Cerebral microbleeds likely do not reduce effectiveness of alteplase in stroke patients

Alteplase did not appear to have reduced treatment effect among patients with acute ischemic stroke with one or more cerebral microbleeds, according to an analysis of a randomized clinical trial published in Neurology.

“To date, no randomized controlled trials of intravenous alteplase in acute ischemic stroke patients stratified by [cerebral microbleed] CMB status on pre-treatment baseline MRI have been conducted, and there are no studies describing the effect of CMB presence, burden, and spatial distribution or presumed pathophysiology on the risk of acute hemorrhagic complications after acute stroke without alteplase treatment,” Ludwig Schlemm, MD, MSc, of the Klinik und Hochschulambulanz für Neurologie, Charité Universitätsmedizin Berlin, Germany, and colleagues wrote. “Thus, while the prognostic importance of CMBs in acute stroke patients treated with alteplase is well documented, the effect of baseline CMB status on the treatment effect of alteplase as compared to placebo is currently unknown.”

Researchers conducted a pre-specified analysis of the prospective, randomized, controlled, multicenter WAKE-UP trial that featured patients with acute ischemic stroke with unknown time of symptom onset and diffusion-weighted imaging-fluid attenuated inversion recovery mismatch on MRI who received either alteplase or placebo. Screening and enrollment occurred between September 2012 and June 2017, with final follow-up in September 2017.

Participants underwent random assignment to treatment with IV thrombolysis with alteplase at 0.9 mg per kg body weight or placebo. Three raters blinded to clinical information who followed a standardized protocol assessed CMB status after study completion. Excellent functional outcomes at 90 days according to modified Rankin Scale score of one or less and symptomatic intracerebral hemorrhage (ICH) according to National Institutes of Neurological Disease and Stroke trial criteria 22 to 36 hours after treatment served as outcome measures.

Schlemm and colleagues analyzed data of 459 (63% men) participants of the WAKE-UP trial. Of these, 98 (21.4%) had one or CMBs on baseline imaging, 45 (9.8%) had one CMB, 37 (8.1%) had between two and four CMBS and 16 (3.5%) had five or more CMBs. CMB presence correlated with a non-significant increased risk for symptomatic ICH but did not affect functional outcome at 90 days. Patients who received alteplase exhibited better functional outcome without evidence of heterogeneity related to CMB presence. Subpopulations with strictly lobar or non-strictly lobar CMB distribution had similar results.

“Our results corroborate findings from previous observational studies indicating that in otherwise eligible patients, intravenous thrombolysis should not be withheld on the basis of a small to moderate number of CMBs alone,” Schlemm and colleagues wrote. “The study was not powered to provide direct evidence of superiority of alteplase over placebo in patients with CMBs. Additional studies are needed to determine the treatment effect of alteplase and its benefit-harm-ratio in patients with a larger number of CMBs.”