Effect of coronary flow on intracoronary alteplase: a prespecified analysis from a randomised trial

Maznyczka, A. M. et al. (2021) Effect of coronary flow on intracoronary alteplase: a prespecified analysis from a randomised trial. Heart, 107(4), pp. 299-312. (doi: 10.1136/heartjnl-2020-317828) (PMID:33436493)

Abstract

Objectives: Persistently impaired culprit artery flow (<TIMI 3) during primary percutaneous coronary intervention is a surrogate for failed myocardial perfusion. We evaluated the effects of intracoronary alteplase according to TIMI flow grade immediately preceding drug administration. Methods: In T-TIME (trial of low-dose adjunctive alTeplase during primary PCI), patients ≤6 hours from onset of ST-elevation myocardial infarction (STEMI) were randomised to placebo, alteplase 10 mg or alteplase 20 mg, administered by infusion into the culprit artery, pre-stenting. In this prespecified, secondary analysis, coronary flow was assessed angiographically at the point immediately before drug administration. Microvascular obstruction, myocardial haemorrhage and infarct size were assessed by cardiovascular magnetic resonance (CMR) at 2–7 days and 3 months. Results: TIMI flow was assessed after first treatment (balloon angioplasty/aspiration thrombectomy), immediately pre-drug administration, in 421 participants (mean age 61±10 years, 85% male) and was 3, 2 or 1 in 267, 134 and 19 participants respectively. In patients with TIMI flow ≤2 pre-drug, there was higher incidence of microvascular obstruction with alteplase (alteplase 20 mg (53.1%) and 10 mg (59.5%) combined versus placebo (34.1%); OR=2.47 (95% CI 1.16 to 5.22, p=0.018) interaction p=0.005) and higher incidence of myocardial haemorrhage (alteplase 20 mg (53.1%) and 10 mg (57.9%) combined vs placebo (27.5%); OR=3.26 (95% CI 1.44 to 7.36, p=0.004) interaction p=0.001). These effects were not observed in participants with TIMI 3 flow pre-drug. There were no interactions between TIMI flow pre-drug, alteplase and 3-month CMR findings. Conclusion: In patients with impaired culprit artery flow (<TIMI 3) after initial balloon angioplasty/thrombus aspiration, intracoronary alteplase was associated with increased presence of microvascular obstruction and myocardial haemorrhage.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Macfarlane, Professor Peter and McEntegart, Dr Margaret and McCartney, Dr Peter and Maznyczka, Dr Annette Marie and Tait, Dr Robert and Eteiba, Professor Hany and McConnachie, Professor Alex and Welsh, Professor Paul and Petrie, Professor Mark and Oldroyd, Dr Keith and Ford, Professor Ian and Berry, Professor Colin and Duklas, Mrs Patrycja and Sattar, Professor Naveed
• Authors: Maznyczka, A. M., McCartney, P., Duklas, P., McEntegart, M., Oldroyd, K., Greenwood, J., Muir, D., Chowdhary, S., Gershlick, A. H., Eteiba, H., Cotton, J., Wragg, A., Curzen, N., Tait, R., Macfarlane, P., Welsh, P., Sattar, N., Petrie, M., Ford, I., Fox, K., 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; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Heart
• Publisher: BMJ Publishing Group
• ISSN: 1355-6037
• ISSN (Online): 1468-201X
• Published Online: 15 January 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Heart 107(4): 299-312
• Publisher Policy: Reproduced in accordance with the publisher copyright policy

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
303944		BHF Centre of Excellence	Rhian Touyz	British Heart Foundation (BHF)	RE/18/6/34217	CAMS - Cardiovascular Science
174049		T-TIME Coronary Physiology Study	Colin Berry	British Heart Foundation (BHF)	FS/16/74/32573	Institute of Cardiovascular & Medical Sciences