Download PDF
Thromb Haemost 2021; 121(07): 854-866
DOI: 10.1055/s-0040-1722188
Review Article

Antithrombotic Therapy in Acute Coronary Syndromes: Current Evidence and Ongoing Issues Regarding Early and Late Management

Paul Guedeney
1   Sorbonne Université, ACTION Study Group, INSERM UMRS_1166, Institut de Cardiologie, Pitié Salpêtrière (AP-HP), Paris, France
,
Jean-Philippe Collet 
1   Sorbonne Université, ACTION Study Group, INSERM UMRS_1166, Institut de Cardiologie, Pitié Salpêtrière (AP-HP), Paris, France
› Author Affiliations Funding None.
› Further Information
   Permissions and Reprints

Abstract

A few decades ago, the understanding of the pathophysiological processes involved in the coronary artery thrombus formation has placed anticoagulant and antiplatelet agents at the core of the management of acute coronary syndrome (ACS). Increasingly potent antithrombotic agents have since been evaluated, in various association, timing, or dosage, in numerous randomized controlled trials to interrupt the initial thrombus formation, prevent ischemic complications, and ultimately improve survival. Primary percutaneous coronary intervention, initial parenteral anticoagulation, and dual antiplatelet therapy with potent P2Y12 inhibitors have become the hallmark of ACS management revolutionizing its prognosis. Despite these many improvements, much more remains to be done to optimize the onset of action of the various antithrombotic therapies, for further treating and preventing thrombotic events without exposing the patients to an unbearable hemorrhagic risk. The availability of various potent P2Y12 inhibitors has opened the door for individualized therapeutic strategies based on the clinical setting as well as the ischemic and bleeding risk of the patients, while the added value of aspirin has been recently challenged. The strategy of dual-pathway inhibition with P2Y12 inhibitors and low-dose non-vitamin K antagonist oral anticoagulant has brought promising results for the early and late management of patients presenting with ACS with and without indication for oral anticoagulation. In this updated review, we aimed at describing the evidence supporting the current gold standard of antithrombotic management of ACS. More importantly, we provide an overview of some of the ongoing issues and promising therapeutic strategies of this ever-evolving topic.

Keywords

antiplatelet agents - acute myocardial infarction - coronary syndrome


Publication History

Received: 23 September 2020

Accepted: 12 November 2020

Article published online:
27 January 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Szummer K, Jernberg T, Wallentin L. From early pharmacology to recent pharmacology interventions in acute coronary syndromes: JACC state-of-the-art review. J Am Coll Cardiol 2019; 74 (12) 1618-1636
    CrossrefPubMedGoogle Scholar
  • 2 Sibbing D, Angiolillo DJ, Huber K. Antithrombotic therapy for acute coronary syndrome: past, present and future. Thromb Haemost 2017; 117 (07) 1240-1248
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Silvain J, Collet J-P, Nagaswami C. et al. Composition of coronary thrombus in acute myocardial infarction. J Am Coll Cardiol 2011; 57 (12) 1359-1367
    CrossrefPubMedGoogle Scholar
  • 4 Silvain J, Collet J-P, Guedeney P. et al. Thrombus composition in sudden cardiac death from acute myocardial infarction. Resuscitation 2017; 113: 108-114
    CrossrefPubMedGoogle Scholar
  • 5 Roth GA, Johnson C, Abajobir A. et al. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J Am Coll Cardiol 2017; 70 (01) 1-25
    CrossrefPubMedGoogle Scholar
  • 6 Guedeney P, Aboyans V, Dalon F. et al. Epidemiology, treatment patterns and outcomes in patients with coronary or lower extremity artery disease in France. Arch Cardiovasc Dis 2019; 112 (11) 670-679
