Residual platelet reactivity is an independent predictor of myocardial injury in acute myocardial infarction patients on antiaggregant therapy

 

 Buy Article Permissions and Reprints

Summary

In this study we sought to evaluate if platelet function measured after percutaneous coronary intervention (PCI) affects the severity of myocardial infarction (MI), measured by markers of cardiac necrosis. We measured platelet function by both a point-of-care assay (PFA-100) and platelet-rich plasma aggregation by two agonists (arachidonic acid –AA- and 2 and 10 μM ADP) in 367 patients with MI after PCI (200 patients on dual antiplatelet agents – group A- and 167 on dual antiplatelet agents plus GpIIb/ IIIa inhibitors – group B). One hundred twenty-one (32.9%) patients were found to have a residual platelet reactivity (RPR) by PFA (CT/EPI <203 sec): 74/200 (37%) in group A and 47/167 (28.1%) in group B (p=0.07). In 129 (35.1%) patients we found a RPR by AA-PA: 80/200 (40%) in group A and 49/167 (29.3%) in group B (p<0.05). Seventeen out of 367 (4.6%) were found to have a RPR by ADP2-PA [15/200 (7.5%) in group A and 2/167 (1.2%) in group B; p<0.005] and 88/367 (23.9%) by ADP10-PA [64/200 (32%) in group A and 24/167 (14.4%) in group B, p<0.0001]. CK-MB and cTnI mean peak values were significantly higher in the first tertile of CT/ADP and CT/EPI distribution with respect to the other tertiles and they were significantly higher in patients with RPR by CT/EPI in both groupA and group B patients. CK-MB and cTnI peak values were significantly higher in the third tertile of AA-PA,ADP 2 μM-PA and ADP 10 μM-PA distribution with respect to the other tertiles and were significantly higher in patients with RPR by AA-PA and by ADP 10-PA in both group A and group B patients. Multivariate analysis revealed platelet function as an independent predictor of CK-MB and cTnI peak values in both groups of patients independently of clinical, laboratory ad procedural parameters. In conclusion, we found that the severity of MI in patients with MI undergoing primary PCI is influenced by a persistent platelet activation on multiple antiplatelet therapy.

