Primary angioplasty or thrombolysis? a topical parable
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《英国医生杂志》
1 Quebec Heart Institute, Laval University, Ste-Foy, Quebec, Canada G1V 4G5, 2 Royal Victoria Hospital, McGill University, Montreal, Canada
Correspondence to: P Bogaty peter.bogaty@med.ulaval.ca
Primary angioplasty is being touted as a revolutionary treatment that should supersede thrombolysis in modern management of acute myocardial infarction. Would our perspective be different if angioplasty had been developed first?
Myocardial infarction used to be a nasty scourge, with 15-25% mortality. Then came the breakthrough discoveries that thrombotic coronary occlusion caused myocardial infarction and that balloon catheters could cross the occlusion, squash the thrombus, and re-establish flow. Thus, it was possible to abort the progression of myocardial infarction and reduce mortality. Cardiologists became interventionists. Cardiac catheterisation laboratories grew like mushrooms. Balloons and hubris were inflated as many lives were saved. A gigantic industry sprang forth of catheters, sophisticated stents, and expensive adjunctive drugs. It seemed that all was now for the best "in the best of all possible worlds" and "that things in general were settled forever."
Creaking system
And yet there were downsides. In a substantial proportion of cases, myocardial perfusion was unsatisfactory, even when coronary artery flow seemed adequate.1 It was speculated that this could be due to distal migration of thrombus secondary to mechanical intervention. This spurred an interest in lassoes, aspirators, and other devices designed to capture such debris during angioplasty. While increasing costs, these failed to satisfactorily resolve this vexing problem. Also, the (insatiable) demands of the mechanical approach were draining the healthcare system and exhausting cardiologists and support staff, who had to get up at ungodly hours to open up people's arteries. A study even showed that mortality of patients treated out of hours was greater than when they were treated during the normal working day.2
Should he have thrombolysis now or be taken to the nearest angioplasty centre?
Credit: SHOUT PICTURE LIBRARY/JOHN CALLAN
Ambulances and helicopters were constantly transporting patients, sometimes over great distances and in difficult circumstances, to and from the nearest catheterisation laboratory to prevent the tertiary cardiac resources from getting clogged up. Although no expense was spared to support this interventionist approach, unfortunately no time or resources remained to assess the effect of these multiple transfers on continuity of care and long term outcomes. The healthcare system groaned and creaked under the rising strain. Some argued that time was (myocardial) muscle and that the inevitable delays before patients could be treated nullified much of the beneficial effect of mechanical intervention. Finally, primary angioplasty was simply beyond the capacities of poorer countries. Creative thinkers pondered an alternative.
New dawn
And then the astounding discovery was made that a bacterial enzyme, streptokinase, could dissolve human clots. The age of thrombolysis had dawned. Patients might now be treated at local hospitals by primary care physicians, a far more rapid and accessible and less expensive approach. Then, faster acting fibrin specific agents that could be given as intravenous boluses were developed. Some speculated that the lower success rate of thrombolysis in opening arteries compared with primary angioplasty was counterbalanced, not only by faster treatment but also by the intrinsic superiority of an approach that created less debris than mechanical intervention.
Controversy ensued. Tertiary high tech versus decentralised simpler treatment? Many clinical trials were performed. A meta-analysis comparing angioplasty with fibrin specific thrombolytics showed that the 1.1% mortality advantage in favour of angioplasty was not significant (95% confidence interval -0.3 to 2.6).3 4 Some conciliatory cardiologists argued for facilitated angioplasty (first thrombolysis, then angioplasty for all) but could not show superiority for this approach that others berated as therapeutic overkill and (facilitated) financial ruin. Finally, a trial compared primary angioplasty with ultrarapid thrombolysis in the home or ambulance followed by rescue angioplasty in the 25% or so cases where thrombolysis seemed ineffective. This judicious strategy led to among the lowest mortality figures (3.8%) recorded in the treatment of myocardial infarction in a large clinical trial with a 1% mortality advantage (albeit not significant) in favour of thrombolysis.5 Enthusiasts proclaimed that the ideal therapeutic approach had been attained. The future will record whether this development truly marked the end of the history of the treatment of acute myocardial infarction.
With thanks to Voltaire and Dickens.
Contributors and sources: PB and JMB have long experience in treating patients with myocardial infarction in both community and tertiary hospitals. Their research interests encompass the pathophysiology of acute ischaemic heart disease and the evaluation of contemporary approaches in cardiac health care.
Competing interests: None declared.
References
Feldman LJ, Coste P, Furber A, Dupouy P, Slama MS, Monassier JP, et al. Incomplete resolution of ST segment elevation is a marker of transient microcirculatory dysfunction after stenting for acute myocardial infarction. Circulation 2003;107: 2684-9.
Henriques JPS, Haasdijk AP, Zijlstra F. Outcome of primary angioplasty for acute myocardial infarction during routine duty hours versus during off-hours. J Am Coll Cardiol 2003;41: 2138-42.
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.
Brophy J, Bogaty P. Primary angioplasty and thrombolysis in acute myocardial infarction: broadening the debate. Ann Intern Med (in press).