    CrossrefPubMedGoogle Scholar
  • 7 Guedeney P, Montalescot G. GLOBAL LEADERS: looking now at the bigger picture. EuroIntervention 2019; 15 (12) e1030-e1032
    CrossrefPubMedGoogle Scholar
  • 8 Guedeney P, Collet J-P. Diagnosis and management of acute coronary syndrome: what is new and why? Insight from the 2020 European Society of Cardiology guidelines. J Clin Med 2020; 9 (11) 3474
    CrossrefPubMedGoogle Scholar
  • 9 Libby P. Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med 2013; 368 (21) 2004-2013
    CrossrefPubMedGoogle Scholar
  • 10 Spronk HMH, Padro T, Siland JE. et al. Atherothrombosis and thromboembolism: position paper from the Second Maastricht Consensus Conference on Thrombosis. Thromb Haemost 2018; 118 (02) 229-250
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Trenk D, Hille L, Leggewie S. et al. Antagonizing P2Y12 receptor inhibitors: current and future options. Thromb Haemost 2019; 119 (10) 1606-1616
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Gorog DA, Geisler T. Platelet inhibition in acute coronary syndrome and percutaneous coronary intervention: insights from the past and present. Thromb Haemost 2020; 120 (04) 565-578
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Zeitouni M, Kerneis M, Nafee T, Collet JP, Silvain J, Montalescot G. Anticoagulation in acute coronary syndrome-state of the art. Prog Cardiovasc Dis 2018; 60 (4–5): 508-513
    CrossrefPubMedGoogle Scholar
  • 14 Geddings JE, Mackman N. Recently identified factors that regulate hemostasis and thrombosis. Thromb Haemost 2014; 111 (04) 570-574
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet 1988; 2 (8607): 349-360
    PubMedGoogle Scholar
  • 16 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
    CrossrefPubMedGoogle Scholar
  • 17 Collet J-P, Hulot J-S, Pena A. et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet 2009; 373 (9660): 309-317
    CrossrefPubMedGoogle Scholar
  • 18 Bonello L, Tantry US, Marcucci R. et al; Working Group on High On-Treatment Platelet Reactivity. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 2010; 56 (12) 919-933
    CrossrefPubMedGoogle Scholar
  • 19 Silvain J, Cayla G, Hulot J-S. et al. High on-thienopyridine platelet reactivity in elderly coronary patients: the SENIOR-PLATELET study. Eur Heart J 2012; 33 (10) 1241-1249
    CrossrefPubMedGoogle Scholar
  • 20 Hulot J-S, Collet J-P, Silvain J. et al. Cardiovascular risk in clopidogrel-treated patients according to cytochrome P450 2C19*2 loss-of-function allele or proton pump inhibitor coadministration: a systematic meta-analysis. J Am Coll Cardiol 2010; 56 (02) 134-143
    CrossrefPubMedGoogle Scholar
  • 21 Sibbing D, Aradi D, Alexopoulos D. et al. Updated expert consensus statement on platelet function and genetic testing for guiding P2Y12 receptor inhibitor treatment in percutaneous coronary intervention. JACC Cardiovasc Interv 2019; 12 (16) 1521-1537
    CrossrefPubMedGoogle Scholar
  • 22 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
    CrossrefPubMedGoogle Scholar
  • 23 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
    CrossrefPubMedGoogle Scholar
  • 24 Montalescot G, Wiviott SD, Braunwald E. et al; TRITON-TIMI 38 investigators. 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 (9665): 723-731
    CrossrefPubMedGoogle Scholar
  • 25 Roffi M, Patrono C, Collet J-P. 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
    CrossrefPubMedGoogle Scholar
  • 26 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
    CrossrefPubMedGoogle Scholar
  • 27 Collet J-P, Thiele H, Barbato E. et al. 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2020; DOI: 10.1093/eurheartj/ehaa575.
