Benefits and safety of transdermal glyceryl trinitrate in acute stroke: a systematic review and meta-analysis of randomised trials (protocol)

INTRODUCTION: High blood pressure (BP) in acute stroke has adverse outcomes. Transdermal glyceryl trinitrate (GTN) has beneficial properties in controlling BP. The 2016 meta-analysis and 2017 Cochrane review showed that transdermal GTN was beneficial in a small patient subgroup with stroke onset ≤6 hours. Larger studies focusing on this patient subgroup have since been conducted. We report the protocol for an updated systematic review and meta-analysis on the safety and benefits of transdermal GTN in acute stroke. METHODS AND ANALYSIS: We will search Medline, Pubmed, Embase, CINAHL and Cochrane Library from inception until June 2020 for randomised trials that report the efficacy and safety of transdermal GTN versus placebo/control therapy among adult patients with acute stroke. Primary outcomes include in-hospital mortality, BP lowering and late functional status. Secondary outcomes include early, late, resource utilisation and surrogate outcomes. Safety outcomes include reported adverse events. Reviewers will first screen titles and abstracts, and then full texts, to identify eligible studies. Independently and in duplicate, they will extract data, assess risk of bias (RoB) using a modified Cochrane RoB tool and quality of evidence using Grading of Recommendations, Assessment, Development and Evaluation. Disagreement will be resolved by discussion and consultation with an external reviewer if necessary. Using a random-effects model, we will report effect sizes using relative risks and 95% CIs. We will perform predefined subgroup analyses: intracerebral haemorrhage versus ischaemic stroke; minor (NIHSS (National Institutes of Health Stroke Scale) ≤five) versus major (NIHSS >five) ischaemic stroke; ischaemic stroke with versus without thrombolysis; prehospital versus non-prehospital settings; time from stroke to randomisation ≤6 versus >6 hours and high versus low overall RoB studies. We will also perform trial sequential analysis for the primary outcomes. ETHICS AND DISSEMINATION: Ethics board approval is unnecessary. PROSPERO registration has been obtained. The results will be disseminated through publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020173093.