Is There Still a Role for Fibrinolysis in ST-Elevation Myocardial Infarction?
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Fibrinolysis had long been the reference treatment in patients with ST-Elevation Myocardial Infarction (STEMI). It was associated with a large reduction in mortality as compared with delayed or no reperfusion in patients managed early, within the first 2 hours from the onset of symptoms. Fibrinolysis also had well-known potential complications: cerebral haemorrhage, especially in patients beyond 75 years, and reinfarction. Primary percutaneous intervention (PCI) has overcome most of these limitations, but at a price: PCI-related delays that can reduce the expected benefit of primary PCI compared with fibrinolysis. That primary PCI is today the treatment of choice in patients with STEMI is no longer discussed. However, fibrinolysis should still maintain a role in the management of acute myocardial infarction (AMI) for three reasons. First, fibrinolysis is no longer a stand-alone treatment. Modern fibrinolytic strategies combine immediate fibrinolysis, loading dose of thienopyridines, and transfer to a PCI hospital for rescue or early PCI within 24 hours. These strategies capitalize on the hub-and-spoke networks that have, or should have, been built everywhere to implement primary PCI. The overall clinical results of these modern fibrinolytic strategies are now similar to those of primary PCI. Second, a substantial number of patients cannot be managed with primary PCI within the reasonable time thresholds set by the guidelines. In the case of long PCI-related delays, patients will benefit from fibrinolysis before or during transfer to a PCI hospital. Third, modern fibrinolytic strategies—immediate fibrinolysis followed by rescue or early PCI—may even offer the best results of all in a subset of patients. Patients of less than 75 years, managed within the first 2 hours and who cannot have immediate PCI, will fare better with a modern fibrinolytic strategy than with primary PCI. Guidelines advocate regional networks between hospitals with and without PCI capabilities, an efficient ambulance service and standardization of AMI management through shared protocols. These regional logistics of care are essential to take full advantage of fibrinolysis strategies. In order to check that these strategies are correctly applied, networks need ongoing registries, as well as benchmarking and quality improvement initiatives.
KeywordsAcute myocardial infarction Thrombolysis Fibrinolysis Networks Guidelines Streptokinase Tenecteplase Reteplase Alteplase Pharmaco-invasive angioplasty Rescue angioplasty Facilitated angioplasty Reperfusion delays STEMI
The authors are grateful to Dr Mikhail Altman for his help in editing the manuscript.
C. El Khoury: none; F. Sibellas: none; E. Bonnefoy: Payment for development of education presentations and has had travel/accommodation expenses covered by Boehringer Ingelheim
References and Recommended Reading
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- 2.GISSI. Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico (GISSI). Lancet. 1986;1:397–402.Google Scholar
- 3.ISIS-2. 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;2:349–60.Google Scholar
- 8.FTT. 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;343:311–22.Google Scholar
- 15.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;97:1549–56.PubMedCrossRefGoogle Scholar
- 17.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;339:753–70.Google Scholar
- 21.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;103:954–60.PubMedCrossRefGoogle Scholar
- 25.GUSTO IIb. 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;336:1621–8.CrossRefGoogle Scholar
- 33.•Jolly SS, Yusuf S, Cairns J, et al. Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial. Lancet. 2011;377:1409–20. This randomized study demonstrated that a radial approach was as effective as a femoral approach for PCI. There was a lower rate of local vascular complications especially in patients with STEMI.PubMedCrossRefGoogle Scholar
- 34.••Steg PG, James SK, Atar D, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). Eur Heart J. Published Online First: 24 Août 2012. doi: 10.1093/eurheartj/ehs215. The new guidelines of the European Society of Cardiology present, comment, and class all available evidences on the management of STEMI. For Europeans, this large report is the most up-to-date and authoritative text on the topic. Even if all the recommendations are not applicable for an American audience, it remains worthwhile to consult and read.
