Differenzierte antithrombozytäre Therapie bei akutem Koronarsyndrom

 

 Buy Article Permissions and Reprints

Zusammenfassung

Die duale antithrombozytäre Therapie ist ein Eckpfeiler der Nachbehandlung interventionell versorgter Patienten mit einem akuten Koronarsyndrom (ST-Hebungsinfarkt, Nicht-ST-Hebungsinfarkt, instabile Angina Pectoris). In den vergangenen Jahren hat sich besonders die zusätzlich zur niedrig-dosierten Acetylsalicylsäuregabe durchgeführte P2Y₁₂-Hemmung intensiver Debatten erfreut. Dies liegt vor allem an den in den letzten Jahren veröffentlichten Daten der großen Phase III-Studien „TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN“ (TRITON) mit Prasugrel sowie „Study of Platelet Inhibition and Patient Outcomes“ (PLATO) mit Ticagrelor jeweils im Vergleich zu Clopidogrel bei Patienten mit akutem Koronarsysndrom. Im vorliegenden Artikel fassen wir nochmals kurz die wichtigen Daten und Subanalysen aus den beiden Studienprogrammen zusammen und zeigen eine klinische Entscheidungsfindung in der Handhabung der drei Substanzen beim akuten Koronarsyndrom auf. Besonderes Augenmerk liegt dabei auf sogenannten Hochrisikokollektiven wie Patienten mit ST-Hebungsinfarkt und bei Diabetes, aber auch auf der Vermeidung von relevanten Blutungen, wie sie unter einer verstärkten Thrombozytenhemmung unabdinglich häufiger auftreten.

Abstract

Dual antiplatelet therapy is the cornerstone of maintenance medication following invasive treatment of patients with acute coronary syndromes (ST elevation myocardial infarction, non-ST elevation myocardial infarction, unstable angina). Over the last decade, P2Y₁₂ inhibition in addition to low-dose acetylsalicylic acid has been intensively debated. The debate was enriched by the results of the large phase III clinical trials for prasugrel (TRITON) and ticagrelor (PLATO) compared to clopidogrel in patients with acute coronary syndromes. This article summarizes the critical details und subanalyses of both study programmes and highlights on clinical decision making when using the three P2Y₁₂ blockers in acute coronary syndromes. A special focus is on higher risk patients such as those with ST elevation myocardial infarction and those with coexisting diabetes, but also on minimizing relevant bleedings, which are common during more intense platelet inhibition.

