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Primary angioplasty or thrombolysis for acute myocardial infarction?
CORRESPONDENCE
Without results from large trials of facilitated PTCA, fibrinolytic strategies remain a treatment option. Withholding fibrinolysis from patients with ST-elevation AMI and transferring them for primary PTCA— as Gregg Stone5 suggested in a Commentary about CAPTIM—cannot be regarded as standard care. Future management of patients with STsegment elevation AMI may favour a strategy that includes early (possibly prehospital) triage to primary PTCA with a reduction in time from onset of symptoms, or hospital admission, to start of balloon angioplasty. Since time to reperfusion remains critical, irrespective of type of reperfusion therapy, thrombolysis remains a valuable option for many patients with ST-segment elevation AMI. We believe it is inappropriate to suggest that PTCA is the only acceptable strategy for treatment of AMI with ST-segment elevation. *Johann Auer, Robert Berent, Thomas Weber, Bernd Eber Department of Cardiology and Intensive Care, General Hospital Wels, A-4600 Wels, Austria (e-mail: [email protected]) 1
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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. Andersen HR. Danish Multicenter Randomized Trial on Thrombolytic Therapy Versus Acute Coronary Angioplasty in Acute Myocardial Infarction (DANAMI-2). American College of Cardiology Annual Scientific Session, Atlanta, GA, USA. March 20, 2002. http://www.acc.org/media/session_ info/late/Acc2002/lbct_wednesday. htm#clot (accessed Feb 5, 2003). Eagle KA, Goodman SG, Avezum A, et al. for the GRACE Investigators. 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: 373–77. Bonnefoy E, Lapostolle F, Leizorovicz A, et al. Primary angioplasty versus prehosptial fibrinolysis in acute myocardial infarction: a randomised study. Lancet 2002; 360: 825–29. Stone GW. Primary angioplasty versus “earlier” thrombolysis—time for a wake up call. Lancet 2002; 360: 814–15.
Sir—Should we believe the unequivocal finding of Ellen Keeley and co-workers1 that “primary PTCA is more effective than thrombolytic therapy for the treatment of ST-segment elevation AMI”? I believe that more stringent scientific evidence is needed to confirm this finding. Although Keeley and colleagues report a significant 2·0% absolute reduction in total mortality in favour of PTCA (p=0·0002), this difference decreases to 1·6% when PTCA is
966
compared with fibrin-specific thrombolytic drugs (p=0·021) and with accelerated tissue-type plasminogen activator (t-PA) (p=0·036). After excluding patients from the SHOCK trial,2 comparison of PTCA with accelerated t-PA (in 5012 patients) gives a non-significant 1·2% absolute reduction in total mortality in favour of PTCA (p=0·081). The SHOCK trial2 did not investigate PTCA versus thrombolysis, but compared mechanical revascularisation with medical therapy in patients with cardiogenic shock. In the SHOCK trial, only 63% of medically treated patients received thrombolysis and only 23% were randomised to treatment within 6 h of onset of symptoms. Thus, there was no opportunity for thrombolysis to be effective. Keeley and co-workers found a 4% reduction in non-fatal reinfarction, but different diagnostic categories between patients treated with PTCA or thrombolysis make interpretation of these data difficult, especially during the first 18 h of AMI. A reduction in reinfarction, per se, does not necessarily mean a reduction in long-term mortality.3 The 0·9% absolute reduction in haemorrhagic stroke and the 1·0% absolute reduction in total stroke that Keeley and co-workers report are established benefits of primary PTCA. Some of this benefit is, however, diluted by the mortality data, because of the high mortality resulting from stroke. By contrast, primary PTCA resulted in a 2·0% absolute excess in major haemorrhage (p = 0·032). Of the 23 trials in Keeley and colleagues’ quantitative review, only two enrolled more than 1000 patients, 15 randomised fewer than 200 patients, and five randomised 100 patients or less. Apart from the ethical issues raised by underpowered trials, I suspect that publication bias4 may have affected the findings of Keeley and co-workers’ analysis. The results of meta-analyses should not be regarded as definitive. The ISIS4 investigators were not able to confirm a meta-analysis of intravenous magnesium in AMI that showed a significant reduction in mortality in patients with AMI. The hypothesis of nitroglycerin in AMI was supported by a meta-analysis, but was not confirmed by the ISIS-4 and GISSI-3 investigators. Similarly, the meta-analysis by F FathOrdoubadi and co-workers5 showed a significant 5% absolute reduction in mortality with a glucose-insulinpotassium infusion, yet this treatment is not recommended for patients with AMI in published guidelines, because
