Angioplasty versus intravenous thrombolysis for acute myocardial infarction☆☆☆

Article Outline

• Abstract
• Take home message
• Objective
• Data sources
• Study selection
• Data extraction
• Main results
• Conclusions
  • Author contact
• Commentary: clinical implication
• Evidence-based medicine teaching points
  • Heterogeneity
  • RR versus RRR
• References
• Copyright

Abstract 

[Gallagher EJ. Angioplasty versus intravenous thrombolysis for acute myocardial infarction. Ann Emerg Med. March 2002;39:299-301.]

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Take home message 

Angioplasty appears to improve short-term outcomes after acute myocardial infarction (AMI) compared with thrombolysis. Angioplasty seems likely to prove superior to thrombolysis in certain discrete subsets of patients ineligible for, or at high risk of, complications from thrombolysis. However, for most patients with ST-segment elevation AMI, thrombolysis currently remains the therapeutic strategy of choice.

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Objective 

To determine whether primary coronary angioplasty is superior to thrombolytic therapy for the treatment of patients with AMI.

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Data sources 

Trials were identified from electronic searches of the Cochrane Library and MEDLINE (to January 1998); reference review from reviews, trials, and previously published meta-analyses; and contact with experts. The review is updated to January 1998.

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Study selection 

Studies were included if they were randomized controlled trials comparing primary angioplasty against intravenous thrombolysis (streptokinase [SK], tissue plasminogen activator [tPA]) in adult patients with AMI.

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Data extraction 

Two authors independently extracted the data and assessed the quality of the trials. The following outcomes were assessed: total mortality at the end of the study, reinfarction, stroke of any type, composite end point of death and reinfarction, recurrent ischemia, severe bleeding, and coronary artery bypass grafting.

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Main results 

Ten trials involving 2,573 participants were identified. Compared with thrombolytic therapy, primary angioplasty was associated with a significant reduction in short-term mortality at the end of the studies (relative risk reduction [RRR] 32%; 95% confidence interval [CI] 5% to 50%). Similar reductions were observed for the rate of reinfarction (RRR 52%; 95% CI 30% to 67%), recurrent ischemia (RRR 54%; 95% CI 39% to 66%) and for the combined criteria death or reinfarction (RRR 46%; 95% CI 30% to 58%). The frequency of strokes of any cause was significantly decreased (RRR 66%; 95% CI 28% to 84%). No significant difference was observed for the incidence of major bleeding (relative risk [RR] 1.18; 95% CI 0.73 to 1.90). The superiority of the primary angioplasty over thrombolysis in terms of the composite end point (mortality and reinfarction) was less with accelerated tPA (RR 0.70; 95% CI 0.51 to 0.97) than with SK (RR 0.30; 95% CI 0.17 to 0.53).

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Conclusions 

This meta-analysis suggests that angioplasty provides a short-term clinical advantage over thrombolysis that may not be sustained. Primary angioplasty, when available promptly at experienced centres, may be considered the preferred strategy for myocardial reperfusion. However, in most situations, optimal thrombolytic therapy should still be regarded as an excellent reperfusion strategy.

Author contact 

Michel Cucherat MD, PhD Department of Clinical Pharmacology University of Lyon Department of Biostatistics Hospital of Lyon Lyon, France

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Commentary: clinical implication 

Reperfusion of ST-segment elevation AMI decreases mortality. This can be accomplished chemically with intravenous thrombolytic agents or mechanically with coronary angioplasty. The efficacy of thrombolysis has been convincingly demonstrated in a large meta-analysis.¹ Treatment of more than a million patients has established the effectiveness of thrombolysis as the global standard against which newer therapies must be measured.