Bonnefoy E, Lapostolle F, Leizorovicz A, Steg G, McFadden EP, Dubien PY, et al. Primary angioplasty versus prehospital fibrinolysis in acute myocardial infarction: a randomized study. Lancet 2002;360: 825-9.(Peter Bogaty, staff cardi)
Correspondence to: P Bogaty peter.bogaty@med.ulaval.ca
Primary angioplasty is being touted as a revolutionary treatment that should supersede thrombolysis in modern management of acute myocardial infarction. Would our perspective be different if angioplasty had been developed first?
Myocardial infarction used to be a nasty scourge, with 15-25% mortality. Then came the breakthrough discoveries that thrombotic coronary occlusion caused myocardial infarction and that balloon catheters could cross the occlusion, squash the thrombus, and re-establish flow. Thus, it was possible to abort the progression of myocardial infarction and reduce mortality. Cardiologists became interventionists. Cardiac catheterisation laboratories grew like mushrooms. Balloons and hubris were inflated as many lives were saved. A gigantic industry sprang forth of catheters, sophisticated stents, and expensive adjunctive drugs. It seemed that all was now for the best "in the best of all possible worlds" and "that things in general were settled forever."
Creaking system
And yet there were downsides. In a substantial proportion of cases, myocardial perfusion was unsatisfactory, even when coronary artery flow seemed adequate.1 It was speculated that this could be due to distal migration of thrombus secondary to mechanical intervention. This spurred an interest in lassoes, aspirators, and other devices designed to capture such debris during angioplasty. While increasing costs, these failed to satisfactorily resolve this vexing problem. Also, the (insatiable) demands of the mechanical approach were draining the healthcare system and exhausting cardiologists and support staff, who had to get up at ungodly hours to open up people's arteries. A study even showed that mortality of patients treated out of hours was greater than when they were treated during the normal working day.2
Should he have thrombolysis now or be taken to the nearest angioplasty centre?
Credit: SHOUT PICTURE LIBRARY/JOHN CALLAN
Ambulances and helicopters were constantly transporting patients, sometimes over great distances and in difficult circumstances, to and from the nearest catheterisation laboratory to prevent the tertiary cardiac resources from getting clogged up. Although no expense was spared to support this interventionist approach, unfortunately no time or resources remained to assess the effect of these multiple transfers on continuity of care and long term outcomes. The healthcare system groaned and creaked under the rising strain. Some argued that time was (myocardial) muscle and that the inevitable delays before patients could be treated nullified much of the beneficial effect of mechanical intervention. Finally, primary angioplasty was simply beyond the capacities of poorer countries. Creative thinkers pondered an alternative.
New dawn
And then the astounding discovery was made that a bacterial enzyme, streptokinase, could dissolve human clots. The age of thrombolysis had dawned. Patients might now be treated at local hospitals by primary care physicians, a far more rapid and accessible and less expensive approach. Then, faster acting fibrin specific agents that could be given as intravenous boluses were developed. Some speculated that the lower success rate of thrombolysis in opening arteries compared with primary angioplasty was counterbalanced, not only by faster treatment but also by the intrinsic superiority of an approach that created less debris than mechanical intervention.
Controversy ensued. Tertiary high tech versus decentralised simpler treatment? Many clinical trials were performed. A meta-analysis comparing angioplasty with fibrin specific thrombolytics showed that the 1.1% mortality advantage in favour of angioplasty was not significant (95% confidence interval -0.3 to 2.6).3 4 Some conciliatory cardiologists argued for facilitated angioplasty (first thrombolysis, then angioplasty for all) but could not show superiority for this approach that others berated as therapeutic overkill and (facilitated) financial ruin. Finally, a trial compared primary angioplasty with ultrarapid thrombolysis in the home or ambulance followed by rescue angioplasty in the 25% or so cases where thrombolysis seemed ineffective. This judicious strategy led to among the lowest mortality figures (3.8%) recorded in the treatment of myocardial infarction in a large clinical trial with a 1% mortality advantage (albeit not significant) in favour of thrombolysis.5 Enthusiasts proclaimed that the ideal therapeutic approach had been attained. The future will record whether this development truly marked the end of the history of the treatment of acute myocardial infarction.
With thanks to Voltaire and Dickens.
Contributors and sources: PB and JMB have long experience in treating patients with myocardial infarction in both community and tertiary hospitals. Their research interests encompass the pathophysiology of acute ischaemic heart disease and the evaluation of contemporary approaches in cardiac health care.
Competing interests: None declared.
References
Feldman LJ, Coste P, Furber A, Dupouy P, Slama MS, Monassier JP, et al. Incomplete resolution of ST segment elevation is a marker of transient microcirculatory dysfunction after stenting for acute myocardial infarction. Circulation 2003;107: 2684-9.
Henriques JPS, Haasdijk AP, Zijlstra F. Outcome of primary angioplasty for acute myocardial infarction during routine duty hours versus during off-hours. J Am Coll Cardiol 2003;41: 2138-42.
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.
Brophy J, Bogaty P. Primary angioplasty and thrombolysis in acute myocardial infarction: broadening the debate. Ann Intern Med (in press).
Bonnefoy E, Lapostolle F, Leizorovicz A, Steg G, McFadden EP, Dubien PY, et al. Primary angioplasty versus prehospital fibrinolysis in acute myocardial infarction: a randomized study. Lancet 2002;360: 825-9.(Peter Bogaty, staff cardi)