McCartney, PJ, Eteiba, H, Maznyczka, AM et al. (31 more authors) (2019) Effect of Low-Dose Intracoronary Alteplase during Primary Percutaneous Coronary Intervention on Microvascular Obstruction in Patients with Acute Myocardial Infarction: A Randomized Clinical Trial. JAMA - Journal of the American Medical Association, 321 (1). pp. 56-68. ISSN 0098-7484
Abstract
Key Points
Question: In patients undergoing primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction (STEMI), does adjunctive fibrinolytic therapy with low-dose intracoronary alteplase given after reperfusion and before stent implant reduce microvascular obstruction?
Findings: In this randomized clinical trial that included 440 participants randomized to receive alteplase 20 mg, alteplase 10 mg, or placebo, the primary analysis demonstrated that the amount of microvascular obstruction (% left ventricular mass) revealed by magnetic resonance imaging was 3.5% in the alteplase 20-mg group and 2.3% in the placebo group, a difference that was not statistically significant.
Meaning: Adjunctive low-dose intracoronary alteplase given early during primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction did not reduce microvascular obstruction.
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
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 American Medical Association. All rights reserved. Reproduced in accordance with the publisher's self-archiving policy. https://doi.org/10.1001/jama.2018.19802. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Biomedical Imaging Science Dept (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 22 Jan 2019 11:35 |
Last Modified: | 01 Jun 2019 00:41 |
Status: | Published |
Publisher: | American Medical Association |
Identification Number: | 10.1001/jama.2018.19802 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:141394 |