Der Klinikarzt 2014; 43(S 01): 12-18
DOI: 10.1055/s-0034-1377050
Schwerpunkt
© Georg Thieme Verlag Stuttgart · New York

Akutes Koronarsyndrom – Zukünftiger Stellenwert der Thrombozytenhemmung und der DOAKs

Acute coronary syndrome – Prospective significance of thrombin receptor inhibition and novel antiplatelet agents
Daniel Dürschmied
1   Klinik für Kardiologie und Angiologie I, Universitäts-Herzzentrum Freiburg – Bad Krozingen und Klinik für Innere Medizin III (Internistische Intensivmedizin), Universitätsklinikum Freiburg
,
Ingo Ahrens
1   Klinik für Kardiologie und Angiologie I, Universitäts-Herzzentrum Freiburg – Bad Krozingen und Klinik für Innere Medizin III (Internistische Intensivmedizin), Universitätsklinikum Freiburg
,
Christoph Bode
1   Klinik für Kardiologie und Angiologie I, Universitäts-Herzzentrum Freiburg – Bad Krozingen und Klinik für Innere Medizin III (Internistische Intensivmedizin), Universitätsklinikum Freiburg
› Author Affiliations
Further Information

Publication History

Publication Date:
07 May 2014 (online)

Zusammenfassung

Wie weitreichend die Konsequenzen der Zulassung von Rivaroxaban in niedriger Dosierung (2 x 2,5 mg) durch die europäischen Behörden zur Behandlung von Patienten mit überlebtem akuten Koronarsyndrom (ACS) sein werden, ist noch unklar. Entsprechend des Designs der ATLAS-2-Studie wird sich die Anwendung auf die Kombinationstherapie mit ASS und Clopidogrel als antithrombotische Tripletherapie beschränken. Die meisten Patienten werden in Deutschland nach ACS jedoch mit einem der neueren Adenosindiphosphat (ADP)-Hemmer Ticagrelor oder Prasugrel und nicht mit Clopidogrel behandelt. Für diese Patienten wird in absehbarer Zeit noch keine plasmatische Antikoagulation in austitrierter, niedriger Dosierung zur Verfügung stehen, obwohl dieses Konzept zur Minimierung der Thrombinbildung pathophysiologisch sinnvoll ist. Überraschend war die negative Beurteilung der intravenösen ADP-Hemmung mit Cangrelor durch das Beratergremium der US-amerikanischen Zulassungsbehörde. Überraschend war aber auch die positive Bewertung der dreifachen Thrombozytenhemmung mit ASS, Clopidogrel und Vorapaxar, dem ersten Vertreter der neuen Substanzklasse der Thrombinrezeptor-Hemmer, zur Sekundärprophylaxe von Patienten mit überlebtem ACS (bei negativer Schlaganfall-Anamnese).

Summary

It is not yet clear how many patients will be treated with the recently approved rivaroxaban after acute coronary syndrome (ACS), because according to the design of the ATLAS-2 trial, it will be combined with aspirin and clopidogrel. Following the European guidelines, most ACS patients are currently treated with one of the newer adenosine diphosphate (ADP) receptor blockers ticagrelor or prasugrel however, and not with clopidogrel. Although the concept of limiting thrombin generation with low-dose anticoagulation is intriguing, it will not be available for these patients in the near future. It was surprising that the Food and Drug Administration advisory panel voted against approving cangrelor for intravenous ADP inhibition, but supported thrombin receptor inhibition with vorapaxar. Vorapaxar is a member of a novel antiplatelet agent class that was beneficial in ACS patients without history of stroke or transitoric ischemic attack in combination with aspirin and clopidogrel.

