doi: 10.1161/01.CIR.0000072930.64775.DC
(Circulation. 2003;107:2533.)
© 2003 American Heart Association, Inc.
Mini-Review: Expert Opinions |
Fibrinolysis for Acute Myocardial Infarction
The Future Is Here and Now
From the Department of Medicine, Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada (P.W.A.); Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Leuven, Belgium (D.C.); and Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass (E.A.).
Correspondence to Paul W. Armstrong, MD, 2-51 Medical Sciences Building, University of Alberta, Edmonton, Alberta, Canada T6G 2H7. E-mail paul.Armstrong{at}ualberta.ca
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Introduction |
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 Top Introduction Evolution of Pharmacological...Choice of Reperfusion StrategyReferences |
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"The reports of my death are greatly exaggerated."
— —Mark Twain, 1897, cable from London to the Associated Press
Pharmacological reperfusion therapy for acute myocardial infarction was incorporated into the armamentarium of clinicians over 15 years ago and has had an extraordinarily beneficial impact on outcome of patients with ST-elevation myocardial infarction (STEMI). There are 3 fundamental components to pharmacological reperfusion; these consist of the core fibrinolytic agent as well as the accompanying antithrombotic and antiplatelet conjunctive therapies. No contemporary therapy in cardiovascular medicine has been as carefully and critically examined in multiple large randomized trials. These have comprehensively examined the efficacy, safety, and impact of novel therapeutic third-generation fibrinolytics and advances in conjunctive therapies aimed at enhancing restoration of myocardial flow in the epicardial infarct-related coronary artery.1–3
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Evolution of Pharmacological Reperfusion Regimens |
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TopIntroductionEvolution of Pharmacological...Choice of Reperfusion StrategyReferences |
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The tissue plasminogen activator (tPA) congeners tenecteplase (TNK-tPA) and reteplase (rPA) that possess initial plasma half-lives of 15 to 30 minutes constitute the newest, most conveniently administered bolus fibrinolytics. They not only reduce the potential for medication errors but also greatly simplify the prospects of prehospital fibrinolysis.2–4 Although these newer agents do not confer additional mortality reduction over that achieved by the 90-minute weight-adjusted accelerated t-PA regimen, the enhanced fibrin specificity of TNK-tPA results in a significant reduction in systemic bleeding.4 Whereas conjunctive therapy with intravenous glycoprotein IIb/IIIa (IV GP IIb/IIIa) inhibitors enhances epicardial flow and myocardial perfusion and reduces reinfarction, these advantages have not resulted in the expected improvement in survival.5,6 Indeed, the increase in systemic bleeding and apparent excess of intracranial hemorrhage among STEMI patients over 75 years has led to reassessment of the suitability of combination reperfusion with IV GP IIb/IIIa inhibitors and reduced dose fibrinolysis.7,8 Currently, the combination of full dose fibrinolysis and low molecular weight heparin or a direct antithrombin appears to be an attractive strategy because of reduced reinfarction and recurrent ischemia.8,9
The major goal of reperfusion therapy is to minimize the time during which the culprit coronary artery remains occluded by rapidly achieving high quality reperfusion at both the epicardial and microcirculatory level and preventing reocclusion after initially successful fibrinolysis. Although Thrombolysis In Myocardial Infarction (TIMI 3) coronary flow has traditionally been viewed as the most reliable surrogate of successful coronary reperfusion, it is now clear that this is an inadequate measure of myocardial perfusion in many patients (irrespective of how it is achieved).10,11 The most readily available and clinically useful tool for assessing reperfusion success is the extent of ST-segment resolution from the baseline electrocardiogram; hence, >50% or 70% ST resolution within the first 60 to 180 minutes after therapy provides excellent insight into the ultimate infarct size, left ventricular function, and survival.12,13
