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Thromb Haemost 2018; 118(02): 415-426
DOI: 10.1160/TH17-08-0564
Atherosclerosis and Ischaemic Disease
Schattauer GmbH Stuttgart

Prognostic Implications of Dual Platelet Reactivity Testing in Acute Coronary Syndrome

Leonardo P. de Carvalho
,
Alan Fong
,
Richard Troughton
,
Bryan P. Yan
,
Chee-Tang Chin
,
Sock-Cheng Poh
,
Melissa Mejin
,
Nancy Huang
,
Aruni Seneviratna
,
Chi-Hang Lee
,
Adrian F. Low
,
Huay-Cheem Tan
,
Siew-Pang Chan
,
Christopher Frampton
,
A. Mark Richards
,
Mark Y. Chan
 Funding Sources The study was funded by the National Medical Research Council of Singapore (NMRC/CSA/028/2010) with platelet reactivity analysers and test kits supplied by Roche Diagnostics (Basel Switzerland). Both sponsors had no role in the study design, site selection, data collection, data analysis or data interpretation.
Further Information

Publication History

16 August 2017

16 November 2017

Publication Date:
29 January 2018 (online)

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Abstract

Studies on platelet reactivity (PR) testing commonly test PR only after percutaneous coronary intervention (PCI) has been performed. There are few data on pre- and post-PCI testing. Data on simultaneous testing of aspirin and adenosine diphosphate antagonist response are conflicting. We investigated the prognostic value of combined serial assessments of high on-aspirin PR (HASPR) and high on-adenosine diphosphate receptor antagonist PR (HADPR) in patients with acute coronary syndrome (ACS). HASPR and HADPR were assessed in 928 ACS patients before (initial test) and 24 hours after (final test) coronary angiography, with or without revascularization. Patients with HASPR on the initial test, compared with those without, had significantly higher intraprocedural thrombotic events (IPTE) (8.6 vs. 1.2%, p ≤ 0.001) and higher 30-day major adverse cardiovascular and cerebrovascular events (MACCE; 5.2 vs. 2.3%, p = 0.05), but not 12-month MACCE (13.0 vs. 15.1%, p = 0.50). Patients with initial HADPR, compared with those without, had significantly higher IPTE (4.4 vs. 0.9%, p = 0.004), but not 30-day (3.5 vs. 2.3%, p = 0.32) or 12-month MACCE (14.0 vs. 12.5%, p = 0.54). The c-statistic of the Global Registry of Acute Coronary Events (GRACE) score alone, GRACE score + ASPR test and GRACE score + ADPR test for discriminating 30-day MACCE was 0.649, 0.803 and 0.757, respectively. Final ADPR was associated with 30-day MACCE among patients with intermediate-to-high GRACE score (adjusted odds ratio [OR]: 4.50, 95% confidence interval [CI]: 1.14–17.66), but not low GRACE score (adjusted OR: 1.19, 95% CI: 0.13–10.79). In conclusion, both HASPR and HADPR predict ischaemic events in ACS. This predictive utility is time-dependent and risk-dependent.

Keywords

antiplatelet therapy - acute coronary syndrome - thrombosis

Supplementary Material

 

