Susan C Fagan, Pharm.D.
At the International Stroke Conference in Nashville, TN, in February, 2015, worldwide headlines were made upon the presentation of 3 independent clinical trials, all proving that endovascular thrombectomy (removal of clot from inside the artery), in selected patients with proximal cerebral artery occlusion, dramatically improves the likelihood of a good outcome at 90 days. The audience, which included stroke specialists and scientists from around the world, broke into sustained applause at the robustly positive results, representing the FIRST really good news in stroke care since the 1995 presentation of the NINDS tPA Stroke Trial (tPA is “clot-busting” drug).
The ESCAPE (North America and the UK)1, EXTEND-IA (Australia and New Zealand)2, and the SWIFT-PRIME (Global) trials were all stopped early because of the previously reported positive results of intraarterial reperfusion therapy from the Netherlands (MR CLEAN)3. In the MR Clean trial, 88% of patients in the IA treated arm received endovascular therapy with a stent retriever, as was the case in the other 3 trials. Both ESCAPE and EXTEND-IA were published together in March, 2015. SWIFT-PRIME has yet to be published.
In all of these trials, stroke patients had to have a proximal occlusion of a large artery (usually the MCA), visible on angiography, and amenable to thrombectomy. Patients had to be treated within 6 hours of onset in SWIFT-PRIME and EXTEND-IA and within 12 hours in ESCAPE. These severely-afflicted patients tend to have dire consequences whether or not they receive intravenous (IV) tPA, with less than 30% of patients achieving independence at 90 days. Another key contributor to the positive impact of thrombectomy was the use of imaging criteria to identify patients with good collateral flow and salvageable tissue.
When the Solitaire stent retriever (see picture above) was advanced through the clot, expanded to “capture” the clot and then removed with the help of suction, there was a vast improvement in the number of patients achieving reperfusion at 24 hours compared to IV tPA alone (100% vs. 37%, p<0.001, in the EXTEND-IA trial), which probably explained the improved outcomes at 90 days in all three trials. In the ESCAPE trial, the largest of the 3 at 316 patients, there was an almost doubling (53% vs. 29%, p<0.001) in the number of patients independent at 90 days and the intervention group also had lower mortality (10.4% vs. 19.0%; p=0.04). There was NO increase in symptomatic intracerebral hemorrhage in any of the 3 trials (over tPA alone), although the statistical power to detect a difference was reduced by stopping study enrollment early (especially in the EXTEND-IA trial which only had 70 patients).
Take away points for clinicians:
- Only ischemic stroke patients with severe stroke, proximal MCA occlusion and good collaterals (small infarct core on imaging) are good candidates for this therapy and this represents <2% of all patients.
- Patients with these characteristics should be transported to a center where this intervention is available since it dramatically improves their chance of a good recovery. Reorganization of stroke care is occurring feverishly at stroke centers around the world to accommodate this new evidence. It is likely that guidelines will change in the near future!
- The Solitaire device (stent retriever) represents advanced technology that more effectively removes the clot and restores perfusion than previously available devices.
- The score is : Reperfusion : 2; Neuroprotection: 0 for ischemic stroke care
- Goyal M, Demchuk AM, Menon BK et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015;372:1019-1030 http://www.nejm.org/doi/full/10.1056/NEJMoa1414905
- Campbell BCV, Mitchell PJ, Kleinig TJ et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015;373:1009-1018 http://www.nejm.org/doi/full/10.1056/NEJMoa1414792
- Berkhemer OA, Fransen PSS, Beumer D et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015;372:11-20 http://www.nejm.org/doi/pdf/10.1056/NEJMoa1411587