Skip to main content

Advertisement

SpringerLink
Log in

Poor outcomes after fibrinolytic therapy for ST-segment elevation myocardial infarction: Impact of age (A Meta-Analysis of a Decade of Trials)

  • Featured Investigations
  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

Background: Fibrinolysis for ST-segment elevation myocardial infarction (STEMI) reduces mortality, but its relative efficacy and risks are age-dependent. We aimed to quantify the outcomes of fibrinolysis and adjunctive antithrombin therapy for STEMI stratified by age.

Methods: We performed a meta-analysis of 11 published (1992–2001) randomized clinical trials of fibrinolysis in STEMI (sample size ≥3000, no age limit, no placebo-controlled arms) identified by MEDLINE through June 2005. Event rates and odds ratios (OR) in elderly vs. younger patients were calculated for mortality, intracranial hemorrhage (ICH) and total stroke (CVA). Elderly patients were defined as ≥75 years (GUSTO I, TIMI 9B, GUSTO III, COBALT, ASSENT-2, InTIME-II TIMI-17, ASSENT-3, GUSTO V, and HERO-2), except when defined as >65 or ≥70 years by the study (INJECT and ISIS-3).

Results: Elderly (n = 24 531) vs. younger (n = 123 568) patients had increased rates of mortality (19.7% vs. 5.5%), ICH (1.4% vs. 0.5%) and CVA (3.5 vs. 1.2%) by 30–35 days; the excess risk for these events was substantial (OR mortality 4.37, 95% CI 4.16–4.58; ICH 2.83, 2.47–3.24; CVA 2.92, 2.62–3.25; p < 0.001 for all).

Conclusions: Despite established mortality reductions with fibrinolysis for STEMI, elderly compared with younger patients, still have a three to four fold increased risk of mortality and adverse events when treated with fibrinolysis and antithrombin therapy in the modern era. These robust estimates of the anticipated rates for mortality, ICH, and CVA can be used as benchmarks to monitor the efficacy and safety of therapies in ongoing and newly completed clinical trials.

Abbreviated abstract

We aimed to quantify the outcomes of death, intracranial hemorrhage (ICH), and total cerebrovascular accidents (CVA) in elderly compared with younger patients treated with fibrinolysis for STEMI based on a meta-analysis of 11 randomized clinical trials (1992–2001) of more than 3000 patients. Elderly (n = 24 531) vs. younger (n = 123 568) patients had increased rates of mortality, ICH and CVA by 30–35 days; the excess risk was substantial (OR 4.37, 2.83, and 2.92 respectively, p < 0.001 for all). These robust estimates can be used as benchmarks to monitor the efficacy and safety of therapies in ongoing and newly completed clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction; A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of patients with acute myocardial infarction). J Am Coll Cardiol 2004;44(3):E1–E211.

    Article  PubMed  Google Scholar 

  2. Kapantais G, Powell-Griner E. Characteristics of persons dying of disease of heart: preliminary data from the 1986 National Mortality Followback Survey. Adv Data 1989(172):1–30.

  3. Eagle KA, Goodman SG, Avezum A, Budaj A, Sullivan CM, Lopez-Sendon J. Practice variation and missed opportunities for reperfusion in ST-segment-elevation myocardial infarction: findings from the Global Registry of Acute Coronary Events (GRACE). Lancet 2002;359(9304):373–377.

    Article  PubMed  Google Scholar 

  4. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Lancet 1994;343(8893):311–322.

    Google Scholar 

  5. ACC/AHA Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction: A Report of the American College of Cardology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction) 2004. Available at http://www.acc.org/clinical/guidelines/stemi/index.pdf.

  6. Stenestrand U, Wallentin L. Fibrinolytic therapy in patients 75 years and older with ST-segment-elevation myocardial infarction: one-year follow-up of a large prospective cohort. Arch Intern Med 2003;163(8):965–971.

    Article  PubMed  Google Scholar 

  7. Berger AK, Radford MJ, Wang Y, Krumholz HM. Thrombolytic therapy in older patients. J Am Coll Cardiol 2000;36(2):366–374.

    Article  CAS  PubMed  Google Scholar 

  8. Boucher JM, Racine N, Thanh TH, et al. Age-related differences in in-hospital mortality and the use of thrombolytic therapy for acute myocardial infarction. Cmaj 2001;164(9):1285–1290.

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Krumholz HM, Murillo JE, Chen J, et al. Thrombolytic therapy for eligible elderly patients with acute myocardial infarction. Jama 1997;277(21):1683–1688.

    Article  CAS  PubMed  Google Scholar 

  10. Rathore SS, Mehta RH, Wang Y, Radford MJ, Krumholz HM. Effects of age on the quality of care provided to older patients with acute myocardial infarction. Am J Med 2003;114(4):307–315.

