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

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. 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. 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. 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. NCT02257294.

Informations de copyright

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

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.