Transdermal glyceryl trinitrate (GTN) has potential beneficial properties in acute stroke including intracerebral hemorrhage (ICH) and possible clinical benefits suggested in ultra-early stroke (≤ 6 hours). Our meta-analysis updated the evidence on its safety and benefits in acute stroke.
We searched major electronic databases for randomised trials comparing transdermal GTN vs placebo/control in acute stroke. Primary outcomes were mortality, 90-day modified Rankin Scale (mRS) and blood pressure (BP) effects. Secondary outcomes included early, late, resource utilisation and surrogate outcomes. Safety outcomes were adverse events. Reviewers identified studies, extracted data, assessed risk of bias (RoB) using a modified Cochrane RoB instrument and quality of evidence (QoE) using GRADE. We also performed a priori subgroup and trial sequential analyses (TSA) on primary outcomes. These subgroup analyses were; ICH vs ischemic stroke; minor (NIHSS ≤ five) vs major (NIHSS > five) ischemic stroke; ischemic stroke with vs without thrombolysis; prehospital vs non prehospital settings; time from stroke to randomization ≤ six vs > six hours and high vs low overall RoB studies.
7 eligible primary trials enrolled 5363 patients. GTN reduced systolic BP [mean difference (MD) -4.74; 95% CIs -6.03 to -3.45 mmHg] and diastolic BP (MD -2.94; 95% CIs -3.74 to -2.13 mmHg) 24 hours post treatment but did not affect 4-10-day mortality [relative risk (RR) 1.11; 95% CIs 0.82 to 1.49], 90-day mortality [RR 0.96; 95% CIs 0.77 to 1.19] and 90-day mRS >2 (RR 0.98; 95% CIs 0.93 to 1.03) compared to control/placebo. The QoE was high for primary outcomes with no subgroup effects detected. GTN did not affect secondary outcomes and increased risk of headache and hypotension. TSA generally supported our conclusions regarding primary outcomes.
Transdermal GTN reduces BP in acute stroke but does not alter clinical outcomes even in ultra-early stroke (≤ 6 hours).

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