Reducing mortality in myocardial infarction
http://www.100md.com
《英国医生杂志》
Treatment in specialised angioplasty centres should follow rapid prehospital thrombolysis
Restoring blood flow promptly in an occluded coronary artery by either thrombolysis or angioplasty reduces mortality in myocardial infarction with ST elevation. With both treatments, the faster reperfusion is achieved, the greater the reduction in mortality.1 2 The relative merits of thrombolysis in hospital and angioplasty have recently been debated in this journal,3 4 but in most developed countries the debate is largely over. Meta-analysis of trials comparing the two treatments showed a reduction in reinfarction and stroke and a small reduction in mortality in favour of angioplasty. 5 Guidelines from the European Society of Cardiology now state that primary angioplasty is the preferred therapeutic option when it can be performed "within 90 minutes after the first medical contact."6
In the United Kingdom no special funding exists for primary angioplasty: thrombolysis in hospital remains the standard treatment. Things may be about to change, however. The Department of Health has earmarked ￡1m ($1.89m; 1.46m) "to pilot the possibility of providing a national 24/7 primary angioplasty service," even though such a service would require enormous reorganisation of services and considerable additional investment. Patients with acute myocardial infarction would bypass their local hospitals and go to specialist centres providing a 24 hour angioplasty service. This proposal entails daunting logistical and financial challenges, and the prospect of large numbers of emergency procedures, many of them performed out of hours, raises questions about the quality of such a service.
There is, however, a "third way" that might deliver equivalent or even better results than primary angioplasty while avoiding many of the associated problems. This is the strategy of rapid, prehospital thrombolysis followed by transfer to angioplasty centres.
Although primary angioplasty can deliver highly effective reperfusion, it is often delayed by slow transport for patients and by lack of available time in catheter laboratories. In essence, prompt reperfusion is sacrificed for effective reperfusion. By contrast, patients can have thrombolysis administered by medical or paramedical staff at first contact before admission to hospital, and there is strong evidence that early administration improves outcome. The association between lives saved and time to thrombolysis is not linear: treatment in the first three hours after infarction is three times as effective as later administration.1
Meta-analysis shows that, compared with thrombolysis in hospital, prehospital thrombolysis is associated with a 17% reduction in mortality.7 In the PRAGUE II study, when thrombolysis was given within three hours of the onset of symptoms, mortality was no higher than that associated with primary angioplasty (7.3% v 7.4%).8 In the CAPTIM study, patients with myocardial infarction and ST elevation were randomly allocated within six hours of the onset of symptoms to receive either primary angioplasty or prehospital thrombolysis coupled with, if thrombolysis failed, transfer to a hospital capable of "rescue" angioplasty.9 The researchers had recruited 840 of the required 1200 patients when the study was terminated early owing to inadequate funding. Although the study was underpowered and a difference in treatment effects cannot be excluded with certainty, the analysis is meaningful and a real difference is unlikely (95% confidence interval for the difference in risk –1.53 to 0.29, P = 0.29). This is the only study making this comparison that has ever been performed and thus, though imperfect, it is the only information available. At termination of the trial the groups were not significantly different in terms of 30 day mortality, rates of reinfarction, or stroke, which together formed the primary end point. Of the patients treated with prehospital thrombolysis only 26% required urgent "rescue" angioplasty, but by 30 days 70% of the CAPTIM thrombolysis group had undergone angioplasty.
Perhaps the most important result came from a subsequent analysis examining the impact of time to treatment, which showed a significant interaction between treatment effect and delay.10 For patients randomised more than two hours after the onset of symptoms 30 day mortality was similar in the two groups, but for those randomised within 2 hours mortality was 2.2% with prehospital thrombolysis compared with 5.7% with angioplasty. Although not significant, the trend was strongly in favour of early thrombolysis for these "golden hour" patients.
In the GRACIA study, routine angiographically guided angioplasty resulted in a marked reduction in the need for revascularisation before discharge and a 50% reduction at 12 months in the combined risk of death, reinfarction, and ischaemia needing revascularisation.11 Thus, in addition to the one quarter of prehospital thrombolysis patients who are likely to require immediate "rescue" angioplasty, the rest should have rapid angiography and appropriate revascularisation.