    CrossrefPubMedGoogle Scholar
  • 28 Montalescot G, Bolognese L, Dudek D. et al; ACCOAST Investigators. Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes. N Engl J Med 2013; 369 (11) 999-1010
    CrossrefPubMedGoogle Scholar
  • 29 Steg PG, Bhatt DL, Hamm CW. et al; CHAMPION Investigators. Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data. Lancet 2013; 382 (9909): 1981-1992
    CrossrefPubMedGoogle Scholar
  • 30 Grimfjärd P, Lagerqvist B, Erlinge D, Varenhorst C, James S. Clinical use of cangrelor: nationwide experience from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Eur Heart J Cardiovasc Pharmacother 2019; 5 (03) 151-157
    CrossrefPubMedGoogle Scholar
  • 31 Montalescot G, Barragan P, Wittenberg O. et al; ADMIRAL Investigators. Abciximab before Direct Angioplasty and Stenting in Myocardial Infarction Regarding Acute and Long-Term Follow-up. Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med 2001; 344 (25) 1895-1903
    CrossrefPubMedGoogle Scholar
  • 32 De Luca G, Navarese E, Marino P. Risk profile and benefits from Gp IIb-IIIa inhibitors among patients with ST-segment elevation myocardial infarction treated with primary angioplasty: a meta-regression analysis of randomized trials. Eur Heart J 2009; 30 (22) 2705-2713
    CrossrefPubMedGoogle Scholar
  • 33 Mehran R, Pocock S, Nikolsky E. et al. Impact of bleeding on mortality after percutaneous coronary intervention results from a patient-level pooled analysis of the REPLACE-2 (randomized evaluation of PCI linking angiomax to reduced clinical events), ACUITY (acute catheterization and urgent intervention triage strategy), and HORIZONS-AMI (harmonizing outcomes with revascularization and stents in acute myocardial infarction) trials. JACC Cardiovasc Interv 2011; 4 (06) 654-664
    CrossrefPubMedGoogle Scholar
  • 34 Neumann F-J, Sousa-Uva M, Ahlsson A. et al; ESC Scientific Document Group. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J 2019; 40 (02) 87-165
    CrossrefPubMedGoogle Scholar
  • 35 Montalescot G, Collet JP, Tanguy ML. et al. Anti-Xa activity relates to survival and efficacy in unselected acute coronary syndrome patients treated with enoxaparin. Circulation 2004; 110 (04) 392-398
    CrossrefPubMedGoogle Scholar
  • 36 Montalescot G, White HD, Gallo R. et al; STEEPLE Investigators. Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention. N Engl J Med 2006; 355 (10) 1006-1017
    CrossrefPubMedGoogle Scholar
  • 37 Guedeney P, Hammoudi N, Duthoit G. et al. Intravenous enoxaparin anticoagulation in percutaneous left atrial cardiac procedures. EuroIntervention 2017; 13 (10) 1226-1233
    CrossrefPubMedGoogle Scholar
  • 38 Collet J-P, Huber K, Cohen M. et al; ATOLL Investigators. A direct comparison of intravenous enoxaparin with unfractionated heparin in primary percutaneous coronary intervention (from the ATOLL trial). Am J Cardiol 2013; 112 (09) 1367-1372
    CrossrefPubMedGoogle Scholar
  • 39 Silvain J, Beygui F, Barthélémy O. et al. Efficacy and safety of enoxaparin versus unfractionated heparin during percutaneous coronary intervention: systematic review and meta-analysis. BMJ 2012; 344: e553
    CrossrefPubMedGoogle Scholar
  • 40 Kastrati A, Neumann F-J, Schulz S. et al; ISAR-REACT 4 Trial Investigators. Abciximab and heparin versus bivalirudin for non-ST-elevation myocardial infarction. N Engl J Med 2011; 365 (21) 1980-1989
    CrossrefPubMedGoogle Scholar
  • 41 Stone GW, Witzenbichler B, Guagliumi G. et al; HORIZONS-AMI Trial Investigators. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008; 358 (21) 2218-2230
    CrossrefPubMedGoogle Scholar
