Strategic Reperfusion in Elderly Patients Early After Myocardial Infarction - STREAM-2

Contribution To Literature:

Highlighted text has been updated as of August 4, 2023.

The STREAM-2 trial showed that pharmaco-invasive therapy with half-dose TNK is effective compared with primary PCI among elderly patients presenting with STEMI who were unable to undergo timely primary PCI within 1 hour, but with a higher risk of intracranial hemorrhage.


The goal of the trial was to compare the safety and efficacy of pharmaco-invasive therapy with half-dose tenecteplase (TNK) compared with primary percutaneous coronary intervention (PCI) among older patients presenting with ST-segment elevation myocardial infarction (STEMI) who were unable to undergo timely primary PCI within 1 hour.

Study Design

Patients were randomized in a 2:1 fashion to either a pharmaco-invasive strategy with half-dose, weight-adjusted bolus TNK followed by PCI within 6-24 hours (n = 401) or primary PCI (n = 203). In the pharmaco-invasive arm, PCI could be pursued sooner if ST-segment resolution of ≥50% did not occur by 90 minutes. Patients in the pharmaco-invasive arm received aspirin 150-325 mg, clopidogrel 300 mg as bolus then 75 mg daily, and enoxaparin (no bolus if age ≥75 years). Patients in the primary PCI arm received aspirin 150-325 mg and P2Y12 antagonist and antithrombin treatment according to local standards.

  • Total number of enrollees: 604
  • Duration of follow-up: 30 days
  • Mean patient age: 71 years
  • Percentage female: 32%

Inclusion criteria:

  • Age ≥60 years (original protocol was ≥70 years, amended due to slow enrollment)
  • STEMI <3 hours from symptom onset with ≥2 mm ST elevation in ≥2 contiguous leads
  • Unable to perform timely primary PCI within 1 hour but before 3 hours of first medical contact

Exclusion criteria:

  • Expected performance of PCI <60 minutes from diagnosis (qualifying ECG) or inability to arrive at the catheterization laboratory within 3 hours
  • Previous coronary artery bypass graft surgery
  • Left bundle branch block or ventricular pacing
  • Patients with cardiogenic shock: Killip class IV
  • Patients with a body weight <55 kg (known or estimated)
  • Uncontrolled hypertension, defined as sustained blood pressure ≥180/110 mm Hg (systolic blood pressure [BP] ≥180 mm Hg and/or diastolic BP ≥110 mm Hg) prior to randomization
  • Known prior stroke or transient ischemic attack
  • Recent administration of any intravenous or subcutaneous anticoagulation within 12 hours, including unfractionated heparin, enoxaparin, and/or bivalirudin or current use of oral anticoagulation (i.e., warfarin or a nonvitamin K oral anticoagulant)
  • Active bleeding or known bleeding disorder/diathesis

Other salient features/characteristics:

  • Killip class I: 92%
  • Systolic BP: 134 mm Hg; heart rate 76 bpm
  • Location of infarct: Anterior: 43%, inferior: 56%
  • Need for rescue angiography/PCI in pharmaco-invasive arm: 34%

Principal Findings:

The primary composite outcome at 30 days (death, heart failure, MI, shock), for pharmaco-invasive therapy vs. primary PCI, was: 12.8% vs. 13.3% (relative risk 0.96, 95% confidence interval 0.62-1.48).

Secondary outcomes for pharmaco-invasive therapy vs. primary PCI: 

  • Symptom onset to start of reperfusion treatment:110 vs. 190 minutes (p < 0.001)
  • Baseline TIMI 0/1 flow prior to PCI: 28.4% vs. 65.6% (p < 0.001)
  • Final TIMI 3 flow: 87.3% vs. 86.9% (p = 0.74)
  • ST-deviation resolution: 71% vs. 62% (p = 0.03)
  • All-cause mortality: 9.3% vs. 8.9% (p > 0.05)
  • Cardiovascular mortality: 7.3% vs. 8.4% (p > 0.05)
  • Total stroke: 2.3% vs. 0.5% (p > 0.05)
  • Intracranial hemorrhage: 1.5% vs. 0% (2 out of 6 patients received additional unfractionated heparin at the time of rescue PCI despite receiving low molecular weight heparin shortly before; 1 patient received TNK despite having uncontrolled hypertension) (p = NS)
  • Major non-intracranial bleed: 1.3% vs. 1.0% (p > 0.05)


The results of this trial indicate that pharmaco-invasive therapy with half-dose TNK is safe and effective compared with primary PCI among elderly patients presenting with STEMI who were unable to undergo timely primary PCI within 1 hour. ST-deviation resolution was superior with a pharmaco-invasive strategy. Despite using half-dose TNK, intracranial hemorrhage rates were high but non-intracranial bleeding was low overall. One-half of the intracranial hemorrhage rates were related to protocol deviations, emphasizing the meticulous attention to detail that is necessary when administering fibrinolytic agents. Overall major adverse cardiovascular event rates were also quite high (30-day mortality >9.0%) and nearly double those noted in STREAM-1. This is partly explained by the higher age (~60 years in STREAM-1 vs. ~71 years in STREAM-2).


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 2023;Jul 13:[Epub ahead of print].

Presented by Dr. Frans J. J. Van de Werf at the American College of Cardiology Annual Scientific Session (ACC.23/WCC), New Orleans, LA, March 5, 2023.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Cardiovascular Care Team, Dyslipidemia, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Prevention, Stable Ischemic Heart Disease, Vascular Medicine, Anticoagulation Management and ACS, Lipid Metabolism, Novel Agents, Acute Heart Failure, Interventions and ACS, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Nuclear Imaging, Chronic Angina

Keywords: ACC23, ACC Annual Scientific Session, Acute Coronary Syndrome, Angiography, Antithrombins, Aspirin, Blood Pressure, Clopidogrel, Enoxaparin, Geriatrics, Heart Failure, Hemorrhage, Heparin, Intracranial Hemorrhages, Myocardial Infarction, Percutaneous Coronary Intervention, Reperfusion, Secondary Prevention, Shock, Cardiogenic, ST Elevation Myocardial Infarction, Stroke, Tenecteplase

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