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)

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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
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 (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

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceRhian TouyzBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science
174049T-TIME Coronary Physiology StudyColin BerryBritish Heart Foundation (BHF)FS/16/74/32573Institute of Cardiovascular & Medical Sciences