We suggest that the United Kingdom should consider a strategy summed up by three Ps: publicity to maximise the proportion of patients treated within three hours, prehospital thrombolysis, and percutaneous coronary intervention either immediately or before discharge. This strategy would need greater investment in prehospital care, but, most importantly, it would depend on effective and continuing publicity aimed at minimising the time between the onset of chest pain and thrombolysis. The public needs to know about the "golden hour."
Jonathan N Townend, consultant cardiologist
(John.Townend@uhb.nhs.uk)
Sagar N Doshi, consultant cardiologist
Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH
Competing interests: None declared.
References
Boersma E, Maas AC, Deckers JW, Simoons ML. Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour. Lancet 1996;348: 771-5.
Juliard JM, Feldman LJ, Golmard JL, Himbert D, Benamer H, Haghighat T, 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: 1401-5.
Channer KS. Primary angioplasty should be first line treatment for acute myocardial infarction: against. BMJ 2004;328: 1256-7.
Smith D. Primary angioplasty should be first line treatment for acute myocardial infarction: for. BMJ 2004;328: 1254-6.
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: 13-20.
The Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology. Management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2003;24: 28-66.
Morrison LJ, Verbeek PR, McDonald AC, Sawadsky BV, Cook DJ. Mortality and prehospital thrombolysis for acute myocardial infarction: A meta-analysis. JAMA 2000;283: 2686-92.
Widimsky P, Budesinsky T, Vorac D, Groch L, Zelizko M, Aschermann M, et al. Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction. Final results of the randomized national multicentre trial--PRAGUE-2. Eur Heart J 2003;24: 94-104.
Bonnefoy E, Lapostolle F, Leizorovicz A, Steg G, McFadden EP, Dubien PY, et al. Primary angioplasty versus prehospital fibrinolysis in acute myocardial infarction: a randomised study. Lancet 2002;360: 825-9.
Steg PG, Bonnefoy E, Chabaud S, Lapostolle F, Dubien PY, Cristofini P, 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.
Fernandez-Aviles F, Alonso JJ, Castro-Beiras A, Vazquez N, Blanco J, Alonso-Briales J, et al. Routine invasive strategy within 24 hours of thrombolysis versus ischaemia-guided conservative approach for acute myocardial infarction with ST-segment elevation (GRACIA-1): a randomised controlled trial. Lancet 2004;364: 1045-53.
Restoring blood flow promptly in an occluded coronary artery by either thrombolysis or angioplasty reduces mortality in myocardial infarction with ST elevation. With both treatments, the faster reperfusion is achieved, the greater the reduction in mortality.1 2 The relative merits of thrombolysis in hospital and angioplasty have recently been debated in this journal,3 4 but in most developed countries the debate is largely over. Meta-analysis of trials comparing the two treatments showed a reduction in reinfarction and stroke and a small reduction in mortality in favour of angioplasty. 5 Guidelines from the European Society of Cardiology now state that primary angioplasty is the preferred therapeutic option when it can be performed "within 90 minutes after the first medical contact."6
In the United Kingdom no special funding exists for primary angioplasty: thrombolysis in hospital remains the standard treatment. Things may be about to change, however. The Department of Health has earmarked ￡1m ($1.89m; 1.46m) "to pilot the possibility of providing a national 24/7 primary angioplasty service," even though such a service would require enormous reorganisation of services and considerable additional investment. Patients with acute myocardial infarction would bypass their local hospitals and go to specialist centres providing a 24 hour angioplasty service. This proposal entails daunting logistical and financial challenges, and the prospect of large numbers of emergency procedures, many of them performed out of hours, raises questions about the quality of such a service.
There is, however, a "third way" that might deliver equivalent or even better results than primary angioplasty while avoiding many of the associated problems. This is the strategy of rapid, prehospital thrombolysis followed by transfer to angioplasty centres.
