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Kardiologie up2date 2016; 12(04): 359-369
DOI: 10.1055/s-0042-120218
Thrombozyten und Gerinnungssystem bei kardiovaskulären Erkrankungen
© Georg Thieme Verlag KG Stuttgart · New York

Dauer der dualen antithrombozytären Therapie bei koronaren Risikopatienten[*]

Dominik Rath
,
Meinrad Gawaz
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Publication History

Publication Date:
22 December 2016 (online)

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Abstract

Recent guidelines suggest a dual antiplatelet therapy after „drug-eluting“ stent (DES) implantation for 6 months in stable patients and for 12 months in patients after acute coronary syndrome (ACS). Serious complications after stent implantation include stent thrombosis, recurrent myocardial infarction, ischemic stroke, cardiovascular death and bleeding. These complications also occur beyond one year after coronary intervention. Thus, the question arises, whether a prolonged dual antiplatelet therapy ( > 12 months after PCI) is of benefit to lower thromboischemic events in high-risk patients. Recent randomized clinical studies (DAPT, ITALIC, OPTIDUAL and PEGASUS) have addressed this important clinical issue. The results of these studies are summarized and discussed.

Kernaussagen

  • Derzeitige Leitlinien empfehlen eine duale antithrombozytäre Therapie für 6 – (12) Monate bei stabiler KHK und für 12 Monate bei ACS nach PCI.

  • Eine Verlängerung der DAPT über die in den Leitlinien empfohlene Dauer hinaus ist nach den Ergebnissen großer randomisierter Studien nicht generell zu empfehlen.

  • Eine verlängerte DAPT geht mit selteneren thromboischämischen Ereignissen einher, aber auch mit signifikant häufigeren schwerwiegenden Blutungen.

  • Hochrisikopatienten wie Patienten mit Diabetes, Niereninsuffizienz oder einem Myokardinfarkt in der Anamnese, die ein hohes langfristiges Risiko für thromboischämische Ereignisse aufweisen, können von einer verlängerten DAPT über die derzeit empfohlene Dauer profitieren.

  • Die aktuellen Leitlinien lassen die Möglichkeit offen, die DAPT in begründeten Einzelfällen – individuell für den Patienten – zu verlängern.

  • Dabei sollte jedoch das individuelle Blutungsrisiko berücksichtigt und die Verlängerung bei Patienten angewendet werden, welche die DAPT initial ohne Blutungsereignisse vertragen haben.

* Aktualisierte und erweiterte Fassung von Rath D, Gawaz M. Wie lange duale antithrombozytäre Therapie bei koronaren Risikopatienten? Aktuel Kardiol 2016; 5: 362 – 366.


 

