CC BY 4.0 · Thromb Haemost 2019; 119(10): 1583-1589
DOI: 10.1055/s-0039-1679903
Theme Issue Article
Georg Thieme Verlag KG Stuttgart · New York

Dual Antiplatelet or Dual Antithrombotic Therapy for Secondary Prevention in High-Risk Patients with Stable Coronary Artery Disease?

Wael Sumaya
1   Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
,
Tobias Geisler
2   Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen, Germany
,
Steen D. Kristensen
3   Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
,
Robert F. Storey
1   Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
› Institutsangaben
Funding W.S. was funded by British Heart Foundation Clinical Research Training Fellowship (FS/15/82/31824).
Weitere Informationen

Publikationsverlauf

11. Oktober 2018

10. Januar 2019

Publikationsdatum:
05. März 2019 (online)

Abstract

Antithrombotic treatment is a key component of secondary prevention following acute coronary syndromes (ACS). Although dual antiplatelet therapy is standard therapy post-ACS, duration of treatment is the subject of ongoing debate. Prolonged dual antiplatelet therapy in high-risk patients with history of myocardial infarction reduced the risk of recurrent myocardial infarction, stroke or cardiovascular death. Similarly, in patients with stable coronary artery disease, two-thirds of whom had a history of myocardial infarction, dual antithrombotic therapy with very-low-dose rivaroxaban and aspirin also resulted in improved ischaemic outcomes. In the absence of head-to-head comparison, choosing the most appropriate treatment strategy can be challenging, particularly when it comes to balancing the risks of ischaemia and bleeding. We aim to review the evidence for currently available antithrombotic treatments and provide a practical algorithm to aid the decision-making process.

