Intravenous thrombolysis versus non-thrombolytic standard care for lacunar ischaemic stroke: a protocol for a systematic review and meta-analysis

Introduction Patients with lacunar ischaemic strokes are at risk of substantial long-term disability and cognitive impairment. However, uncertainty remains surrounding the use of intravenous thrombolysis or antithrombotic medications acutely in this subpopulation, as no trials have been dedicated to specifically studying acute lacunar strokes. To address this knowledge gap, we will conduct a systematic review and meta-analysis of existing literature examining the comparative effectiveness and safety surrounding the use (or non-use) of thrombolytic agents in lacunar strokes. Methods and analysis MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched with librarian assistance. Eligible studies will include randomised controlled trials (RCTs) and post-hoc analyses of RCTs investigating the use of an intravenous thrombolytic agent and report outcomes in adult patients with lacunar ischaemic stroke as a population or subgroup. The primary outcome will be the proportion of patients achieving a modified Rankin Scale (mRS) score of 0–1 at 90 days. Data on participant characteristics, study design, interventions, comparators and outcomes will be extracted. Study quality will be assessed using the Cochrane Risk of Bias 2.0 (RoB 2) tool for RCTs and post-hoc analyses; heterogeneity will be assessed using the I 2 statistic. The primary quantitative synthesis will be a pairwise meta-analysis comparing intravenous thrombolysis with non-thrombolytic standard of care. An exploratory Bayesian network meta-analysis will also be performed if there is adequate direct or indirect evidence and no significant concerns regarding transitivity, homogeneity and consistency. Prospero registration number CRD420261355006 Ethics and dissemination Formal ethics is not required as no primary data will be collected. Findings will be disseminated through peer-reviewed publications and scientific conference presentations. This review will aid healthcare teams in decision-making on the choice of intravenous thrombolysis and non-thrombolytic standard care in patients with ischaemic lacunar stroke and may guide the development of future treatment trials and guidelines.