• Literatur

• 1 Prasugrel for the treatment of acute coronary syndromes with percutaneous coronary intervention. 2009 http://www.nice.org.uk
  PubMed
• 2 NDA 22-433 Brilinta (ticagrelor) Efficacy Review Cardio-Renal Advisory Committee Meeting. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM221383.pdf 28-7-2010.
  PubMed
• 3 Gurbel PA, Bliden KP, Butler K et al. 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 2009; 120: 2577-2585
  CrossrefPubMedGoogle Scholar
• 4 Haffner SM, Lehto S, Ronnemaa T et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998; 339: 229-234
  CrossrefPubMedGoogle Scholar
• 5 Hamm CW, Bassand JP, Agewall S et al. 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 2011; 32: 2999-3054
  CrossrefPubMedGoogle Scholar
• 6 Heestermans AA, van Werkum JW, Taubert D et al. Impaired bioavailability of clopidogrel in patients with a ST-segment elevation myocardial infarction. Thromb Res 2008; 122: 776-781
  CrossrefPubMedGoogle Scholar
• 7 Held C, Asenblad N, Bassand JP et al. Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes Undergoing Coronary Artery Bypass Surgery Results From the PLATO (Platelet Inhibition and Patient Outcomes) Trial. J Am Coll Cardiol 2011; 57: 672-684
  CrossrefPubMedGoogle Scholar
• 8 James S, Akerblom A, Cannon CP et al. Comparison of ticagrelor, the first reversible oral P2Y(12) receptor antagonist, with clopidogrel in patients with acute coronary syndromes: Rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial. Am Heart J 2009; 157: 599-605
  CrossrefPubMedGoogle Scholar
• 9 James S, Angiolillo DJ, Cornel JH et al. Ticagrelor vs. clopidogrel in patients with acute coronary syndromes and diabetes: a substudy from the PLATelet inhibition and patient Outcomes (PLATO) trial. Eur Heart J 2010; 31: 3006-3016
  CrossrefPubMedGoogle Scholar
• 10 James S, Budaj A, Aylward P et al. Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function: results from the Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation 2010; 122: 1056-1067
  CrossrefPubMedGoogle Scholar
• 11 James SK, Roe MT, Cannon CP et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management: substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial. BMJ 2011; 342: d3527
  CrossrefPubMedGoogle Scholar
• 12 James SK, Storey RF, Khurmi NS et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes and a history of stroke or transient ischemic attack. Circulation 2012; 125: 2914-2921
  CrossrefPubMedGoogle Scholar
• 13 Kastrati A, Mehilli J, Neumann FJ et al. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial. JAMA 2006; 295: 1531-1538
  CrossrefPubMedGoogle Scholar
• 14 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
• 15 Mehta SR, Yusuf S, Peters RJ et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001; 358: 527-533
  CrossrefPubMedGoogle Scholar
• 16 Michelson AD, Frelinger III AL, Braunwald E et al. Pharmacodynamic assessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITON-TIMI 38 trial. Eur Heart J 2009; 30: 1753-1763
  CrossrefPubMedGoogle Scholar
• 17 Montalescot G, Wiviott SD, Braunwald E et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet 2009; 373: 723-731
  CrossrefPubMedGoogle Scholar
• 18 Osmancik P, Jirmar R, Hulikova K et al. A comparison of the VASP index between patients with hemodynamically complicated and uncomplicated acute myocardial infarction. Catheter Cardiovasc Interv 2010; 75: 158-166
  CrossrefPubMedGoogle Scholar
• 19 Roe MT, Armstrong PW, Fox KA et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med 2012; 367: 1297-1309
  CrossrefPubMedGoogle Scholar
• 20 Ryden L, Standl E, Bartnik M et al. [Guidelines on diabetes, pre-diabetes, and cardiovascular diseases]. Rev Esp Cardiol 2007; 60: 1e-64e
  PubMedGoogle Scholar
• 21 Schäfer A, Flierl U, Kössler J et al. Early determination of clopidogrel responsiveness by platelet reactivity index identifies patients at risk for cardiovascular events after myocardial infarction. Thromb Haemost 2011; 106: 141-148
  Article in Thieme ConnectPubMedGoogle Scholar
• 22 Schramm TK, Gislason GH, Kober L et al. Diabetes patients requiring glucose-lowering therapy and nondiabetics with a prior myocardial infarction carry the same cardiovascular risk: a population study of 3.3 million people. Circulation 2008; 117: 1945-1954
  CrossrefPubMedGoogle Scholar
• 23 Silber S, Borggrefe M, Hasenfuß G et al. Kommentare zu den Leitlinien der Europäischen Gesellschaft für Kardiologie (ESC) zur Diagnostik und Therapie von Patienten mit ST-Streckenhebungsinfarkt (STEMI). Kardiologe 2010; 4: 84-92
  CrossrefPubMedGoogle Scholar
• 24 Steg PG, James S, Harrington RA et al. Ticagrelor versus clopidogrel in patients with ST-elevation acute coronary syndromes intended for reperfusion with primary percutaneous coronary intervention: A Platelet Inhibition and Patient Outcomes (PLATO) trial subgroup analysis. Circulation 2010; 122: 2131-2141
  CrossrefPubMedGoogle Scholar
• 25 Steg PG, James SK, Atar D et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). Eur Heart J 2012; 33: 2569-2619
  CrossrefPubMedGoogle Scholar
• 26 Steinhubl SR, Berger PB, Brennan DM et al. Optimal timing for the initiation of pre-treatment with 300 mg clopidogrel before percutaneous coronary intervention. J Am Coll Cardiol 2006; 47: 939-943
  CrossrefPubMedGoogle Scholar
• 27 The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345: 494-502
  CrossrefPubMedGoogle Scholar
• 28 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
  CrossrefPubMedGoogle Scholar
• 29 Wijns W, Kolh P, Danchin N et al. Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2010; 31: 2501-2555
  CrossrefPubMedGoogle Scholar
• 30 Wiviott SD, Antman EM, Gibson CM et al. Evaluation of prasugrel compared with clopidogrel in patients with acute coronary syndromes: design and rationale for the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38). Am Heart J 2006; 152: 627-635
  CrossrefPubMedGoogle Scholar
• 31 Wiviott SD, Braunwald E, Angiolillo DJ et al. Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-Thrombolysis in Myocardial Infarction 38. Circulation 2008; 118: 1626-1636
  CrossrefPubMedGoogle Scholar
• 32 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
  CrossrefPubMedGoogle Scholar
• 33 Wiviott SD, Trenk D, Frelinger AL et al. 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 2007; 116: 2923-2932
  CrossrefPubMedGoogle Scholar
• 34 Zeymer U, Arntz HR, Mark B et al. 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 2012; 101: 305-312
  CrossrefPubMedGoogle Scholar
• 35 Montalescot G, Bolognese L, Dudek D et al. Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes. N Engl J Med 2013; 369: 999-1010
  CrossrefPubMedGoogle Scholar
• 36 Steg PG, Mehta SR, Pollack CV et al. Anticoagulation with otamixaban and ischemic events in non-ST-segment elevation acute coronary syndromes: the TAO randomized clinical trial. JAMA 2013; 310: 1145-1155
  CrossrefPubMedGoogle Scholar