 
  • References

  • 1 Roffi M, Patrono C, Collet JP. , et al; ESC Scientific Document Group. 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 (03) 267-315
  • 2 Ibanez B, James S, Agewall S. , et al; ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2018; 39 (02) 119-177
  • 3 Bonaca MP, Bhatt DL, Cohen M. , et al; PEGASUS-TIMI 54 Steering Committee and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015; 372 (19) 1791-1800
  • 4 Udell JA, Bonaca MP, Collet JP. , et al. Long-term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta-analysis of randomized trials. Eur Heart J 2016; 37 (04) 390-399
  • 5 Eikelboom JW, Connolly SJ, Bosch J. , et al; COMPASS Investigators. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med 2017; 377 (14) 1319-1330
  • 6 Storey RF. Biology and pharmacology of the platelet P2Y12 receptor. Curr Pharm Des 2006; 12 (10) 1255-1259
  • 7 Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. ; 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 (07) 494-502
  • 8 Wiviott SD, Braunwald E, McCabe CH. , et al; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357 (20) 2001-2015
  • 9 Wallentin L, Becker RC, Budaj A. , et al; PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361 (11) 1045-1057
  • 10 Borst O, Münzer P, Alnaggar N. , et al. Inhibitory mechanisms of very low-dose rivaroxaban in non-ST-elevation myocardial infarction. Blood Adv 2018; 2 (06) 715-730
  • 11 Sumaya W, Parker WAE, Fretwell R. , et al. Pharmacodynamic effects of a 6-hour regimen of enoxaparin in patients undergoing primary percutaneous coronary intervention (PENNY PCI Study). Thromb Haemost 2018; 118 (07) 1250-1256
  • 12 Sumaya W, Wallentin L, James SK. , et al. Fibrin clot properties independently predict adverse clinical outcome following acute coronary syndrome: a PLATO substudy. Eur Heart J 2018; 39 (13) 1078-1085
  • 13 Roe MT, Armstrong PW, Fox KA. , et al; TRILOGY ACS Investigators. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med 2012; 367 (14) 1297-1309
  • 14 Jernberg T, Hasvold P, Henriksson M, Hjelm H, Thuresson M, Janzon M. Cardiovascular risk in post-myocardial infarction patients: nationwide real world data demonstrate the importance of a long-term perspective. Eur Heart J 2015; 36 (19) 1163-1170
  • 15 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 (16) 1706-1717
  • 16 Mauri L, Kereiakes DJ, Yeh RW. , et al; DAPT Study Investigators. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 2014; 371 (23) 2155-2166
  • 17 Yeh RW, Kereiakes DJ, Steg PG. , et al; DAPT Study Investigators. Benefits and risks of extended duration dual antiplatelet therapy after PCI in patients with and without acute myocardial infarction. J Am Coll Cardiol 2015; 65 (20) 2211-2221
  • 18 Storey RF, Angiolillo DJ, Bonaca MP. , et al. Platelet inhibition with ticagrelor 60 mg versus 90 mg twice daily in the PEGASUS-TIMI 54 trial. J Am Coll Cardiol 2016; 67 (10) 1145-1154
  • 19 Bonaca MP, Bhatt DL, Oude Ophuis T. , et al. Long-term tolerability of ticagrelor for the secondary prevention of major adverse cardiovascular events: a secondary analysis of the PEGASUS-TIMI 54 trial. JAMA Cardiol 2016; 1 (04) 425-432
  • 20 Bonaca MP, Bhatt DL, Storey RF. , et al. Ticagrelor for prevention of ischemic events after myocardial infarction in patients with peripheral artery disease. J Am Coll Cardiol 2016; 67 (23) 2719-2728
  • 21 Magnani G, Storey RF, Steg G. , et al. Efficacy and safety of ticagrelor for long-term secondary prevention of atherothrombotic events in relation to renal function: insights from the PEGASUS-TIMI 54 trial. Eur Heart J 2016; 37 (04) 400-408
  • 22 Bhatt DL, Bonaca MP, Bansilal S. , et al. Reduction in ischemic events with ticagrelor in diabetic patients with prior myocardial infarction in PEGASUS-TIMI 54. J Am Coll Cardiol 2016; 67 (23) 2732-2740
  • 23 Bansilal S, Bonaca MP, Cornel JH. , et al. Ticagrelor for secondary prevention of atherothrombotic events in patients with multivessel coronary disease. J Am Coll Cardiol 2018; 71 (05) 489-496
  • 24 Valgimigli M, Bueno H, Byrne RA. , et al; ESC Scientific Document Group; ESC Committee for Practice Guidelines (CPG); ESC National Cardiac Societies. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: the Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2018; 39 (03) 213-260
  • 25 Smith P, Arnesen H, Holme I. The effect of warfarin on mortality and reinfarction after myocardial infarction. N Engl J Med 1990; 323 (03) 147-152
  • 26 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 (17) 1084-1089
  • 27 Leon MB, Baim DS, Popma JJ. , et al; Stent Anticoagulation Restenosis Study Investigators. A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. N Engl J Med 1998; 339 (23) 1665-1671
  • 28 Alexander JH, Lopes RD, James S. , et al; APPRAISE-2 Investigators. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med 2011; 365 (08) 699-708
  • 29 Mega JL, Braunwald E, Wiviott SD. , et al; ATLAS ACS 2–TIMI 51 Investigators. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2012; 366 (01) 9-19
  • 30 Ohman EM, Roe MT, Steg PG. , et al. Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial. Lancet 2017; 389 (10081): 1799-1808
  • 31 Bonaca MP, Bhatt DL, Steg G. , et al. Efficacy of long-term ticagrelor in stented patients in PEGASUS-TIMI 54. J Am Coll Cardiol 2015; 66 (Suppl B): B36
  • 32 Zannad F, Anker SD, Byra WM. , et al; COMMANDER HF Investigators. Rivaroxaban in patients with heart failure, sinus rhythm, and coronary disease. N Engl J Med 2018; 379 (14) 1332-1342
  • 33 Costa F, van Klaveren D, James S. , et al; PRECISE-DAPT Study Investigators. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet 2017; 389 (10073): 1025-1034
  • 34 Caplain H, Donat F, Gaud C, Necciari J. Pharmacokinetics of clopidogrel. Semin Thromb Hemost 1999; 25 (Suppl. 02) 25-28
  • 35 Stone GW, Witzenbichler B, Weisz G. , et al; ADAPT-DES Investigators. Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study. Lancet 2013; 382 (9892): 614-623
  • 36 Orme RC, Parker WAE, Thomas MR. , et al. Study of two dose regimens of ticagrelor compared with clopidogrel in patients undergoing percutaneous coronary intervention for stable coronary artery disease (STEEL-PCI). Circulation 2018. Doi: CIRCULATIONAHA.118.034790
  • 37 Payne CD, Li YG, Small DS. , et al. Increased active metabolite formation explains the greater platelet inhibition with prasugrel compared to high-dose clopidogrel. J Cardiovasc Pharmacol 2007; 50 (05) 555-562
  • 38 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 (25) 2577-2585
  • 39 Berwanger O, Nicolau JC, Carvalho AC. , et al; TREAT Study Group. Ticagrelor vs clopidogrel after fibrinolytic therapy in patients with ST-elevation myocardial infarction: a randomized clinical trial. JAMA Cardiol 2018; 3 (05) 391-399
  • 40 Welsh JD, Stalker TJ, Voronov R. , et al. A systems approach to hemostasis: 1. The interdependence of thrombus architecture and agonist movements in the gaps between platelets. Blood 2014; 124 (11) 1808-1815