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JAMA. 2019 Jan 1;321(1):56-68. doi: 10.1001/jama.2018.19802.

Effect of Low-Dose Intracoronary Alteplase During Primary Percutaneous Coronary Intervention on Microvascular Obstruction in Patients With Acute Myocardial Infarction: A Randomized Clinical Trial.

Author information

1
British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
2
West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank, Clydebank, United Kingdom.
3
Leeds University and Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom.
4
James Cook University Hospital NHS Trust, Middlesbrough, United Kingdom.
5
South Manchester Hospitals NHS Trust, Manchester, United Kingdom.
6
Leicester University Hospitals NHS Trust, Leicester, United Kingdom.
7
Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, United Kingdom.
8
Royal Wolverhampton University Hospital NHS Trust, Wolverhampton, United Kingdom.
9
Barts and the London Hospital, London, United Kingdom.
10
University Hospital Southampton Foundation Trust, Southampton, United Kingdom.
11
Greater Glasgow and Clyde Health Board, Glasgow, United Kingdom.
12
Electrocardiography Core Laboratory, University of Glasgow, Glasgow, United Kingdom.
13
Department of Haematology, Royal Infirmary, Glasgow, United Kingdom.
14
University Hospital Hairmyres, East Kilbride, United Kingdom.
15
University of Edinburgh, Edinburgh, United Kingdom.
16
Robertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom.

Abstract

Importance:

Microvascular obstruction commonly affects patients with acute ST-segment elevation myocardial infarction (STEMI) and is associated with adverse outcomes.

Objective:

To determine whether a therapeutic strategy involving low-dose intracoronary fibrinolytic therapy with alteplase infused early after coronary reperfusion will reduce microvascular obstruction.

Design, Setting, and Participants:

Between March 17, 2016, and December 21, 2017, 440 patients presenting at 11 hospitals in the United Kingdom within 6 hours of STEMI due to a proximal-mid-vessel occlusion of a major coronary artery were randomized in a 1:1:1 dose-ranging trial design. Patient follow-up to 3 months was completed on April 12, 2018.

Interventions:

Participants were randomly assigned to treatment with placebo (n = 151), alteplase 10 mg (n = 144), or alteplase 20 mg (n = 145) by manual infusion over 5 to 10 minutes. The intervention was scheduled to occur early during the primary PCI procedure, after reperfusion of the infarct-related coronary artery and before stent implant.

Main Outcomes and Measures:

The primary outcome was the amount of microvascular obstruction (% left ventricular mass) demonstrated by contrast-enhanced cardiac magnetic resonance imaging (MRI) conducted from days 2 through 7 after enrollment. The primary comparison was the alteplase 20-mg group vs the placebo group; if not significant, the alteplase 10-mg group vs the placebo group was considered a secondary analysis.

Results:

Recruitment stopped on December 21, 2017, because conditional power for the primary outcome based on a prespecified analysis of the first 267 randomized participants was less than 30% in both treatment groups (futility criterion). Among the 440 patients randomized (mean age, 60.5 years; 15% women), the primary end point was achieved in 396 patients (90%), 17 (3.9%) withdrew, and all others were followed up to 3 months. In the primary analysis, the mean microvascular obstruction did not differ between the 20-mg alteplase and placebo groups (3.5% vs 2.3%; estimated difference, 1.16%; 95% CI, -0.08% to 2.41%; P = .32) nor in the analysis of 10-mg alteplase vs placebo groups (2.6% vs 2.3%; estimated difference, 0.29%; 95% CI, -0.76% to 1.35%; P = .74). Major adverse cardiac events (cardiac death, nonfatal MI, unplanned hospitalization for heart failure) occurred in 15 patients (10.1%) in the placebo group, 18 (12.9%) in the 10-mg alteplase group, and 12 (8.2%) in the 20-mg alteplase group.

Conclusions and Relevance:

Among patients with acute STEMI presenting within 6 hours of symptoms, adjunctive low-dose intracoronary alteplase given during the primary percutaneous intervention did not reduce microvascular obstruction. The study findings do not support this treatment.

Trial Registration:

ClinicalTrials.gov Identifier: NCT02257294.

PMID:
30620371
DOI:
10.1001/jama.2018.19802

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