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)

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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:McEntegart, Dr Margaret and McCartney, Dr Peter and Corcoran, Dr David and Maznyczka, Dr Annette Marie and Eteiba, Dr Hany and McConnachie, Professor Alex and Welsh, Dr Paul and Oldroyd, Dr Keith and Ford, Professor Ian and Berry, Professor Colin and Orchard, Miss Vanessa and Sattar, Professor Naveed and Ford, Mr Thomas 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 > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
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

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
174049T-TIME Coronary Physiology StudyColin BerryBritish Heart Foundation (BHF)FS/16/74/32573Institute of Cardiovascular & Medical Sciences