 
  • Literatur

  • 1 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
  • 2 Steg PG, James SK, Atar D et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33: 2569-2619
  • 3 Heusch G. Cardioprotection: chances and challenges of its translation to the clinic. Lancet 2013; 381: 166-175
  • 4 Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med 2007; 357: 1121-1135
  • 5 Hopenfeld B, John MS, Fischell DR et al. The Guardian: an implantable system for chronic ambulatory monitoring of acute myocardial infarction. Journal of electrocardiology 2009; 42: 481-486
  • 6 Asbach S, Weiss I, Wenzel B, Bode C, Zehender M. Intrathoracic far-field electrocardiogram allows continuous monitoring of ischemia after total coronary occlusion. Pacing and clinical electrophysiology: PACE 2006; 29: 1334-1340
  • 7 Fischell TA, Fischell DR, Avezum A et al. Initial clinical results using intracardiac electrogram monitoring to detect and alert patients during coronary plaque rupture and ischemia. J Am Coll Cardiol 2010; 56: 1089-1098
  • 8 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
  • 9 Mahaffey KW, Wojdyla DM, Carroll K et al. Ticagrelor compared with clopidogrel by geographic region in the Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation 2011; 124: 544-554
  • 10 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
  • 11 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
  • 12 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
  • 13 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
  • 14 Heestermans T, van 't Hof AW, ten Berg JM et al. The golden hour of prehospital reperfusion with triple antiplatelet therapy: a sub-analysis from the Ongoing Tirofiban in Myocardial Evaluation 2 (On-TIME 2) trial early initiation of triple antiplatelet therapy. Am Heart J 2010; 160: 1079-1084
  • 15 Stone GW, Witzenbichler B, Guagliumi G et al. Heparin plus a glycoprotein IIb/IIIa inhibitor versus bivalirudin monotherapy and paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction (HORIZONS-AMI): final 3-year results from a multicentre, randomised controlled trial. Lancet 2011; 377: 2193-2204
  • 16 Stone GW, Witzenbichler B, Guagliumi G et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008; 358: 2218-2230
  • 17 Davi G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007; 357: 2482-2494
  • 18 Leon MB, Baim DS, Popma JJ et al. A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators. N Engl J Med 1998; 339: 1665-1671
  • 19 Duerschmied D, Bode C, Moser M. Clopidogrel in acute coronary syndrome: implications of recent study findings. Expert Rev Cardiovasc Ther 2010; 8: 1215-1229
  • 20 Yusuf S, Mehta SR, Zhao F et al. Early and late effects of clopidogrel in patients with acute coronary syndromes. Circulation 2003; 107: 966-972
  • 21 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
  • 22 Harrington RA, Stone GW, McNulty S et al. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med 2009; 361: 2318-2329
  • 23 Bhatt DL, Lincoff AM, Gibson CM et al. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med 2009; 361: 2330-2341
  • 24 Bhatt DL, Stone GW, Mahaffey KW et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med 2013; 368: 1303-1313
  • 25 Steg PG, Bhatt DL, Hamm CW et al. Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data. Lancet 2013; 382: 1981-1992
  • 26 Duerschmied D, Bode C. Vorapaxar expands antiplatelet options. Which patients may benefit from thrombin receptor antagonism?. Hamostaseologie 2012; 32: 221-227
  • 27 Tricoci P, Huang Z, Held C et al. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med 2012; 366: 20-33
  • 28 Leonardi S, Tricoci P, White HD et al. Effect of vorapaxar on myocardial infarction in the thrombin receptor antagonist for clinical event reduction in acute coronary syndrome (TRA.CER) trial. Eur Heart J 2013; 34: 1723-1731
  • 29 Morrow DA, Braunwald E, Bonaca MP et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med 2012; 366: 1404-1413
  • 30 Silvain J, Collet JP, Nagaswami C et al. Composition of coronary thrombus in acute myocardial infarction. J Am Coll Cardiol 2011; 57: 1359-1367
  • 31 Duerschmied D, Bode C. Brauchen wir Plättchenhemmer und Antikoagulation nach einem akuten Koronarsyndrom?. Vasomed 2013; 3: 138-141
  • 32 Rothberg MB, Celestin C, Fiore LD et al. Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: meta-analysis with estimates of risk and benefit. Ann Intern Med 2005; 143: 241-250
  • 33 Duerschmied D, Moser M, Bode C. Neueste Daten und praktische Erfahrungen mit neuen oralen Antikoagulantien (NOAK) – Welche Patientenkollektive profitieren besonders?. Klinikarzt 2013; 42 (S1): 9-14
  • 34 Uchino K, Hernandez AV et al. Dabigatran association with higher risk of acute coronary events: meta-analysis of noninferiority randomized controlled trials.. Arch Intern Med 2012; 172: 397-402
  • 35 Schulman S, Kearon C, Kakkar AK et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 2013; 368: 709-718
  • 36 Alexander JH, Lopes RD, James S et al. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med 2011; 365: 699-708
  • 37 Mega JL, Braunwald E, Wiviott SD et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2012; 366: 9-19
  • 38 Mega JL, Braunwald E, Murphy SA et al. Rivaroxaban in Patients Stabilized after a ST-Elevation Myocardial Infarction: Results from the ATLAS ACS 2-TIMI 51 Trial. J Am Coll Cardiol 2013; 61: 1853-1859
  • 39 Verheugt FW. Antithrombotic therapy during and after percutaneous coronary intervention in patients with atrial fibrillation. Circulation 2013; 128: 2058-2061
  • 40 Moser M, Olivier CB, Bode C. Triple antithrombotic therapy in cardiac patients: more questions than answers. Eur Heart J 2014; 35: 216-223
  • 41 Ahrens I, Peter K, Lip GY, Bode C. Development and clinical applications of novel oral anticoagulants. Part II. Drugs under clinical investigation. Discov Med 2012; 13: 445-450