(Circulation. 2003;108:2828.)
© 2003 American Heart Association, Inc.
Focused Perspectives |
From The TIMI Study Group, Cardiovascular Division, Brigham and Womens Hospital, and the Department of Medicine, Harvard Medical School, Boston, Mass.
Correspondence to: Eugene Braunwald, MD, TIMI Study Group, 350 Longwood Ave, Boston. MA 02115. E-mail ebraunwald{at}partners.org
Key Words: Editorials myocardial infarction reperfusion angioplasty fibrinolysis
| Introduction |
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See p 2851
Thus, it became logical to compare these 2 improvements in reperfusion therapy in the Comparison of Angioplasty and Prehospital Thrombolysis In acute Myocardial infarction (CAPTIM) trial,5 in which the median time from symptom onset to therapy for patients receiving prehospital fibrinolysis was 130 minutes, and was 60 minutes longer in the primary PCI group. There was no difference at 30 days in the primary composite of death, non-fatal reinfarction, and non-fatal stroke (8.2% for fibrinolysis versus 6.2% for PCI, P=0.29) or in mortality alone (3.8% versus 4.8%, P=0.61). Furthermore, as described in a provocative analysis by Steg et al6 in the current issue of Circulation, there was a strong trend toward lower mortality (2.2% versus 5.7%, P=0.058) and a reduction of cardiogenic shock (1.3% versus 5.3%, P=0.032), but no difference in the primary triple endpoint (7.4% versus 6.6%, P=0.86) in patients treated with prehospital fibrinolysis within 2 hours of symptom onset. Thus, the above-described superiority of PCI over fibrinolysis appears not always to be present in a small but important subgroup of patients, ie, those who can receive treatment in the first 2 hours after symptom onset.
| Reassessment of the Golden Hours |
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| Benefits of Reperfusion After 2 to 3 Hours |
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smaller infarct
improved survival) to include other potential benefits of an open infarct-related artery, which include perfusion of hibernating myocardium, improved healing, the prevention of infarct expansion, and of ventricular remodeling.13,14 Because PCI is very effective (>90%) at restoring epicardial flow and improving microvascular flow even hours after the onset of coronary occlusion, it is especially well suited to reap these purported benefits of arterial opening in patients who present relatively late. Although progressively longer delays in time to presentation are associated with higher rates of complications after fibrinolysis, the same pattern appears less evident for primary PCI.15 | A Rational Approach to Reperfusion Therapy |
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When PCI is not available or when the delay between presentation to a hospital and primary PCI is anticipated to be in excess of 90 minutes (which is more likely to occur in low-volume centers, in patients requiring transfer to a second facility or presenting between 6 PM and 8 AM), fibrinolytic therapy should be considered in patients who can be treated within 2 to 3 hours of symptom onset and who are not at high risk for intracranial hemorrhage. In such patients with fresh thrombus, fibrinolytic therapy is especially effective in opening an occluded infarct artery. Because the time to onset of treatment can be shortened by prehospital treatment, administration of fibrinolytic therapy in the ambulance, if available, is most appropriate in patients who present early. This may be followed by PCI to achieve maximal sustained patency of the infarct artery. Indeed, in the fibrinolytic arm of the CAPTIM trial, an early "rescue" intervention was used in 26% of patients and PCI was carried out in an additional 46% within the first month.5 The Southwest German International Study in Acute Myocardial Infarction (SIAM) III trial18 suggests that even better outcomes might have been obtained had all patients receiving early fibrinolytic therapy undergone early angiography and revascularization, as transfer for stenting within 6 hours after fibrinolytic therapy was associated with a halving (25.6% versus 50.6%, P=0.001) of the composite outcome of death, reinfarction, ischemic events, and target lesion revascularization compared with a strategy of delayed elective coronary angiography at 2 weeks.
Because aging thrombi become more resistant to lysis, the efficacy of fibrinolytic therapy in establishing reperfusion and salvaging ischemic myocardium falls off with time from symptom onset, whereas the efficacy of PCI in achieving complete reperfusion and salvaging ischemic myocardium is far less time-dependent.11,19 In addition, patients who present later tend to be older, have more comorbidities, and are at increased risk for intracranial bleeding. Patients over the age of 75 years experience a 3-fold increase in death, reinfarction, or stroke after fibrinolysis compared with primary PCI.20 Thus, patients who cannot receive fibrinolytic therapy within 2 to 3 hours of symptom onset, but who can receive PCI within the next 90 minutes, should be offered this therapy, even if this entails transfer to another facility. Patients who present more than 2 to 3 hours after symptom onset with continued ischemic pain and/or ST-segment elevation, but who cannot be treated with PCI within the next 2 hours, should (if they have no contraindications) receive fibrinolytic therapy, as some myocardial salvage may still be achieved. These patients should be considered for immediate adjunctive PCI after fibrinolysis, particularly if they experience continued ischemic discomfort or ST elevation, recurrent ischemia, or have signs of left ventricular dysfunction, or later if they are not at low risk after noninvasive assessment.