  • Literatur

  • 1 Gawaz M, Langer H, May AE. Platelets in inflammation and atherogenesis. J Clin Invest 2005; 115: 3378-3384
    CrossrefPubMedGoogle Scholar
  • 2 May AE, Seizer P, Gawaz M. Platelets: inflammatory firebugs of vascular walls. Arterioscler Thromb Vasc Biol 2008; 28: 5-10
    CrossrefPubMedGoogle Scholar
  • 3 Müller I, Besta F, Schulz C et al. Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb Haemost 2003; 89: 783-787
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Geisler T, Langer H, Wydymus M et al. Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation. Eur Heart J 2006; 27: 2420-2425
    CrossrefPubMedGoogle Scholar
  • 5 Hochholzer W, Trenk D, Bestehorn HP et al. Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement. J Am Coll Cardiol 2006; 48: 1742-1750
    CrossrefPubMedGoogle Scholar
  • 6 Vasina E, Heemskerk JW, Weber C et al. Platelets and platelet-derived microparticles in vascular inflammatory disease. Inflamm Allergy Drug Targets 2010; 9: 346-354
    CrossrefPubMedGoogle Scholar
  • 7 Burgstahler C, Geisler T, Lindemann S et al. Elevated coronary calcium scores are associated with higher residual platelet aggregation after clopidogrel treatment in patients with stable angina pectoris. Int J Cardiol 2009; 135: 132-135
    CrossrefPubMedGoogle Scholar
  • 8 Fateh-Moghadam S, Li Z, Ersel S et al. Platelet degranulation is associated with progression of intima-media thickness of the common carotid artery in patients with diabetes mellitus type 2. Arterioscler Thromb Vasc Biol 2005; 25: 1299-1303
    CrossrefPubMedGoogle Scholar
  • 9 Fateh-Moghadam S, Bocksch W, Ruf A et al. Changes in surface expression of platelet membrane glycoproteins and progression of heart transplant vasculopathy. Circulation 2000; 102: 890-897
    CrossrefPubMedGoogle Scholar
  • 10 Massberg S, Brand K, Grüner S et al. A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation. J Exp Med 2002; 196: 887-896
    CrossrefPubMedGoogle Scholar
  • 11 Chatterjee M, Gawaz M. Platelet-derived CXCL12 (SDF-1α): basic mechanisms and clinical implications. J Thromb Haemost 2013; 11: 1954-1967
    CrossrefPubMedGoogle Scholar
  • 12 Gawaz M, Vogel S. Platelets in tissue repair: control of apoptosis and interactions with regenerative cells. Blood 2013; 122: 2550-2554
    CrossrefPubMedGoogle Scholar
  • 13 Daub K, Langer H, Seizer P et al. Platelets induce differentiation of human CD34+ progenitor cells into foam cells and endothelial cells. FASEB J 2006; 20: 2559-2561
    CrossrefPubMedGoogle Scholar
  • 14 Siegel-Axel D, Daub K, Seizer P et al. Platelet lipoprotein interplay: trigger of foam cell formation and driver of atherosclerosis. Cardiovasc Res 2008; 78: 8-17
    CrossrefPubMedGoogle Scholar
  • 15 Schober A. Bedeutung von Chemokinen in der Atherogenese. Kardiologie up2date 2011; 7: 269-275
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Windecker S, Kolh P, Alfonso F. Authors/Task Force members et al. 2014 ESC/EACTS 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). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2014; 35: 2541-2619
    CrossrefPubMedGoogle Scholar
  • 17 Müller I, Seyfarth M, Rüdiger S et al. Effect of a high loading dose of clopidogrel on platelet function in patients undergoing coronary stent placement. Heart 2001; 85: 92-93
    CrossrefPubMedGoogle Scholar
  • 18 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
  • 19 Geisler T, Zürn C, Simonenko R et al. Early but not late stent thrombosis is influenced by residual platelet aggregation in patients undergoing coronary interventions. Eur Heart J 2010; 31: 59-66
    CrossrefPubMedGoogle Scholar
  • 20 Sibbing D, Barthel P, Abbrederis K et al. Intracardiac right ventricular metastatic tumor of malignant T-cell lymphoma. Int J Cardiol 2007; 117: 84-85
    CrossrefPubMedGoogle Scholar
  • 21 Yusuf S, Zhao F, Mehta SR et al. 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
  • 22 Reny JL, Berdagué P, Poncet A et al. Antiplatelet Drug Resistances and Ischemic Events (ADRIE) Study Group. Antiplatelet Drug Response Status Does Not Predict Recurrent Ischaemic Events in Stable Cardiovascular Patients: Results of the Antiplatelet Drug Resistances and Ischaemic Events Study. Circulation 2012; 125: 3201-3210
    CrossrefPubMedGoogle Scholar
  • 23 Pettersen AÅ, Seljeflot I, Abdelnoor M et al. High On-Aspirin Platelet Reactivity and Clinical Outcome in Patients With Stable Coronary Artery Disease: Results From ASCET (Aspirin Nonresponsiveness and Clopidogrel Endpoint Trial). J Amer Heart Association 2012; 1: e000703
    PubMedGoogle Scholar
  • 24 Stone GW, Moses JW, Ellis SG et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med 2007; 356: 998-1008
    CrossrefPubMedGoogle Scholar
  • 25 Levine GN, Bates ER, Blankenship JC et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation 2011; 124: 574-651
    CrossrefPubMedGoogle Scholar
  • 26 Windecker S, Kolh P, Alfonso F. Authors/Task Force members et al. 2014 ESC/EACTS 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) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2014; 35: 2541-2619
    CrossrefPubMedGoogle Scholar
  • 27 Roffi M, Patrono C, Collet JP et al. Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 2016; 37: 267-315
    CrossrefPubMedGoogle Scholar
  • 28 Levine GN, Bates ER, Bittl JA. Focused Update Writing Group et al. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2016; 152: 1243-1275
    PubMedGoogle Scholar
  • 29 Claessen BE, Henriques JP, Jaffer FA et al. Stent thrombosis: a clinical perspective. JACC Cardiovasc Interv 2014; 7: 1081-1092
    CrossrefPubMedGoogle Scholar
  • 30 Bhatt DL, Fox KA, Hacke W et al. CHARISMA Investigators. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006; 354: 1706-1717
    CrossrefPubMedGoogle Scholar
  • 31 Mauri L, Kereiakes DJ, Yeh RW. DAPT Study Investigators et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 2014; 371: 2155-2166
    CrossrefPubMedGoogle Scholar
  • 32 Gilard M, Barragan P, Noryani AA et al. 6- versus 24-month dual antiplatelet therapy after implantation of drug-eluting stents in patients nonresistant to aspirin: the randomized, multicenter ITALIC trial. J Am Coll Cardiol 2015; 65: 777-786
    CrossrefPubMedGoogle Scholar
  • 33 Helft G, Steg PG, Le Feuvre C. OPTImal DUAL Antiplatelet Therapy Trial Investigators et al. Stopping or continuing clopidogrel 12 months after drug-eluting stent placement: the OPTIDUAL randomized trial. Eur Heart J 2016; 37: 365-374
    PubMedGoogle Scholar
  • 34 Bonaca MP, Bhatt DL, Cohen M. PEGASUS-TIMI 54 Steering Committee and Investigators et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015; 372: 1791-1800
    CrossrefPubMedGoogle Scholar
  • 35 Krumholz HM, Wang Y, Chen J et al. Reduction in acute myocardial infarction mortality in the United States: risk-standardized mortality rates from 1995–2006. JAMA 2009; 302: 767-773
    CrossrefPubMedGoogle Scholar
  • 36 Nauta ST, Deckers JW, Akkerhuis M et al. Changes in clinical profile, treatment, and mortality in patients hospitalised for acute myocardial infarction between 1985 and 2008. PLoS One 2011; 6: e26917
    CrossrefPubMedGoogle Scholar
  • 37 Bhatt DL, Eagle KA, Ohman EM. REACH Registry Investigators et al. Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis. JAMA 2010; 304: 1350-1357
    CrossrefPubMedGoogle Scholar
  • 38 Rioufol G, Finet G, Ginon I et al. Multiple atherosclerotic plaque rupture in acute coronary syndrome: a three-vessel intravascular ultrasound study. Circulation 2002; 106: 804-808
    CrossrefPubMedGoogle Scholar
  • 39 Nakatani D, Sakata Y, Suna S. Osaka Acute Coronary Insufficiency Study (OACIS) Investigators et al. Incidence, predictors, and subsequent mortality risk of recurrent myocardial infarction in patients following discharge for acute myocardial infarction. Circ J 2013; 77: 439-446
    CrossrefPubMedGoogle Scholar