@article {Maznyczka299, author = {Annette Marie Maznyczka and Peter McCartney and Patrycja Duklas and Margaret McEntegart and Keith G Oldroyd and John P Greenwood and Douglas Muir and Saqib Chowdhary and Anthony H Gershlick and Clare Appleby and Hany Eteiba and James Cotton and Andrew Wragg and Nick Curzen and R Campbell Tait and Peter MacFarlane and Paul Welsh and Naveed Sattar and Mark C Petrie and Ian Ford and Keith A A Fox and Alex McConnachie and Colin Berry}, editor = {,}, title = {Effect of coronary flow on intracoronary alteplase: a prespecified analysis from a randomised trial}, volume = {107}, number = {4}, pages = {299--312}, year = {2021}, doi = {10.1136/heartjnl-2020-317828}, publisher = {BMJ Publishing Group Ltd}, 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{\textendash}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{\textpm}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.}, issn = {1355-6037}, URL = {https://heart.bmj.com/content/107/4/299}, eprint = {https://heart.bmj.com/content/107/4/299.full.pdf}, journal = {Heart} }