  • 42 Capodanno D, De Caterina R. Bivalirudin for acute coronary syndromes: premises, promises and doubts. Thromb Haemost 2015; 113 (04) 698-707
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Valgimigli M, Frigoli E, Leonardi S. et al; MATRIX Investigators. Bivalirudin or unfractionated heparin in acute coronary syndromes. N Engl J Med 2015; 373 (11) 997-1009
    CrossrefPubMedGoogle Scholar
  • 44 Erlinge D, Omerovic E, Fröbert O. et al. Bivalirudin versus heparin monotherapy in myocardial infarction. N Engl J Med 2017; 377 (12) 1132-1142
    CrossrefPubMedGoogle Scholar
  • 45 Bikdeli B, McAndrew T, Crowley A. et al. Individual patient data pooled analysis of randomized trials of bivalirudin versus heparin in acute myocardial infarction: rationale and methodology. Thromb Haemost 2020; 120 (02) 348-362
    Article in Thieme ConnectPubMedGoogle Scholar
  • 46 Stone GW. Individual patient data pooled analysis of randomized trials of bivalirudin versus heparin in acute myocardial infarction. TCT connect 2020. Accessed December 7, 2020: 2020. . Available at: https://www.tctmd.com/slide/individual-patient-data-pooled-analysis-randomized-trials-bivalirudin-versus-heparin-acute
    Google Scholar
  • 47 Mehta SR, Yusuf S, Peters RJ. et al; Clopidogrel in Unstable angina to prevent Recurrent Events trial (CURE) Investigators. 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 (9281): 527-533
    CrossrefPubMedGoogle Scholar
  • 48 Montalescot G, Collet J-P, Ecollan P. et al; ACCOAST Investigators. Effect of prasugrel pre-treatment strategy in patients undergoing percutaneous coronary intervention for NSTEMI: the ACCOAST-PCI study. J Am Coll Cardiol 2014; 64 (24) 2563-2571
    CrossrefPubMedGoogle Scholar
  • 49 Bellemain-Appaix A, Kerneis M, O'Connor SA. et al; ACTION Study Group. Reappraisal of thienopyridine pretreatment in patients with non-ST elevation acute coronary syndrome: a systematic review and meta-analysis. BMJ 2014; 349: g6269
    CrossrefPubMedGoogle Scholar
  • 50 Almendro-Delia M, Gonzalez-Torres L, Garcia-Alcantara Á. et al; ARIAM-Andalucía Group. Prognostic impact of clopidogrel pretreatment in patients with acute coronary syndrome managed invasively. Am J Cardiol 2015; 115 (08) 1019-1026
    CrossrefPubMedGoogle Scholar
  • 51 Dworeck C, Redfors B, Angerås O. et al. Association of pretreatment with P2Y12 receptor antagonists preceding percutaneous coronary intervention in non-ST-segment elevation acute coronary syndromes with outcomes. JAMA Netw Open 2020; 3 (10) e2018735
    CrossrefPubMedGoogle Scholar
  • 52 Lindholm D, Varenhorst C, Cannon CP. et al. Ticagrelor vs. clopidogrel in patients with non-ST-elevation acute coronary syndrome with or without revascularization: results from the PLATO trial. Eur Heart J 2014; 35 (31) 2083-2093
    CrossrefPubMedGoogle Scholar
  • 53 Tarantini G, Mojoli M, Varbella F. et al. Timing of oral P2Y12 inhibitor administration in patients with non-ST-segment elevation acute coronary syndrome. J Am Coll Cardiol 2020; 76 (21) 2450-2459
    CrossrefPubMedGoogle Scholar
  • 54 Montalescot G. Non-ST-segment elevation acute coronary syndrome: the last nail in the coffin of pre-treatment.   J Am Coll Cardiol 2020; 76 (21) 2460-2462
    CrossrefPubMedGoogle Scholar
  • 55 Montalescot G, van 't Hof AW, Lapostolle F. et al; ATLANTIC Investigators. Prehospital ticagrelor in ST-segment elevation myocardial infarction. N Engl J Med 2014; 371 (11) 1016-1027
    CrossrefPubMedGoogle Scholar
  • 56 Tavenier AH, Hermanides RS, Fabris E. et al; ATLANTIC investigators. Efficacy and safety of glycoprotein IIb/IIIa inhibitors on top of ticagrelor in STEMI: a subanalysis of the ATLANTIC trial. Thromb Haemost 2020; 120 (01) 65-74