    Article  PubMed  Google Scholar 

  11. Brass LM, Lichtman JH, Wang Y, Gurwitz JH, Radford MJ, Krumholz HM. Intracranial hemorrhage associated with thrombolytic therapy for elderly patients with acute myocardial infarction: results from the Cooperative Cardiovascular Project. Stroke 2000;31(8):1802–1811.

    Article  CAS  PubMed  Google Scholar 

  12. Gurwitz JH, Gore JM, Goldberg RJ, et al. Risk for intracranial hemorrhage after tissue plasminogen activator treatment for acute myocardial infarction. Participants in the National Registry of Myocardial Infarction 2. Ann Intern Med 1998;129(8):597–604.

    Article  CAS  PubMed  Google Scholar 

  13. ISIS-3: a randomised comparison of streptokinase vs. tissue plasminogen activator vs. anistreplase and of aspirin plus heparin vs. aspirin alone among 41,299 cases of suspected acute myocardial infarction. ISIS-3 (Third International Study of Infarct Survival) Collaborative Group. Lancet 1992;339(8796):753–770.

    Article  Google Scholar 

  14. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. The GUSTO investigators. N Engl J Med 1993;329(10):673–682.

    Article  Google Scholar 

  15. Randomised, double-blind comparison of reteplase double-bolus administration with streptokinase in acute myocardial infarction (INJECT): trial to investigate equivalence. International Joint Efficacy Comparison of Thrombolytics. Lancet 1995;346(8971):329–336.

    Article  Google Scholar 

  16. Antman EM. Hirudin in acute myocardial infarction. Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9B trial. Circulation 1996;94(5):911–921.

    Article  CAS  PubMed  Google Scholar 

  17. A comparison of reteplase with alteplase for acute myocardial infarction. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO III) Investigators. N Engl J Med 1997;337(16):1118–1123.

    Article  Google Scholar 

  18. A comparison of continuous infusion of alteplase with double-bolus administration for acute myocardial infarction. The Continuous Infusion versus Double-Bolus Administration of Alteplase (COBALT) Investigators. N Engl J Med 1997;337(16):1124–1130.

    Article  Google Scholar 

  19. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Assessment of the Safety and Efficacy of a New Thrombolytic Investigators. Lancet 1999;354(9180):716–722.

    Article  Google Scholar 

  20. Intravenous NPA for the treatment of infarcting myocardium early; InTIME-II, a double-blind comparison of single-bolus lanoteplase vs. accelerated alteplase for the treatment of patients with acute myocardial infarction. Eur Heart J 2000;21(24):2005–2013.

    Google Scholar 

  21. White H. Thrombin-specific anticoagulation with bivalirudin versus heparin in patients receiving fibrinolytic therapy for acute myocardial infarction: the HERO-2 randomised trial. Lancet 2001;358(9296):1855–1863.

    Article  CAS  PubMed  Google Scholar 

  22. 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(9282):605–613.

  23. Topol EJ. 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(9272):1905–1914.

    Article  CAS  PubMed  Google Scholar 

  24. Mehta RH, Granger CB, Alexander KP, Bossone E, White HD, Sketch MH, Jr. Reperfusion strategies for acute myocardial infarction in the elderly: benefits and risks. J Am Coll Cardiol 2005;45(4):471–478.

    Article  PubMed  Google Scholar 

  25. Kizer JR, Cannon CP, McCabe CH, et al. Trends in the use of pharmacotherapies for acute myocardial infarction among physicians who design and/or implement randomized trials versus physicians in routine clinical practice: the MILIS-TIMI experience. Multicenter Investigation on Limitation of Infarct Size. Thrombolysis in Myocardial Infarction. Am Heart J 1999;137(1):79–92.

    Article  CAS  PubMed  Google Scholar 

  26. Mehta RH, Rathore SS, Radford MJ, Wang Y, Wang Y, Krumholz HM. Acute myocardial infarction in the elderly: differences by age. J Am Coll Cardiol 2001;38(3):736–741.

    Article  CAS  PubMed  Google Scholar 

  27. Devlin W, Cragg D, Jacks M, Friedman H, O’Neill W, Grines C. Comparison of outcome in patients with acute myocardial infarction aged >75 years with that in younger patients. Am J Cardiol 1995;75(8):573–576.

    Article  CAS  PubMed  Google Scholar 

  28. Gurwitz JH, Gore JM, Goldberg RJ, Rubison M, Chandra N, Rogers WJ. Recent age-related trends in the use of thrombolytic therapy in patients who have had acute myocardial infarction. National Registry of Myocardial Infarction. Ann Intern Med 1996;124(3):283–291.