Major evolution in both the location and timing of fibrinolysis has occurred since the initial intracoronary administration of streptokinase in the cardiac catheterization laboratory over a quarter century ago14 (Figure 1). Moving the location of fibrinolysis earlier to the prehospital setting results in a significant reduction in mortality over that achieved by in-hospital fibrinolytic therapy, as demonstrated by a meta-analysis of 6434 patients (odds ratio 0.83, 95% confidence interval 0.70 to 0.98).15 Recognition of the fundamental importance of time on the impact of fibrinolytic treatment on survival was underscored by the "golden hour" metaphor, the time during which 65 lives per 1000 patients treated were saved as compared with only 10 lives per 1000 patients treated between 6 and 12 hours after symptom onset.16 Interest in moving diagnosis and therapy earlier into the field has received additional impetus on the basis of the disappointing outcome of the Rapid Early Action for Coronary Treatment (REACT) study. Despite an intense public education campaign over 18 months, the time from symptom onset to hospital presentation remained unaltered in patients with ischemic symptoms.17 Hence, a substantial further reduction in time to treatment is likely best achieved by enhancing prehospital diagnosis and therapy rather than by expecting patients to seek medical attention earlier.18
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Choice of Reperfusion Strategy |
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TopIntroductionEvolution of Pharmacological...Choice of Reperfusion StrategyReferences |
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The debate concerning the preferred reperfusion strategy was substantially intensified over the past year after the presentation of the much heralded but still unpublished (at the time of this writing) DANish trial in Acute Myocardial Infarction (DANAMI 2) study. In this trial, 1572 STEMI patients were randomized within 12 hours of symptom onset to a fibrinolytic versus a primary percutaneous coronary intervention (PCI) strategy in both community (n=1129) and primary PCI (n=443) hospitals.19 This study integrated an inter-institutional transfer policy for those randomized to primary PCI if it could be achieved within 3 hours. The Data and Safety Monitoring Board prematurely terminated DANAMI 2 because of the perception of "clear benefit" of primary PCI. Although DANAMI 2 did show a substantial reduction in the composite 30-day endpoint of death, re-MI, and disabling stroke (13.7% versus 8.0%; P=0.003) in favor of the primary PCI strategy, this outcome was overwhelmingly influenced by the reduction in reinfarction (from 6.3% to 1.6%; P<0.0001). Importantly, this reduction in reinfarction occurred in a clinical environment where transfer from a community hospital was considered "investigational" if a mechanical intervention after fibrinolysis was needed. Hence, urgent PCI occurred in only 2.5% of patients, even though 28% of the patients were randomized in interventional institutions. An additional study, interpreted by some as impetus to move to an overall primary PCI strategy, was conducted by the Cardiovascular Patients Outcomes Research Team (C-PORT) investigators who randomized 451 STEMI patients within 12 hours of symptom onset to primary PCI versus tPA.20 Although there was no difference in mortality, there was a substantial reduction in the composite endpoints of death, re-MI, and stroke with primary PCI (17.7% versus 10.7% with tPA; P=0.03); this was again largely accounted for by a reduction in an unusually high reinfarction rate amongst fibrinolytic-treated versus PCI-treated patients (8.8% versus 4%; P=0.04). Hence, in both the aforementioned studies, which used unfractionated heparin as the antithrombin fibrinolytic partner, the recurrent infarction rate was by far the most important element in the composite endpoint and seemed unusually high relative to other trials. This is well demonstrated in Figure 2, where we compare the incidence of recurrent infarction in a number of recent STEMI studies that evaluated fibrinolysis and antithrombin therapy; it is useful to evaluate them in the context of the frequency with which mechanical cointervention with PCI was used.
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Although a recent quantitative review of 23 randomized trials suggests that primary PCI is more effective than fibrinolysis in STEMI, the largest component of this difference was reinfarction.21 This work failed to provide individual patient data, thereby potentially masking heterogeneity and important treatment differences. Although the authors propose that emergency hospital transfer is both feasible and safe, a 1.2% complication rate amongst transported patients was recently reported in the Primary Angioplasty in patients transferred from General community hospitals to specialized PTCA Units with or without Emergency thrombolysis 2 (PRAGUE 2) study, in which 2 patients died and 3 developed ventricular fibrillation.22 In our view, this analysis is hypothesis-generating and a signal for caution rather than convincing evidence for practice change.