    Article in Thieme ConnectPubMedGoogle Scholar
  • 57 Motovska Z, Hlinomaz O, Miklik R. et al; PRAGUE-18 Study Group. Prasugrel versus ticagrelor in patients with acute myocardial infarction treated with primary percutaneous coronary intervention: multicenter randomized PRAGUE-18 study. Circulation 2016; 134 (21) 1603-1612
    CrossrefPubMedGoogle Scholar
  • 58 Basra SS, Wang TY, Simon DN. et al. Ticagrelor use in acute myocardial infarction: insights from the national cardiovascular data registry. J Am Heart Assoc 2018; 7 (12) 7
    CrossrefPubMedGoogle Scholar
  • 59 Jneid H. Ticagrelor or prasugrel in acute coronary syndromes - the winner takes it all?. N Engl J Med 2019; 381 (16) 1582-1585
    CrossrefPubMedGoogle Scholar
  • 60 Schüpke S, Neumann F-J, Menichelli M. et al; ISAR-REACT 5 Trial Investigators. Ticagrelor or prasugrel in patients with acute coronary syndromes. N Engl J Med 2019; 381 (16) 1524-1534
    CrossrefPubMedGoogle Scholar
  • 61 Menichelli M, Neumann F-J, Ndrepepa G. et al. Age- and weight-adapted dose of prasugrel versus standard dose of ticagrelor in patients with acute coronary syndromes : results from a randomized trial. Ann Intern Med 2020; 173 (06) 436-444
    CrossrefPubMedGoogle Scholar
  • 62 Navarese EP, Khan SU, Kołodziejczak M. et al. Comparative efficacy and safety of oral P2Y12 inhibitors in acute coronary syndrome: network meta-analysis of 52 816 patients from 12 randomized trials. Circulation 2020; 142 (02) 150-160
    CrossrefPubMedGoogle Scholar
  • 63 Schnorbus B, Daiber A, Jurk K. et al. Effects of clopidogrel vs. prasugrel vs. ticagrelor on endothelial function, inflammatory parameters, and platelet function in patients with acute coronary syndrome undergoing coronary artery stenting: a randomized, blinded, parallel study. Eur Heart J 2020; 41 (33) 3144-3152
    CrossrefPubMedGoogle Scholar
  • 64 Valina C, Neumann FJ, Menichelli M. Ticagrelor or prasugrel in patients with non-ST-segment elevation acute coronary syndromes. J Am Coll Cardiol 2020; 76 (21) 2436-2446 ; In press
    CrossrefPubMedGoogle Scholar
  • 65 Guedeney P, Vogel B, Mehran R. Non-vitamin K antagonist oral anticoagulant after acute coronary syndrome: is there a role?. Interv Cardiol (Lond) 2018; 13 (02) 93-98
    PubMedGoogle Scholar
  • 66 Sharma A, Hagström E, Wojdyla DM. et al; Apixaban for Prevention of Acute Ischemic Safety Events APPRAISE-2 Steering Committee and Investigators. Clinical consequences of bleeding among individuals with a recent acute coronary syndrome: Insights from the APPRAISE-2 trial. Am Heart J 2019; 215: 106-113
    CrossrefPubMedGoogle Scholar
  • 67 Oldgren J, Budaj A, Granger CB. et al; RE-DEEM Investigators. Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial. Eur Heart J 2011; 32 (22) 2781-2789
    CrossrefPubMedGoogle Scholar
  • 68 Alexander JH, Becker RC, Bhatt DL. et al; APPRAISE Steering Committee and Investigators. Apixaban, an oral, direct, selective factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome: results of the Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) trial. Circulation 2009; 119 (22) 2877-2885
    CrossrefPubMedGoogle Scholar
  • 69 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
    CrossrefPubMedGoogle Scholar
  • 70 Mega JL, Braunwald E, Mohanavelu S. et al; ATLAS ACS-TIMI 46 study group. Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial. Lancet 2009; 374 (9683): 29-38
    CrossrefPubMedGoogle Scholar
  • 71 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
