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Effect of coronary flow on intracoronary alteplase: a prespecified analysis from a randomised trial
Annette Marie Maznyczka1,2, Peter McCartney1, Patrycja Duklas3
1Department of Cardiology, Golden Jubilee National Hospital, Glasgow, UK.
Insights
Intracoronary alteplase in STEMI patients with poor artery flow post-PCI increased microvascular obstruction and myocardial hemorrhage. These adverse effects were linked to impaired TIMI flow before treatment, not TIMI 3 flow.
Area of Science:
- Cardiology
- Interventional Cardiology
- Biomedical Imaging
Background:
- Persistent impaired culprit artery flow (TIMI < 3) after primary percutaneous coronary intervention (PCI) indicates failed myocardial perfusion.
- The T-TIME trial investigated low-dose adjunctive alteplase during primary PCI for ST-elevation myocardial infarction (STEMI).
- This study is a secondary analysis of the T-TIME trial, focusing on intracoronary alteplase effects based on pre-drug TIMI flow grade.
Purpose of the Study:
- To evaluate the impact of intracoronary alteplase on myocardial perfusion and injury.
- To assess whether pre-treatment TIMI flow grade modifies the effects of intracoronary alteplase.
- To determine the association between intracoronary alteplase and microvascular obstruction, myocardial hemorrhage, and infarct size.
Main Methods:
- Patients with STEMI within 6 hours of onset were randomized to placebo, 10 mg, or 20 mg alteplase infused into the culprit artery pre-stenting.
- Coronary flow was assessed angiographically (TIMI flow grade) immediately before drug administration.
- Microvascular obstruction, myocardial hemorrhage, and infarct size were evaluated using cardiovascular magnetic resonance (CMR) at 2-7 days and 3 months.
Main Results:
- In patients with TIMI flow ≤2 pre-drug, alteplase administration was associated with a higher incidence of microvascular obstruction (OR=2.47) and myocardial hemorrhage (OR=3.26) compared to placebo.
- These adverse effects were not observed in patients with TIMI 3 flow prior to alteplase administration.
- No interactions were found between pre-drug TIMI flow, alteplase, and 3-month CMR findings regarding infarct size.
Conclusions:
- Intracoronary alteplase in STEMI patients with impaired culprit artery flow (
- The findings suggest that the benefit of intracoronary alteplase may be limited or potentially harmful in patients with poor initial flow.
- Further research is needed to refine treatment strategies based on pre-procedural coronary flow assessment.
Objectives:
Persistently impaired culprit artery flow (
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 (
Trial Registration Number:
NCT02257294.
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