February 11, 2015 will be an important milestone in the history of Interventional Neuroradiology. Three positive trials (ESCAPE, EXTEND-IA, and SWIFT-PRIME) evaluating mechanical thrombectomy in acute ischemic stroke were presented under the applause of a large audience. Both ESCAPE and EXTEND-IA trials were published online in NEJM the day of ISC presentation (February 11, 2014).
The positive results of MR CLEAN presented at the World Stroke Conference in Istanbul in October 2014 was prompting the performance of interim analyses in several running RCTs evaluating mechanical thrombectomy (ESCAPE, EXTEND-IA, SWIFT-PRIME) that were all positive.
The ESCAPE (Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing CT to recanalization times) trial (presented by Michael D Hill, Calgary, Canada) was interrupted after randomization of 315 patients. Inclusion criteria were NIHSS > 5, occlusion of the middle cerebral artery trunk and its immediate branches with or without ICA occlusion, small infarct core (ASPECT 6 to 10), moderate to good collaterals on CTA. Enrollment was possible up to 12 hours. The patients received rtPA if they were eligible for this treatment.
A total of 316 patients underwent randomization before the trial was stopped: 165 in the thrombectomy group and 150 in the control group (1 patient was excluded). About 75% of patients received IV rt-PA and stent-retrievers were used in 86.1% of patients in the thrombectomy group. The adjusted risk ratio for a mRS shift with thrombectomy at 90 days was 3.1. A mRS of 0-2 at 90 days was observed in 53.0% in thrombectomy vs. 29.3% in controls (p<0.001). Mortality was significantly lower in intervention group (10.4%) compared to 19.0% in control group. All subgroups of patients had similar benefit, including the elderly.
The EXTEND-IA (EXtending the time for Thrombolysis in Emergency Neurological Deficits with Intra-Arterial therapy) trial (presented by Stephen M Davis, Parkville, Australia) was prematurely stopped because of a positive interim analysis of the first 70 randomized patients (35 in the intervention group and 35 in the control group). Patients were eligible if they could receive rt-PA within 4.5 hours after the onset of anterior circulation ischemic stroke and had occlusion of the internal carotid artery or of the first or second segment of the middle cerebral artery on CTA or MRA, to have received IV thrombolysis < 4.5 hours. CT perfusion imaging (use of the fully automated software RAPID) was used to identify potentially salvageable brain tissue. Endovascular therapy had to be initiated (groin puncture) within 6 hours after stroke onset and completed within 8 hours after onset.
A total of 70 patients were included in the trial (35 in intervention arm and 35 in IV rt-PA arm). All patients in the intervention group were treated with Solitaire. Early reperfusion of the ischemic tissue at 24h hours was 100% in intervention group vs. 37% in the control group (p<0.001). Early neurologic improvement (NIHSS reduction ≥ 8 points or NIHSS 0-1 at 3 days) was 80% in intervention group vs 37% in the control group (p<0.001). mRS 0-2 at 90 days was 71% in thrombectomy patients and 40% in controls (p<0.01). There was a trend towards reduction of mortality (9% in intervention group; 20% in control group; p=0.18).
The SWIFT PRIME (Solitaire™ With the Intention For Thrombectomy as PRIMary treatment for acute ischemic strokE) trial (presented by Jeffrey L Saver) was prematurely stopped after a positive interim analysis of the first 196 patients. To be included, patients have to receive IV thrombolysis 4.5 hours after stroke onset, a NIHSS between 8 and 29, CTA or MRA confirmation of large vessel occlusion (intracranial internal carotid artery or M1 segment of the MCA), and an ASPECTS > 6.
As ESCAPE and EXTEND-IA, SWIFT-PRIME was prematurely halted due to positive interim analysis. A total of 196 patients were randomized, 98 in each group (intervention and IV rt-PA). In Intervention group, TICI 2b/3 was obtained in 88.0% of patients. The OR for a mRS shift at 90 days with thrombectomy using the Solitaire™ FR stent retriever was highly significant (p= 0.0002). Good functional outcome (mRS 0-2 at 90 days) was obtained in 60.2% in intervention group and 35.5% in IV rt-PA group (p < 0.001). Death at 90 days was 9.2% in intervention group and 12.4% in rt-PA group (p=0.5).
In summary, following the positive results of MR CLEAN, a further 3 positive trials have validated the use of mechanical thrombectomy for patients with acute ischemic stroke with large vessel occlusion in the anterior circulation. Indeed, these results will have a tremendous impact on the management of these patients and also on the organization of stroke care.
All investigators and sponsors of these trials should be congratulated for their tremendous work!
Laurent Pierot – Reims – France