The Comparison of Angioplasty and Prehospital Thrombolysis In acute Myocardial Infarction (CAPTIM) investigators contributed important observations by comparing prehospital fibrinolysis with primary PCI.23 Although these investigators reported a trend toward improvement in the composite of death, reinfarction, and disabling stroke for PCI versus fibrinolysis (6.2% versus 8.2%; P=0.29), the 30-day mortality was 3.8% for patients receiving accelerated rtPA with unfractionated heparin versus 4.8% in those undergoing primary PCI. Hence, the major advantage was again related predominantly to a reduction in reinfarction in patients undergoing PCI.18 A substudy from the Plasminogen Angioplasty Compatibility Trial (PACT) investigators underscores the deleterious effects of delay in PCI-associated reperfusion.24 When delay to reperfusion increased from 30 through 120 minutes, there was progressively worse left ventricular function, leading these investigators to suggest that incorporation of pharmacological reperfusion may be indicated when door-to-balloon times exceeds 60 minutes. In our view, there is substantial need for caution before accepting the suggestion that widespread application of primary PCI for STEMI be undertaken, given current knowledge and available resources. Indeed, the suggestion that a 3-hour delay in administering life-saving fibrinolytic therapy is appropriate to deliver primary PCI is, in our judgment, both unwise and unsubstantiated by current data and the realities of clinical practice.25 In this regard, it is especially noteworthy that the preponderance of patients undergoing treatment with primary PCI in the C-PORT study as well as the National Registry of Myocardial Infarction (NRMI) registry did so between the hours of 0800 AM and 1600 PM. Clearly, this time window does not conform to the temporal presentation of STEMI and biases the data toward shorter door-to-balloon times than are likely achievable in routine clinical practice.26 A primary invasive approach is neither always feasible or successful nor without hazard: Results are dependent on patient age, time to treatment, operator experience, and institutional volume.26,27
Rather than engaging in unnecessarily strident debate on an either/or treatment proposition, STEMI patients can be best served by embracing an integrated approach to management, as depicted in Figure 3. This approach emphasizes an assessment at the earliest point of medical contact with prompt evaluation of the elapsed time from symptom onset. Antiplatelet and antithrombin therapy should be administered as early as possible in patients identified as having STEMI. Simultaneously, 4 key questions need to be addressed: (1) What is the time from symptom onset to medical contact? (2) What is the risk of the myocardial infarction based on initial clinical and electrocardiographic assessment? (3) What are the risks of fibrinolytic therapy particularly as it relates to systemic and intracranial bleeding? (4) What is the estimated time before the affected individual could be transported to a skilled interventional facility to access primary mechanical intervention? We believe ideal targets should be delivery of fibrinolysis within 60 minutes of call for medical help and within 90 minutes for the delivery of primary PCI. In patients receiving fibrinolysis, careful surveillance over the first 1 to 3 hours is critical to ensure that successful reperfusion occurs, as indicated by relief of symptoms and/or any hemodynamic or electrical instability coupled with at least 50% resolution of the initial ST elevation.12,13 Careful subsequent observation for recurrent ischemia and ischemia brought on by noninvasive testing should lead to prompt angiography and appropriate revascularization. Progress in information technology that facilitates computer-assisted electrocardiographic diagnosis, patient risk modeling, reliable transmission to a remote facility, and triage to the most appropriate healthcare facility is likely to serve patients best. For patients in cardiogenic shock, those with contraindications to fibrinolysis, and others who have rapid, ie, <90 minute, access to expert PCI facilities, primary PCI is the preferred reperfusion strategy.
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For other STEMI patients, who will likely constitute the majority, early prehospital or emergency department administration of fibrinolysis may be best. Notwithstanding concerns about excess complications in the elderly, irrespective of which reperfusion strategy is used, analysis from the Fibrinolytic Therapy Trials’ (FTT) overview provides compelling data that the greatest absolute benefit from fibrinolysis actually occurs in patients over the age of 75, ie, 40 lives per 1000 patients treated versus 20 for those under 75 years of age treated within 12 hours (Colin Baigent, Clinical Trial Service Unit, Oxford, UK, personal communication, 2002). In sharp contrast to the fibrinolytic-treated patients in the DANAMI 2 trial, it should be anticipated that in approximately 1 of 4 fibrinolytic-treated patients would require rescue PCI if clinical and/or electrocardiographic evidence of reperfusion failure were observed.23 Emphasis should be placed on the need to carefully evaluate patients after fibrinolytic therapy for spontaneous or provokable ischemia followed by timely in-hospital co-intervention that will minimize reinfarction (Figure 3). Risk stratification with intense secondary prevention will optimize care. Advances in PCI suggest that routine invasive study deserves consideration and further study.