    Article  CAS  PubMed  Google Scholar 

  29. White HD, Barbash GI, Califf RM, et al. Age and outcome with contemporary thrombolytic therapy. Results from the GUSTO-I trial. Global Utilization of Streptokinase and TPA for Occluded coronary arteries trial. Circulation 1996;94(8):1826–1833.

    Article  CAS  PubMed  Google Scholar 

  30. Lowe GD, Rumley A, Woodward M, et al. Epidemiology of coagulation factors, inhibitors and activation markers: the Third Glasgow MONICA Survey. I. Illustrative reference ranges by age, sex and hormone use. Br J Haematol 1997;97(4):775–784.

    Article  CAS  PubMed  Google Scholar 

  31. Mangoni AA, Jackson SH. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol 2004;57(1):6–14.

    Article  CAS  PubMed  Google Scholar 

  32. Goldberg RJ, McCormick D, Gurwitz JH, Yarzebski J, Lessard D, Gore JM. Age-related trends in short- and long-term survival after acute myocardial infarction: a 20-year population-based perspective (1975–1995). Am J Cardiol 1998;82(11):1311–1317.

    Article  CAS  PubMed  Google Scholar 

  33. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003;361(9351):13–20.

    Article  PubMed  Google Scholar 

  34. de Boer MJ, Ottervanger JP, van’t Hof AW, Hoorntje JC, Suryapranata H, Zijlstra F. Reperfusion therapy in elderly patients with acute myocardial infarction: a randomized comparison of primary angioplasty and thrombolytic therapy. J Am Coll Cardiol 2002;39(11):1723–1728.

    Article  PubMed  Google Scholar 

  35. Grines CL, Browne KF, Marco J, et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. The Primary Angioplasty in Myocardial Infarction Study Group. N Engl J Med 1993;328(10):673–679.

    Article  CAS  PubMed  Google Scholar 

  36. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. The Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) Angioplasty Substudy Investigators. N Engl J Med 1997;336(23):1621–1628.

    Article  Google Scholar 

  37. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock. N Engl J Med 1999;341(9):625–634.

    Article  CAS  PubMed  Google Scholar 

  38. Zijlstra F, Patel A, Jones M, et al. Clinical characteristics and outcome of patients with early (<2 h), intermediate (2–4 h) and late (>4 h) presentation treated by primary coronary angioplasty or thrombolytic therapy for acute myocardial infarction. Eur Heart J 2002;23(7):550–557.

    Article  CAS  PubMed  Google Scholar 

  39. Grines C, Patel A, Zijlstra F, Weaver WD, Granger C, Simes RJ. Primary coronary angioplasty compared with intravenous thrombolytic therapy for acute myocardial infarction: six-month follow up and analysis of individual patient data from randomized trials. Am Heart J 2003;145(1):47–57.

    Article  CAS  PubMed  Google Scholar 

  40. DeGeare VS, Stone GW, Grines L, et al. Angiographic and clinical characteristics associated with increased in-hospital mortality in elderly patients with acute myocardial infarction undergoing percutaneous intervention (a pooled analysis of the primary angioplasty in myocardial infarction trials). Am J Cardiol 2000;86(1):30–34.

    Article  CAS  PubMed  Google Scholar 

  41. 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(12):1179–1189.

    Article  CAS  PubMed  Google Scholar 

  42. COMMIT trial confirms clinical benefit in MI. www.theheart.org [HeartWire>News], March 9, 2005 (Accessed July 19, 2005).

  43. Antman EM, Morrow DA, McCabe CH, et al. Enoxaparin versus unfractionated heparin as antithrombin therapy in patients receiving fibrinolysis for ST-elevation myocardial infarction. Design and rationale for the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction study 25 (ExTRACT-TIMI 25). Am Heart J 2005;149(2):217–226.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. TIMI Study Group, Cardiovascular Division, Brigham & Women’s Hospital and the Department of Medicine, Harvard Medical School, USA

    Shaheeda Ahmed, Elliott M. Antman MD, Sabina A. Murphy, Robert P. Giugliano, Christopher P. Cannon, David A. Morrow & Eugene Braunwald

  2. Harvey White Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand

    Harvey White

  3. 350 Longwood Avenue, First Floor, Boston, MA, 02215, USA

    Elliott M. Antman MD

Authors
  1. Shaheeda Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elliott M. Antman MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sabina A. Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert P. Giugliano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christopher P. Cannon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Harvey White
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. David A. Morrow
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Eugene Braunwald
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elliott M. Antman MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ahmed, S., Antman, E.M., Murphy, S.A. et al. Poor outcomes after fibrinolytic therapy for ST-segment elevation myocardial infarction: Impact of age (A Meta-Analysis of a Decade of Trials). J Thromb Thrombolysis 21, 119–129 (2006). https://doi.org/10.1007/s11239-006-5485-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-006-5485-9

Key Words

Search

Navigation