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Thromb Haemost 2015; 114(05): 945-957
DOI: 10.1160/TH15-03-0204
Review Article
Schattauer GmbH

Management of adjunctive antithrombotic therapy in STEMI patients treated with fibrinolysis undergoing rescue or delayed PCI

Davide Capodanno
1   Ferrarotto Hospital, University of Catania, Catania, Italy
2   University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
,
Dominick J. Angiolillo
2   University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
› Author Affiliations
Further Information

Publication History

Received: 06 March 2015

Accepted after major revision: 05 June 2015

Publication Date:
06 December 2017 (online)

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Summary

Although primary percutaneous coronary intervention (PCI) is the recommended method of reperfusion in patients presenting with ST-segment elevation myocardial infarction (STEMI), fibrinolysis remains a beneficial alternative in patients who cannot be reperfused timely with primary PCI, and is still the preferred revascularisation strategy in many parts of the world where PCI facilities are unavailable. Because fibrinolysis is known to activate platelets and promote thrombin activity, concomitant administration of antiplatelet and anticoagulant therapies is needed to lower the risk for re-occlusion and to support mechanical interventions in patients undergoing rescue or delayed PCI. However, the addition of oral antiplatelet and parenteral anticoagulant drugs on top of fibrinolysis may come at the price of an increased risk of bleeding. The current availability of several antiplatelet and anticoagulant therapies often leads to questions about the optimal selection in STEMI patients treated with fibrinolytics. This article appraises current evidences for the management of adjunctive antiplatelet and anticoagulant therapies in patients with STEMI undergoing fibrinolysis followed by rescue or delayed PCI.