    CrossrefPubMedGoogle Scholar
  • 72 Parodi G, Valenti R, Bellandi B. et al. Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation myocardial infarction patients: RAPID (Rapid Activity of Platelet Inhibitor Drugs) primary PCI study. J Am Coll Cardiol 2013; 61 (15) 1601-1606
    CrossrefPubMedGoogle Scholar
  • 73 Rollini F, Franchi F, Hu J. et al. Crushed prasugrel tablets in patients with STEMI undergoing primary percutaneous coronary intervention: the CRUSH study. J Am Coll Cardiol 2016; 67 (17) 1994-2004
    CrossrefPubMedGoogle Scholar
  • 74 Alexopoulos D, Dragasis S, Kafkas N. Loading with oral P2Y12 receptor inhibitors: to crush or not to crush?. Thromb Haemost 2019; 119 (07) 1037-1047
    Article in Thieme ConnectPubMedGoogle Scholar
  • 75 Niezgoda P, Sikora J, Barańska M. et al. Crushed sublingual versus oral ticagrelor administration strategies in patients with unstable angina. A pharmacokinetic/pharmacodynamic study. Thromb Haemost 2017; 117 (04) 718-726
    Article in Thieme ConnectPubMedGoogle Scholar
  • 76 Parodi G, Xanthopoulou I, Bellandi B. et al. Ticagrelor crushed tablets administration in STEMI patients: the MOJITO study. J Am Coll Cardiol 2015; 65 (05) 511-512
    CrossrefPubMedGoogle Scholar
  • 77 Asher E, Tal S, Mazin I. et al. Effect of chewing vs swallowing ticagrelor on platelet inhibition in patients with ST-segment elevation myocardial infarction: a randomized clinical trial. JAMA Cardiol 2017; 2 (12) 1380-1384
    CrossrefPubMedGoogle Scholar
  • 78 Asher E, Frydman S, Katz M. et al; For The PLATIS (Platelets and Thrombosis in Sheba) Study Group. Chewing versus swallowing ticagrelor to accelerate platelet inhibition in acute coronary syndrome - the CHEERS study. Thromb Haemost 2017; 117 (04) 727-733
    Article in Thieme ConnectPubMedGoogle Scholar
  • 79 Franchi F, Rollini F, Rivas A. et al. Platelet inhibition with cangrelor and crushed ticagrelor in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Circulation 2019; 139 (14) 1661-1670
    CrossrefPubMedGoogle Scholar
  • 80 Vlachojannis George J, Wilschut Jeroen M, Vogel Rosanne F. et al. Effect of pre-hospital crushed prasugrel tablets in patients with STEMI planned for primary percutaneous coronary intervention: the randomized COMPARE CRUSH trial. Circulation 2020; 142 (24) 2316-2328
    CrossrefPubMedGoogle Scholar
  • 81 Ibrahim K, Christoph M, Schmeinck S. et al. High rates of prasugrel and ticagrelor non-responder in patients treated with therapeutic hypothermia after cardiac arrest. Resuscitation 2014; 85 (05) 649-656
    CrossrefPubMedGoogle Scholar
  • 82 Weeks PA, Sieg A, Paruthi C, Rajapreyar I. Antiplatelet therapy considerations in ischemic cardiogenic shock: implications of metabolic bioactivation. J Cardiovasc Pharmacol Ther 2015; 20 (04) 370-377
    CrossrefPubMedGoogle Scholar
  • 83 Schoergenhofer C, Hobl E-L, Staudinger T. et al. Prasugrel in critically ill patients. Thromb Haemost 2017; 117 (08) 1582-1587
    Article in Thieme ConnectPubMedGoogle Scholar
  • 84 Prüller F, Bis L, Milke OL. et al. Cangrelor induces more potent platelet inhibition without increasing bleeding in resuscitated patients. J Clin Med 2018; 7 (11) 442
    CrossrefPubMedGoogle Scholar
  • 85 Storey RF, Gurbel PA, Ten Berg J. et al. Pharmacodynamics, pharmacokinetics, and safety of single-dose subcutaneous administration of selatogrel, a novel P2Y12 receptor antagonist, in patients with chronic coronary syndromes. Eur Heart J 2020; 41 (33) 3132-3140
    CrossrefPubMedGoogle Scholar
  • 86 Hulot J-S, Montalescot G. Do we need a new P2Y12 receptor antagonist?. Eur Heart J 2020; 41 (33) 3141-3143
