Skip to main content
Erschienen in: Der Kardiologe 5/2012

01.10.2012 | Klinische Pharmakologie

Plättchenaggregationshemmer

verfasst von: PD Dr. D. Sibbing, Prof. Dr. S. Massberg

Erschienen in: Die Kardiologie | Ausgabe 5/2012

Einloggen, um Zugang zu erhalten

Zusammenfassung

Patienten mit koronarer Herzerkrankung und erfolgter Stentimplantation im Rahmen einer perkutanen Koronarintervention (PCI) sind auf eine adäquate Hemmung der Blutplättchen während und in den Monaten nach dem Eingriff angewiesen. In diesem Zusammenhang spielen die Aktivierung und die Aggregation von Thrombozyten eine zentrale Rolle bei der Entstehung thrombotischer Ereignisse wie z. B. der Stentthrombose. Mittels einer dualen antithrombozytären Therapie soll das Risiko für ischämische Ereignisse minimiert werden. Dieses Therapieregime beinhaltet die Gabe des Cyclooxygenasehemmers Aspirin, dessen Einnahme in der Regel lebenslang notwendig ist sowie die gleichzeitige Gabe eines P2Y12-Rezeptor-Antagonisten. Hier stehen heutzutage mit den oralen Plättchenhemmern Clopidogrel, Prasugrel und Ticagrelor verschiedene Therapieoptionen zur Auswahl. Die Wahl des P2Y12-Hemmers wird bestimmt durch die klinische Situation, in der sich der Patient befindet, durch relevante Begleiterkrankungen des Patienten sowie durch das Nebenwirkungsprofil der einzelnen Medikamente. Auch das Monitoring der Plättchenhemmung durch Verfahren der Thrombozytenaggregationsmessung kann hilfreich sein. Die eigentliche Schwierigkeit bei der Auswahl dieser unterschiedlich potenten P2Y12-Rezeptor-Antagonisten besteht in der Balance zwischen der Vermeidung thrombotischer Ereignisse und der Induktion von Blutungen.
Literatur
1.
Zurück zum Zitat (o A) (1996) A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 348:1329–1339 (o A) (1996) A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 348:1329–1339
2.
Zurück zum Zitat Bonello L, Tantry US, Marcucci R et al (2010) Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 56:919–933PubMedCrossRef Bonello L, Tantry US, Marcucci R et al (2010) Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 56:919–933PubMedCrossRef
3.
Zurück zum Zitat Cattaneo M (2007) Laboratory detection of ‚aspirin resistance’: what test should we use (if any)? Eur Heart J 28:1673–1675PubMedCrossRef Cattaneo M (2007) Laboratory detection of ‚aspirin resistance’: what test should we use (if any)? Eur Heart J 28:1673–1675PubMedCrossRef
4.
Zurück zum Zitat Geiger J, Brich J, Honig-Liedl P et al (1999) Specific impairment of human platelet P2Y(AC) ADP receptor-mediated signaling by the antiplatelet drug clopidogrel. Arterioscler Thromb Vasc Biol 19:2007–2011PubMedCrossRef Geiger J, Brich J, Honig-Liedl P et al (1999) Specific impairment of human platelet P2Y(AC) ADP receptor-mediated signaling by the antiplatelet drug clopidogrel. Arterioscler Thromb Vasc Biol 19:2007–2011PubMedCrossRef
5.
Zurück zum Zitat Gurbel PA, Bliden KP, Butler K et al (2010) Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study. Circulation 121:1188–1199PubMedCrossRef Gurbel PA, Bliden KP, Butler K et al (2010) Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study. Circulation 121:1188–1199PubMedCrossRef
6.
Zurück zum Zitat Gurbel PA, Bliden KP, Butler K et al (2009) Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation 120:2577–2585PubMedCrossRef Gurbel PA, Bliden KP, Butler K et al (2009) Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation 120:2577–2585PubMedCrossRef
7.
Zurück zum Zitat Gurbel PA, Bliden KP, Hiatt BL et al (2003) Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 107:2908–2913PubMedCrossRef Gurbel PA, Bliden KP, Hiatt BL et al (2003) Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 107:2908–2913PubMedCrossRef
8.
Zurück zum Zitat Hamm CW, Bassand JP, Agewall S et al (2011) 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 32:2999–3054PubMedCrossRef Hamm CW, Bassand JP, Agewall S et al (2011) 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 32:2999–3054PubMedCrossRef
