Skip to main content
Erschienen in: Clinical Research in Cardiology 12/2014

01.12.2014 | Original Paper

A high ratio of ADP–TRAP induced platelet aggregation is associated more strongly with increased mortality after coronary stent implantation than high conventional ADP induced aggregation alone

verfasst von: Christoph B. Olivier, Katharina Schnabel, Christoph Brandt, Patrick Weik, Manfred Olschewski, Qian Zhou, Christoph Bode, Philipp Diehl, Martin Moser

Erschienen in: Clinical Research in Cardiology | Ausgabe 12/2014

Einloggen, um Zugang zu erhalten

Abstract

Objective

This study aimed to evaluate whether a high relative ADP induced aggregation (r-ADP-agg) is associated with an increased mortality in patients after coronary stent implantation.

Background

Several trials were not able to improve clinical outcome by adapting platelet inhibition in patients after coronary stent implantation and high platelet reactivity (HPR). Platelet monitoring is complex and conventional definition of adenosindiphosphate (ADP) induced aggregation alone might not transfer the whole picture of adequate platelet inhibition in vivo.

Methods

In a prospective single-centre observational trial multiple electrode aggregometry was performed in whole blood of patients after stent implantation. r-ADP-agg was defined as the ADP–thrombin receptor activating peptide ratio to reflect an individual degree of P2Y12 dependent platelet inhibition with a cut-off value for HPR of ≥50 %. The primary end point was mortality.

Results

Follow-up was completed in 176 of 184 patients (96 %) with a mean follow-up time of 3.7 years. 35 (20 %) patients revealed an r-ADP-agg ≥50 %. An r-ADP-agg ≥50 % was associated with an increased mortality [unadjusted hazard ratio (HR) 7.006 (2.561–19.17); p = 0.0001]. In a multivariable Cox regression analysis mortality was independently associated with an r-ADP-agg ≥50 % [HR 3.324 (1.542–7.165); p = 0.0022], ACS-setting [HR 3.249 (1.322–7.989); p = 0.0102] and severely reduced LV function [HR 5.463 (2.098–14.26); p = 0.0005].