    CrossrefPubMedGoogle Scholar
  • 87 Sinnaeve P, Fahrni G, Schelfaut D. et al. Subcutaneous selatogrel inhibits platelet aggregation in patients with acute myocardial infarction. J Am Coll Cardiol 2020; 75 (20) 2588-2597
    CrossrefPubMedGoogle Scholar
  • 88 Silvain J, Zeitouni M, Kerneis M. Selatogrel for acute myocardial infarction: the promise and challenges of self-medication. J Am Coll Cardiol 2020; 75 (20) 2598-2601
    CrossrefPubMedGoogle Scholar
  • 89 Levine GN, Bates ER, Bittl JA. 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; 68 (10) 1082-1115
    CrossrefPubMedGoogle Scholar
  • 90 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
    CrossrefPubMedGoogle Scholar
  • 91 Stone GW, Maehara A, Lansky AJ. et al; PROSPECT Investigators. A prospective natural-history study of coronary atherosclerosis. N Engl J Med 2011; 364 (03) 226-235
    CrossrefPubMedGoogle Scholar
  • 92 Guedeney P, Giustino G, Sorrentino S. et al. Efficacy and safety of alirocumab and evolocumab: a systematic review and meta-analysis of randomized controlled trials. Eur Heart J 2019; DOI: 10.1093/eurheartj/ehz430.
    CrossrefPubMedGoogle Scholar
  • 93 Guedeney P, Sorrentino S, Giustino G. et al. Indirect comparison of the efficacy and safety of alirocumab and evolocumab: a systematic review and network meta-analysis. Eur Heart J Cardiovasc Pharmacother 2020; DOI: 10.1093/ehjcvp/pvaa024.
    CrossrefPubMedGoogle Scholar
  • 94 Hahn J-Y, Song YB, Oh J-H. et al; SMART-DATE investigators. 6-Month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial. Lancet 2018; 391 (10127): 1274-1284
    CrossrefPubMedGoogle Scholar
  • 95 Kedhi E, Fabris E, van der Ent M. et al. Six months versus 12 months dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction (DAPT-STEMI): randomised, multicentre, non-inferiority trial. BMJ 2018; 363: k3793
    CrossrefPubMedGoogle Scholar
  • 96 Urban P, Mehran R, Colleran R. et al. Defining high bleeding risk in patients undergoing percutaneous coronary intervention: a consensus document from the Academic Research Consortium for High Bleeding Risk. Eur Heart J 2019; 40 (31) 2632-2653
    CrossrefPubMedGoogle Scholar
  • 97 Collet J-P, Cuisset T, Rangé G. et al; ARCTIC Investigators. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 2012; 367 (22) 2100-2109
    CrossrefPubMedGoogle Scholar
  • 98 Cayla G, Cuisset T, Silvain J. et al; ANTARCTIC investigators. Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomised controlled superiority trial. Lancet 2016; 388 (10055): 2015-2022
    CrossrefPubMedGoogle Scholar
  • 99 Sibbing D, Aradi D, Jacobshagen C. et al; TROPICAL-ACS Investigators. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet 2017; 390 (10104): 1747-1757
    CrossrefPubMedGoogle Scholar
  • 100 Claassens DMF, Vos GJA, Bergmeijer TO. et al. A genotype-guided strategy for oral P2Y12 inhibitors in primary PCI. N Engl J Med 2019; 381 (17) 1621-1631
    CrossrefPubMedGoogle Scholar
  • 101 Pereira NL, Farkouh ME, So D. et al. Effect of genotype-guided oral P2Y12 inhibitor selection vs conventional clopidogrel therapy on ischemic outcomes after percutaneous coronary intervention: the TAILOR-PCI randomized clinical trial. JAMA 2020; 324 (08) 761-771
    CrossrefPubMedGoogle Scholar
  • 102 Armstrong PCJ, Leadbeater PD, Chan MV. et al. In the presence of strong P2Y12 receptor blockade, aspirin provides little additional inhibition of platelet aggregation. J Thromb Haemost 2011; 9 (03) 552-561
    CrossrefPubMedGoogle Scholar
  • 103 Capodanno D, Mehran R, Valgimigli M. et al. Aspirin-free strategies in cardiovascular disease and cardioembolic stroke prevention. Nat Rev Cardiol 2018; 15 (08) 480-496