9.
Zurück zum Zitat Kazui M, Nishiya Y, Ishizuka T et al (2010) Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metab Dispos 38:92–99PubMedCrossRef Kazui M, Nishiya Y, Ishizuka T et al (2010) Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metab Dispos 38:92–99PubMedCrossRef
10.
Zurück zum Zitat Leon MB, Baim DS, Popma JJ et al (1998) A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators. N Engl J Med 339:1665–1671PubMedCrossRef Leon MB, Baim DS, Popma JJ et al (1998) A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators. N Engl J Med 339:1665–1671PubMedCrossRef
11.
Zurück zum Zitat Massberg S, Brand K, Gruner S et al (2002) A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation. J Exp Med 196:887–896PubMedCrossRef Massberg S, Brand K, Gruner S et al (2002) A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation. J Exp Med 196:887–896PubMedCrossRef
12.
Zurück zum Zitat Massberg S, Gawaz M, Gruner S et al (2003) A crucial role of glycoprotein VI for platelet recruitment to the injured arterial wall in vivo. J Exp Med 197:41–49PubMedCrossRef Massberg S, Gawaz M, Gruner S et al (2003) A crucial role of glycoprotein VI for platelet recruitment to the injured arterial wall in vivo. J Exp Med 197:41–49PubMedCrossRef
13.
Zurück zum Zitat Massberg S, Schulz C, Gawaz M (2003) Role of platelets in the pathophysiology of acute coronary syndrome. Semin Vasc Med 3:147–162PubMedCrossRef Massberg S, Schulz C, Gawaz M (2003) Role of platelets in the pathophysiology of acute coronary syndrome. Semin Vasc Med 3:147–162PubMedCrossRef
14.
Zurück zum Zitat Mega JL, Close SL, Wiviott SD et al (2009) Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation 119:2553–2560PubMedCrossRef Mega JL, Close SL, Wiviott SD et al (2009) Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation 119:2553–2560PubMedCrossRef
15.
Zurück zum Zitat Mega JL, Simon T, Collet JP et al (2010) Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA 304:1821–1830PubMedCrossRef Mega JL, Simon T, Collet JP et al (2010) Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA 304:1821–1830PubMedCrossRef
16.
Zurück zum Zitat Muller I, Seyfarth M, Rudiger S et al (2001) Effect of a high loading dose of clopidogrel on platelet function in patients undergoing coronary stent placement. Heart 85:92–93PubMedCrossRef Muller I, Seyfarth M, Rudiger S et al (2001) Effect of a high loading dose of clopidogrel on platelet function in patients undergoing coronary stent placement. Heart 85:92–93PubMedCrossRef
17.
Zurück zum Zitat Paikin JS, Eikelboom JW, Cairns JA et al (2010) New antithrombotic agents – insights from clinical trials. Nat Rev Cardiol 7:498–509PubMedCrossRef Paikin JS, Eikelboom JW, Cairns JA et al (2010) New antithrombotic agents – insights from clinical trials. Nat Rev Cardiol 7:498–509PubMedCrossRef
18.
Zurück zum Zitat Schömig A, Neumann FJ, Kastrati A et al (1996) A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med 334:1084–1089PubMedCrossRef Schömig A, Neumann FJ, Kastrati A et al (1996) A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med 334:1084–1089PubMedCrossRef
19.
Zurück zum Zitat Shuldiner AR, O’Connell JR, Bliden KP et al (2009) Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 302:849–857PubMedCrossRef Shuldiner AR, O’Connell JR, Bliden KP et al (2009) Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 302:849–857PubMedCrossRef
20.
Zurück zum Zitat Sibbing D, Byrne RA, Bernlochner I et al (2011) High platelet reactivity and clinical outcome – fact and fiction. Thromb Haemost 106:191–202PubMedCrossRef Sibbing D, Byrne RA, Bernlochner I et al (2011) High platelet reactivity and clinical outcome – fact and fiction. Thromb Haemost 106:191–202PubMedCrossRef
21.
