Introduction: MR CLEAN showed benefit of intra-arterial therapy (IAT) with retrievable stents in patients with acute ischemic stroke caused by a proximal intracranial occlusion in the anterior circulation. Uncertainty exists about the effect of IAT in patients who are not eligible for pretreatment with intravenous alteplase (IVT). We tested for treatment effect modification of IAT by IVT.
Hypothesis: The effect of IAT is not modified by IVT in patients with acute ischemic stroke.
Methods: All 500 patients who were randomized in MR CLEAN were included in this substudy. We distinguished between patients who were and were not pretreated with IVT. Primary outcome was the modified Rankin Scale (mRS) at 90 days. We estimated the effect of IAT on the shift on the mRS and tested for interaction of IVT with IAT by introducing a multiplicative term in a multivariable ordinal logistic regression model. We then combined published unadjusted treatment effect estimates in patients without IVT from MR CLEAN, REVASCAT and ESCAPE trials, of treatment effect in patients without IVT in a fixed effects model after testing for heterogeneity.
Results: In MR CLEAN, 55 (11%) patients were not pre-treated with IVT, The effect size in patients not treated with IVT was 2.06 [95% Confidence Interval (CI): 0.69-6.13], and 1.71 [95% CI: 1.22-2.40] in patients pretreated with IVT, without statistical interaction between IAT and IVT (p=0.92). In REVASCAT, the effect of IAT in 56 patients not treated with IVT was 2.6 [95% CI: 1.0-7.1]) and in ESCAPE it was 2.6 [95% CI: 1.1-5.9] in 76 patients. The combined estimate was 2.3 [95% CI: 1.5-3.7], without heterogeneity (p=0.78).
Conclusion: The available evidence suggests that patients with acute ischemic stroke and a proximal intracranial anterior circulation occlusion, presenting within 6 hours with contra-indications for intravenous alteplase, benefit from IAT.