High on-treatment platelet reactivity by more than one agonist predicts 12-month follow-up cardiovascular death and non-fatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting

Rossella Marcucci; Anna Maria Gori; Rita Paniccia; Betti Giusti; Serafina Valente; Cristina Giglioli; Piergiovanni Buonamici; David Antoniucci; Rosanna Abbate; Gian Franco Gensini

doi:10.1160/TH10-01-0007

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2010; 104(02): 279-286
DOI: 10.1160/TH10-01-0007

Platelets and Blood Cells

Schattauer GmbH

High on-treatment platelet reactivity by more than one agonist predicts 12-month follow-up cardiovascular death and non-fatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting

Rossella Marcucci

¹Department of Medical and Surgical Critical Care, University of Florence; Centre for the study at molecular and clinical level of chronic, degenerative and neoplastic diseases to develop novel therapies, University of Florence, Florence, Italy

³Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

,

Anna Maria Gori

¹Department of Medical and Surgical Critical Care, University of Florence; Centre for the study at molecular and clinical level of chronic, degenerative and neoplastic diseases to develop novel therapies, University of Florence, Florence, Italy

³Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

³Centro S.Maria agli Ulivi, Fondazione Don Carlo Gnocchi Onlus IRCCS, Impruneta, Florence, Italy

,

Rita Paniccia

¹Department of Medical and Surgical Critical Care, University of Florence; Centre for the study at molecular and clinical level of chronic, degenerative and neoplastic diseases to develop novel therapies, University of Florence, Florence, Italy

³Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

,

Betti Giusti

¹Department of Medical and Surgical Critical Care, University of Florence; Centre for the study at molecular and clinical level of chronic, degenerative and neoplastic diseases to develop novel therapies, University of Florence, Florence, Italy

³Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

,

Serafina Valente

³Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

,

Cristina Giglioli

³Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

,

Piergiovanni Buonamici

³Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

,

David Antoniucci

¹Department of Medical and Surgical Critical Care, University of Florence; Centre for the study at molecular and clinical level of chronic, degenerative and neoplastic diseases to develop novel therapies, University of Florence, Florence, Italy

,

Rosanna Abbate

¹Department of Medical and Surgical Critical Care, University of Florence; Centre for the study at molecular and clinical level of chronic, degenerative and neoplastic diseases to develop novel therapies, University of Florence, Florence, Italy

,

Gian Franco Gensini

¹Department of Medical and Surgical Critical Care, University of Florence; Centre for the study at molecular and clinical level of chronic, degenerative and neoplastic diseases to develop novel therapies, University of Florence, Florence, Italy

³Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

³Centro S.Maria agli Ulivi, Fondazione Don Carlo Gnocchi Onlus IRCCS, Impruneta, Florence, Italy

