Comprehensive Summary
Berkhemer et al. conducted a multicenter randomized clinical trial in the Netherlands (December 2010 to March 2014) assessing whether intraarterial treatment plus usual care resulted in greater functional benefits compared to usual care alone in acute ischemic stroke patients. Among 500 patients enrolled from 16 medical centers, 233 were assigned to the intervention group and 267 to the control group. Eligible participants had proximal arterial occlusion in the anterior cerebral circulation confirmed by vessel imaging and could be treated within six hours of stroke onset. Intraarterial treatment consisted of mechanical thrombectomy, intraarterial thrombolysis, or both. The majority of patients in both groups (approximately 90%) received intravenous alteplase as standard care. The primary outcome was functional independence at 90 days, measured by a modified Rankin scale (range 0 to 6, where 0 indicates no symptoms and 6 indicates death; scores ≤ 2 indicate functional independence). The intervention group showed significantly better outcomes, with 32.6% achieving functional independence compared to 19.1% in the control group (adjusted common odds ratio 1.67, 95% CI 1.21-2.30), representing an absolute difference of 13.5%. The NIHSS score (measuring stroke severity) was assessed at baseline, 24 hours, and 5 to 7 days or at discharge. The intervention group demonstrated greater neurological improvement, with NIHSS scores 2.9 points lower at 5 to 7 days (95% CI 1.5-4.3). No significant differences were observed in mortality rates (21% intervention vs. 22% control) or overall serious adverse events. However, new ischemic strokes in different vascular territories occurred more frequently in the intervention group (5.6% vs. 0.4%).
Outcomes and Implications
This landmark MR CLEAN trial demonstrated that intraarterial treatment significantly improves functional outcomes in acute ischemic stroke with proximal anterior circulation occlusions, with a 13.5% absolute increase in functional independence at 90 days. This represents a number needed to treat of approximately 7, meaning one additional patient achieves functional independence for every seven treated. The findings are particularly important because IV alteplase alone, while effective for many strokes, has limited efficacy against large vessel occlusions, which account for approximately one-third of acute anterior circulation strokes and carry the worst prognoses. The study's pragmatic design, including patients with IV alteplase contraindications and allowing various thrombectomy techniques, enhanced generalizability to real-world practice. The similar mortality rates between groups, coupled with improved functional outcomes, suggest the intervention shifts patients toward better recovery rather than simply keeping them alive in disabled states. However, the increased rate of new ischemic strokes in different territories (5.6% vs. 0.4%) warrants careful patient selection and procedural technique. Important limitations include the unblinded design, heterogeneous interventional approaches, and enrollment restricted to patients treatable within six hours. This trial, along with subsequent confirmatory studies, established mechanical thrombectomy as standard of care for eligible stroke patients and transformed stroke systems to prioritize rapid access to thrombectomy-capable centers.