Official reprint from UpToDate®
www.uptodate.com ©2018 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Management of failed fibrinolysis (thrombolysis) or threatened reocclusion in acute ST elevation myocardial infarction

C Michael Gibson, MS, MD
J Brent Muhlestein, MD
Section Editors
Donald Cutlip, MD
James Hoekstra, MD
Deputy Editor
Gordon M Saperia, MD, FACC


Coronary reperfusion with fibrinolysis or primary percutaneous coronary intervention (PCI) substantially improves survival in patients with an acute ST elevation (Q wave) myocardial infarction compared to no reperfusion therapy. Primary PCI is preferred for most patients if it can be performed by an experienced operator with less than a 90 minute delay from presentation to the emergency department. However, fibrinolysis remains an important therapeutic modality, due in part to limited availability of primary PCI. (See "Acute ST elevation myocardial infarction: Selecting a reperfusion strategy" and "Primary percutaneous coronary intervention in acute ST elevation myocardial infarction: Determinants of outcome" and "Fibrinolysis for acute ST elevation myocardial infarction: Initiation of therapy".)

The principle reason for the preference of PCI to fibrinolysis is the relatively high frequency of failure of fibrinolysis to establish reperfusion (primary failure). In addition, early reocclusion occurs in a significant number of cases. (See 'Primary failure' below and 'Threatened reocclusion' below.)

Primary failure of fibrinolysis is often manifested clinically by persistent or worsening chest pain (particularly if associated with other symptoms such as dyspnea and diaphoresis), persistent or worsening ST segment elevation, and/or hemodynamic instability or heart failure [1]. However, these clinical factors are not sufficiently predictive in all patients. As a result, in the absence of clear indications of reperfusion, the clinician must maintain a high index of suspicion for primary failure [2]. Additionally, in patients who undergo diagnostic angiography after fibrinolysis, both TIMI 0/1 and TIMI 2 flow are associated with increased mortality compared to those with TIMI 3 (normal) flow [3]. (See 'Diagnosis of primary failure' below.)

These observations have provided the rationale for immediate angiography with intent to perform rescue PCI, as well as routine early elective angiography one to two days after fibrinolysis. However, angiography in the first two hours after fibrinolytic therapy, when bleeding risks are higher, is reserved for patients with overt evidence of failed fibrinolysis. The use of routine angiography after fibrinolysis is discussed separately. (See "Acute ST elevation myocardial infarction: Selecting a reperfusion strategy", section on 'Fibrinolysis followed by PCI'.)

If initial fibrinolysis fails to establish reperfusion or if threatened reocclusion occurs, further efforts to achieve reperfusion should be attempted. This topic will review the roles of angiography followed by PCI (or coronary artery bypass graft surgery if indicated) for failed fibrinolysis or threatened reocclusion and of retreatment with fibrinolytic drugs for threatened reocclusion.