› Institutsangaben

Abstract

als PDF herunterladen

Summary

There is some data available on the role of high on-treatment platelet reactivity by ADP whereas, as regards arachidonic acid or other agonists, there is no proof of the best cut-off for identifying populations with a different cardiovascular outcome by the construction of appropriate receiver-operator characteristics (ROC) curves. We enrolled 1,108 acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI) with stent implantation and followed them up for 12 months. Platelet reactivity was assessed by light transmission aggregometry (LTA) using 10 μM ADP, 1 mM arachidonic acid (AA) and 2 μg/ml collagen. At a 12-month follow-up, we found 37 cardiovascular deaths (3.3%), 54 non-fatal myocardial infarctions (MI) (4.8%) and 154 target vessel revascularisations (TVR) (13.8%). ROC analysis demonstrated that 10 μM ADP LTA, 1 mM AA and 2 μg/ml collagen LTA were able to distinguish between patients with and without subsequent cardiovascular death and non-fatal MI (area under the curve for 10 μM ADP 0.63 (0.55–0.71), p<0.001; for 1 mM AA 0.68 (0.61–0.76), p<0.0001; for 2 μg/ml collagen 0.62 (0.52–0.73), p<0.0111), whereas no association was demonstrated with the occurrence of TVR. Ten μM ADP LTA ≥55%, 1 mM AA LTA ≥15% and 2 μg/ml collagen LTA ≥31% were identified as the optimal cut-off to predict cardiovascular death and non-fatal MI at 12-month follow-up. The contemporary platelet hyperreactivity to more than one agonist was associated with a higher risk of 12-month cardiovascular death and MI, whereas isolated platelet hyperreactivity to only one agonist had not a predictive value [10 μM ADP LTA ≥55% + 1 mM AA LTA ≥15%: odds ratio [OR]=3.6(2.4–6.1), p<0.0001; ADP LTA ≥55% + 1 mM AA LTA ≥15% + 2 μg/ml collagen LTA ≥31%: OR=4.7(2.9–7.7), p<0.0001]. In this prospective study on a large number of acute coronary syndrome patients undergoing stent implantation, we have found that high on-treatment platelet reactivity measured by LTA induced by more than one agonist – AA, ADP, collagen – is an independent risk factor for 12-month cardiovascular death and non-fatal MI. Isolated platelet hyperreactivity to only one agonist has not a predictive value for clinical recurrences.

Keywords

Acute myocardial infarction - aspirin resistance - atherothrombosis

PDF (925 kb)