Keywords

Antiplatelet agents - antithrombin - fibrinogen / fibrin
 

  • References

  • 1 O'Gara PT, Kushner FG, Ascheim DD. et al 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013; 127: e362-425.
    CrossrefPubMedGoogle Scholar
  • 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.
    CrossrefPubMedGoogle Scholar
  • 3 Windecker S, Kolh P, Alfonso F. et al 2014 ESC/EACTS Guidelines on myocardial revascularisation: The Task Force on Myocardial Revascularisation 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
  • 4 Capodanno D, Dangas G. Facilitated/pharmaco-invasive approaches in STEMI. Curr Cardiol Rev 2012; 8: 177-180.
    CrossrefPubMedGoogle Scholar
  • 5 Kristensen SD, Fajadet J, Di Mario C. et al. Implementation of primary angioplasty in Europe: stent for life initiative progress report. EuroIntervention 2012; 8: 35-42.
    CrossrefPubMedGoogle Scholar
  • 6 Kristensen SD, Laut KG, Fajadet J. et al. Reperfusion therapy for ST elevation acute myocardial infarction 2010/2011: current status in 37 ESC countries. Eur Heart J 2014; 35: 1957-1970.
    CrossrefPubMedGoogle Scholar
  • 7 Topol EJ. Acute myocardial infarction: thrombolysis. Heart 2000; 83: 122.
    CrossrefPubMedGoogle Scholar
  • 8 Cannon CP, McCabe CH, Gibson CM. et al. TNK-tissue plasminogen activator in acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) 10A dose-ranging trial. Circulation 1997; 95: 351-356.
    CrossrefPubMedGoogle Scholar
  • 9 Bode C, Smalling RW, Berg G. et al. Randomized comparison of coronary thrombolysis achieved with double-bolus reteplase (recombinant plasminogen activator) and frontloaded, accelerated alteplase (recombinant tissue plasminogen activator) in patients with acute myocardial infarction. Circulation 1996; 94: 891-898.
    CrossrefPubMedGoogle Scholar
  • 10 The GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 1993; 329: 1615-1622.
    CrossrefPubMedGoogle Scholar
  • 11 Neuhaus KL, von Essen R, Tebbe U. et al. Improved thrombolysis in acute myocardial infarction with front-loaded administration of alteplase: results of the rt-PA-APSAC patency study (TAPS). J Am Coll Cardiol 1992; 19: 885-891.
    CrossrefPubMedGoogle Scholar
  • 12 Martin GV, Sheehan FH, Stadius M. et al. Intravenous streptokinase for acute myocardial infarction: effects on global and regional systolic function. Circulation 1988; 78: 258-266.
    CrossrefPubMedGoogle Scholar
  • 13 Kunadian V, Gibson CM. Thrombolytics and myocardial infarction. Cardiovasc Ther 2012; 30: e81-88.
    CrossrefPubMedGoogle Scholar
  • 14 Windecker S, Kolh P, Alfonso F. et al 2014 ESC/EACTS Guidelines on myocardial revascularisation. Eur Heart J 2014; 35: 2541-2619.
    CrossrefPubMedGoogle Scholar
  • 15 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. J Am Coll Cardiol 2011; 58: 44-122.
    PubMedGoogle Scholar
  • 16 Maioli M, Bellandi F, Leoncini M. et al. Randomized early versus late abciximab in acute myocardial infarction treated with primary coronary intervention (RELAx-AMI Trial). J Am Coll Cardiol 2007; 49: 1517-1524.
    CrossrefPubMedGoogle Scholar
  • 17 Antman EM, Giugliano RP, Gibson CM. et al. Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI) 14 trial. The TIMI 14 Investigators. Circulation 1999; 99: 2720-2732.
    CrossrefPubMedGoogle Scholar
  • 18 Gersh BJ, Stone GW, White HD. et al. Pharmacological facilitation of primary percutaneous coronary intervention for acute myocardial infarction: is the slope of the curve the shape of the future?. J Am Med Assoc 2005; 293: 979-986.
    CrossrefPubMedGoogle Scholar
  • 19 The ASSENT-4 PCI Investigators. Primary versus tenecteplase facilitated percutaneous coronary intervention in patients with STsegment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial. Lancet 2006; 367: 569-578.
    CrossrefPubMedGoogle Scholar
  • 20 Ellis SG, Tendera M, de Belder MA. et al. Facilitated PCI in patients with ST-elevation myocardial infarction. N Engl J Med 2008; 358: 2205-2217.
    CrossrefPubMedGoogle Scholar
  • 21 Ellis SG, Tendera M, de Belder MA. et al. 1-year survival in a randomized trial of facilitated reperfusion: results from the FINESSE (Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events) trial. JACC Cardiovasc Interv 2009; 2: 909-916.
    CrossrefPubMedGoogle Scholar
  • 22 Capodanno D, Dangas G. Facilitated/pharmaco-invasive approaches in STEMI. Curr Cardiol Rev 2012; 8: 177-180.
    CrossrefPubMedGoogle Scholar
  • 23 Di Mario C, Dudek D, Piscione F. et al. Immediate angioplasty versus standard therapy with rescue angioplasty after thrombolysis in the Combined Abciximab REteplase Stent Study in Acute Myocardial Infarction (CARESS-in-AMI): an open, prospective, randomised, multicentre trial. Lancet 2008; 371: 559-568.
    CrossrefPubMedGoogle Scholar
  • 24 Cantor WJ, Fitchett D, Borgundvaag B. et al. Routine early angioplasty after fibrinolysis for acute myocardial infarction. N Engl J Med 2009; 360: 2705-2718.
    CrossrefPubMedGoogle Scholar
  • 25 Armstrong PW, Gershlick AH, Goldstein P. et al. Fibrinolysis or primary PCI in ST-segment elevation myocardial infarction. N Engl J Med 2013; 368: 1379-1387.
    CrossrefPubMedGoogle Scholar