Thrombolysis, however, is not for everyone. It does not appear to benefit patients with AMI and ST-segment depression,¹ the very elderly (>75 years),¹ those in cardiogenic shock,² and patients with severe hypertension. Finally, approximately 10% to 15% of those receiving thrombolytic agents fail to establish satisfactory reperfusion.³The present meta-analysis of 10 trials showed a clinically and statistically significant reduction in short-term mortality (number needed to treat [NNT] 49; 95% CI 26 to 334), reinfarction (NNT 27; 95% CI 18 to 53), recurrent ischemia (NNT 12; 95% CI 9 to 18), and stroke (NNT 60; 95% CI 35 to 155) associated with angioplasty versus thrombolysis. Nevertheless, there are several reasons why it would be premature to conclude that angioplasty should become the standard of care in ST-segment elevation AMI. First, the 2 strategies under comparison both represent moving targets. Thrombolysis appears to be improving as more is learned about induction of sustained coronary patency. In addition, promising therapies, such as stents and glycoprotein IIb/IIIa inhibitors, were used in only a small number of patients included in the current meta-analysis.

Furthermore, all study end points were short term (<4 weeks). The 3 trials reporting 6-month mortality had a combined sample size too small to provide precise estimates of survival. However, the Global Use of Strategies to Open Occluded Coronary Arteries in acute coronary syndromes (GUSTO IIb) trial difference of 4.1% (95% CI 0.3% to 7.8%) favoring angioplasty in the composite end point at 30 days, decreased to 2.4% by 6 months and was no longer statistically significant.⁴ Thus, the apparent short-term advantage of angioplasty may not be sustained over time.Finally, in contrast with the virtually ubiquitous availability of thrombolytic agents, less than 20% and 10% of institutions in the United States and Europe, respectively, have emergency angioplasty capability.⁵ Because duration of coronary occlusion in AMI is so critical to outcome, transfer of patients from facilities lacking angioplasty to ones able to perform this procedure is not warranted on the basis of available evidence. Angioplasty seems likely to prove superior to thrombolysis in certain discrete subsets of patients ineligible for, or at high risk of, complications from thrombolysis. However, at the present time, in the great majority of individuals with ST-segment elevation AMI, thrombolysis appears to be the therapeutic strategy likely to do the most good for the most patients.

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Evidence-based medicine teaching points 

Heterogeneity 

Failure to detect heterogeneity in a meta-analysis does not necessarily imply homogeneity of merged studies. The test is of low statistical power and may not detect clinically important heterogeneity. For example, the composite end point of death + nonfatal reinfarction + nonfatal disabling stroke used in the GUSTO IIb study, which contributed most of the patients to this systematic review, was different from the primary composite end point of death + nonfatal reinfarction used for the overall meta-analysis. Yet, the associated P value of .11 did not detect this.

RR versus RRR 

RR is the ratio of the absolute risk for each of 2 groups under comparison. It reflects the number of times more likely (RR>1) or less likely (RR<1) an event is to happen. Because the events used as end points in this meta-analysis were all adverse outcomes, an RR favoring the experimental intervention (angioplasty) over the control intervention (thrombolysis) would be less than 1. If the RR is “statistically significant,” the limits of its 95% CI will not embrace the null point of 1. The RRR is the complement of the RR (RRR=1−RR), which is a measure of the proportionate reduction in risk when the experimental intervention is compared with the control.

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References 

1. Fibrinolytic Therapy Trialists FTT Collaborative Group . Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1,000 patients. Lancet. 1994;343:311–322
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2. Hochman JS, Sleeper LA, White HD, et al.  One-year survival following early revascularization for cardiogenic shock. JAMA. 2001;285:190–192
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3. Cucherat M, Bonnefoy E, Tremeau G. Primary angioplasty versus intravenous thrombolysis for acute myocardial infarction. Cochrane Database Systematic Review. In: The Cochrane Library. Issue 1. Oxford, United Kingdom: Update Software, Inc; 2001;
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4. The GUSTO IIb Investigators . A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. N Engl J Med. 1997;336:1621–1628
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5. Lange RA, Hillis LD. Should thrombolysis or primary angioplasty be the treatment of choice for acute myocardial infarction?. N Engl J Med. 1996;335:1311–1317
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