• References

• 1 Aukrust P, Muller F, Ueland T. et al. Enhanced levels of soluble and membrane-bound CD40 ligand in patients with unstable angina: possible reflection of T lymphocyte and platelet involvement in the pathogenesis of acute coronary syndromes.. Circulation 1999; 100: 314-320.
  PubMedGoogle Scholar
• 2 Ikeda H, Takajo Y, Ichiki K. et al. Increased soluble form of P-selectin in patients with unstable angina.. Circulation 1995; 92: 1693-1696.
  CrossrefPubMedGoogle Scholar
• 3 Ott I, Neumann FJ, Gawaz M. et al. Increased neutrophil- platelet adhesion in patients with unstable angina.. Circulation 1996; 94: 1239-1246.
  CrossrefPubMedGoogle Scholar
• 4 Sarma J, Laan CA, Alam S. et al. Increased platelet binding to cicrculating monocytes in acute coronary syndromes.. Circulation 2002; 105: 2166-2171.
  CrossrefPubMedGoogle Scholar
• 5 Yusuf S, Mehta SR, Zhao F. et al. Clopidogrel in unstable angina to prevent recurrent events trial investigators. Early and late effects of clopidogrel in patients with acute coronary syndromes.. Circulation 2003; 107: 966-972.
  CrossrefPubMedGoogle Scholar
• 6 Boersma E, Akkerhuis KM, Theroux P. et al. Platelet glycoprotein IIb/IIIa receptor inhibition in non- ST-elevation acute coronary syndromes: early benefit during medical treatment only, with additional protection during percutaneous coronary intervention.. Circulation 1999; 100: 2045-2048.
  CrossrefPubMedGoogle Scholar
• 7 Roffi M, Chew DP, Mukherjee D. et al. Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment elevation acute coronary syndromes.. Circulation 2001; 104: 2767-2771.
  CrossrefPubMedGoogle Scholar
• 8 ISIS-2 (second international study of infarct survival) Collaborative Group.. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2.. Lancet 1988; 332: 349-360.
  CrossrefPubMedGoogle Scholar
• 9 Keeley EC, Grines CL. Primary percutaneous coronary intervention for every patient with ST-segment elevation myocardial infarction: what stands in the way?. Ann Intern Med 2004; 141: 298-304.
  CrossrefPubMedGoogle Scholar
• 10 Frossard M, Fuchs I, Leitner J. et al. Platelet function predicts myocardial damage in patients with acute myocardial infarction.. Circulation 2004; 110: 1392-1397.
  CrossrefPubMedGoogle Scholar
• 11 Steinhubl SR, Charnigo R, Moliterno DJ. Resistance to antiplatelet resistance is it justified?. J Am Coll Cardiol 2005; 45: 1757-1758.
  CrossrefPubMedGoogle Scholar
• 12 Wiviott SD, Antman EM. Clopidogrel resistance: a new chapter in a fast-moving story.. Circulation 2004; 109: 3064-3067.
  CrossrefPubMedGoogle Scholar
• 13 Shantsila E, Watson T, Lip GY. Aspirin resistance: What, why and when?. Thromb Res 2007; 119: 551-554.
  CrossrefPubMedGoogle Scholar
• 14 Chen WH, Lee PY, Ng W. et al. Aspirin resistance is associated with a high incidence of myonecrosis after non-urgent percutaneous coronary interventions despite clopidogrel pre-treatment.. J Am Coll Cardiol 2004; 43: 1122-1126.
  CrossrefPubMedGoogle Scholar
• 15 Chobanian AV, Bakris GL, Black HR. et al. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.. Hypertension 2003; 42: 1206-1252.
  CrossrefPubMedGoogle Scholar
• 16 Third Report of the national cholesterol education program (NCEP) export panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult treatment panel III) final report.. Circulation 2002; 106: 3143-3172.
  CrossrefPubMedGoogle Scholar
• 17 Report of the expert committee on the diagnosis and classification of diabetes mellitus.. Diabetes Care 2003; 26 (01) S5-20.
  CrossrefPubMedGoogle Scholar
• 18 Borna C, Lazarowski E, van Heusden C. et al. Resistance to aspirin is increased by ST-elevation myocardial infarction and correlates with adenosine diphosphate levels.. Thromb J 2005; 26: 3-10.
  PubMedGoogle Scholar
• 19 Harrison P, Mackie I, Mathur A. et al. Platelet hyper-function in acute coronary syndromes.. Blood Coagul Fibrinolysis 2005; 16: 557-562.
  CrossrefPubMedGoogle Scholar
• 20 Rasmanins G, Vesterqvist O, Green K. et al. Effects of intermittent treatment with aspirin on thromboxane and prostacyclin formation in patients with acute myocardial infarction.. Lancet 1988; 2: 245-247.
  PubMedGoogle Scholar
• 21 Heper G, Bayraktaroglu M. The importance of von Willebrand factor level and heart rate changes in acute coronary syndromes: a comparison with chronic ischemic conditions.. Angiology 2003; 54: 27-99.
  PubMedGoogle Scholar