Patients presenting more than approximately 6 hours after symptom onset, especially patients whose chest pain and ST elevation have subsided, will demonstrate only modest benefit from fibrinolysis but may be considered for coronary angiography as soon as feasible, as this approach permits risk stratification, allows for PCI when the anatomy is suitable, and identifies patients who would benefit from coronary artery bypass surgery. The window may be longer (up to 12 hours) in patients with preexisting coronary collaterals, persistent pain, and ST-segment elevation. The benefit of even later (>48 hours) opening of an occluded infarct artery is under investigation in the ongoing Occluded Artery Trial (OAT).21
| Areas for Future Investigation |
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| Footnotes |
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| References |
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2. 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: 1320.[CrossRef][Medline] [Order article via Infotrieve]
3. Boersma E, Mercado N, Poldermans D, et al. Acute myocardial infarction. Lancet. 2003; 361: 847858.[CrossRef][Medline] [Order article via Infotrieve]
4. Morrison LJ, Verbeek PR, McDonald AC, et al. Mortality and prehospital thrombolysis for acute myocardial infarction: a meta-analysis. JAMA. 2000; 283: 26862692.
5. Bonnefoy E, Lapostolle F, Leizorovicz A, et al. Primary angioplasty versus prehospital fibrinolysis in acute myocardial infarction: a randomised study. Lancet. 2002; 360: 825829.[CrossRef][Medline] [Order article via Infotrieve]
6. 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: 28512856.
7. Boersma E, Maas AC, Deckers JW, et al. Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour. Lancet. 1996; 348: 771775.[CrossRef][Medline] [Order article via Infotrieve]
8. Morrow DA, Antman EM, Sayah A, et al. Evaluation of the time saved by prehospital initiation of reteplase for ST-elevation myocardial infarction: results of the Early Retavase-Thrombolysis In Myocardial Infarction (ER-TIMI) 19 trial. J Am Coll Cardiol. 2002; 40: 7177.
9. Cannon CP, 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: 29412947.
10. Milavetz JJ, Giebel DW, Christian TF, et al. Time to therapy and salvage in myocardial infarction. J Am Coll Cardiol. 1998; 31: 12461251.
11. Schomig A, Ndrepepa G, Mehilli J, et al. Therapy-dependent influence of time-to-treatment interval on myocardial salvage in patients with acute myocardial infarction treated with coronary artery stenting or thrombolysis. Circulation. 2003; 108: 10841088.
12. Brodie BR, Stuckey TD, Wall TC, et al. Importance of time to reperfusion for 30-day and late survival and recovery of left ventricular function after primary angioplasty for acute myocardial infarction. J Am Coll Cardiol. 1998; 32: 13121319.
13. Braunwald E. Myocardial reperfusion, limitation of infarct size, reduction of left ventricular dysfunction, and improved survival: should the paradigm be expanded? Circulation. 1989; 79: 441444.
14. Kim CB, Braunwald E. Potential benefits of late reperfusion of infarcted myocardium: the open artery hypothesis. Circulation. 1993; 88: 24262436.
15. Zijlstra F, Patel A, Jones M, et al. Clinical characteristics and outcome of patients with early (<2 h), intermediate (24 h) and late (>4 h) presentation treated by primary coronary angioplasty or thrombolytic therapy for acute myocardial infarction. Eur Heart J. 2002; 23: 550557.
16. Nallamothu BK, Bates ER. Percutaneous coronary intervention versus fibrinolytic therapy in acute myocardial infarction: is timing (almost) everything? Am J Cardiol. 2003; 42: 824826.
17. Berger PB, Ellis SG, Holmes DR, Jr, et al. Relationship between delay in performing direct coronary angioplasty and early clinical outcome in patients with acute myocardial infarction: results from the global use of strategies to open occluded arteries in Acute Coronary Syndromes (GUSTO-IIb) trial. Circulation. 1999; 100: 1420.
18. Scheller B, Hennen B, Hammer B, et al. Beneficial effects of immediate stenting after thrombolysis in acute myocardial infarction. J Am Coll Cardiol. 2003; 42: 634641.
19. Juliard JM, Feldman LJ, Golmard JL, et al. Relation of mortality of primary angioplasty during acute myocardial infarction to door-to-Thrombolysis In Myocardial Infarction (TIMI) time. Am J Cardiol. 2003; 91: 14011405.[CrossRef][Medline] [Order article via Infotrieve]
20. de Boer MJ, Ottervanger JP, van t Hof AW, et al. Reperfusion therapy in elderly patients with acute myocardial infarction: a randomized comparison of primary angioplasty and thrombolytic therapy. J Am Coll Cardiol. 2002; 39: 17231728.
21. Sadanandan S, Buller C, Menon V, et al. The late open artery hypothesis: a decade later. Am Heart J. 2001; 142: 411421.[CrossRef][Medline] [Order article via Infotrieve]
22. Dauerman HL, Sobel BE. Synergistic treatment of ST segment elevation myocardial infarction with pharmacoinvasive recanalization. J Am Coll Cardiol. 2003; 42: 646651.
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