Intra-arterial treatment not only enhanced reperfusion but improved patients’ functional recovery after acute ischemic stroke caused by a proximal intracranial arterial occlusion of the anterior circulation in the MR CLEAN trial, a multicenter, open-label, randomized, controlled phase III study.
Contrary to the findings of recent randomized, controlled trials that failed to show such a benefit from intra-arterial therapy, these results clearly demonstrated “a clinically significant increase in functional independence in daily life by 3 months, without any increase in mortality,” said Dr. Olvert A. Berkhemer of the department of radiology at Academic Medical Center, Amsterdam, and the department of neurology at Erasmus University Medical Center, Rotterdam, the Netherlands, and his associates.
They performed the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) study to compare intra-arterial treatment – using a microcatheter to deliver a thrombolytic agent, mechanical thrombectomy, or both at the level of occlusion – against usual care in 500 adults aged 23-96 years. All study participants were treated within 6 hours of stroke onset. Usual care could include intravenous alteplase, and mechanical treatment could include thrombus retraction, aspiration, wire disruption, or use of a retrievable stent, all at the discretion of the treating interventionist, the investigators said (N. Engl. J. Med. 2014 Dec. 17 [doi:10.1056/NEJMoa1411587]).
The primary outcome – functional status at 90 days, as measured by the modified Rankin scale – was superior for intra-arterial treatment, with 32.6% of patients achieving functional independence, compared with only 19.1% of the usual-care group. All secondary outcomes also favored intra-arterial treatment, including scores on the National Institutes of Health Stroke Scale (NIHSS) and on measures of activities of daily living and health-related quality of life. In addition, absence of residual occlusion was markedly more frequent with intra-arterial treatment (75.4%) than with usual care (32.9%), and infarct volume was smaller.
There were no significant differences between the two study groups in mortality at 7, 30, or 90 days of follow-up. However, complications related to intra-arterial treatment included embolization into new intracranial territories in 20 patients (8.6%), vessel dissections in 4 patients (1.7%), and vessel perforations in 2 patients (0.9%). In addition, 30 patients who received intra-arterial treatment (13%) also underwent a simultaneous second revascularization, usually cervical carotid stenting, at the discretion of the interventionist. “This complexity needs to be considered when interpreting our trial results,” Dr. Berkhemer and his associates said.
Although MR CLEAN is the first trial to cut through some of the criticisms of previous trials that used intra-arterial therapy by enrolling patients with severe strokes and have proof of proximal vessel occlusion, initiating treatment as early as possible, and using modern thrombectomy devices, it is “premature to conclude that there is no longer equipoise regarding thrombectomy. We need and will get results from other well-designed trials [several of which are ongoing], not only to confirm or refute the results of MR CLEAN but also to look at effects in subgroups (according to stroke severity, occlusion site, or time to treatment initiation), for which most single trials are underpowered,” wrote Dr. Werner Hacke of the department of neurology at University Hospital Heidelberg (Germany) in an accompanying editorial (N. Engl. J. Med. 2014 Dec. 17 [doi:10.1056/NEJMe1413346]).
MR CLEAN was funded by the Dutch Heart Foundation, AngioCare, Covidien/ev3, Medac/Lamepro, and Penumbra. Dr. Berkhemer reported having no financial conflicts of interest, but his associates reported ties to Stryker, BALT, Toshiba, Codman/DePuy Synthes, Sequent Medical, and Covidien/ev3. Dr. Hacke reported grant support from Boehringer Ingelheim, and personal fees from Bayer, Daiichi Sankyo, and Covidien outside his submitted work.