In addition to early bolus therapy, the future for fibrinolysis will likely involve conjunctive therapy with a direct antithrombin or low molecular weight heparin to minimize reinfarction.8,9,28 The optimal pharmacological approach is still evolving. Ongoing trials are evaluating whether a combined strategy of early pharmacological therapy with further dose modification of fibrinolytic for the elderly combined with GP IIb/IIIa inhibitors ultimately facilitates more effective percutaneous intervention. Attempts to develop single bolus fibrinolytics with higher fibrin specificity (eg, pegylated staphylokinase or amediplase) along with anticoagulants other than low molecular weight heparin (eg, factor Xa inhibitors, heparin-derived pentasaccharide) and novel antiplatelet agents are underway, but the risk/benefit and cost-effectiveness ratios remain to be determined.
In our opinion, fibrinolytic therapy, like Mark Twain, will continue contributing in a vigorous and productive way long after the premature reports of its demise.
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Acknowledgments |
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The editorial assistance of Karen Buck is appreciated.
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Footnotes |
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The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.
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References |
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TopIntroductionEvolution of Pharmacological...Choice of Reperfusion StrategyReferences |
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1. Fibrinolytic Therapy Trials’ (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomized trials of more than 1000 patients. Lancet. 1994; 343: 311–322.[CrossRef][Medline] [Order article via Infotrieve]
2. Armstrong PW, Collen D. Fibrinolysis for acute myocardial infarction: current status and new horizons for pharmacological reperfusion: part 1. Circulation. 2001; 103: 2862–2866.
3. Armstrong PW, Collen D. Fibrinolysis for acute myocardial infarction: current status and new horizons for pharmacological reperfusion: part 2. Circulation. 2001; 103: 2987–2992.
4. Assessment of the Safety and Efficacy of a New Fibrinolytic Investigators. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double blind randomized trial. Lancet. 1999; 354: 716–722.[CrossRef][Medline] [Order article via Infotrieve]
5. Antman EM, Giugliano RP, Gibson CM, et al. Abciximab facilitates the rate and extent of thrombolysis: results from the Thrombolysis in Myocardial Infarction (TIMI) 14 Trial. Circulation. 1999; 99: 2720–2732.
6. Strategies for Patency Enhancement in the Emergency Department (SPEED) Group. Trial of abciximab with and without low-dose reteplase for acute myocardial infarction. Circulation. 2000; 101: 2788–2794.
7. GUSTO V Investigators. Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition. Lancet. 357: 1905–1914.
8. The Assessment of the Safety and Efficacy of a New Fibrinolytic Regimen (ASSENT)-3 Investigators. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomized trial in acute myocardial infarction. Lancet. 2001;2001; 358: 605–613.[CrossRef][Medline] [Order article via Infotrieve]
9. HERO 2 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.[CrossRef][Medline] [Order article via Infotrieve]
10. de Lemos JA, Antman EM, Gibson CM, et al. Abciximab improves both epicardial flow and myocardial reperfusion in ST elevation myocardial infarction. Circulation. 2000; 101: 239–243.
11. Matetzky S, Novikov M, Gruberg L, et al. The significance of persistent ST elevation versus early resolution of ST segment elevation after primary PTCA. J Am Coll Cardiol. 1999; 34: 1932–1938.