- 38.Francone M, Bucciarelli-Ducci C, Carbone I, et al. Impact of primary coronary angioplasty delay on myocardial salvage, infarct size, and microvascular damage in patients with ST-segment elevation myocardial infarction: insight from cardiovascular magnetic resonance. J Am Coll Cardiol. 2009;54:2145–53.PubMedCrossRefGoogle Scholar
- 42.Danchin N, Coste P, Ferrières J, et al. Comparison of thrombolysis followed by broad use of percutaneous coronary intervention with primary percutaneous coronary intervention for ST-segment-elevation acute myocardial infarction: data from the french registry on acute ST-elevation myocardial infarction (FAST-MI). Circulation. 2008;118:268–76.PubMedCrossRefGoogle Scholar
- 50.Sutton AGC, 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;44:287–96.PubMedCrossRefGoogle Scholar
- 51.•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;54:118–26. Long-term follow-up of the landmark REACT trial. This study showed that rescue PCI was superior to both repeat thrombolysis and conservative therap. Benefit is maintained at one year in terms of mortality.PubMedCrossRefGoogle Scholar
- 54.Armstrong PW. A comparison of pharmacologic therapy with/without timely coronary intervention vs. primary percutaneous intervention early after ST-elevation myocardial infarction: the WEST (Which Early ST-elevation myocardial infarction Therapy) study. Eur Heart J. 2006;27:1530–8.PubMedCrossRefGoogle Scholar
- 56.Thiele H, Eitel I, Meinberg C, et al. Randomized comparison of pre-hospital-initiated facilitated percutaneous coronary intervention versus primary percutaneous coronary intervention in acute myocardial infarction very early after symptom onset: the LIPSIA-STEMI trial (Leipzig immediate prehospital facilitated angioplasty in ST-segment myocardial infarction). JACC Cardiovasc Interv. 2011;4:605–14.PubMedCrossRefGoogle Scholar
- 57.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;57:1867–73.PubMedCrossRefGoogle Scholar
- 59.Gurbel PA, Serebruany VL, Shustov AR, et al. Effects of reteplase and alteplase on platelet aggregation and major receptor expression during the first 24 hours of acute myocardial infarction treatment. GUSTO-III Investigators. Global Use of Strategies to Open Occluded Coronary Arteries. J Am Coll Cardiol. 1998;31:1466–73.PubMedCrossRefGoogle Scholar
- 62.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;371:559–68.PubMedCrossRefGoogle Scholar
- 63.•Cantor WJ, Fitchett D, Borgundvaag B, et al. Routine early angioplasty after fibrinolysis for acute myocardial infarction. N Engl J Med. 2009;360:2705–18. In patients managed in a non-PCI hospital with fibrinolysis, a strategy of immediate transfer to PCI within 6 hours was associated with fewer ischemic complications than was standard treatment.PubMedCrossRefGoogle Scholar
- 66.Zeymer U, Arntz H-R, Dirks B, et al. Reperfusion rate and inhospital mortality of patients with ST segment elevation myocardial infarction diagnosed already in the prehospital phase: results of the German Prehospital Myocardial Infarction Registry (PREMIR). Resuscitation. 2009;80:402–6.PubMedCrossRefGoogle Scholar
- 67.•Steg PG, Bonnefoy E, Chabaud S, et al. Impact of time to treatment on mortality after prehospital fibrinolysis or primary angioplasty: data from the CAPTIM randomized clinical trial. Circulation. 2003;108:2851–6. This analysis of the CAPTIM study assessed the interaction of delay with the reperfusion strategies. Prehospital thrombolysis with transfer to an interventional facility (and, if needed, percutaneous intervention) may be preferable to primary PCI for patients treated within the first 2 hours after symptom onset.PubMedCrossRefGoogle Scholar
- 68.•Bonnefoy E, Steg PG, Boutitie F, et al. Comparison of primary angioplasty and pre-hospital fibrinolysis in acute myocardial infarction (CAPTIM) trial: a 5-year follow-up. Eur Heart J. 2009;30:1598–606. The 5-year follow-up of the CAPTIM study shows that for patients included within 2 h of a STEMI, 5-year mortality was lower with a strategy of pre-hospital lysis followed by transfer to an interventional center than with primary PCI.PubMedCrossRefGoogle Scholar
- 69.•Puymirat E, Simon T, Steg PG, et al. Association of Changes in Clinical Characteristics and Management With Improvement in Survival Among Patients With ST-Elevation Myocardial Infarction. JAMA. 2012;308:1–8. This article presents an analysis of four 1-month French nationwide registries, conducted 5 years apart from 1995 to 2010. It assessed changes over time in 30-day mortality.CrossRefGoogle Scholar
- 75.•The Myocardial Ischaemia National Audit Project. Report 2011. http://www.hqip.org.uk/assets/NCAPOP-Library/MINAP-public-report-2011.pdf. This is the last report of the MINAP project. This important document describes the evolution of STEMI management until 2010 and the effects of an active strategy prioritizing primary PCI in England and Wales.