Effect of Glyceryl Trinitrate on Hemodynamics in Acute Stroke

Appleton, Jason P.; Woodhouse, Lisa J; Bereczki, Dániel; Berge, Eivind; Christensen, Hanne; Collins, Rónán; Gommans, John; Ntaios, George; Öztürk, Şerefnur; Szatmári, Szabolcs; Wardlaw, Joanna M.; Sprigg, Nikola; Rothwell, Peter M.; Bath, Philip M

doi:10.1161/strokeaha.118.023190

Cited by 7 publications

(7 citation statements)

References 38 publications

(44 reference statements)

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“…The included studies showed great differences in the time intervals posttreatment in reporting BP changes. Most studies 19,20,39–44 reported mean systolic and diastolic BP (with SDs) 24 h posttreatment while some studies reported BP measurements after varying shorter (15 min to 2 h) 19,20,36,37,41,45 or longer periods (4–10 days) 19,20,38–44 posttreatment. We reported pooled differences in mean systolic and diastolic BP 24 h posttreatment for GTN versus control/placebo because these parameters were consistently reported in the majority of studies.…”

Section: Resultsmentioning

confidence: 99%

“…All included articles (seven randomized trials, 19,20,36–40 four subgroup analyses, 41–44 and one secondary analysis 45 ) reported changes in BP between GTN versus control/placebo. The included studies showed great differences in the time intervals posttreatment in reporting BP changes.…”

Section: Resultsmentioning

confidence: 99%

“…The included studies showed great differences in the time intervals posttreatment in reporting BP changes. Most studies 19, 20,39-4 4 reported mean systolic and diastolic BP (with SDs) 24 h posttreatment while some studies reported BP measurements after varying shorter (15 min to 2 h) 19,20,36,37,41,45 or longer periods (4-10 days) 19, 20,38-4 4 F I G U R E 1 Selection of studies in review of transdermal GTN in acute stroke. GTN Note: Secondary analysis refers to an added publication that used the same cohort from the primary trial but investigated additional outcome(s).…”

Section: Bp Measurementsmentioning

confidence: 99%

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Benefits and safety of transdermal glyceryl trinitrate in acute stroke: A systematic review and meta‐analysis of randomized trials

Lim

Lee

et al. 2021

Academic Emergency Medicine

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Background: 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 h). Our meta-analysis updated the evidence on its safety and benefits in acute stroke. Methods:We searched major electronic databases for randomized trials comparing transdermal GTN versus 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 utilization, and surrogate outcomes. Safety outcomes were adverse events. Reviewers identified studies, extracted data, and 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 versus ischemic stroke, minor (NIHSS ≤5) versus major (NIHSS >5) ischemic stroke, ischemic stroke with versus without thrombolysis, prehospital versus non prehospital settings, time from stroke to randomization ≤6 h versus >6 h, and high versus low overall RoB studies.Results: Seven eligible primary trials enrolled 5363 patients. GTN reduced BP (mean difference [MD] = -4.74 mm Hg, 95% confidence interval [CI] = -6.03 to -3.45 mm Hg] and diastolic BP (MD = -2.94 mm Hg, 95% CI = -3.74 to −2.13 mm Hg) 24 h posttreatment but did not affect 4-to 10-day mortality (relative risk [RR] = 1.11, 95% CI = 0.82 to 1.49), 90-day mortality (RR = 0.96, 95% CI = 0.77 to 1.19), and 90-day mRS >2 (RR = 0.98, 95% CI = 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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Bp Measurementsmentioning

confidence: 99%

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Benefits and safety of transdermal glyceryl trinitrate in acute stroke: A systematic review and meta‐analysis of randomized trials

Lim

Lee

et al. 2021

Academic Emergency Medicine

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“…Second, there were few BP readings recorded in the trial; two measurements prerandomisation and two measurements on day 2. Therefore, we were unable to assess any effect of BP variability, which has been shown to be a stronger predictor of clinical outcome in acute ICH21 22 and ischaemic stroke23 than absolute BP. Nor could we adjust for early BP change within the first hours after ICH.…”