Zurück zum Zitat Sibbing D, Koch W, Gebhard D et al (2010) Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation 121:512–518PubMedCrossRef Sibbing D, Koch W, Gebhard D et al (2010) Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation 121:512–518PubMedCrossRef
22.
Zurück zum Zitat Sibbing D, Mayer K, Bernlochner I et al (2012) Platelet function testing guided use of prasugrel in patients with high on-clopidogrel treatment platelet reactivity reduces the risk of early stent thrombosis. J Am Coll Cardiol 59:E265CrossRef Sibbing D, Mayer K, Bernlochner I et al (2012) Platelet function testing guided use of prasugrel in patients with high on-clopidogrel treatment platelet reactivity reduces the risk of early stent thrombosis. J Am Coll Cardiol 59:E265CrossRef
23.
Zurück zum Zitat Sibbing D, Steinhubl SR, Schulz S et al (2010) Platelet aggregation and its association with stent thrombosis and bleeding in clopidogrel-treated patients: initial evidence of a therapeutic window. J Am Coll Cardiol 56:317–318PubMedCrossRef Sibbing D, Steinhubl SR, Schulz S et al (2010) Platelet aggregation and its association with stent thrombosis and bleeding in clopidogrel-treated patients: initial evidence of a therapeutic window. J Am Coll Cardiol 56:317–318PubMedCrossRef
24.
Zurück zum Zitat Steinhubl SR, Berger PB, Mann JT III et al (2002) Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 288:2411–2420PubMedCrossRef Steinhubl SR, Berger PB, Mann JT III et al (2002) Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 288:2411–2420PubMedCrossRef
25.
Zurück zum Zitat Stone GW (2011) ADAPT-DES: a large-scale, prospective, multicenter registry examining the relationship of platelet responsiveness to stent thrombosis after DES implantation. Transcatheter Cardiovascular Therapeutics, San Francisco Stone GW (2011) ADAPT-DES: a large-scale, prospective, multicenter registry examining the relationship of platelet responsiveness to stent thrombosis after DES implantation. Transcatheter Cardiovascular Therapeutics, San Francisco
26.
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
27.
Zurück zum Zitat Wallentin L, Becker RC, Budaj A et al (2009) Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 361:1045–1057PubMedCrossRef Wallentin L, Becker RC, Budaj A et al (2009) Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 361:1045–1057PubMedCrossRef
28.
Zurück zum Zitat Wijns W, Kolh P, Danchin N et al (2010) Guidelines on myocardial revascularization. Eur Heart J 31:2501–2555PubMedCrossRef Wijns W, Kolh P, Danchin N et al (2010) Guidelines on myocardial revascularization. Eur Heart J 31:2501–2555PubMedCrossRef
29.
Zurück zum Zitat Wiviott SD, Braunwald E, McCabe CH et al (2007) Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 357:2001–2015PubMedCrossRef Wiviott SD, Braunwald E, McCabe CH et al (2007) Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 357:2001–2015PubMedCrossRef
30.
Zurück zum Zitat Wiviott SD, Trenk D, Frelinger AL et al (2007) 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 116:2923–2932PubMedCrossRef Wiviott SD, Trenk D, Frelinger AL et al (2007) 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 116:2923–2932PubMedCrossRef
31.
Zurück zum Zitat Yusuf S, Zhao F, Mehta SR et al (2001) Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 345:494–502PubMedCrossRef Yusuf S, Zhao F, Mehta SR et al (2001) Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 345:494–502PubMedCrossRef
Metadaten
Titel
Plättchenaggregationshemmer
verfasst von
PD Dr. D. Sibbing
Prof. Dr. S. Massberg
Publikationsdatum
01.10.2012
Verlag
Springer-Verlag
Erschienen in
Die Kardiologie / Ausgabe 5/2012
Print ISSN: 2731-7129
Elektronische ISSN: 2731-7137
DOI
https://doi.org/10.1007/s12181-012-0428-5

Weitere Artikel der Ausgabe 5/2012

Der Kardiologe 5/2012 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

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