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Original research
Effect of coronary flow on intracoronary alteplase: a prespecified analysis from a randomised trial
  1. Annette Marie Maznyczka1,2,
  2. Peter McCartney1,
  3. Patrycja Duklas3,
  4. Margaret McEntegart1,
  5. Keith G Oldroyd1,2,
  6. John P Greenwood4,5,
  7. Douglas Muir6,
  8. Saqib Chowdhary7,
  9. Anthony H Gershlick8,
  10. Clare Appleby9,
  11. Hany Eteiba1,
  12. James Cotton10,
  13. Andrew Wragg11,
  14. Nick Curzen12,
  15. R Campbell Tait13,
  16. Peter MacFarlane14,
  17. Paul Welsh2,
  18. Naveed Sattar2,
  19. Mark C Petrie2,
  20. Ian Ford3,
  21. Keith A A Fox15,
  22. Alex McConnachie3,
  23. Colin Berry1,2
  24. T-TIME (Trial of low-dose adjunctive alTeplase during primary PCI) investigators
  1. 1 Department of Cardiology, Golden Jubilee National Hospital, Glasgow, UK
  2. 2 British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
  3. 3 Robertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
  4. 4 Department of Cardiology, Leeds General Infirmary, Leeds, UK
  5. 5 Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
  6. 6 James Cook University Hospital, Middlesbrough, UK
  7. 7 Manchester University NHS Foundation Trust, Manchester, UK
  8. 8 Division of Cardiology, University of Leicester, Leicester, UK
  9. 9 Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK
  10. 10 Department of Cardiology, Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, Wolverhampton, UK
  11. 11 Barts and The London Hospital, London, UK
  12. 12 Wessex Cardiac Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  13. 13 Department of Haematology, Glasgow Royal Infirmary, Glasgow, UK
  14. 14 Electrocardiology Group, Royal Infirmary, Glasgow, UK
  15. 15 Department of Cardiology, University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, UK
  1. Correspondence to Professor Colin Berry, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK; colin.berry{at}


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.

Trial registration number NCT02257294.

  • acute myocardial infarction

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  • Twitter @amaznyczka, @NickCurzen, @colinberrymd

  • Contributors AMM wrote the manuscript. AMM and CB conceived the idea for the manuscript. AMM, CB and MM performed the angiogram analyses. AMM, PD and AM performed the statistical analyses. PMcC and CB analysed the magnetic resonance images. PMaC analysed the ECGs. RCT analysed the coagulation data. JG, KGO, MM, CB, DM, SC, AHG, CA, HE, JC, AW and NC contributed to data acquisition. KAAF, RCT and NC contributed to interpreting the data and revising the work critically for intellectual content. All authors made the decision to submit. CB is guarantor.

  • Funding AMM is funded by a fellowship from the British Heart Foundation (FS/16/74/32573). CB is supported by grants from the British Heart Foundation (RE/18/6/34217; FS/16/74/32573). T-TIME was supported by grant 12/170/4 from the Efficacy and Mechanism Evaluation (EME) programme of the National Institute for Health Research (NIHR-EME). Boehringer-Ingelheim UK Ltd provided the study drugs (alteplase 10 mg, 20 mg and matched placebo). The research was in part supported by the National Institute for Health Research infrastructure at Leeds.

  • Competing interests AMM holds a fellowship from the British Heart Foundation in support of this study (FS/16/74/32573). CB, based on contracts with the University of Glasgow, has held research and/or consultancy agreements with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, HeartFlow, GSK, Novartis, Philip and Siemens Healthcare. He has held grants from NIHR-EME (reference 12/170/45) and the British Heart Foundation (reference FS/16/74/32573; RE/18/6/34217) in support of the current study. NC has received an unrestricted grant and fees for lectures and consultancy from Abbott Vascular and Boson Scientific. JC has received research support and speaker fees from Abbott Vascular. KGO has received speaker fees and research support from Abbott Vascular and Boston Scientific. KAAF has received grants and personal fees from Bayer/Janssen, grants from AstraZeneca, personal fees from Sanofi/Regeneron and Verseon.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the West of Scotland Research Ethics Committee (reference 13-WS-0119).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available from the corresponding author on reasonable request.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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