: 290-299.
69 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. J Am Med Assoc 2011; 306: 1215-1223.
70 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: 849-856.
71 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: 838-843.