  • References

  • 1 McEntegart MB, Kirtane AJ, Cristea E. , et al. Intraprocedural thrombotic events during percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes are associated with adverse outcomes: analysis from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial. J Am Coll Cardiol 2012; 59 (20) 1745-1751
    CrossrefPubMedGoogle Scholar
  • 2 Kirtane AJ, Sandhu P, Mehran R. , et al. Association between intraprocedural thrombotic events and adverse outcomes after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (a Harmonizing Outcomes With RevasculariZatiON and Stents in Acute Myocardial Infarction [HORIZONS-AMI] Substudy). Am J Cardiol 2014; 113 (01) 36-43
    CrossrefPubMedGoogle Scholar
  • 3 Thune JJ, Signorovitch JE, Kober L. , et al. Predictors and prognostic impact of recurrent myocardial infarction in patients with left ventricular dysfunction, heart failure, or both following a first myocardial infarction. Eur J Heart Fail 2011; 13 (02) 148-153
    CrossrefPubMedGoogle Scholar
  • 4 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
    CrossrefPubMedGoogle Scholar
  • 5 James S, Akerblom A, Cannon CP. , et al. Comparison of ticagrelor, the first reversible oral P2Y(12) receptor antagonist, with clopidogrel in patients with acute coronary syndromes: rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial. Am Heart J 2009; 157 (04) 599-605
    CrossrefPubMedGoogle Scholar
  • 6 Roe MT, Armstrong PW, Fox KA. , et al; TRILOGY ACS Investigators. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med 2012; 367 (14) 1297-1309
    CrossrefPubMedGoogle Scholar
  • 7 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
    CrossrefPubMedGoogle Scholar
  • 8 Bagai A, Peterson ED, McCoy LA. , et al. Association of measured platelet reactivity with changes in P2Y12 receptor inhibitor therapy and outcomes after myocardial infarction: Insights into routine clinical practice from the TReatment with ADP receptor iNhibitorS: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) study. Am Heart J 2017; 187: 19-28
    CrossrefPubMedGoogle Scholar
  • 9 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
    CrossrefPubMedGoogle Scholar
  • 10 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
    CrossrefPubMedGoogle Scholar
  • 11 Yong G, Rankin J, Ferguson L. , et al. Randomized trial comparing 600- with 300-mg loading dose of clopidogrel in patients with non-ST elevation acute coronary syndrome undergoing percutaneous coronary intervention: results of the Platelet Responsiveness to Aspirin and Clopidogrel and Troponin Increment after Coronary intervention in Acute coronary Lesions (PRACTICAL) Trial. Am Heart J 2009; 157 (01) 60.e1-60.e9
    CrossrefPubMedGoogle Scholar
  • 12 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 (09) 863-871
    CrossrefPubMedGoogle Scholar
  • 13 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
    CrossrefPubMedGoogle Scholar
  • 14 Cattaneo M. Mechanisms of variability in antiplatelet agents response. Thromb Res 2012; 130 (Suppl. 01) S27-S28
    CrossrefPubMedGoogle Scholar
  • 15 Breet NJ, van Werkum JW, Bouman HJ. , et al. High on-treatment platelet reactivity to both aspirin and clopidogrel is associated with the highest risk of adverse events following percutaneous coronary intervention. Heart 2011; 97 (12) 983-990
    CrossrefPubMedGoogle Scholar
  • 16 Peace AJ, Tedesco AF, Foley DP, Dicker P, Berndt MC, Kenny D. Dual antiplatelet therapy unmasks distinct platelet reactivity in patients with coronary artery disease. J Thromb Haemost 2008; 6 (12) 2027-2034
    CrossrefPubMedGoogle Scholar
  • 17 Thygesen K, Alpert JS, Jaffe AS. , et al; Joint ESC/ACCF/AHA/WHF Task Force for Universal Definition of Myocardial Infarction; Authors/Task Force Members Chairpersons; Biomarker Subcommittee; ECG Subcommittee; Imaging Subcommittee; Classification Subcommittee; Intervention Subcommittee; Trials & Registries Subcommittee; Trials & Registries Subcommittee; Trials & Registries Subcommittee; Trials & Registries Subcommittee; ESC Committee for Practice Guidelines (CPG); Document Reviewers. Third universal definition of myocardial infarction. J Am Coll Cardiol 2012; 60 (16) 1581-1598
    CrossrefPubMedGoogle Scholar
  • 18 Taylor J. 2012 ESC Guidelines on acute myocardial infarction (STEMI). Eur Heart J 2012; 33 (20) 2501-2502
    CrossrefPubMedGoogle Scholar
  • 19 Amsterdam EA, Wenger NK, Brindis RG. , et al; ACC/AHA Task Force Members. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 130 (25) e344-e426
    CrossrefPubMedGoogle Scholar
  • 20 Smith Jr SC, Feldman TE, Hirshfeld Jr JW. , et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention. ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to update the 2001 Guidelines for Percutaneous Coronary Intervention). Catheter Cardiovasc Interv 2006; 67 (01) 87-112
    CrossrefPubMedGoogle Scholar
  • 21 von Pape KW, Dzijan-Horn M, Bohner J, Spannagl M, Weisser H, Calatzis A. Control of aspirin effect in chronic cardiovascular patients using two whole blood platelet function assays. PFA-100 and Multiplate [in German]. Hamostaseologie 2007; 27 (03) 155-160 , quiz 161–162
