Strategic Reperfusion Early After Myocardial Infarction - STREAM

Description:

The goal of the trial was to evaluate a strategy of fibrinolysis and coronary angiography within 6 to 24 hours compared with primary percutaneous coronary intervention (PCI) among patients with ST-segment elevation myocardial infarction (STEMI) who were unable to undergo primary PCI within 1 hour.

Study Design

  • Randomized
  • Parallel

Patient Populations:

  • Patients with STEMI who presented within 3 hours of symptom onset and could not undergo primary PCI within 1 hour

    Number of screened applicants: 1,915
    Number of enrollees: 1,892
    Duration of follow-up: 30 days
    Mean patient age: 60 years
    Percentage female: 21%

Primary Endpoints:

  • All-cause death, MI, shock, or congestive heart failure at 30 days

Secondary Endpoints:

  • Ischemic stroke
  • Intracranial hemorrhage
  • Nonintracranial hemorrhage

Drug/Procedures Used:

Patients with STEMI who presented within 3 hours of symptom onset and could not undergo primary PCI within 1 hour were randomized to fibrinolysis and coronary angiography within 6 to 24 hours (n = 944) versus primary PCI (n = 948).

In the fibrinolysis group, patients received weight-based tenecteplase, intravenous enoxaparin 30 mg, then subcutaneous enoxaparin 1 mg/kg twice daily (0.75 mg/kg twice daily for patients ≥75 years), clopidogrel 300 mg loading dose (omitted for patients ≥75 years) followed by 75 mg daily, and daily aspirin. After 21% of participants were randomized, the protocol was amended to reduce the dose of tenecteplase by approximately 50% for patients ≥75 years. Coronary angiography was performed within 6 to 24 hours unless rescue PCI was required.

Principal Findings:

Overall, 1,892 patients were randomized. The mean age was 60 years, 21% were women, 48% presented with an anterior STEMI, 12% had diabetes, 81% of participants underwent randomization in an ambulance setting, and 19% underwent randomization in a community hospital. The median time between symptom onset and reperfusion was 100 minutes in the fibrinolysis group versus 178 minutes in the primary PCI group (p < 0.001). Rescue PCI was required in 36% of the fibrinolysis group.

All-cause death, MI, shock, or congestive heart failure at 30 days occurred in 12.4% of the fibrinolysis group versus 14.3% of the primary PCI group (p = 0.21). No treatment interaction was found among the tested subgroups, including age, anterior STEMI, diabetes, or time to randomization.

- All-cause mortality: 4.6% vs. 4.4% (p = 0.88), respectively, for fibrinolysis vs. primary PCI
- Reinfarction: 2.5% vs. 2.2% (p = 0.74), respectively
- Congestive heart failure: 6.1% vs. 7.6% (p = 0.18), respectively

- TIMI 3 flow pre-PCI: 59% vs. 21% (p < 0.001), respectively
- TIMI 3 flow post-PCI: 91% vs. 92% (p = 0.41), respectively

- Total strokes: 1.6% vs. 0.5% (p = 0.03), respectively
- Intracranial hemorrhage: 1.0% vs. 0.2% (p = 0.05), respectively
- Intracranial hemorrhage after protocol amendment: 0.5% vs. 0.3% (p = 0.45), respectively
- Major nonintracranial bleeding: 6.5% vs. 4.8% (p = 0.11), respectively

At 1 year:
- Death: 6.7% vs. 5.9% (p = 0.52), respectively, for fibrinolysis vs. primary PCI
- Cardiovascular death: 4.0% vs. 4.1% (p = 0.93), respectively

Before the protocol amendment, all-cause mortality favored primary PCI; however, after the protocol amendment, all-cause mortality was similar between treatment groups (p for interaction = 0.05).

Interpretation:

Among patients with STEMI who were unable to undergo timely primary PCI, a strategy of fibrinolysis and coronary angiography within 6 to 24 hours resulted in similar clinical outcomes (death, reinfarction, shock, or congestive heart failure at 30 days) as primary PCI. This was true among all tested subgroups. However, fibrinolysis was associated with an increased risk in intracranial hemorrhage. After a protocol amendment which halved the dose of tenecteplase among patients ≥75 years, there was no longer a significant observed excess in intracranial hemorrhage.

Earlier studies such as ASSENT-4 documented that immediate PCI after fibrinolysis (i.e., facilitated PCI) is harmful (excess strokes and thrombotic complications). Due to the period of enrollment, these earlier studies did not employ potent adjunctive antiplatelet therapy. Timely primary PCI remains the treatment of choice for STEMI, but when that is not possible for logistical reasons, the approach tested here might be considered.

References:

Presented by Dr. Peter Sinnaeve at the American Heart Association Scientific Sessions, Dallas, TX, November 18, 2013.

Armstrong PW, Gerschlick AH, Goldstein P, et al., on behalf of the STREAM Investigative Team. Fibrinolysis or primary PCI in ST-segment elevation myocardial infarction. N Engl J Med 2013;368:1379-87.

Presented by Dr. Frans van de Werf at ACC.13, San Francisco, March 10, 2013.


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