Tenecteplase Therapy as a Reperfusion Strategy in Older Patients With Early STEMI

In older patients with STEMI presenting within 3 hours of symptom onset, half-dose tenecteplase is an effective reperfusion strategy.

Half-dose tenecteplase in a pharmaco-invasive strategy may provide effective reperfusion in older patients with ST-segment-elevation myocardial infarction (STEMI) who present within 3 hours of symptom onset, according to a study in Circulation.

The open-label, prospective, randomized STREAM-2 (Strategic Reperfusion in Elderly Patients Early After Myocardial Infarction; ClinicalTrials.gov Identifier: NCT02777580) trial was conducted in 49 centers in 10 countries.

The participants were aged 60 years or older, weighed 55 kg or more, and presented within 3 hours after symptom onset with electrocardiographic evidence of STEMI (ST-segment elevation of ≥2 mm in 2 contiguous leads) and were eligible for randomization if they were unable to receive primary percutaneous coronary intervention (PCI) within 1 hour but before 3 hours after first medical contact.

The patients were randomly assigned 2:1 to a pharmaco-invasive strategy or primary PCI. Coronary angiography was performed 6 to 24 hours postrandomization.

The primary efficacy endpoints were reperfusion efficacy according to the proportion of patients with 50% or higher ST-segment-elevation resolution in the lead with worst ST-segment elevation, resolution of ST deviations after last angiography, and the composite of all-cause mortality, shock, heart failure, and reinfarction at 30 days.

A total 401 participants were allocated to a pharmaco-invasive strategy and 203 to primary PCI from August 1, 2017, to September 12, 2022. Their mean age was 70.5 years, 166 patients (27.5%) were aged 75 years or older, and 32.7% were women.

The median times from symptom onset to randomization were 97 minutes for the pharmaco-invasive group and 92 minutes for the primary PCI group. Bolus tenecteplase was administered a median of 10 minutes postrandomization, and arterial sheath insertion was performed after 81 minutes in the primary PCI arm.

During the prespecified times early after PCI or last angiography if no PCI was performed, 85.2% of participants in the pharmaco-invasive group vs 78.4% in the primary PCI group achieved 50% or higher ST-segment-elevation resolution. For the pharmaco-invasive group, the investigator-reported thrombolysis in myocardial infarction (TIMI) flow grade 3 after tenecteplase was 53.8% vs 18.9% before primary PCI. After PCI or at last angiography, the 2 groups had TIMI-3 flow grades of about 87%.

If timely PCI is unavailable, this pharmaco-invasive strategy is a reasonable alternative, provided that contraindications to fibrinolysis are observed and excess anticoagulation is avoided.

The combined clinical efficacy endpoint at 30 days was observed in 12.8% of patients in the pharmaco-invasive group and 13.3% in the PCI group (relative risk, 0.96; 95% CI, 0.62-1.48).

All-cause and cardiac deaths were 9.3% and 7.3% in the pharmaco-invasive group and 8.9% and 8.4% in the PCI group, respectively. The pharmaco-invasive arm had 6 intracranial hemorrhages (ICHs; 1.5%), of which 3 were fatal (0.75%). No ICHs occurred in the primary PCI group. The pharmaco-invasive group had 3 ischemic strokes (0.75%) vs 1 in the primary PCI group (0.5%). The major nonintracranial bleeding rate was 1.3% in the pharmaco-invasive group and 1.0% in the primary PCI group.

Among several limitations, the 95% CIs did not allow statistical confirmation of similarity between the 2 treatment groups. Also, the study was unblinded, bias in investigator reporting cannot be excluded, and natural evolution in some ST-segment changes in the pharmaco-invasive group cannot be ruled out.

“If timely PCI is unavailable, this pharmaco-invasive strategy is a reasonable alternative, provided that contraindications to fibrinolysis are observed and excess anticoagulation is avoided,” wrote the investigators.

Disclosure: The trial received funding from Boehringer Ingelheim. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Van de Werf F, Ristić AD, Averkov OV, et al; on behalf of the STREAM-2 Investigators. Half-dose tenecteplase or primary percutaneous coronary intervention in older patients with ST-segment–elevation myocardial infarction in STREAM-2: a randomized, open-label trial. Circulation. Published online July 13, 2023. doi: 10.1161/CIRCULATIONAHA.123.064521