Conclusion

An r-ADP-agg ≥50 % is associated with an increased mortality in patients after coronary stent implantation. Furthermore, r-ADP-agg might represent a better tool to predict clinical outcome than the conventional ADP induced platelet aggregation alone.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Lopez AD, Mathers CD, Ezzati M et al (2006) Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 367:1747–1757PubMedCrossRef Lopez AD, Mathers CD, Ezzati M et al (2006) Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 367:1747–1757PubMedCrossRef
2.
Zurück zum Zitat Sofi F, Marcucci R, Gori AM et al (2010) Clopidogrel non-responsiveness and risk of cardiovascular morbidity. An updated meta-analysis. Thromb Haemost 103:841–848PubMedCrossRef Sofi F, Marcucci R, Gori AM et al (2010) Clopidogrel non-responsiveness and risk of cardiovascular morbidity. An updated meta-analysis. Thromb Haemost 103:841–848PubMedCrossRef
3.
Zurück zum Zitat Trip MD, Cats VM, van Capelle FJ et al (1990) Platelet hyperreactivity and prognosis in survivors of myocardial infarction. N Engl J Med 322:1549–1554PubMedCrossRef Trip MD, Cats VM, van Capelle FJ et al (1990) Platelet hyperreactivity and prognosis in survivors of myocardial infarction. N Engl J Med 322:1549–1554PubMedCrossRef
4.
Zurück zum Zitat Muller I, Besta F, Schulz C et al (2003) Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb Haemost 89:783–787PubMed Muller I, Besta F, Schulz C et al (2003) Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb Haemost 89:783–787PubMed
5.
Zurück zum Zitat Zeymer U, Arntz HR, Mark B et al (2012) Efficacy and safety of a high loading dose of clopidogrel administered prehospitally to improve primary percutaneous coronary intervention in acute myocardial infarction: the randomized CIPAMI trial. Clin Res Cardiol 101:305–312PubMedCrossRef Zeymer U, Arntz HR, Mark B et al (2012) Efficacy and safety of a high loading dose of clopidogrel administered prehospitally to improve primary percutaneous coronary intervention in acute myocardial infarction: the randomized CIPAMI trial. Clin Res Cardiol 101:305–312PubMedCrossRef
6.
Zurück zum Zitat Diehl P, Olivier C, Halscheid C et al (2010) Clopidogrel affects leukocyte dependent platelet aggregation by P2Y12 expressing leukocytes. Basic Res Cardiol 105:379–387PubMedCrossRef Diehl P, Olivier C, Halscheid C et al (2010) Clopidogrel affects leukocyte dependent platelet aggregation by P2Y12 expressing leukocytes. Basic Res Cardiol 105:379–387PubMedCrossRef
7.
Zurück zum Zitat Stone GW, Witzenbichler B, Weisz G et al (2013) Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study. Lancet 382:614–623PubMedCrossRef Stone GW, Witzenbichler B, Weisz G et al (2013) Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study. Lancet 382:614–623PubMedCrossRef
8.
Zurück zum Zitat Collet JP, Cuisset T, Range G et al (2012) Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 367:2100–2109PubMedCrossRef Collet JP, Cuisset T, Range G et al (2012) Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 367:2100–2109PubMedCrossRef
9.
Zurück zum Zitat Gurbel PA, Erlinge D, Ohman EM et al (2012) Platelet function during extended prasugrel and clopidogrel Therapy for patients with ACS treated without revascularization: the TRILOGY ACS platelet function substudy. JAMA 308(17):1785–1794. doi:10.1001/jama.2012.17312 Gurbel PA, Erlinge D, Ohman EM et al (2012) Platelet function during extended prasugrel and clopidogrel Therapy for patients with ACS treated without revascularization: the TRILOGY ACS platelet function substudy. JAMA 308(17):1785–1794. doi:10.​1001/​jama.​2012.​17312
10.
Zurück zum Zitat Price MJ, Berger PB, Teirstein PS et al (2011) Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 305:1097–1105PubMedCrossRef Price MJ, Berger PB, Teirstein PS et al (2011) Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 305:1097–1105PubMedCrossRef
11.
Zurück zum Zitat Trenk D, Stone GW, Gawaz M et al (2012) 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 59:2159–2164PubMedCrossRef Trenk D, Stone GW, Gawaz M et al (2012) 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 59:2159–2164PubMedCrossRef
12.