the hypothesis is still considered exploratory and needs to be confirmed in a large trial. The work by Keeley and colleagues is extremely interesting, but needs confirmation in a large trial to compare primary PTCA with the quick infusion of a modern thrombolytic agent; such a trial must to be of sufficient power to show a reduction in mortality as its primary end point. Until proven otherwise, thrombolysis should not be regarded as an inferior therapy. Giovanni Melandri Istituto di Cardiologia, Policlinico S OrsolaMalpighi, Università di Bologna, 40138 Bologna, Italy (e-mail: [email protected]) 1
2
3
4
5
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. 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: 625–34 Lincoff AM, Califf RM, Van De Werf F, et al. Mortality at 1 Year With Combination Platelet Glycoprotein IIb/IIIa Inhibition and Reduced-Dose Fibrinolytic Therapy vs Conventional Fibrinolytic Therapy for Acute Myocardial Infarction: GUSTO V Randomized Trial. JAMA 2002; 288: 2130–35. Agema W, Jukema J, Zwinderman A, van der Wall E. A meta-analysis of the angiotensin-converting enzyme gene polymorphism and restenosis after percutaneous transluminal coronary revascularization: evidence for publication bias. Am Heart J 2002; 144: 760–68. Fath-Ordoubadi F, Beatt KJ. Glucoseinsulin-potassium therapy for treatment of acute myocardial infarction: an overview of randomized placebo-controlled trials. Circulation 1997; 96: 1152–56.
Sir—Although Ellen Keeley and colleagues1 highlight several limitations of their analysis, they overlook some important issues. The largest component of the difference they report between primary angioplasty and intravenous fibrinolytic therapy is in the re-infarction rate, which varied from 0 to 15% with fibrinolysis. Moreover, the most substantial differences between treatment groups were observed from two of the largest studies that have neither been peer-reviewed nor published.2,3 Keeley and co-workers incorrectly describe the use of accelerated tissuetype plasminogen activator (t-PA) in the trial by Cindy Grines and colleagues4—in fact, 32% of the patients in that trial received streptokinase and the remainder t-PA or reteplase. Although Keeley and colleagues suggest that emergent hospital transfer
THE LANCET • Vol 361 • March 15, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Without results from large trials of facilitated PTCA, fibrinolytic strategies remain a treatment option. Withholding fibrinolysis from patients with ST-elevation AMI and transferring them for primary PTCA— as Gregg Stone5 suggested in a Commentary about CAPTIM—cannot be regarded as standard care. Future management of patients with STsegment elevation AMI may favour a strategy that includes early (possibly prehospital) triage to primary PTCA with a reduction in time from onset of symptoms, or hospital admission, to start of balloon angioplasty. Since time to reperfusion remains critical, irrespective of type of reperfusion therapy, thrombolysis remains a valuable option for many patients with ST-segment elevation AMI. We believe it is inappropriate to suggest that PTCA is the only acceptable strategy for treatment of AMI with ST-segment elevation. *Johann Auer, Robert Berent, Thomas Weber, Bernd Eber Department of Cardiology and Intensive Care, General Hospital Wels, A-4600 Wels, Austria (e-mail: [email protected]) 1
2
3
4
5
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. Andersen HR. Danish Multicenter Randomized Trial on Thrombolytic Therapy Versus Acute Coronary Angioplasty in Acute Myocardial Infarction (DANAMI-2). American College of Cardiology Annual Scientific Session, Atlanta, GA, USA. March 20, 2002. http://www.acc.org/media/session_ info/late/Acc2002/lbct_wednesday. htm#clot (accessed Feb 5, 2003). Eagle KA, Goodman SG, Avezum A, et al. for the GRACE Investigators. 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: 373–77. Bonnefoy E, Lapostolle F, Leizorovicz A, et al. Primary angioplasty versus prehosptial fibrinolysis in acute myocardial infarction: a randomised study. Lancet 2002; 360: 825–29. Stone GW. Primary angioplasty versus “earlier” thrombolysis—time for a wake up call. Lancet 2002; 360: 814–15.