• 22 Haubelt H, Anders C, Vogt A. et al. Variables influencing platelet function analyzer-100 closure times in healthy individuals.. Br J Haematol 2005; 130: 759-797.
  CrossrefPubMedGoogle Scholar
• 23 Gum PA, Kottke-Marchant K, Welsh PA. et al. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease.. J Am Coll Cardiol 2003; 41: 961-965.
  CrossrefPubMedGoogle Scholar
• 24 Eikelboom JW, Hirsch J, Weitz JI. et al. Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events.. Circulation 2002; 105: 1650-1655.
  CrossrefPubMedGoogle Scholar
• 25 Grotemeyer KH, Scharafinski HW, Husstedt IW. Two-year follow up of aspirin responder and aspirin non responder. A pilot study including 180 post-stroke patients.. Thromb Res 1993; 71: 397-403.
  CrossrefPubMedGoogle Scholar
• 26 Chen WH, Lee PY, Ng W. et al. Relation of aspirin resistance to coronary flow reserve in patients undergoing elective percutaneous coronary intervention.. Am J Cardiol 2005; 96: 760-763.
  CrossrefPubMedGoogle Scholar
• 27 Wenaweser P, Dorffler-Melly J, Imboden K. et al. Stent thrombosis is associated with an impaired response to antiplatelet therapy.. J Am Coll Cardiol 2005; 45: 1748-1752.
  CrossrefPubMedGoogle Scholar
• 28 Ajzenberg N, Aubry P, Huisse MG. et al. Enhanced shear-induced platelet aggregation in patients who experience subacute stent thrombosis.. J Am Coll Cardiol 2005; 45: 1753-1756.
  CrossrefPubMedGoogle Scholar
• 29 Gurbel PA, Bliden KP, Hiatt BL. et al. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pre-treatment platelet reactivity.. Circulation 2003; 107: 2908-2913.
  CrossrefPubMedGoogle Scholar
• 30 Lepantalo A, Virtanen KS, Heikkila J. et al. Limited early antiplatelet effect of 300 mg clopidogrel in patients with aspirin therapy undergoing percutaneous coronary interventions.. Eur Heart J 2004; 25: 476-483.
  CrossrefPubMedGoogle Scholar
• 31 Samara WM, Bliden KP, Tantry US. et al. The difference between clopidogrel responsiveness and post-treatment platelet reactivity.. Thromb Res 2005; 115: 89-94.
  CrossrefPubMedGoogle Scholar
• 32 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.
  CrossrefPubMedGoogle Scholar
• 33 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.
  CrossrefPubMedGoogle Scholar
• 34 Gurbel PA, Bliden KP, Hayes KM. et al. The relation of dosing to clopidogrel responsiveness and the incidence of high post-treatment platelet aggregation in patients undergoing coronary stenting.. J Am Coll Cardiol 2005; 45: 1392-1396.
  CrossrefPubMedGoogle Scholar
• 35 Buonamici PG, Marcucci R, Migliorini A. et al. Impact of platelet reactivity following clopidogrel administration on drug-eluting stent thrombosis.. J Am Coll Cardiol. ; in press.
  PubMedGoogle Scholar
• 36 Barragan P, Bouvier JL, Roquebert PO. et al. Resistance to thienopyridines: clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation.. Catheter Cardiovasc Interv 2003; 59: 295-302.
  CrossrefPubMedGoogle Scholar
• 37 Matetzky S, Shenkman B, Guetta V. et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction.. Circulation 2004; 109: 3171-3175.
  CrossrefPubMedGoogle Scholar
• 38 Cuisset T, Frere C, Quilici J. et al. High post-treatment platelet reactivity identified low-responders to dual antiplatelet therapy at increased risk of recurrent cardiovascular events after stenting for acute coronary syndrome.. J Thromb Haemost 2006; 4: 542-549.
  CrossrefPubMedGoogle Scholar
• 39 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: 2420-2425.
  CrossrefPubMedGoogle Scholar
• 40 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.
  CrossrefPubMedGoogle Scholar
• 41 Prisco D, Antonucci E, Fedi S. et al. D-dimer increase after percutaneous transluminal angioplasty and clinical recurrence after primary revascularization in acute myocardial infarction. A pilot study.. Clin Exp Med 2001; 1: 219-224.
  CrossrefPubMedGoogle Scholar
• 42 Andreotti F, Lefroy DC, Sciahbasi A. et al. Platelet and thrombin activity following cardiac catheterization despite treatment with aspirin.. J Thromb Thrombolysis 1998; 6: 141-145.
  CrossrefPubMedGoogle Scholar
• 43 Fischetti D, Sciahbasi A, Leone AM. et al. Ticlopidine and aspirin fail to suppress the increased platelet aggregability that follows percutaneous coronary interventions.. J Thromb Thrombolysis 2000; 10: 265-269.
  CrossrefPubMedGoogle Scholar
• 44 Patel P, Gonzales R, Dokainish H, Lakkis N. Impact of adenosine diphosphate and calcium chelation on platelet aggregation testing in patients receiving clopidogrel therapy.. J Am Coll Cardiol 2006; 47: 465.
  CrossrefPubMedGoogle Scholar