  • 26 Sinnaeve PR. One year mortality in STEMI patients randomized to primary PCI or a pharmaco-invasive strategy. The STREAM 1 year follow-up. Presented at: American Heart Association Scientific Sessions; November 18 2013 Dallas. TX.:
    PubMedGoogle Scholar
  • 27 Collet JP, Montalescot G, Le May M, Borentain M, Gershlick A. Percutaneous coronary intervention after fibrinolysis: a multiple metaanalyses approach according to the type of strategy. J Am Coll Cardiol 2006; 48: 1326-1335.
    CrossrefPubMedGoogle Scholar
  • 28 Rapold HJ. Promotion of thrombin activity by thrombolytic therapy without simultaneous anticoagulation. Lancet 1990; 335: 481-482.
    PubMedGoogle Scholar
  • 29 Rapold HJ, Kuemmerli H, Weiss M, Baur H, Haeberli A. Monitoring of fibrin generation during thrombolytic therapy of acute myocardial infarction with recombinant tissue-type plasminogen activator. Circulation 1989; 79: 980-989.
    CrossrefPubMedGoogle Scholar
  • 30 Fitzgerald DJ, Catella F, Roy L, FitzGerald GA. Marked platelet activation in vivo after intravenous streptokinase in patients with acute myocardial infarction. Circulation 1988; 77: 142-150.
    CrossrefPubMedGoogle Scholar
  • 31 Moliterno DJ, Topol EJ. Conjunctive use of platelet glycoprotein IIb/IIIa antagonists and thrombolytic therapy for acute myocardial infarction. Thromb Haemost 1997; 78: 214-219.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Owen J, Friedman KD, Grossman BA, Wilkins C, Berke AD, Powers ER. Thrombolytic therapy with tissue plasminogen activator or streptokinase induces transient thrombin activity. Blood 1988; 72: 616-620.
    PubMedGoogle Scholar
  • 33 Merlini PA, Bauer KA, Oltrona L. et al. Thrombin generation and activity during thrombolysis and concomitant heparin therapy in patients with acute myocardial infarction. J Am Coll Cardiol 1995; 25: 203-209.
    CrossrefPubMedGoogle Scholar
  • 34 Silvain J, Collet JP, Nagaswami C. et al. Composition of coronary thrombus in acute myocardial infarction. J Am Coll Cardiol 2011; 57: 1359-1367.
    CrossrefPubMedGoogle Scholar
  • 35 Zalewski J, Bogaerts K, Desmet W. et al. Intraluminal thrombus in facilitated versus primary percutaneous coronary intervention: an angiographic substudy of the ASSENT-4 PCI (Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention) trial. J Am Coll Cardiol 2011; 57: 1867-1873.
    CrossrefPubMedGoogle Scholar
  • 36 Beygui F, Collet J-P, Nagaswami C, Weisel JW, vMontalescot G. Architecture of intracoronary thrombi in ST-elevation acute myocardial infarction. Time makes the difference. Circulation 2006; 113: e21-23.
    CrossrefPubMedGoogle Scholar
  • 37 Capodanno D, Angiolillo DJ. Antithrombotic therapy in the elderly. J Am Coll Cardiol 2010; 56: 1683-1692.
    CrossrefPubMedGoogle Scholar
  • 38 ISIS-2 Investigators. 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: 349-360.
    PubMedGoogle Scholar
  • 39 Freimark D, Matetzky S, Leor J. et al. Timing of aspirin administration as a determinant of survival of patients with acute myocardial infarction treated with thrombolysis. Am J Cardiol 2002; 89: 381-385.
    CrossrefPubMedGoogle Scholar
  • 40 Sabatine MS, Cannon CP, Gibson CM. et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 2005; 352: 1179-1189.
    CrossrefPubMedGoogle Scholar
  • 41 Scirica BM, Sabatine MS, Morrow DA. et al. The role of clopidogrel in early and sustained arterial patency after fibrinolysis for ST-segment elevation myocardial infarction: the ECG CLARITY-TIMI 28 Study. J Am Coll Cardiol 2006; 48: 37-42.
    CrossrefPubMedGoogle Scholar
  • 42 Sabatine MS, Cannon CP, Gibson CM. et al. Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study. J Am Med Assoc 2005; 294: 1224-1232.
    CrossrefPubMedGoogle Scholar
  • 43 Ferreiro JL, Angiolillo DJ. Clopidogrel response variability: current status and future directions. Thromb Haemost 2009; 102: 7-14.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 44 Bonello L, Tantry US, Marcucci R. et al. Consensus and future directions on the definition of high ontreatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 2010; 56: 919-933.
    CrossrefPubMedGoogle Scholar
  • 45 Serebruany VL, DiNicolantonio JJ. Viewpoint: mismatch between the European and American guidelines on oral antiplatelet P2Y12 inhibitors after acute coronary syndromes. Thromb Haemost 2013; 110: 5-10.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 46 Serebruany VL, Fortmann SD. Viewpoint: “underutilisation of novel antiplatelet agents--myths, generics, and economics”. Thromb Haemost 2014; 112: 4-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 47 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
  • 48 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
  • 49 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.
    CrossrefPubMedGoogle Scholar
  • 50 Bertram U, Moser M, Peter K. et al. Effects of different thrombolytic treatment regimen with abciximab and tirofiban on platelet aggregation and platelet-leukocyte interactions: a subgroup analysis from the GUSTO V and FASTER trials. J Thromb Thrombolysis 2002; 14: 197-203.
    CrossrefPubMedGoogle Scholar
  • 51 Coulter SA, Cannon CP, Ault KA. et al. High levels of platelet inhibition with abciximab despite heightened platelet activation and aggregation during thrombolysis for acute myocardial infarction: results from TIMI (thrombolysis in myocardial infarction) 14. Circulation 2000; 101: 2690-2695.