Although primary angioplasty can deliver highly effective reperfusion, it is often delayed by slow transport for patients and by lack of available time in catheter laboratories. In essence, prompt reperfusion is sacrificed for effective reperfusion. By contrast, patients can have thrombolysis administered by medical or paramedical staff at first contact before admission to hospital, and there is strong evidence that early administration improves outcome. The association between lives saved and time to thrombolysis is not linear: treatment in the first three hours after infarction is three times as effective as later administration.1
Meta-analysis shows that, compared with thrombolysis in hospital, prehospital thrombolysis is associated with a 17% reduction in mortality.7 In the PRAGUE II study, when thrombolysis was given within three hours of the onset of symptoms, mortality was no higher than that associated with primary angioplasty (7.3% v 7.4%).8 In the CAPTIM study, patients with myocardial infarction and ST elevation were randomly allocated within six hours of the onset of symptoms to receive either primary angioplasty or prehospital thrombolysis coupled with, if thrombolysis failed, transfer to a hospital capable of "rescue" angioplasty.9 The researchers had recruited 840 of the required 1200 patients when the study was terminated early owing to inadequate funding. Although the study was underpowered and a difference in treatment effects cannot be excluded with certainty, the analysis is meaningful and a real difference is unlikely (95% confidence interval for the difference in risk –1.53 to 0.29, P = 0.29). This is the only study making this comparison that has ever been performed and thus, though imperfect, it is the only information available. At termination of the trial the groups were not significantly different in terms of 30 day mortality, rates of reinfarction, or stroke, which together formed the primary end point. Of the patients treated with prehospital thrombolysis only 26% required urgent "rescue" angioplasty, but by 30 days 70% of the CAPTIM thrombolysis group had undergone angioplasty.
Perhaps the most important result came from a subsequent analysis examining the impact of time to treatment, which showed a significant interaction between treatment effect and delay.10 For patients randomised more than two hours after the onset of symptoms 30 day mortality was similar in the two groups, but for those randomised within 2 hours mortality was 2.2% with prehospital thrombolysis compared with 5.7% with angioplasty. Although not significant, the trend was strongly in favour of early thrombolysis for these "golden hour" patients.
In the GRACIA study, routine angiographically guided angioplasty resulted in a marked reduction in the need for revascularisation before discharge and a 50% reduction at 12 months in the combined risk of death, reinfarction, and ischaemia needing revascularisation.11 Thus, in addition to the one quarter of prehospital thrombolysis patients who are likely to require immediate "rescue" angioplasty, the rest should have rapid angiography and appropriate revascularisation.
We suggest that the United Kingdom should consider a strategy summed up by three Ps: publicity to maximise the proportion of patients treated within three hours, prehospital thrombolysis, and percutaneous coronary intervention either immediately or before discharge. This strategy would need greater investment in prehospital care, but, most importantly, it would depend on effective and continuing publicity aimed at minimising the time between the onset of chest pain and thrombolysis. The public needs to know about the "golden hour."
Jonathan N Townend, consultant cardiologist
(John.Townend@uhb.nhs.uk)
Sagar N Doshi, consultant cardiologist
Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH
Competing interests: None declared.
References
Boersma E, Maas AC, Deckers JW, Simoons ML. Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour. Lancet 1996;348: 771-5.
Juliard JM, Feldman LJ, Golmard JL, Himbert D, Benamer H, Haghighat T, 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: 1401-5.
Channer KS. Primary angioplasty should be first line treatment for acute myocardial infarction: against. BMJ 2004;328: 1256-7.
Smith D. Primary angioplasty should be first line treatment for acute myocardial infarction: for. BMJ 2004;328: 1254-6.
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: 13-20.
The Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology. Management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2003;24: 28-66.
Morrison LJ, Verbeek PR, McDonald AC, Sawadsky BV, Cook DJ. Mortality and prehospital thrombolysis for acute myocardial infarction: A meta-analysis. JAMA 2000;283: 2686-92.
Widimsky P, Budesinsky T, Vorac D, Groch L, Zelizko M, Aschermann M, et al. Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction. Final results of the randomized national multicentre trial--PRAGUE-2. Eur Heart J 2003;24: 94-104.
Bonnefoy E, Lapostolle F, Leizorovicz A, Steg G, McFadden EP, Dubien PY, et al. Primary angioplasty versus prehospital fibrinolysis in acute myocardial infarction: a randomised study. Lancet 2002;360: 825-9.
Steg PG, Bonnefoy E, Chabaud S, Lapostolle F, Dubien PY, Cristofini P, 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.
Fernandez-Aviles F, Alonso JJ, Castro-Beiras A, Vazquez N, Blanco J, Alonso-Briales J, et al. Routine invasive strategy within 24 hours of thrombolysis versus ischaemia-guided conservative approach for acute myocardial infarction with ST-segment elevation (GRACIA-1): a randomised controlled trial. Lancet 2004;364: 1045-53.