Elsevier

The Lancet

Volume 364, Issue 9439, 18–24 September 2004, Pages 1045-1053
The Lancet

Articles
Routine invasive strategy within 24 hours of thrombolysis versus ischaemia-guided conservative approach for acute myocardial infarction with ST-segment elevation (GRACIA-1): a randomised controlled trial

https://doi.org/10.1016/S0140-6736(04)17059-1Get rights and content

Summary

Background

In patients with ST-segment elevated myocardial infarction (STEMI), early post-thrombolysis routine angioplasty has been discouraged because of its association with high incidence of events. The GRACIA-1 trial was designed to reassess the benefits of an early post-thrombolysis interventional approach in the era of stents and new antiplatelet agents.

Methods

500 patients with thrombolysed STEMI (with recombinant tissue plasminogen activator) were randomly assigned to angiography and intervention if indicated within 24 h of thrombolysis, or to an ischaemia-guided conservative approach. The primary endpoint was the combined rate of death, reinfarction, or revascularisation at 12 months. Analysis was by intention to treat.

Findings

Invasive treatment included stenting of the culprit artery in 80% (199 of 248) patients, bypass surgery in six (2%), non-culprit artery stenting in three, and no intervention in 40 (16%). Predischarge revascularisation was needed in 51 of 252 patients in the conservative group. By comparison with patients receiving conservative treatment, by 1 year, patients in the invasive group had lower frequency of primary endpoint (23 [9%] vs 51 [21%], risk ratio 0·44 [95% CI 0·28<–0·70], p=0·0008), and they tended to have reduced rate of death or reinfarction (7% vs 12%, 0·59 [0·33–1·05], p=0·07). Index time in hospital was shorter in the invasive group, with no differences in major bleeding or vascular complications. At 30 days both groups had a similar incidence of cardiac events. In-hospital incidence of revascularisation induced by spontaneous recurrence of ischaemia was higher in patients in the conservative group than in those in the invasive group.

Interpretation

In patients with STEMI, early post-thrombolysis catheterisation and appropriate intervention is safe and might be preferable to a conservative strategy since it reduces the need for unplanned in-hospital revascularisation, and improves 1-year clinical outcome.

Introduction

Primary percutaneous coronary intervention is recommended as a reperfusion strategy for continuing myocardial infarction.1, 2, 3, 4 However, because of the low availability of such treatment, even in developed countries, most patients with ST-segment elevated myocardial infarction (STEMI) are reperfused with intravenous thrombolysis.5, 6

Despite the effectiveness and worldwide availability of intravenous thrombolysis, the usefulness of this therapy is greatly threatened by a high proportion of failed reperfusion, and a substantial rate of reocclusion.7, 8, 9, 10 The early interventional approach for STEMI patients receiving thrombolytics has been based on the hypothesis that mechanical repair of the infarct-related artery allows stable normal flow and prevents ischaemic events related to reocclusion, which is itself closely associated with the presence and severity of residual stenosis.11, 12, 13 However, in the era of balloon percutaneous coronary intervention, routine percutaneous intervention immediately or hours after thrombolysis has been associated with increased rate of cardiac and non-cardiac complications, and has not been effective against reocclusion and its clinical consequences.14, 15, 16, 17 Therefore the practice of angioplasty within hours of thrombolysis is strongly discouraged by current guidelines (class III), which recommend a policy of watchful waiting.1, 2, 3 This recommendation was based on randomised studies from an earlier era of percutaneous coronary intervention that preceded the use of stents and new antiplatelet agents.

Coronary stent implantation improves clinical outcome and reduces restenosis even in patients with severe thrombotic conditions, especially when it is done under the protection of glycoprotein IIb or GP IIIa inhibitors or thyenopyridines.18, 19, 20 Moreover, recent non-randomised studies show that stent implantation soon after thrombolysed STEMI is safe and is associated with a low rate of reocclusion and related events.21, 22, 23 We designed the GRACIA-1 trial to test the hypothesis that, for patients with STEMI, routine early cardiac catheterisation with adequate myocardial revascularisation (if indicated) is better than the classic conservative ischaemia-guided strategy.

Section snippets

Trial design and participants

From March 10, 2000, to Nov 26, 2001, we enrolled 500 patients from 22 Spanish and Portuguese centres, 15 of which had interventional facilities. Multicentre national ethical approval and local ethics committee approval were obtained. An information brochure was given to each patient who met inclusion criteria, and informed written consent was obtained from all patients 6 h after thrombolysis. The patient was then randomly and externally assigned to the interventional strategy or to the

Results

500 patients were randomly assigned, 248 to invasive strategy and 252 to the conservative approach (figure 1). 1-year follow-up was completed in 98% of patients (1 year visit of the last patient included was on Nov 28, 2002).

Table 1, Table 2 show clinical characteristics of patients at baseline and 1 year. Anterior acute myocardial infarction was diagnosed in 200 patients (40%) and only two (0·4%) had an unidentifiable infarction. Thrombolysis was given within 2 h of onset of pain in both

Discussion

We have shown that the strategy of early post-thrombolysis cardiac catheterisation and appropriate intervention is safe, does not increase cardiac events and bleeding in the short term, and reduces duration of hospital stay. Moreover, this approach significantly reduces need for revascularisation induced by spontaneous recurrence of ischaemia during the index hospital stay. The early post-thrombolysis interventional strategy also significantly reduces the combined primary endpoint of death,

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