Low-dose alteplase during primary percutaneous coronary intervention according to ischemic time

McCartney, P. J. et al. (2020) Low-dose alteplase during primary percutaneous coronary intervention according to ischemic time. Journal of the American College of Cardiology, 75(12), pp. 1406-1421. (doi: 10.1016/j.jacc.2020.01.041) (PMID:32216909) (PMCID:PMC7109518)

Abstract

Background: Microvascular obstruction affects one-half of patients with ST-segment elevation myocardial infarction and confers an adverse prognosis. Objectives: This study aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intracoronary alteplase infused early after coronary reperfusion associates with ischemic time. Methods: This study was conducted in a prospective, multicenter, parallel group, 1:1:1 randomized, dose-ranging trial in patients undergoing primary percutaneous coronary intervention. Ischemic time, defined as the time from symptom onset to coronary reperfusion, was a pre-specified subgroup of interest. Between March 17, 2016, and December 21, 2017, 440 patients, presenting with ST-segment elevation myocardial infarction within 6 h of symptom onset (<2 h, n = 107; ≥2 h but <4 h, n = 235; ≥4 h to 6 h, n = 98), were enrolled at 11 U.K. hospitals. Participants were randomly assigned to treatment with placebo (n = 151), alteplase 10 mg (n = 144), or alteplase 20 mg (n = 145). The primary outcome was the amount of microvascular obstruction (MVO) (percentage of left ventricular mass) quantified by cardiac magnetic resonance imaging at 2 to 7 days (available for 396 of 440). Results: Overall, there was no association between alteplase dose and the extent of MVO (p for trend = 0.128). However, in patients with an ischemic time ≥4 to 6 h, alteplase increased the mean extent of MVO compared with placebo: 1.14% (placebo) versus 3.11% (10 mg) versus 5.20% (20 mg); p = 0.009 for the trend. The interaction between ischemic time and alteplase dose was statistically significant (p = 0.018). Conclusion: In patients presenting with ST-segment elevation myocardial infarction and an ischemic time ≥4 to 6 h, adjunctive treatment with low-dose intracoronary alteplase during primary percutaneous coronary intervention was associated with increased MVO. Intracoronary alteplase may be harmful for this subgroup. (A Trial of Low-Dose Adjunctive Alteplase During Primary PCI [T-TIME]; NCT02257294)

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McConnachie, Professor Alex and Ford, Thomas and McEntegart, Dr Margaret and Welsh, Professor Paul and McCartney, Dr Peter and Corcoran, Dr David and Oldroyd, Dr Keith and Ford, Professor Ian and Berry, Professor Colin and Maznyczka, Dr Annette Marie and Orchard, Miss Vanessa and Eteiba, Professor Hany and Sattar, Professor Naveed and Radjenovic, Dr Aleksandra
• Authors: McCartney, P. J., Maznyczka, A. M., Eteiba, H., McEntegart, M., Oldroyd, K. G., Greenwood, J. P., Mareida, N., Schmitt, M., McCann, G. P., Fairbairn, T., McAlindon, E., Tait, C., Welsh, P., Sattar, N., Orchard, V., Corcoran, D., Ford, T. J., Radjenovic, A., Ford, I., McConnachie, A., and Berry, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: Journal of the American College of Cardiology
• Publisher: Elsevier
• ISSN: 0735-1097
• ISSN (Online): 1558-3597
• Published Online: 23 March 2020
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in Journal of the American College of Cardiology 75(12):1406-1421
• Publisher Policy: Reproduced under a Creative Commons license

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
174049		T-TIME Coronary Physiology Study	Colin Berry	British Heart Foundation (BHF)	FS/16/74/32573	Institute of Cardiovascular & Medical Sciences