Local Versus Systemic Thrombolysis for Acute Ischemic Stroke - SYNTHESIS Expansion


The goal of the trial was to evaluate treatment with endovascular therapy compared with intravenous thrombolytic therapy among patients with an acute ischemic stroke.


Endovascular therapy will improve outcomes.

Study Design

  • Randomized
  • Blinded

Patient Populations:

  • Patients 18-80 years of age within 4.5 hours of symptom onset of acute ischemic stroke
  • Intracranial hemorrhage ruled out

    Number of enrollees: 362
    Duration of follow-up: 3 months
    Mean patient age: 66 years
    Percentage female: 41%

Primary Endpoints:

  • Survival free of disability at 3 months

    Disability at 3 months was assessed with the modified Rankin Scale.

Secondary Endpoints:


Drug/Procedures Used:

Patients who presented with an acute ischemic stroke were randomized to endovascular therapy (n = 181) within 6 hours of symptom onset versus intravenous thrombolytic therapy (n = 181) within 4.5 hours of symptom onset.

Endovascular therapy was performed with intra-arterial thrombolysis with tissue plasminogen activator (t-PA) delivered through a microcatheter, mechanical thrombus disruption or retrieval, or a combination of these approaches. Intravenous thrombolytic therapy was performed with t-PA.

Antiplatelet and anticoagulant therapies were avoided during the first 24 hours, except for heparin during endovascular therapy and antiplatelet agents for patients that received a stent.

Principal Findings:

Overall, 362 patients were randomized. In the endovascular therapy group, the mean age was 66 years, 41% were women, 8% had atrial fibrillation (16% had atrial fibrillation in the intravenous thrombolytic therapy group), and mean blood pressure was 155/84 mm Hg. The cause of the stroke was cardioembolic in 32%, large artery atherosclerosis in 30%, and dissection in 8% (2% had dissection in the intravenous thrombolytic therapy group). The median time from symptom onset to the start of treatment was 3.75 hours with endovascular therapy versus 2.75 hours with intravenous t-PA (p < 0.001).

The primary outcome, freedom from disability at 3 months, was 30.4% among the endovascular therapy group versus 34.8% among the intravenous thrombolytic therapy group (adjusted p = 0.16). Outcomes were similar among all tested subgroups, including time to treatment and center volume.

- Deaths: 14.4% versus 9.9% (p = 0.22), respectively

- Symptomatic intracranial hemorrhage: 6% versus 6% (p = 0.99), respectively

- Recurrent ischemic stroke: 2% versus 2% (p = 0.99), respectively, for endovascular therapy versus intravenous thrombolytic therapy


Among patients with acute ischemic stroke, the use of endovascular therapy was not superior to intravenous thrombolytic therapy with t-PA. Time to treatment was approximately 1 hour longer with endovascular therapy; however, subgroup testing did not identify any effect modification with short treatment times. Multiple devices were used which might have limited the opportunity to demonstrate superiority with endovascular therapy. Moreover, the latest generation devices, stentrievers, were infrequently used at the time the trial was conducted.


Ciccone A, Valvassori L, Nichelatti M, et al., on behalf of the SYNTHESIS Expansion Investigators. Endovascular treatment for acute ischemic stroke. N Engl J Med 2013;368:904-13.

Clinical Topics: Anticoagulation Management, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Lipid Metabolism

Keywords: Thrombolytic Therapy, Stroke, Atherosclerosis, Follow-Up Studies, Platelet Aggregation Inhibitors, Heparin, Blood Pressure, Fibrinolytic Agents, Stents, Intracranial Hemorrhages, Thrombosis, Tissue Plasminogen Activator

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