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Sibbing D, Morath T, Braun S. , et al. Clopidogrel response status assessed with Multiplate point-of-care analysis and the incidence and timing of stent thrombosis over six months following coronary stenting. Thromb Haemost 2010; 103 (01) 151-159
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 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
    CrossrefPubMedGoogle Scholar
  • 24 Park Y, Jeong YH, Kim IS. , et al. The concordance and correlation of measurements by multiple electrode and light transmittance aggregometries based on the pre-defined cutoffs of high and low on-treatment platelet reactivity. Platelets 2012; 23 (04) 290-298
    CrossrefPubMedGoogle Scholar
  • 25 Al-Azzam SI, Alzoubi KH, Khabour O, Alowidi A, Tawalbeh D. The prevalence and factors associated with aspirin resistance in patients premedicated with aspirin. Acta Cardiol 2012; 67 (04) 445-448
    CrossrefPubMedGoogle Scholar
  • 26 Chan MY, Shah BR, Gao F. , et al. Recalibration of the Global Registry of Acute Coronary Events risk score in a multiethnic Asian population. Am Heart J 2011; 162 (02) 291-299
    CrossrefPubMedGoogle Scholar
  • 27 Hamm CW, Bassand JP, Agewall S. , et al; ESC Committee for Practice Guidelines. 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 (23) 2999-3054
    CrossrefPubMedGoogle Scholar
  • 28 Roe MT, Messenger JC, Weintraub WS. , et al. Treatments, trends, and outcomes of acute myocardial infarction and percutaneous coronary intervention. J Am Coll Cardiol 2010; 56 (04) 254-263
    CrossrefPubMedGoogle Scholar
  • 29 Wessler JD, Généreux P, Mehran R. , et al. Which intraprocedural thrombotic events impact clinical outcomes after percutaneous coronary intervention in acute coronary syndromes? A pooled analysis of the HORIZONS-AMI and ACUITY trials. JACC Cardiovasc Interv 2016; 9 (04) 331-337
    CrossrefPubMedGoogle Scholar
  • 30 McManus DD, Gore J, Yarzebski J, Spencer F, Lessard D, Goldberg RJ. Recent trends in the incidence, treatment, and outcomes of patients with STEMI and NSTEMI. Am J Med 2011; 124 (01) 40-47
    CrossrefPubMedGoogle Scholar
  • 31 D'Ascenzo F, Barbero U, Bisi M. , et al. The prognostic impact of high on-treatment platelet reactivity with aspirin or ADP receptor antagonists: systematic review and meta-analysis. BioMed Res Int 2014; 2014: 610296
    PubMedGoogle Scholar
  • 32 Zocca P, van der Heijden LC, Kok MM, Lowik MM, Hartmann M, Stoel MG. , et al. Clopidogrel or ticagrelor in acute coronary syndrome patients treated with newer-generation drug-eluting stents: CHANGE DAPT. EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. 2017; Nov 20; 13 (10) 1168-1176 . PubMed PMID: 29151439.
    PubMedGoogle Scholar
  • 33 Cuisset T, Deharo P, Quilici J. , et al. Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study. Eur Heart J 2017; 38 (41) 3070-3078
    CrossrefPubMedGoogle Scholar
  • 34 Sibbing D, Aradi D, Jacobshagen C. , et al; TROPICAL-ACS Investigators. A randomised trial on platelet function-guided de-escalation of antiplatelet treatment in ACS patients undergoing PCI. Rationale and design of the Testing Responsiveness to Platelet Inhibition on Chronic Antiplatelet Treatment for Acute Coronary Syndromes (TROPICAL-ACS) Trial. Thromb Haemost 2017; 117 (01) 188-195
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Harrison RW, Aggarwal A, Ou FS. , et al; American College of Cardiology National Cardiovascular Data Registry. Incidence and outcomes of no-reflow phenomenon during percutaneous coronary intervention among patients with acute myocardial infarction. Am J Cardiol 2013; 111 (02) 178-184
    CrossrefPubMedGoogle Scholar
  • 36 Généreux P, Stone GW, Harrington RA. , et al; CHAMPION PHOENIX Investigators. Impact of intraprocedural stent thrombosis during percutaneous coronary intervention: insights from the CHAMPION PHOENIX Trial (Clinical Trial Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention). J Am Coll Cardiol 2014; 63 (07) 619-629
    CrossrefPubMedGoogle Scholar
  • 37 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 (04) 209-215
    CrossrefPubMedGoogle Scholar
  • 38 Chan MY, Du X, Eccleston D. , et al. Acute coronary syndrome in the Asia-Pacific region. Int J Cardiol 2016; 202: 861-869
    CrossrefPubMedGoogle Scholar
  • 39 Masoudi FA, Ponirakis A, Yeh RW. , et al. Cardiovascular care facts: a report from the national cardiovascular data registry: 2011. J Am Coll Cardiol 2013; 62 (21) 1931-1947
    CrossrefPubMedGoogle Scholar
  • 40 Roe MT, White JA, Kaul P. , et al. Regional patterns of use of a medical management strategy for patients with non-ST-segment elevation acute coronary syndromes: insights from the EARLY ACS Trial. Circ Cardiovasc Qual Outcomes 2012; 5 (02) 205-213
    CrossrefPubMedGoogle Scholar
  • 41 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-eluting stent implantation. J Am Coll Cardiol 2011; 58 (25) 2630-2639
    CrossrefPubMedGoogle Scholar
  • 42 Chan MY, Mahaffey KW, Sun LJ. , et al. Prevalence, predictors, and impact of conservative medical management for patients with non-ST-segment elevation acute coronary syndromes who have angiographically documented significant coronary disease. JACC Cardiovasc Interv 2008; 1 (04) 369-378
    CrossrefPubMedGoogle Scholar