Zurück zum Zitat Voisin S, Bongard V, Tidjane MA et al (2011) Are P2Y12 reaction unit (PRU) and % inhibition index equivalent for the expression of P2Y12 inhibition by the VerifyNow assay? Role of haematocrit and haemoglobin levels. Thromb Haemost 106:227–229PubMedCrossRef Voisin S, Bongard V, Tidjane MA et al (2011) Are P2Y12 reaction unit (PRU) and % inhibition index equivalent for the expression of P2Y12 inhibition by the VerifyNow assay? Role of haematocrit and haemoglobin levels. Thromb Haemost 106:227–229PubMedCrossRef
13.
Zurück zum Zitat Gremmel T, Calatzis A, Steiner S et al (2010) Is TRAP-6 suitable as a positive control for platelet reactivity when assessing response to clopidogrel? Platelets 21:515–521PubMedCrossRef Gremmel T, Calatzis A, Steiner S et al (2010) Is TRAP-6 suitable as a positive control for platelet reactivity when assessing response to clopidogrel? Platelets 21:515–521PubMedCrossRef
14.
Zurück zum Zitat Olivier C, Diehl P, Bode C et al (2013) Thrombin receptor antagonism in antiplatelet therapy. Cardiol Therapy 2:57–68CrossRef Olivier C, Diehl P, Bode C et al (2013) Thrombin receptor antagonism in antiplatelet therapy. Cardiol Therapy 2:57–68CrossRef
15.
Zurück zum Zitat Olivier CB, Diehl P, Schnabel K et al (2013) Third generation P2Y12 antagonists inhibit platelet aggregation more effectively than clopidogrel in a myocardial infarction registry. Thromb Haemost 111:266–272PubMedCrossRef Olivier CB, Diehl P, Schnabel K et al (2013) Third generation P2Y12 antagonists inhibit platelet aggregation more effectively than clopidogrel in a myocardial infarction registry. Thromb Haemost 111:266–272PubMedCrossRef
16.
Zurück zum Zitat Diehl P, Halscheid C, Olivier C et al (2011) Discontinuation of long term clopidogrel therapy induces platelet rebound hyperaggregability between 2 and 6 weeks post cessation. Clin Res Cardiol 100:765–771PubMedCrossRef Diehl P, Halscheid C, Olivier C et al (2011) Discontinuation of long term clopidogrel therapy induces platelet rebound hyperaggregability between 2 and 6 weeks post cessation. Clin Res Cardiol 100:765–771PubMedCrossRef
17.
Zurück zum Zitat Cutlip DE, Windecker S, Mehran R et al (2007) Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 115:2344–2351PubMedCrossRef Cutlip DE, Windecker S, Mehran R et al (2007) Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 115:2344–2351PubMedCrossRef
18.
Zurück zum Zitat Chesebro JH, Knatterud G, Roberts R et al (1987) Thrombolysis in myocardial infarction (TIMI) trial, phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation 76:142–154PubMedCrossRef Chesebro JH, Knatterud G, Roberts R et al (1987) Thrombolysis in myocardial infarction (TIMI) trial, phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation 76:142–154PubMedCrossRef
19.
Zurück zum Zitat Peduzzi P, Concato J, Feinstein AR et al (1995) Importance of events per independent variable in proportional hazards regression analysis. II. Accuracy and precision of regression estimates. J Clin Epidemiol 48:1503–1510PubMedCrossRef Peduzzi P, Concato J, Feinstein AR et al (1995) Importance of events per independent variable in proportional hazards regression analysis. II. Accuracy and precision of regression estimates. J Clin Epidemiol 48:1503–1510PubMedCrossRef
20.
Zurück zum Zitat Kwok CS, Jeevanantham V, Dawn B et al (2013) No consistent evidence of differential cardiovascular risk amongst proton-pump inhibitors when used with clopidogrel: meta-analysis. Int J Cardiol 167:965–974PubMedCrossRef Kwok CS, Jeevanantham V, Dawn B et al (2013) No consistent evidence of differential cardiovascular risk amongst proton-pump inhibitors when used with clopidogrel: meta-analysis. Int J Cardiol 167:965–974PubMedCrossRef
21.
Zurück zum Zitat Geisler T, Langer H, Wydymus M et al (2006) Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation. Eur Heart J 27:2420–2425PubMedCrossRef Geisler T, Langer H, Wydymus M et al (2006) Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation. Eur Heart J 27:2420–2425PubMedCrossRef
22.
Zurück zum Zitat Badr Eslam R, Lang IM, Koppensteiner R et al (2012) Residual platelet activation through protease-activated receptors (PAR)-1 and -4 in patients on P2Y12 inhibitors. Int J Cardiol 168(1):403–406. doi:10.1016/j.ijcard.2012.09.103 Badr Eslam R, Lang IM, Koppensteiner R et al (2012) Residual platelet activation through protease-activated receptors (PAR)-1 and -4 in patients on P2Y12 inhibitors. Int J Cardiol 168(1):403–406. doi:10.​1016/​j.​ijcard.​2012.​09.​103