Sir—Should we believe the unequivocal finding of Ellen Keeley and co-workers1 that “primary PTCA is more effective than thrombolytic therapy for the treatment of ST-segment elevation AMI”? I believe that more stringent scientific evidence is needed to confirm this finding. Although Keeley and colleagues report a significant 2·0% absolute reduction in total mortality in favour of PTCA (p=0·0002), this difference decreases to 1·6% when PTCA is
966
compared with fibrin-specific thrombolytic drugs (p=0·021) and with accelerated tissue-type plasminogen activator (t-PA) (p=0·036). After excluding patients from the SHOCK trial,2 comparison of PTCA with accelerated t-PA (in 5012 patients) gives a non-significant 1·2% absolute reduction in total mortality in favour of PTCA (p=0·081). The SHOCK trial2 did not investigate PTCA versus thrombolysis, but compared mechanical revascularisation with medical therapy in patients with cardiogenic shock. In the SHOCK trial, only 63% of medically treated patients received thrombolysis and only 23% were randomised to treatment within 6 h of onset of symptoms. Thus, there was no opportunity for thrombolysis to be effective. Keeley and co-workers found a 4% reduction in non-fatal reinfarction, but different diagnostic categories between patients treated with PTCA or thrombolysis make interpretation of these data difficult, especially during the first 18 h of AMI. A reduction in reinfarction, per se, does not necessarily mean a reduction in long-term mortality.3 The 0·9% absolute reduction in haemorrhagic stroke and the 1·0% absolute reduction in total stroke that Keeley and co-workers report are established benefits of primary PTCA. Some of this benefit is, however, diluted by the mortality data, because of the high mortality resulting from stroke. By contrast, primary PTCA resulted in a 2·0% absolute excess in major haemorrhage (p = 0·032). Of the 23 trials in Keeley and colleagues’ quantitative review, only two enrolled more than 1000 patients, 15 randomised fewer than 200 patients, and five randomised 100 patients or less. Apart from the ethical issues raised by underpowered trials, I suspect that publication bias4 may have affected the findings of Keeley and co-workers’ analysis. The results of meta-analyses should not be regarded as definitive. The ISIS4 investigators were not able to confirm a meta-analysis of intravenous magnesium in AMI that showed a significant reduction in mortality in patients with AMI. The hypothesis of nitroglycerin in AMI was supported by a meta-analysis, but was not confirmed by the ISIS-4 and GISSI-3 investigators. Similarly, the meta-analysis by F FathOrdoubadi and co-workers5 showed a significant 5% absolute reduction in mortality with a glucose-insulinpotassium infusion, yet this treatment is not recommended for patients with AMI in published guidelines, because
the hypothesis is still considered exploratory and needs to be confirmed in a large trial. The work by Keeley and colleagues is extremely interesting, but needs confirmation in a large trial to compare primary PTCA with the quick infusion of a modern thrombolytic agent; such a trial must to be of sufficient power to show a reduction in mortality as its primary end point. Until proven otherwise, thrombolysis should not be regarded as an inferior therapy. Giovanni Melandri Istituto di Cardiologia, Policlinico S OrsolaMalpighi, Università di Bologna, 40138 Bologna, Italy (e-mail: [email protected]) 1
2
3
4
5
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. 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: 625–34 Lincoff AM, Califf RM, Van De Werf F, et al. Mortality at 1 Year With Combination Platelet Glycoprotein IIb/IIIa Inhibition and Reduced-Dose Fibrinolytic Therapy vs Conventional Fibrinolytic Therapy for Acute Myocardial Infarction: GUSTO V Randomized Trial. JAMA 2002; 288: 2130–35. Agema W, Jukema J, Zwinderman A, van der Wall E. A meta-analysis of the angiotensin-converting enzyme gene polymorphism and restenosis after percutaneous transluminal coronary revascularization: evidence for publication bias. Am Heart J 2002; 144: 760–68. Fath-Ordoubadi F, Beatt KJ. Glucoseinsulin-potassium therapy for treatment of acute myocardial infarction: an overview of randomized placebo-controlled trials. Circulation 1997; 96: 1152–56.
Sir—Although Ellen Keeley and colleagues1 highlight several limitations of their analysis, they overlook some important issues. The largest component of the difference they report between primary angioplasty and intravenous fibrinolytic therapy is in the re-infarction rate, which varied from 0 to 15% with fibrinolysis. Moreover, the most substantial differences between treatment groups were observed from two of the largest studies that have neither been peer-reviewed nor published.2,3 Keeley and co-workers incorrectly describe the use of accelerated tissuetype plasminogen activator (t-PA) in the trial by Cindy Grines and colleagues4—in fact, 32% of the patients in that trial received streptokinase and the remainder t-PA or reteplase. Although Keeley and colleagues suggest that emergent hospital transfer
THE LANCET • Vol 361 • March 15, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.