Download PDF
Der Klinikarzt 2012; 41(12): 604-608
DOI: 10.1055/s-0033-1333799
Im Fokus
© Georg Thieme Verlag Stuttgart · New York

Neue Thrombozytenaggregationshemmung bei Patienten mit akutem Koronarsyndrom – Umbruch einer langjährigen antithrombozytären Praxis

New antiplatelet therapy in patients with myocardial infarction – Change in a long lasting antiplatelet practice
Helge Möllmann
1   Kerckhoff Herz- und Thoraxzentrum, Bad Nauheim
,
Matthias Willmer
1   Kerckhoff Herz- und Thoraxzentrum, Bad Nauheim
,
Christian W Hamm
1   Kerckhoff Herz- und Thoraxzentrum, Bad Nauheim
› Author Affiliations
Further Information

Publication History

Publication Date:
14 January 2013 (online)

Also available at
    Permissions and Reprints

Die antithrombozytäre Therapie stellt einen Eckpfeiler in der Sekundärprophylaxe bei Patienten nach akutem Koronarsyndrom dar. Die langjährige Praxis der festen Kombination aus Acetylsalicylsäure und Clopidogrel steht vor einem Umbruch – neue antithrombozytäre Medikamente wie Ticagrelor und Prasugrel sind zugelassen und haben aufgrund nachgewiesener Überlegenheit gegenüber Clopidogrel Einzug in die Leitlinien gefunden. Weitere Wirkstoffe sind in der klinischen Erprobung. Der nachfolgende Artikel soll einen Überblick über Wirkung und Nebenwirkungen, pharmakokinetische Eigenschaften sowie aktuelle Entwicklungen im Bereich der pharmakologischen Forschung der Thrombozyteninhibierung liefern.

Antiplatelet therapy is a milestone of secondary prevention after myocardial infarction since the introduction of acetylsalicylic acid. Several years ago this monotherapy was supplemented by thienopyridine. However, modern antiplatelet drugs like Prasugrel or Ticagrelor have been shown to be superior in comparison to Clopidogrel and are therefore now included in the current guidelines. In addition, further developments are underway and will be available in the next years. This article summarizes the (side-) effects of the new drugs and provides an outlook on upcoming therapeutical options.

Key words

Myocardial infarction - secondary prophylaxis - antiplatelet therapy
 

  • Literatur

  • 1 Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study. Lancet 1997; 349: 1498-1504
    CrossrefPubMedGoogle Scholar
  • 2 Antman EM. Hirudin in acute myocardial infarction. Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9B trial. Circulation 1996; 94: 911-921
    CrossrefPubMedGoogle Scholar
  • 3 Yusuf S, Zhao F, Mehta SR et al. 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
  • 4 Price MJ, Berger PB, Teirstein PS et al. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 2011; 305: 1097-1105
    CrossrefPubMedGoogle Scholar
  • 5 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
  • 6 Antman EM, Wiviott SD, Murphy SA et al. Early and late benefits of prasugrel in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis. J Am Coll Cardiol 2008; 51: 2028-2033
    CrossrefPubMedGoogle Scholar
  • 7 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
  • 8 Alexopoulos D, Theodoropoulos KC, Stavrou EF et al. Prasugrel Versus High Dose Clopidogrel to Overcome Early High on Clopidogrel Platelet Reactivity in Patients with ST Elevation Myocardial Infarction. Cardiovasc Drugs Ther 2012; 26: 393-400
    CrossrefPubMedGoogle Scholar
  • 9 Li Y, Tai B-C, Sia W et al. Angiographic and platelet reactivity outcomes with prasugrel 60 mg pretreatment and clopidogrel 600 mg pretreatment in primary percutaneous coronary intervention. J Thromb Thrombolysis 2012; 34: 499-505
    CrossrefPubMedGoogle Scholar
  • 10 Roe MT, Armstrong PW, Fox KAA et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med 2012; 367: 1297-1309
    CrossrefPubMedGoogle Scholar
  • 11 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
  • 12 Hamm CW, Bassand J-P, 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
  • 13 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
  • 14 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
    PubMedGoogle Scholar
  • 15 Cannon CP, Harrington RA, James S et al. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study. Lancet 2010; 375: 283-293
    CrossrefPubMedGoogle Scholar
  • 16 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
  • 17 Chackalamannil S, Wang Y, Greenlee WJ et al. Discovery of a novel, orally active himbacine-based thrombin receptor antagonist (SCH 530348) with potent antiplatelet activity. J Med Chem 2008; 51: 3061-3064
    CrossrefPubMedGoogle Scholar
  • 18 Tricoci P, Huang Z, Held C et al. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med 2012; 366: 20-33
    CrossrefPubMedGoogle Scholar
  • 19 Morrow DA, Scirica BM, Fox KAA et al. Evaluation of a novel antiplatelet agent for secondary prevention in patients with a history of atherosclerotic disease: design and rationale for the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2 degrees P)-TIMI 50 trial. Am Heart J 2009; 158
    PubMedGoogle Scholar
  • 20 O'Donoghue ML, Bhatt DL, Wiviott SD et al. Safety and tolerability of atopaxar in the treatment of patients with acute coronary syndromes: the lessons from antagonizing the cellular effects of Thrombin – Acute Coronary Syndromes Trial. Circulation 2011; 123: 1843-1853
    CrossrefPubMedGoogle Scholar
  • 21 Wiviott SD, Flather MD, O'Donoghue ML et al. Randomized trial of atopaxar in the treatment of patients with coronary artery disease: the lessons from antagonizing the cellular effect of Thrombin – Coronary Artery Disease Trial. Circulation 2011; 123: 1854-1863
    CrossrefPubMedGoogle Scholar
  • 22 Goto S, Ogawa H, Takeuchi M et al. Double-blind, placebo-controlled Phase II studies of the protease-activated receptor 1 antagonist E5555 (atopaxar) in Japanese patients with acute coronary syndrome or high-risk coronary artery disease. Eur Heart J 2010; 31: 2601-2613
    CrossrefPubMedGoogle Scholar
  • 23 Welsh RC, Rao SV, Zeymer U et al. A randomized, double-blind, active-controlled phase 2 trial to evaluate a novel selective and reversible intravenous and oral P2Y12 inhibitor elinogrel versus clopidogrel in patients undergoing nonurgent percutaneous coronary intervention: the INNOVATE-PCI trial. Circ Cardiovasc Interv 2012; 5: 336-346
    CrossrefPubMedGoogle Scholar
  • 24 Storey RF, Sanderson HM, White AE et al. The central role of the P(2T) receptor in amplification of human platelet activation, aggregation, secretion and procoagulant activity. Br J Haematol 2000; 110: 925-934
    CrossrefPubMedGoogle Scholar
  • 25 Harrington RA, Stone GW, McNulty S et al. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med 2009; 361: 2318-2329
    CrossrefPubMedGoogle Scholar
  • 26 Bhatt DL, Lincoff AM, Gibson CM et al. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med 2009; 361: 2330-2341
    CrossrefPubMedGoogle Scholar
  • 27 Leonardi S, Mahaffey KW, White HD et al. Rationale and design of the Cangrelor versus standard therapy to acHieve optimal Management of Platelet InhibitiON PHOENIX trial. Am Heart J 2012; 163
    PubMedGoogle Scholar
  • 28 Duerschmied D, Bode C. Vorapaxar expands antiplatelet options. Which patients may benefit from thrombin receptor antagonism?. Hämostaseologie 2012; 32: 221-227
    Article in Thieme ConnectPubMedGoogle Scholar