23.
Zurück zum Zitat Steg PG, Fox KA, Eagle KA et al (2009) Mortality following placement of drug-eluting and bare-metal stents for ST-segment elevation acute myocardial infarction in the global registry of acute coronary events. Eur Heart J 30:321–329PubMedCrossRef Steg PG, Fox KA, Eagle KA et al (2009) Mortality following placement of drug-eluting and bare-metal stents for ST-segment elevation acute myocardial infarction in the global registry of acute coronary events. Eur Heart J 30:321–329PubMedCrossRef
24.
Zurück zum Zitat Aradi D, Tornyos A, Pinter T et al (2014) 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 63:1061–1070PubMedCrossRef Aradi D, Tornyos A, Pinter T et al (2014) 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 63:1061–1070PubMedCrossRef
25.
Zurück zum Zitat Seivani Y, Abdel-Wahab M, Geist V et al (2013) Long-term safety and efficacy of dual therapy with oral anticoagulation and clopidogrel in patients with atrial fibrillation treated with drug-eluting stents. Clin Res Cardiol 102:799–806PubMedCrossRef Seivani Y, Abdel-Wahab M, Geist V et al (2013) Long-term safety and efficacy of dual therapy with oral anticoagulation and clopidogrel in patients with atrial fibrillation treated with drug-eluting stents. Clin Res Cardiol 102:799–806PubMedCrossRef
26.
Zurück zum Zitat Liosis S, Bauer T, Schiele R et al (2013) Predictors of 1-year mortality in patients with contemporary guideline-adherent therapy after acute myocardial infarction: results from the OMEGA study. Clin Res Cardiol 102:671–677PubMedCrossRef Liosis S, Bauer T, Schiele R et al (2013) Predictors of 1-year mortality in patients with contemporary guideline-adherent therapy after acute myocardial infarction: results from the OMEGA study. Clin Res Cardiol 102:671–677PubMedCrossRef
27.
Zurück zum Zitat Theidel U, Asseburg C, Giannitsis E et al (2013) Cost-effectiveness of ticagrelor versus clopidogrel for the prevention of atherothrombotic events in adult patients with acute coronary syndrome in Germany. Clin Res Cardiol 102:447–458PubMedCrossRef Theidel U, Asseburg C, Giannitsis E et al (2013) Cost-effectiveness of ticagrelor versus clopidogrel for the prevention of atherothrombotic events in adult patients with acute coronary syndrome in Germany. Clin Res Cardiol 102:447–458PubMedCrossRef
28.
Zurück zum Zitat Stark R, Kirchberger I, Hunger M et al (2014) Improving care of post-infarct patients: effects of disease management programmes and care according to international guidelines. Clin Res Cardiol 103:237–245PubMedCrossRef Stark R, Kirchberger I, Hunger M et al (2014) Improving care of post-infarct patients: effects of disease management programmes and care according to international guidelines. Clin Res Cardiol 103:237–245PubMedCrossRef
29.
Zurück zum Zitat Zusman O, Amit G, Gilutz H et al (2012) The significance of new onset atrial fibrillation complicating acute myocardial infarction. Clin Res Cardiol 101:17–22PubMedCrossRef Zusman O, Amit G, Gilutz H et al (2012) The significance of new onset atrial fibrillation complicating acute myocardial infarction. Clin Res Cardiol 101:17–22PubMedCrossRef
30.
Zurück zum Zitat Gremmel T, Steiner S, Seidinger D et al (2009) Comparison of methods to evaluate clopidogrel-mediated platelet inhibition after percutaneous intervention with stent implantation. Thromb Haemost 101:333–339PubMed Gremmel T, Steiner S, Seidinger D et al (2009) Comparison of methods to evaluate clopidogrel-mediated platelet inhibition after percutaneous intervention with stent implantation. Thromb Haemost 101:333–339PubMed
Metadaten
Titel
A high ratio of ADP–TRAP induced platelet aggregation is associated more strongly with increased mortality after coronary stent implantation than high conventional ADP induced aggregation alone
verfasst von
Christoph B. Olivier
Katharina Schnabel
Christoph Brandt
Patrick Weik
Manfred Olschewski
Qian Zhou
Christoph Bode
Philipp Diehl
Martin Moser
Publikationsdatum
01.12.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Clinical Research in Cardiology / Ausgabe 12/2014
Print ISSN: 1861-0684
Elektronische ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-014-0737-8

Weitere Artikel der Ausgabe 12/2014

Clinical Research in Cardiology 12/2014 Zur Ausgabe

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.