REPORT FROM THE 67TH AMERICAN ACADEMY OF NEUROLOGY (AAN) ANNUAL MEETING – WASHINGTON DC, APRIL 18-25, 2015 – The use of tissue plasminogen activators (tPA) in patients with ischemic stroke is limited by the narrow therapeutic time window, and poor efficacy in opening proximal occlusions of the major intracranial arteries. Intraarterial interventions, such as thrombectomy with mechanical devices, are potentially useful but studies to date have produced mixed results, in large part because of trial design and patient selection.
A series of recent studies have attempted to clarify the role of thrombectomy post-stroke, and these were summarized in an invited science session hosted by the AAN in conjunction with the American Heart Association and the American Stroke Association (AAN 2015; S54).
Rapid endovascular treatment in conjunction with standard care in patients with acute ischemic stroke was evaluated in the ESCAPE trial (Goyal et al. N Engl J Med 2015;372:1019-1030). All subjects had a proximal intracranial arterial occlusion with a small infarct core and moderate-to-good collateral circulation, as determined by computed tomography (CT) and CT angiography. A total of 238 of 316 subjects (75%) received intravenous alteplase. The intervention group also underwent thrombectomy. The median time from CT to first reperfusion was 84 minutes.
The intervention group demonstrated a higher rate of functional independence (90-day modified Rankin score of 0-2) compared to the standard-care group (53.0% vs. 29.3%), and reduced mortality (10.4% vs. 19.0%). The rate of symptomatic intracerebral hemorrhage was nonsignificantly higher with the intervention (3.6% vs. 2.7%).
Similar results were reported in the MR CLEAN trial (Berkhemer et al. N Engl J Med 2015;372:11-20). Subjects with acute ischemic stroke caused by a proximal intracranial arterial occlusion as confirmed by vessel imaging were randomized to usual care with/without intraarterial treatment. Alteplase was part of usual care in 89% of patients. Intraarterial treatment, administered within 6 hours of stroke onset, consisted of retrievable stents in 81.5% of patients. Intraarterial treatment resulted in a higher proportion of patients achieving functional independence (32.6% vs. 19.1%). No differences were seen in the occurrence of symptomatic intracerebral hemorrhage or mortality.
In the phase II EXTEND-IA trial, ischemic stroke patients with occlusion of the internal carotid or middle cerebral artery, an ischemic core < 70 mL on CT perfusion imaging and evidence of salvageable brain tissue were randomized to alteplase 0.9 mg/kg with or without thrombectomy with the Solitaire stent retriever (Campbell et al. N Engl J Med 2015;372:1009-1018). The extent of reperfusion at 24 hours was significantly greater in the intervention group compared to the alteplase-only group (median 100% vs. 37%). Clot retrieval at a median of 210 minutes after stroke onset improved neurological outcomes at three and 90 days post-intervention, with a significantly higher proportion achieving functional independence (modified Rankin score 0-2) compared to alteplase alone (71% vs. 37%).
The Solitaire device was also used in the SWIFT PRIME (Saver et al. N Engl J Med 2015; epublished April 17, 2015) and REVASCAT trials (Molina et al. Int J Stroke 2013; epublished November 10, 2013). In SWIFT PRIME, the median time from imaging to start of intra-arterial therapy was 57 minutes. The proportion of patients with functional independence was 60% with endovascular intervention versus 35% with tPA alone. There were no significant differences in 90-day mortality (9% vs. 12%).
Guest Reviewer: Dr. Daniel Selchen, Head of Neurology, St. Michael’s Hospital, Toronto, Canada