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Dec 2017. | This topic last updated: Jun 20, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2018 UpToDate, Inc.
  1. Sutton AG, Campbell PG, Graham R, et al. A randomized trial of rescue angioplasty versus a conservative approach for failed fibrinolysis in ST-segment elevation myocardial infarction: the Middlesbrough Early Revascularization to Limit INfarction (MERLIN) trial. J Am Coll Cardiol 2004; 44:287.
  2. Schömig A, Ndrepepa G, Mehilli J, et al. A randomized trial of coronary stenting versus balloon angioplasty as a rescue intervention after failed thrombolysis in patients with acute myocardial infarction. J Am Coll Cardiol 2004; 44:2073.
  3. GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993; 329:673.
  4. Anderson JL, Karagounis LA, Califf RM. Metaanalysis of five reported studies on the relation of early coronary patency grades with mortality and outcomes after acute myocardial infarction. Am J Cardiol 1996; 78:1.
  5. Vogt A, von Essen R, Tebbe U, et al. Impact of early perfusion status of the infarct-related artery on short-term mortality after thrombolysis for acute myocardial infarction: retrospective analysis of four German multicenter studies. J Am Coll Cardiol 1993; 21:1391.
  6. 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.
  7. Simes RJ, Topol EJ, Holmes DR Jr, et al. Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion. Importance of early and complete infarct artery reperfusion. GUSTO-I Investigators. Circulation 1995; 91:1923.
  8. Ross AM, Coyne KS, Moreyra E, et al. Extended mortality benefit of early postinfarction reperfusion. GUSTO-I Angiographic Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Trial. Circulation 1998; 97:1549.
  9. Holmes DR Jr, Gersh BJ, Ellis SG. Rescue percutaneous coronary intervention after failed fibrinolytic therapy: have expectations been met? Am Heart J 2006; 151:779.
  10. Gibson CM, Cannon CP, Murphy SA, et al. Relationship of the TIMI myocardial perfusion grades, flow grades, frame count, and percutaneous coronary intervention to long-term outcomes after thrombolytic administration in acute myocardial infarction. Circulation 2002; 105:1909.
  11. Van de Werf F, Bax J, Betriu A, et al. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J 2008; 29:2909.
  12. 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.
  13. O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013; 127:529.
  14. Goldman LE, Eisenberg MJ. Identification and management of patients with failed thrombolysis after acute myocardial infarction. Ann Intern Med 2000; 132:556.
  15. de Lemos JA, Antman EM, Giugliano RP, et al. ST-segment resolution and infarct-related artery patency and flow after thrombolytic therapy. Thrombolysis in Myocardial Infarction (TIMI) 14 investigators. Am J Cardiol 2000; 85:299.
  16. de Lemos JA, Morrow DA, Gibson CM, et al. Early noninvasive detection of failed epicardial reperfusion after fibrinolytic therapy. Am J Cardiol 2001; 88:353.
  17. Califf RM, O'Neil W, Stack RS, et al. Failure of simple clinical measurements to predict perfusion status after intravenous thrombolysis. Ann Intern Med 1988; 108:658.
  18. de Lemos JA, Braunwald E. ST segment resolution as a tool for assessing the efficacy of reperfusion therapy. J Am Coll Cardiol 2001; 38:1283.
  19. Armstrong PW, Fu Y, Chang WC, et al. Acute coronary syndromes in the GUSTO-IIb trial: prognostic insights and impact of recurrent ischemia. The GUSTO-IIb Investigators. Circulation 1998; 98:1860.
  20. Langer A, Krucoff MW, Klootwijk P, et al. Prognostic significance of ST segment shift early after resolution of ST elevation in patients with myocardial infarction treated with thrombolytic therapy: the GUSTO-I ST Segment Monitoring Substudy. J Am Coll Cardiol 1998; 31:783.
  21. Topol EJ, Califf RM, George BS, et al. A randomized trial of immediate versus delayed elective angioplasty after intravenous tissue plasminogen activator in acute myocardial infarction. N Engl J Med 1987; 317:581.
  22. Ohman EM, Califf RM, Topol EJ, et al. Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction. TAMI Study Group. Circulation 1990; 82:781.
  23. Hudson MP, Granger CB, Topol EJ, et al. Early reinfarction after fibrinolysis: experience from the global utilization of streptokinase and tissue plasminogen activator (alteplase) for occluded coronary arteries (GUSTO I) and global use of strategies to open occluded coronary arteries (GUSTO III) trials. Circulation 2001; 104:1229.
  24. Gibson CM, Karha J, Murphy SA, et al. Early and long-term clinical outcomes associated with reinfarction following fibrinolytic administration in the Thrombolysis in Myocardial Infarction trials. J Am Coll Cardiol 2003; 42:7.
  25. Barbash GI, Birnbaum Y, Bogaerts K, et al. Treatment of reinfarction after thrombolytic therapy for acute myocardial infarction: an analysis of outcome and treatment choices in the global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries (gusto I) and assessment of the safety of a new thrombolytic (assent 2) studies. Circulation 2001; 103:954.
  26. Dönges K, Schiele R, Gitt A, et al. Incidence, determinants, and clinical course of reinfarction in-hospital after index acute myocardial infarction (results from the pooled data of the maximal individual therapy in acute myocardial infarction [MITRA], and the myocardial infarction registry [MIR]). Am J Cardiol 2001; 87:1039.
