Elsevier

The Lancet

Volume 371, Issue 9612, 16–22 February 2008, Pages 559-568
The Lancet

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Immediate angioplasty versus standard therapy with rescue angioplasty after thrombolysis in the Combined Abciximab REteplase Stent Study in Acute Myocardial Infarction (CARESS-in-AMI): an open, prospective, randomised, multicentre trial

https://doi.org/10.1016/S0140-6736(08)60268-8Get rights and content

Summary

Background

Thrombolysis remains the treatment of choice in ST-segment elevation myocardial infarction (STEMI) when primary percutaneous coronary intervention (PCI) cannot be done within 90 min. However, the best subsequent management of patients after thrombolytic therapy remains unclear. To assess the best management, we randomised patients with STEMI treated by thrombolysis and abciximab at a non-interventional hospital to immediate transfer for PCI, or to standard medical therapy with transfer for rescue angioplasty.

Methods

600 patients aged 75 years or younger with one or more high-risk features (extensive ST-segment elevation, new-onset left bundle branch block, previous myocardial infarction, Killip class >2, or left ventricular ejection fraction ≤35%) in hospitals in France, Italy, and Poland were treated with half-dose reteplase, abciximab, heparin, and aspirin, and randomly assigned to immediate transfer to the nearest interventional centre for PCI, or to management in the local hospital with transfer only in case of persistent ST-segment elevation or clinical deterioration. The primary outcome was a composite of death, reinfarction, or refractory ischaemia at 30 days, and analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number 00220571.

Findings

Of the 299 patients assigned to immediate PCI, 289 (97·0%) underwent angiography, and 255 (85·6%) received PCI. Rescue PCI was done in 91 patients (30·3%) in the standard care/rescue PCI group. The primary outcome occurred in 13 patients (4·4%) in the immediate PCI group compared with 32 (10·7%) in the standard care/rescue PCI group (hazard ratio 0·40; 95% CI 0·21–0·76, log rank p=0·004). Major bleeding was seen in ten patients in the immediate group and seven in the standard care/rescue group (3·4% vs 2·3%, p=0·47). Strokes occurred in two patients in the immediate group and four in the standard care/rescue group (0·7% vs 1·3%, p=0·50).

Interpretation

Immediate transfer for PCI improves outcome in high-risk patients with STEMI treated at a non-interventional centre with half-dose reteplase and abciximab.

Introduction

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for patients with ST-segment elevation myocardial infarction (STEMI).1, 2 However, a review of consecutive admissions for STEMI in 365 US hospitals in 2005 found that most patients do not receive primary angioplasty within 90 min.3 Even with an optimum network of community hospitals, tertiary referral centres with 24 h immediate PCI availability, and a technically advanced ambulance service using electrocardiogram (ECG) telediagnosis and helicopters, most patients from rural areas do not qualify for primary angioplasty.4, 5, 6 The attempt to extend to these patients the benefit of mechanical revascularisation using initial thrombolysis followed by PCI has been hampered by a higher frequency of both bleeding and ischaemic events after the intervention.

One study showed a deleterious effect of early PCI after tenecteplase compared with primary angioplasty.7 In most cases, patients are still managed conservatively at non-PCI centres, with initial thrombolytic therapy followed by transfer for PCI only if there is no evidence of reperfusion or the patient develops haemodynamic instability. We postulated that early pharmacological reperfusion at a non-PCI centre, addressing the need for a rapid and powerful platelet inhibition that overcomes the initial activation induced by thrombolytics, could be safely followed by immediate transfer for PCI. We expected this strategy to be better than the current standard management with selective late transfer for rescue PCI.

The Combined Abciximab Reteplase Stent Study in Acute Myocardial Infarction (CARESS-in-AMI) was a multicentre trial that randomly assigned high-risk patients with STEMI admitted to non-PCI hospitals to immediate transfer for PCI or to standard treatment with rescue PCI if needed.

Section snippets

Patients and procedures

The design features of CARESS-in-AMI have been published previously8 and the amended protocol, modified in its sample size but with no change in endpoints or any other aspect, has been registered on the ClinicalTrials.gov website (number 00220571).

The study involved networks of non-PCI (so-called spoke) centres and specialist PCI (hub) centres in Poland (14 spoke and three hub sites), Italy (21 spokes and 12 hubs), and France (six spokes and five hubs) that worked together to manage patients in

Results

Between December, 2002, and February, 2007, 600 patients were randomly assigned to either immediate PCI (299 patients) or standard care/rescue PCI (301 patients, figure 1). Baseline clinical characteristics were well balanced between the two groups (table 1). Time from symptom onset to admission was 120 (IQR 75–196) min and time from admission to reteplase administration 42 (30–61) min. The distribution of time from symptom onset to administration of reteplase was well balanced between the two

Discussion

Our study shows that in patients 75 years or younger with large STEMI admitted to centres without PCI facilities, a strategy of immediate transfer for PCI after a combination of half-dose reteplase plus abciximab is better than continuing standard management at the same centre. The driving component of the composite endpoint was refractory ischaemia, since death and reinfarction were lower but not significantly different in the immediate PCI group. The late rise in reinfarction and refractory

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