    CrossrefPubMedGoogle Scholar
  • 104 Dewilde WJM, Oirbans T, Verheugt FWA. et al; WOEST study investigators. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 2013; 381 (9872): 1107-1115
    CrossrefPubMedGoogle Scholar
  • 105 Gibson CM, Mehran R, Bode C. et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med 2016; 375 (25) 2423-2434
    CrossrefPubMedGoogle Scholar
  • 106 Cannon CP, Bhatt DL, Oldgren J. et al; RE-DUAL PCI Steering Committee and Investigators. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med 2017; 377 (16) 1513-1524
    CrossrefPubMedGoogle Scholar
  • 107 Lopes RD, Heizer G, Aronson R. et al; AUGUSTUS Investigators. Antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation. N Engl J Med 2019; 380 (16) 1509-1524
    CrossrefPubMedGoogle Scholar
  • 108 Vranckx P, Valgimigli M, Eckardt L. et al. Edoxaban-based versus vitamin K antagonist-based antithrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised, open-label, phase 3b trial. Lancet 2019; 394 (10206): 1335-1343
    CrossrefPubMedGoogle Scholar
  • 109 Lopes RD, Hong H, Harskamp RE. et al. Optimal antithrombotic regimens for patients with atrial fibrillation undergoing percutaneous coronary intervention: an updated network meta-analysis. JAMA Cardiol 2020; 5 (05) 582-589
    CrossrefPubMedGoogle Scholar
  • 110 Watanabe H, Domei T, Morimoto T. et al; STOPDAPT-2 Investigators. Effect of 1-month dual antiplatelet therapy followed by clopidogrel vs 12-month dual antiplatelet therapy on cardiovascular and bleeding events in patients receiving PCI: the STOPDAPT-2 randomized clinical trial. JAMA 2019; 321 (24) 2414-2427
    CrossrefPubMedGoogle Scholar
  • 111 Hahn J-Y, Song YB, Oh J-H. et al; SMART-CHOICE Investigators. Effect of P2Y12 inhibitor monotherapy vs dual antiplatelet therapy on cardiovascular events in patients undergoing percutaneous coronary intervention: the SMART-CHOICE randomized clinical trial. JAMA 2019; 321 (24) 2428-2437
    CrossrefPubMedGoogle Scholar
  • 112 Vranckx P, Valgimigli M, Jüni P. et al; GLOBAL LEADERS Investigators. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial. Lancet 2018; 392 (10151): 940-949
    CrossrefPubMedGoogle Scholar
  • 113 Mehran R, Baber U, Sharma SK. et al. Ticagrelor with or without aspirin in high-risk patients after PCI. N Engl J Med 2019; 381 (21) 2032-2042
    CrossrefPubMedGoogle Scholar
  • 114 Guedeney P, Mesnier J, Sorrentino S. et al. Early aspirin discontinuation following acute coronary syndrome or percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials. J Clin Med 2020; 9 (03) 9
    CrossrefPubMedGoogle Scholar
  • 115 Giustino G, Baber U, Sartori S. et al. Duration of dual antiplatelet therapy after drug-eluting stent implantation: a systematic review and meta-analysis of randomized controlled trials. J Am Coll Cardiol 2015; 65 (13) 1298-1310
    CrossrefPubMedGoogle Scholar
  • 116 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
    CrossrefPubMedGoogle Scholar
  • 117 Collet J-P, Silvain J, Barthélémy O. et al; ARCTIC investigators. Dual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial. Lancet 2014; 384 (9954): 1577-1585
    CrossrefPubMedGoogle Scholar
  • 118 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
    CrossrefPubMedGoogle Scholar
  • 119 Bainey KR, Welsh RC, Connolly SJ. et al; COMPASS Investigators. Rivaroxaban plus aspirin versus aspirin alone in patients with prior percutaneous coronary intervention (COMPASS-PCI). Circulation 2020; 141 (14) 1141-1151
    CrossrefPubMedGoogle Scholar