Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial

Summary

Background

Primary percutaneous coronary intervention (PCI) is more effective than fibrinolytic therapy for ST-segment elevation acute myocardial infarction (STEMI), but time to intervention can be considerable. Our aim was to investigate whether the administration of full-dose tenecteplase before a delayed PCI could mitigate the negative effect of this delay.

Methods

We did a randomised study in which we assigned patients with STEMI of less than 6 h duration (scheduled to undergo primary PCI with an anticipated delay of 1–3 h) to standard PCI (n=838) or PCI preceded by administration of full-dose tenecteplase (n=829). All patients received aspirin and a bolus, without an infusion, of unfractionated heparin. Our primary endpoint was death or congestive heart failure or shock within 90 days. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00168792.

Findings

We planned to enrol 4000 patients, but early cessation of enrolment was recommended by the data and safety monitoring board because of a higher in-hospital mortality in the facilitated than in the standard PCI group (6% [43 of 664] vs 3% [22 of 656], p=0·0105). Of those enrolled, six were lost to follow-up in the facilitated PCI group and seven in the other group. Median time from randomisation to first balloon inflation was similar in both groups. The median time from bolus tenecteplase to first balloon inflation was 104 min. We noted the primary endpoint in 19% (151 of 810) of patients assigned facilitated PCI versus 13% (110 of 819) of those randomised to primary PCI (relative risk 1·39, 95% CI 1·11–1·74; p=0·0045). During hospital stay, significantly more strokes (1·8% [15 of 829] vs 0, p<0·0001), but not major non-cerebral bleeding complications (6% [46 of 829] vs 4% [37 of 838], p=0·3118), were reported in patients assigned facilitated rather than standard PCI. We also noted more ischaemic cardiac complications, such as reinfarction (6% [49 of 805] vs 4% [30 of 820], p=0·0279) or repeat target vessel revascularisation (7% [53 of 805] vs 3% [28 of 818], p=0·0041) within 90 days in this study group.

Interpretation

A strategy of full-dose tenecteplase with antithrombotic co-therapy, as used in this study and preceding PCI by 1–3 h, was associated with more major adverse events than PCI alone in STEMI and cannot be recommended.

Introduction

Primary percutaneous coronary intervention (PCI) is better than fibrinolytic therapy when delivered soon after onset of symptoms by an experienced team.¹ As such, US and European guidelines2, 3 recommend that primary PCI is done within 90 min of presentation or within 60 min of the time to fibrinolysis. Although such a timeframe is generally achievable in randomised studies, in general practice it is often not met. The logistics of transporting patients between hospitals greatly increase time to treatment. In the latest report of the National Registry of Myocardial Infarction,⁴ for example, the median delay between arrival in a community hospital and first balloon inflation after transfer to a tertiary care hospital was more than 3 h. Fibrinolytic therapy has a similar effect on survival as primary PCI when administered to patients within 2–3 h after onset of their symptoms.5, 6, 7 The greatest benefits of reperfusion are noted in this early time window. These considerations, and the fact that outcomes after primary PCI are much improved when the procedure is done on an open vessel,⁸ provide the rationale for the notion of facilitated PCI.

The use in facilitated PCI of fibrinolytic agents,9, 10, 11, 12, 13, 14 glycoprotein IIb/IIIa inhibitors,15, 16, 17, 18, 19, 20, 21, 22 or a combination of the two23, 24, 25 has been studied previously, but only in small numbers of patients; no clear clinical benefit has been noted. Our aim was to ascertain whether facilitated PCI is more effective than delayed standard primary PCI in patients who have large myocardial infarctions.