    CrossrefPubMedGoogle Scholar
  • 52 Jong P, Cohen EA, Batchelor W. et al. Bleeding risks with abciximab after fulldose thrombolysis in rescue or urgent angioplasty for acute myocardial infarction. Am Heart J 2001; 141: 218-225.
    CrossrefPubMedGoogle Scholar
  • 53 SPEED Investigators. Trial of abciximab with and without low-dose reteplase for acute myocardial infarction. Strategies for Patency Enhancement in the Emergency Department (SPEED) Group. Circulation 2000; 101: 2788-2794.
    CrossrefPubMedGoogle Scholar
  • 54 Antman EM, Giugliano RP, Gibson CM. et al. Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI) 14 trial. The TIMI 14 Investigators. Circulation 1999; 99: 2720-2732.
    CrossrefPubMedGoogle Scholar
  • 55 Brener SJ, Zeymer U, Adgey AA. et al. Eptifibatide and low-dose tissue plasminogen activator in acute myocardial infarction: the integrilin and low-dose thrombolysis in acute myocardial infarction (INTRO AMI) trial. J Am Coll Cardiol 2002; 39: 377-386.
    PubMedGoogle Scholar
  • 56 Herrmann HC, Moliterno DJ, Ohman EM. et al. Facilitation of early percutaneous coronary intervention after reteplase with or without abciximab in acute myocardial infarction: results from the SPEED (GUSTO-4 Pilot) Trial. J Am Coll Cardiol 2000; 36: 1489-1496.
    CrossrefPubMedGoogle Scholar
  • 57 Topol EJ. GUSTO V Investigators Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial. Lancet 2001; 357: 1905-1914.
    CrossrefPubMedGoogle Scholar
  • 58 Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 Investigators. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. Lancet 2001; 358: 605-613.
    CrossrefPubMedGoogle Scholar
  • 59 Mahaffey KW, Granger CB, Collins R. et al. Overview of randomized trials of intravenous heparin in patients with acute myocardial infarction treated with thrombolytic therapy. Am J Cardiol 1996; 77: 551-556.
    CrossrefPubMedGoogle Scholar
  • 60 Bleich SD, Nichols TC, Schumacher RR. et al. Effect of heparin on coronary arterial patency after thrombolysis with tissue plasminogen activator in acute myocardial infarction. Am J Cardiol 1990; 66: 1412-1417.
    CrossrefPubMedGoogle Scholar
  • 61 Hsia J, Hamilton WP, Kleiman N. et al. A comparison between heparin and lowdose aspirin as adjunctive therapy with tissue plasminogen activator for acute myocardial infarction. Heparin-Aspirin Reperfusion Trial (HART) Investigators. N Engl J Med 1990; 323: 1433-1437.
    CrossrefPubMedGoogle Scholar
  • 62 Krishnaswamy A, Lincoff AM, Cannon CP. The use and limitations of unfractionated heparin. Crit Pathw Cardiol 2010; 9: 35-40.
    CrossrefPubMedGoogle Scholar
  • 63 Lavi S, Cantor WJ, Casanova A. et al. Efficacy and safety of enoxaparin compared with unfractionated heparin in the pharmacoinvasive management of acute ST-segment elevation myocardial infarction: Insights from the TRANSFER-AMI trial. Am Heart J 2012; 163: 176-181. e2.
    CrossrefPubMedGoogle Scholar
  • 64 Ferguson JJ, Califf RM, Antman EM. et al. Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. J Am Med Assoc 2004; 292: 45-54.
    PubMedGoogle Scholar
  • 65 Yusuf S, Mehta SR, Chrolavicius S. et al. Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. J Am Med Assoc 2006; 295: 1519-1530.
    CrossrefPubMedGoogle Scholar
  • 66 Warkentin TE, Greinacher A, Koster A. Bivalirudin. Thromb Haemost 2008; 99: 830-839.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 67 White HD, Aylward PE, Frey MJ. et al. Randomized, double-blind comparison of hirulog versus heparin in patients receiving streptokinase and aspirin for acute myocardial infarction (HERO). Hirulog Early Reperfusion/Occlusion (HERO) Trial Investigators. Circulation 1997; 96: 2155-2161.
    CrossrefPubMedGoogle Scholar
  • 68 White H. Hirulog and Early Reperfusion or Occlusion (HERO)-2 Trial Investigators. Thrombin-specific anticoagulation with bivalirudin versus heparin in patients receiving fibrinolytic therapy for acute myocardial infarction: the HERO-2 randomised trial. Lancet 2001; 358: 1855-1863.
    CrossrefPubMedGoogle Scholar
  • 69 Capodanno D, De Caterina R. Bivalirudin for acute coronary syndromes: premises, promises and doubts. Thromb Haemost 2015; 113: 698-707.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 70 Capodanno D, Gargiulo G, Capranzano P. et al. Bivalirudin versus heparin with or without glycoprotein IIb/IIIa inhibitors in patients with STEMI undergoing primary PCI: An updated meta-analysis of 10,350 patients from five randomized clinical trials. Eur Heart J Acute Cardiovasc Care. 2015 Epub ahead of print.
    PubMedGoogle Scholar
  • 71 Clemmensen P, Wiberg S, Van't Hof A. et al. Acute stent thrombosis after primary percutaneous coronary intervention: insights from the EUROMAX trial (European Ambulance Acute Coronary Syndrome Angiography). JACC Cardiovasc Interv 2015; 8: 214-220.
    CrossrefPubMedGoogle Scholar
  • 72 Johnman C, Pell JP, Mackay DF. et al. Clinical outcomes following radial versus femoral artery access in primary or rescue percutaneous coronary intervention in Scotland: retrospective cohort study of 4534 patients. Heart 2012; 98: 552-557.
    CrossrefPubMedGoogle Scholar