12. Schroder R, Dissmann R, Bruggemann T, et al. Extent of early ST segment elevation resolution: a simple but strong predictor of outcome in patients with acute myocardial infarction. J Am Coll Cardiol. 1994; 24: 384–391.[Abstract]
13. Anderson DR, White HD, Ohman ME, et al. Predicting outcome after thrombolysis in acute myocardial infarction according to ST-segment resolution at 90 minutes: a substudy of the GUSTO III trial. Am Heart J. 2002; 144: 81–88.[CrossRef][Medline] [Order article via Infotrieve]
14. Rentrop KP, Blanke H, Karsch KR, et al. Acute myocardial infarction: intracoronary application of nitroglycerin and streptokinase in combination with transluminal recanalization. Clin Cardiol. 1979; 2: 354–363.[Medline] [Order article via Infotrieve]
15. Morrison LJ, Verbeek PR, McDonald AC, et al. Mortality and pre-hospital thrombolysis for acute myocardial infarction: a meta-analysis. JAMA. 2000; 283: 2686–2692.
16. Boersma E, Maas AC, Deckers JW, et al. Early fibrinolytic treatment in acute myocardial infarction: reappraisal of the golden hour. Lancet. 1996; 348: 771–775.[CrossRef][Medline] [Order article via Infotrieve]
17. Luepker RV, Raczynski JM, Osganian S, et al. Effect of a community intervention on patient delay and emergency medical service use in acute coronary heart disease. JAMA. 2000; 284: 60–67.
18. Morrow DA, Antman EA, Sayah A, et al. Evaluation of the time saved by prehospital initiation of reteplase for ST-elevation myocardial infarction. J Am Coll Cardiol. 2002; 40: 71–77.
19. Anderson HR. Danish Multicenter Randomized Trial on Thrombolytic Therapy Versus Acute Coronary Angioplasty in Acute Myocardial Infarction (DANAMI-2). Presented at the American College of Cardiology Annual Scientific Sessions, Atlanta, Ga, March 20, 2002. Available at: http://www.acc.org/media/session_info/late/Acc2002/lbct_wednesday.htm clot. Accessed May 6, 2003.
20. Aversano T, Aversano LT, Passamani E, et al. Thrombolytic therapy vs. primary percutaneous coronary intervention for myocardial infarction in patients presenting to hospitals without on-site cardiac surgery. JAMA. 87: 1943–1951.
21. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of23 randomised trials. Lancet. 2003; 361: 13–20.[CrossRef][Medline] [Order article via Infotrieve]
22. Widimsky P, Budesinsky D, Vorac D, et al. Long distance transport for primary angioplasty vs immediate thrombosis in acute myocardial infarction: final results of the randomized national multicentre trial: PRAGUE-2. Eur Heart J. 2003; 24: 94–104.
23. Bonnefoy E, Lapostolle F, Leizorovicz A, et al. Primary angioplasty versus pre-hospital fibrinolysis in acute myocardial infarction: a randomized study. Lancet. 2002; 360: 825–829.[CrossRef][Medline] [Order article via Infotrieve]
24. Lundergan CF, Reiner JS, Ross Am et al. How long is too long? Association of time delay to successful reperfusion and ventricular function outcome in acute myocardial infarction: the case for thrombolytic therapy before planned angioplasty for acute myocardial infarction. Am Heart J. 2002; 144: 456–462.[CrossRef][Medline] [Order article via Infotrieve]
25. Stone GW. Primary angioplasty versus "earlier" thrombolysis: time for a wake-up call. Lancet. 2002; 360: 814–816.[CrossRef][Medline] [Order article via Infotrieve]
26. Cannon C, Gibson CM, Lambrew CT, et al. Relationship of symptom-onset-to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acute myocardial infarction. JAMA. 2000; 283: 2941–2947.
27. Magid DJ, Calonge BN, Rumsfeld JS, et al. Relation between hospital primary angioplasty volume and mortality for patients with acute MI treated with primary angioplasty vs thrombolytic therapy. JAMA. 2000; 284: 3131–3138.
28. Antman EM, Louwerenburg HW, Baars HF, et al. Enoxaparin as adjunctive antithrombin therapy for ST-elevation myocardial infarction: results of the ENTIRE-Thrombolysis in Myocardial Infarction (TIMI) 23 Trial. Circulation. 2002; 105: 1642–1649.
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