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STREAM-2 RCT | Half-Dose Tenecteplase for STEMI

October 27, 2023

Written by Laura Murphy

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The STREAM-2 trial found half-dose tenecteplase was effective in treating STEMI patients ≥60, though with increased risk of intracranial hemorrhage.

DownSTREAM effects of half-dose tenecteplase
This adds to the STREAM-1 trial, in which a pharmaco-invasive strategy was as effective as primary PCI in patients with early STEMI but was associated with higher rates of intracranial hemorrhage. A modified approach of half-dose tenecteplase for patients 75 and older led to decreased rates of ICH, mandating the STREAM-2 study for the half-dose protocol in the entire cohort of patients age ≥60.

STREAM-2 included patients ≥60 with STEMI presenting within 3 hours of symptom onset who were unable to undergo PCI within 1 hour. 600 patients were randomized at a rate of 2:1 to pharmaco-invasive with half-dose tenecteplase (see supplement for weight-based dosing) or primary PCI, either in the ambulance or at a community hospital. Primary outcomes focused on reperfusion efficacy (ST segment elevation resolution of ≥50% in lead with worst ST elevation), resolution of ST deviations, and a more patient-centered outcome: 30-day composite of death, shock, heart failure or reinfarction. A total of 85.2% of patients in pharmaco-invasive group and 78.4% of patients undergoing primary PCI had resolution of ST-segment elevation, but the rate of the composite clinical endpoint was similar: 12.8% for pharmaco-invasive vs 13.3% for primary PCI, RR 0.96 (95%CI 0.62-1.48).

Despite a half-dose strategy, ICH occurred in 1.5% of patients in the tenecteplase group compared to 0% in the PCI group. However, 3 of 6 cases had protocol violations (excessive anticoagulation and uncontrolled BP), which likely contributed to this. Another interesting finding was that 42.2% of patients in the pharmaco-invasive arm had urgent angiography performed at a median of 142 minutes after randomization (compared to 36.3% in STREAM-1); the authors raised concern that a half-dose strategy may not be as effective as full-dose. More studies will be needed to compare half-dose tenecteplase to full-dose tenecteplase rather than to PCI. Finally, it is also worth noting that PCI commenced within 120 minutes of diagnostic ECG in the majority of patients in the PCI arm (median time 99 minutes); the use of a pharmaco-invasive strategy may be even more important in patients with longer transport times to a PCI center.

How will this change my practice?
Half-dose tenecteplase may be a safe option for older patients with STEMI who present within 3 hours but are unable to undergo primary PCI within 1 hour.  However, I will be looking for additional studies directly comparing half-dose vs full-dose tenecteplase treatment to better understand this comparison.

STREAM-2: Half-Dose Tenecteplase or Primary Percutaneous Coronary Intervention in Older Patients With ST-Segment-Elevation Myocardial Infarction: A Randomized, Open-Label Trial. Circulation. 2023 Aug 29;148(9):753-764. doi: 10.1161/CIRCULATIONAHA.123.064521. Epub 2023 Jul 13.

What are your thoughts?