  27. Edmond JJ, French JK, Stewart RA, et al. Frequency of recurrent ST-elevation myocardial infarction after fibrinolytic therapy in a different territory as a manifestation of multiple unstable coronary arterial plaques. Am J Cardiol 2006; 97:947.
  28. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction. www.acc.org/qualityandscience/clinical/statements.htm (Accessed on August 24, 2006).
  29. Ellis SG, da Silva ER, Heyndrickx G, et al. Randomized comparison of rescue angioplasty with conservative management of patients with early failure of thrombolysis for acute anterior myocardial infarction. Circulation 1994; 90:2280.
  30. Gershlick AH, Stephens-Lloyd A, Hughes S, et al. Rescue angioplasty after failed thrombolytic therapy for acute myocardial infarction. N Engl J Med 2005; 353:2758.
  31. Carver A, Rafelt S, Gershlick AH, et al. Longer-term follow-up of patients recruited to the REACT (Rescue Angioplasty Versus Conservative Treatment or Repeat Thrombolysis) trial. J Am Coll Cardiol 2009; 54:118.
  32. Wijeysundera HC, Vijayaraghavan R, Nallamothu BK, et al. Rescue angioplasty or repeat fibrinolysis after failed fibrinolytic therapy for ST-segment myocardial infarction: a meta-analysis of randomized trials. J Am Coll Cardiol 2007; 49:422.
  33. Gibson, M, Schweiger, et al. Outcomes of adjunctive PTCA/stenting for TIMI grade 2 flow following thrombolysis (abstract). J Am Coll Cardiol 1998; 31:231A.
  34. Ellis SG, Lincoff AM, George BS, et al. Randomized evaluation of coronary angioplasty for early TIMI 2 flow after thrombolytic therapy for the treatment of acute myocardial infarction: a new look at an old study. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. Coron Artery Dis 1994; 5:611.
  35. Smith SC Jr, Dove JT, Jacobs AK, et al. ACC/AHA guidelines of percutaneous coronary interventions (revision of the 1993 PTCA guidelines)--executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (committee to revise the 1993 guidelines for percutaneous transluminal coronary angioplasty). J Am Coll Cardiol 2001; 37:2215.
  36. Gibson CM, Kirtane AJ, Boundy K, et al. Association of a negative residual stenosis following rescue/adjunctive percutaneous coronary intervention with impaired myocardial perfusion and adverse outcomes among ST-segment elevation myocardial infarction patients. J Am Coll Cardiol 2005; 45:357.
  37. Madsen JK, Grande P, Saunamäki K, et al. Danish multicenter randomized study of invasive versus conservative treatment in patients with inducible ischemia after thrombolysis in acute myocardial infarction (DANAMI). DANish trial in Acute Myocardial Infarction. Circulation 1997; 96:748.
  38. White HD, Cross DB, Williams BF, Norris RM. Safety and efficacy of repeat thrombolytic treatment after acute myocardial infarction. Br Heart J 1990; 64:177.
  39. White H. Thrombolytic treatment for recurrent myocardial infarction. BMJ 1991; 302:429.
  40. Barbash GI, Hod H, Roth A, et al. Repeat infusion of recombinant tissue-type plasminogen activator in patients with acute myocardial infarction and early recurrent myocardial ischemia. J Am Coll Cardiol 1990; 16:779.
  41. Simoons ML, Arnout J, van den Brand M, et al. Retreatment with alteplase for early signs of reocclusion after thrombolysis. The European Cooperative Study Group. Am J Cardiol 1993; 71:524.
  42. Fears R, Hearn J, Standring R, et al. Lack of influence of pretreatment antistreptokinase antibody on efficacy in a multicenter patency comparison of intravenous streptokinase and anistreplase in acute myocardial infarction. Am Heart J 1992; 124:305.
  43. Gemmill JD, Hogg KJ, Dunn FG, et al. Pre-dosing antibody levels and efficacy of thrombolytic drugs containing streptokinase. Br Heart J 1994; 72:222.
  44. Buchalter MB, Suntharalingam G, Jennings I, et al. Streptokinase resistance: when might streptokinase administration be ineffective? Br Heart J 1992; 68:449.
  45. Squire IB, Lawley W, Fletcher S, et al. Humoral and cellular immune responses up to 7.5 years after administration of streptokinase for acute myocardial infarction. Eur Heart J 1999; 20:1245.
  46. Arnout J, Simoons M, de Bono D, et al. Correlation between level of heparinization and patency of the infarct-related coronary artery after treatment of acute myocardial infarction with alteplase (rt-PA). J Am Coll Cardiol 1992; 20:513.
  47. Randomized trial of intravenous heparin versus recombinant hirudin for acute coronary syndromes. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIa Investigators. Circulation 1994; 90:1631.
  48. Antman EM. Hirudin in acute myocardial infarction. Safety report from the Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9A Trial. Circulation 1994; 90:1624.
  49. 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.
  50. 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.
  51. Muhlestein JB, Karagounis LA, Treehan S, Anderson JL. "Rescue" utilization of abciximab for the dissolution of coronary thrombus developing as a complication of coronary angioplasty. J Am Coll Cardiol 1997; 30:1729.
  52. Gersh BJ, Chesebro JH, Braunwald E, et al. Coronary artery bypass graft surgery after thrombolytic therapy in the Thrombolysis in Myocardial Infarction Trial, Phase II (TIMI II). J Am Coll Cardiol 1995; 25:395.
  53. Armstrong PW, Collen D. Fibrinolysis for acute myocardial infarction: current status and new horizons for pharmacological reperfusion, part 1. Circulation 2001; 103:2862.
  54. Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC), Steg PG, James SK, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33:2569.