Referenzen

References
1 Krasopoulos G, Brister SJ, Beattie WS. et al. Aspirin „resistance“ and risk of cardiovascular morbidity: systematic review and meta-analysis. Br Med J 2008; 336: 195-198.
2 Sofi F, Marcucci R, Gori AM. et al. Residual platelet reactivity on aspirin therapy and recurrent cardiovascular events – A meta-analysis. Int J Cardiol 2008; 128: 166-171.
3 Snoep JD, Hovens MM, Eikenboom JC. et al. Association of laboratory-defined aspirin resistance with a higher risk of recurrent cardiovascular events: a systematic review and meta-analysis. Arch Intern Med 2007; 167: 1593-1599.
4 Snoep JD, Hovens MM, Eikenboom JC. et al. Clopidogrel nonresponsiveness in patients undergoing percutaneous coronary intervention with stenting: a systematic review and meta-analysis. Am Heart J 2007; 154: 221-231.
5 Buonamici PG, Marcucci R, Migliorini A. et al. Impact of platelet reactivity after clopidogrel administration on drugeluting stent thrombosis. J Am Coll Cardiol 2007; 24: 2312-2317.
6 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.
7 Sibbing D, Braun S, Jawansky S. et al. Assessment of ADP-induced platelet aggregation with light transmission aggregometry and multiple electrode platelet aggregometry before and after clopidogrel treatment. Thromb Haemost 2008; 99: 121-126.
8 Aleil B, Ravanat C, Cazenave JP. et al. Flow cytometric analysis of intraplatelet VASP phosphorylation for the detection of clopidogrel resistance in patients with ischemic cardiovascular diseases. J Thromb Haemost 2005; 03: 85-92.
9 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.
10 Bonello L, Camoin-Jau L, Arques S. et al. Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel resistance: a multicenter randomized prospective study. J Am Coll Cardiol 2008; 51: 1404-1411.
11 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: 237-242.
12 Kuliczkowsi W, Witkowski A, Polonski L. et al. Interindividual variability in the response to oral antiplatelet drugs: a position apper of the Working Group on anti-platelet drugs resistance appointed by the Section of Cardiovacular Interventions of the Polish cardiac society, endorsed by the Working group on thrombosis of the European society of cardiology. Eur Heart J 2009; 30: 426-435.
13 Frelinger AL, Li Y, Linden MD. et al. Association of cyclooxigenase-1-dependent and –independent platelet function assays with adverse clinical outcomes in as-pirin-treated patients presenting for cardiac catheterization. Circulation 2009; 120: 2586-2596.
14 De Miguel Castro A, Cuellas Ramon C, Diego Nieto A. et al. Post treatment platelet reactivity predicts long term adverse events better han the response to clopidogrel in patients with non-ST-segment elevation acute coronary syndrome. Rev Esp Cardiol 2009; 62: 126-135.
15 Foussas SG, Zairis MN, Tsirimpis VG. et al. The impact of aspirin resistance on the long term cardiovascular mortality in patients with non-ST segment elevation acute coronary syndromes. Clin Cardiol 2009; 32: 142-147.
16 Geisler T, Grass D, Bigalke B. et al. The Residual platelet aggregation after deployment of intracoronary stent (PREDICT) score. J Thromb Haemost 2008; 06: 54-61.
17 Hobikoglu GF, Norgaz T, Aksu H. et al. The effect of acetylsalicylic acid resistance on prognosis of aptients who have developed acute coronary sindrome durino acetylsalicylic acid therapy. Can J Cardiol 2007; 23: 201-206.
18 Hovens MM, Snoep JD, Eikelboom JC. et al. Prevalence of persistent platelet reactivity despite use of aspirin: a systematic rview. Am Heart J 200 (153) 175-181.
19 Pamukcu B, Oflaz H, Oncul A. et al. The role of aspirin resistance on outcome in patients with acute coronary sindrome and the effect of clopidogrel therapy in the prevention of major cardiovascular events. J thromb Thrombolysis 2006; 22: 103-110.
20 2007 Focused Update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention. J Am Coll Cardiol 2008; 51: 172-209.
21 Paniccia R, Antonucci E, Gori AM. et al. Different methodologies for evaluating the effect of clopidogrel on platelet function in high-risk coronary artery disease patients. J Thromb Haemost 2007; 05: 1839-1847.
22 Shankar H, Garcia A, Prabhakar J. et al. P2Y12 receptor-mediated potentiation of thrombin-induced thromboxane A2 generation in platelets occurs through regulation of Erk1/2 activation. J Thromb Haemost 2006; 04: 638-647.
23 Andrè P, La Rocca T, Delaney SM. et al. Anticoagulants (thrombin inhibitors) and aspirin synergize with P2Y12 receptor antagonism in thrombosis. Circulation 2003; 108: 2697-2703.
24 Varga-Szabo D, Pleines I, Nieswandt B. Cell adhesion mechanisms in platelets. Arterioscler Thromb Vasc Biol 2008; 28: 403-412.
25 Wiviott SD, Braunwald E, McCabe CH. et al. TRITON-TIMI 38 Investigators.Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001-2015.
26 Angiolillo DJ, Shoemaker SB, Desai B. et al. Randomized comparison of a high clopidogrel maintenance dose in patients with diabetes mellitus and coronary artery disease: results of the optimizing Antiplatelet therapy in Diabetes Mellitus (OPTIMUS) study. Circulation 2007; 115: 708-716.
27 Jeong YH, Lee SW, Choi BR. et al. Randomized comparison of adjunctive cilostazol versus high maintenance dose clopidogrel in patients with high post-treatment platelet reactivity. J Am Coll Cardiol 2009; 53: 1101-1109.
28 Valgimigli M, Campo G, de Cesare N. et al. Tailoring treatment with tirofiban in patients showing resistance to aspirin and/or resistance to clopidogrel (3T/2R). Rationale for the study and protocol design. Cardiovasc Drugs Ther 2008; 22: 313-320.
29 Becker RC, Moliterno DJ, Jennings LK. et al. TRA-PCI investigators. Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: a randomized, double-bind, placebo-controlled phase II study. Lancet 2009; 373: 919-928.
30 Gori AM, Marcucci R, Migliorini A. et al. Incidence and clinical impact of dual nonresponsiveness to aspirin and clopidogrel in patients with drug-eluting stents. J Am Coll Cardiol 2008; 52: 734-739.