Keeley EC Boura JA Grines CL Reference

Lancet 2003; 361: 13-20 Abstract

BACKGROUND: Many trials have been done to compare primary percutaneous transluminal coronary angioplasty (PTCA) with thrombolytic therapy for acute ST-segment elevation myocardial infarction (AMI). Our aim was to look at the combined results of these trials and to ascertain which reperfusion therapy is most effective. METHODS: We did a search of published work and identified 23 trials, which together randomly assigned 7739 thrombolytic-eligible patients with ST-segment elevation AMI to primary PTCA (n = 3872) or thrombolytic therapy (n = 3867). Streptokinase was used in eight trials (n = 1837), and fibrin-specific agents in 15 (n = 5902). Most patients who received thrombolytic therapy (76%, n = 2939) received a fibrin-specific agent. Stents were used in 12 trials, and platelet glycoprotein IIb/IIIa inhibitors were used in eight. We identified short-term and long-term clinical outcomes of death, non-fatal reinfarction, and stroke, and did subgroup analyses to assess the effect of type of thrombolytic agent used and the strategy of emergent hospital transfer for primary PTCA. All analyses were done with and without inclusion of the SHOCK trial data. FINDINGS: Primary PTCA was better than thrombolytic therapy at reducing overall short-term death (7% [n = 270] vs 9% [360]; p = 0.0002), death excluding the SHOCK trial data (5% [199] vs 7% [276]; p = 0.0003), non-fatal reinfarction (3% [80] vs 7% [222]; p < 0.0001), stroke (1% [30] vs 2% [64]; p = 0.0004), and the combined endpoint of death, non-fatal reinfarction, and stroke (8% [253] vs 14% [442]; p < 0.0001). The results seen with primary PTCA remained better than those seen with thrombolytic therapy during long-term follow-up, and were independent of both the type of thrombolytic agent used, and whether or not the patient was transferred for primary PTCA. INTERPRETATION: Primary PTCA is more effective than thrombolytic therapy for the treatment of ST-segment elevation AMI.

Summary

A total of 23 trials comparing primary percutaneous coronary intervention (PPCI) to thromboly-sis have been combined in one meta-analysis of 7739 patients. This has allowed a comparison of major end points of death, non-fatal myocardial infarction (MI), stroke, and bleeding. All were significantly lower in the PPCI group. In addition, analysis of subgroups suggested that use of fibrin-specific agents such as tissue plasminogen activator (tPA) did not alter the result. The SHOCK trial, with a comparison of a strategy of initial revascularization with initial medical therapy for cardiogenic shock was different from other trials as up to 36 h could have elapsed since the onset of symptoms. Exclusion or inclusion of this trial did not substantially alter the results (Figure 1).

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Figure 1 There are significant reductions in total mortality (p < 0.0002), non-fatal MI (p < 0.0001), stroke (p = 0.0004), and the combined end point of death, non-fatal MI, and stroke (p < 0.0001). Adapted from Keeley et al., 2003.

Citation Count 171

Related References

1. Weaver WD, Simes RJ, Betriu A, et al. Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review. JAMA 1997;278: 2093-2098.

2. Dalby M, Bouzamondo A, Lechat P, Montalescot G. Transfer for primary angioplasty versus immediate thrombolysis in acute myocardial infarction: a meta-analysis. Circulation 2003; 108: 1809-1814.

Key message

PPCI is safer and more effective than thrombolysis.

Why it's important

No individual trial has managed to show a mortality advantage to PPCI. All published trials except Comparison of Angioplasty and Prehospital Thrombolysis in Acute Myocardial Infarction (CAPTIM) suggest this trend. Use of meta-analysis suggests that there is a morbidity and mortality advantage to PPCI as the treatment of ST-elevation myocardial infarction (STEMI).

Strengths

This is the largest meta-analysis performed to date. It thus allowed some further questions to be addressed. Thus, for example, the presence of only off-site facilities, entailing transfer to another hospital for PPCI appeared to have little effect on safety.

Weaknesses

A comparison of accelerated tPA vs. PPCI appears the best test of the effect of PPCI. Use of accelerated tPA was limited to 12 of the 23 trials, and if only these trials are used, then the amount of benefit for PPCI becomes non-significant. The absence of significance does not exclude the presence of clinical benefit, however. A randomized trial to address the issue would need 4400 patients, and is unlikely to ever be done. The advantage of PPCI over prehospital thrombolysis also could not be assessed.

An additional criticism that has been levelled at this trial is that there is no comparison of PPCI with stent and PPCI without stent. However, use of stents is now almost universal and has never been shown to be a disadvantage in terms of major adverse cardiac events compared to plain balloon angioplasty in any setting.

Finally, although tests of heterogeneity were negative in the 23 trials, there could still have been a biased assessment (e.g. from publication bias).

Relevance

Mortality reduction is the ultimate gold standard for any treatment modality. With the presence of trained interventionals, and an increase in cardiac catheter laboratory capacity, PPCI will become feasible for a large number of patients with STEMI. Well-researched meta-analysis informs the debate to allow development of the service. This paper, in combination with the DANish trial in Acute Myocardial Infarction (DANAMI) and PRAGUE-2 studies, is the catalyst for major change in the treatment of STEMI.

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