Section: Discussionmentioning

confidence: 99%

Effects of blood pressure and tranexamic acid in spontaneous intracerebral haemorrhage: a secondary analysis of a large randomised controlled trial

et al. 2023

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BackgroundTranexamic acid reduced haematoma expansion and early death, but did not improve functional outcome in the tranexamic acid for hyperacute spontaneous intracerebral haemorrhage-2 (TICH-2) trial. In a predefined subgroup, there was a statistically significant interaction between prerandomisation baseline systolic blood pressure (SBP) and the effect of tranexamic acid on functional outcome (p=0.019).MethodsTICH-2 was an international prospective double-blind placebo-controlled randomised trial evaluating intravenous tranexamic acid in patients with acute spontaneous intracerebral haemorrhage (ICH). Prerandomisation baseline SBP was split into predefined ≤170 and >170 mm Hg groups. The primary outcome at day 90 was the modified Rankin Scale (mRS), a measure of dependency, analysed using ordinal logistic regression. Haematoma expansion was defined as an increase in haematoma volume of >33% or >6 mL from baseline to 24 hours. Data are OR or common OR (cOR) with 95% CIs, with significance at p<0.05.ResultsOf 2325 participants in TICH-2, 1152 had baseline SBP≤170 mm Hg and were older, had larger lobar haematomas and were randomised later than 1173 with baseline SBP>170 mm Hg. Tranexamic acid was associated with a favourable shift in mRS at day 90 in those with baseline SBP≤170 mm Hg (cOR 0.73, 95% CI 0.59 to 0.91, p=0.005), but not in those with baseline SBP>170 mm Hg (cOR 1.05, 95% CI 0.85 to 1.30, p=0.63). In those with baseline SBP≤170 mm Hg, tranexamic acid reduced haematoma expansion (OR 0.62, 95% CI 0.47 to 0.82, p=0.001), but not in those with baseline SBP>170 mm Hg (OR 1.02, 95% CI 0.77 to 1.35, p=0.90).ConclusionsTranexamic acid was associated with improved clinical and radiological outcomes in ICH patients with baseline SBP≤170 mm Hg. Further research is needed to establish whether certain subgroups may benefit from tranexamic acid in acute ICH.Trial registration numberISRCTN93732214.

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“…Early continuation of anti-hypertensives was associated with worse clinical outcomes, whilst in patients randomised 12–48 h after ictus a neutral effect was observed in the aforementioned meta-analysis. 8 In the crucial first hours after stroke, absolute BP changes and increased BP variability may have a greater influence on the ischaemic penumbra than on established infarction 27 and on unstable haemorrhage than stable clot, 28 which may account for the time-dependent effect on clinical outcome observed.…”

Section: Discussionmentioning

confidence: 99%

Effect of continuing versus stopping pre-stroke antihypertensive agents within 12 h on outcome after stroke: A subgroup analysis of the efficacy of nitric oxide in stroke (ENOS) trial

et al. 2022

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Background It is not known whether to continue or temporarily stop existing antihypertensive drugs in patients with acute stroke.Methods We performed a prospective subgroup analysis of patients enrolled into the Efficacy of Nitric Oxide in Stroke (ENOS) trial who were randomised to continue vs stop prior antihypertensive therapy within 12 h of stroke onset. The primary outcome was functional outcome, assessed with the modified Rankin Scale at 90 days by observers blinded to treatment assignment, and analysed with ordinal logistic regression.Findings Of 4011 patients recruited into ENOS from 2001 to 2014, 2097 patients were randomised to continue vs stop prior antihypertensive treatment, and 384 (18.3%, continue 185, stop 199) were enrolled within 12 h of ictus: mean (SD) age 71.8 (11.8) years, female 193 (50.3%), ischaemic stroke 342 (89.1%) and total anterior circulation syndrome 114 (29.7%). As compared with stopping, continuing treatment within 12 h of onset lowered blood pressure by 15.5/9.6 mmHg (p<0.001/<0.001) by 7 days, shifted the modified Rankin Scale to a worse outcome by day 90, adjusted common odds ratio (OR) 1.46 (95% CI 1.01−2.11), and was associated with an increased death rate by day 90 (hazard ratio 2.17, 95% CI 1.24−3.79). Other outcomes (disability -Barthel Index, quality of life -EQ-visual analogue scale, cognition -telephone mini-mental state examination, and mood -Zung depression scale) were also worse with continuing treatment.Interpretation In this pre-specified subgroup analysis of the large ENOS trial, continuing prior antihypertensive therapy within 12 h of stroke onset in a predominantly ischaemic stroke population was unsafe with worse

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Effect of Glyceryl Trinitrate on Hemodynamics in Acute Stroke

Abstract: Supplemental Digital Content is available in the text.

Cited by 7 publications

References 38 publications

Benefits and safety of transdermal glyceryl trinitrate in acute stroke: A systematic review and meta‐analysis of randomized trials

Benefits and safety of transdermal glyceryl trinitrate in acute stroke: A systematic review and meta‐analysis of randomized trials

Effects of blood pressure and tranexamic acid in spontaneous intracerebral haemorrhage: a secondary analysis of a large randomised controlled trial

Effect of continuing versus stopping pre-stroke antihypertensive agents within 12 h on outcome after stroke: A subgroup analysis of the efficacy of nitric oxide in stroke (ENOS) trial

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