Neue Ansätze und Indikationen zur Plättchenfunktionsdiagnostik in der Kardiologie

Summary

Inhibiting platelet function is a key therapeutic principle in cardiology because platelets play a pivotal role in triggering cardiovascular events. In addition to acetylsalicylic acid, a cyclooxygenase inhibitor, ADP-receptor blockers are frequently used for anti-platelet therapy. This therapy does not abolish platelet activation and aggregation. Platelets may still be activated by alternative routes such as the thrombin receptor-mediated pathway. New, more potent inhibitors of platelet function continue to lower the risk of ischaemic events but several trials and clinical registries have also shown that this advantage was frequently offset by an increased risk of bleeding complications. As a consequence, the individual risk of ischaemia and bleeding of a patient must be taken into consideration to select the platelet inhibitor offering the best benefit-risk ratio. Modern laboratory diagnostics may help to achieve this goal by complementing functional platelet tests with pharmacogenomic analyses consistent with the idea of „personalized medicine“.

Zusammenfassung

Der Thrombozyt spielt eine zentrale Rolle in der Entstehung kardiovaskulärer Ereignisse, die Beeinflussung seiner Funktion ist daher wichtiges therapeutisches Ziel. Neben dem Cyclooxygenasehemmer ASS werden nach koronarer Stentimplantation bzw. bei akuten Koronarsyndromen zusätzlich ADP-Rezeptorblocker als Thrombozytenaggregationshemmer eingesetzt. Dabei wird der Thrombozyt nicht vollständig inhibiert; er kann noch über Alternativwege, beispielsweise thrombinrezeptorvermittelt aktiviert werden. Neue potentere Plättchenfunktionshemmer führen zu einer stetigen Verringerung des Risikos für ischämische Ereignisse. Eine Reihe von Studien und Registern zeigt aber auch, dass dieser Vorteil häufig mit dem Nachteil einer erhöhten Blutungskomplikationsrate erkauft werden muss. Das Ziel sollte daher eine möglichst individuelle Einschätzung des Ischämie-bzw. Blutungsrisikos der Patienten sein, um das Medikament mit dem besten Nutzen-RisikoVerhältnis zu wählen. Ein Ansatz hierzu könnte die moderne Labordiagnostik sein, welche künftig neben der funktionellen Thrombozytenuntersuchung auch die Bestimmung pharmakogenetisch relevanter Genloci im Rahmen der “personalized medicine” erlaubt.

Keywords

Platelet - coronary artery disease - myocardial infarction - thienopyridin

Schlüsselwörter

Thrombozyt - Koronare Herzkrankheit - Herz-infarkt - Thienopyridin

• Literatur

• 1 Angiolillo DJ, Fernandez-Ortiz A, Bernardo E. et al. Variability in individual responsiveness to clopidogrel. Clinical implications, management, and future perspectives. J Am Coll Cardiol 2007; 49: 1505-1516.
• 2 Babapulle MN, Eisenberg MJ. Coated stents for the prevention of restenosis: part II. Circulation 2002; 106: 2859-2866.
• 3 Boersma E, Harrington RA, Moliterno DJ. et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials. Lancet 2002; 359: 189-198.
• 4 Born GV. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962; 194: 927-929.
• 5 Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2 (Second International Study of Infarct Survival). Lancet 1988; 02: 349-360.
• 6 Garg P, Mauri L. The conundrum of late and very late stent thrombosis following drug-eluting stent implantation. Curr Opin Cardiol 2007; 22: 565-571.
• 7 Grines CL, Bonow RO, Casey Jr DE. et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. J Am Coll Cardiol 2007; 49: 734-739.
• 8 Hankey GJ, Eikelboom JW. Aspirin resistance. Lancet 2006; 367: 606-617.
• 9 Harrington RA, Stone GW, McNulty S. et al. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med 2009; 361: 2318-2329.
• 10 Holmes Jr DR, Dehmer GJ, Kaul S. et al. ACCF/AHA Clopidogrel Clinical Alert: Approaches to the FDA “Boxed Warning”A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the American Heart Association. Circulation 2010; 122: 537-557.
• 11 Ivandic BT, Schlick P, Staritz P. et al. Determination of clopidogrel resistance by whole blood platelet aggregometry and inhibitors of the P2Y12 receptor. Clin Chem 2006; 52: 383-388.
• 12 Ivandic BT, Giannitsis E, Schlick P. et al. Determination of aspirin responsiveness by use of whole blood platelet aggregometry. Clin Chem 2007; 53: 614-619.
• 13 Ivandic BT, Kurz K, Keck F. et al. Tirofiban optimizes platelet inhibition for immediate percutaneous coronary intervention in high-risk acute coronary syndromes. Thromb Haemost 2008; 100: 648-654.
• 14 Ivandic BT, Sausemuth M, Ibrahim H. et al. Dual antiplatelet drug resistance is a risk factor for cardiovascular events after percutaneous coronary intervention. Clin Chem 2009; 55: 1171-1176.
• 15 Ivandic B, Sigl M, Spanuth E. et al. Platelet stimulation capacity (PSC) using platelet markers to determine platelet reactivity. Hämostaseologie. 2009 29. A61, PP4.3–3.
• 16 Kastrati A, Mehilli J, Dirschinger J. et al. Restenosis after coronary placement of various stent types. Am J Cardiol 2001; 87: 34-39.
• 17 Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003; 361: 13-20.
• 18 Mauri L, Hsieh WH, Massaro JM. et al. Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med 2007; 356: 1020-1029.
• 19 Mega JL, Close SL, Wiviott SD. et al. Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation 2009; 119: 2553-2560.
• 20 Roukoz H, Bavry AA, Sarkees ML. et al. Comprehensive meta-analysis on drug-eluting stents versus bare-metal stents during extended follow-up. Am J Med 2009; 122: 581 e1–10..
• 21 Serruys PW, Strauss BH, Beatt KJ. et al. Angiographic follow-up after placement of a self-expanding coronary-artery stent. N Engl J Med 1991; 324: 13-17.
• 22 Schömig A, Neumann FJ, Kastrati A. et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med 1996; 334: 1084-1089.
• 23 Staritz P, Kurz K, Stoll M. et al. Platelet reactivity and clopidogrel resistance are associated with the H2 haplotype of the P2Y12-ADP receptor gene. Int J Cardiol 2009; 133: 341-345.
• 24 Stone GW. Ischaemia versus bleeding: the art of clinical decision-making. Lancet 2009; 373: 695-696.
• 25 Wallentin L, Becker RC, Budaj A. et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045-1057.
• 26 Wiviott SD, Braunwald E, McCabe CH. et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001-2015.