The Effect of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Blood Pressure and Platelet Function in Acute Stroke

Background High blood pressure is common in acute stroke and associated with a worse functional outcome. Glyceryl trinitrate, a nitric oxide donor, lowers blood pressure in acute stroke and may improve outcome. Aims Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) tested the feasibility of performing a UK multicenter ambulance-based stroke trial, and the safety and efficacy of glyceryl trinitrate when administered by paramedics before hospital admission. Methods Paramedic-led ambulance-based multicenter prospective randomized single-blind blinded-endpoint parallel-group controlled trial of transdermal glyceryl trinitrate (given for four days) versus sham in patients with ultra-acute (<4 h) presumed stroke. Data are number (%), median (interquartile range) or mean (standard deviation). Results Recruitment ran from October 2015 to 31 May 2018. A total 1149 patients were recruited from eight UK ambulance services and taken to 54 acute hospitals. Baseline characteristics include: mean age 73 (15) years; female 555 (48%); median time from stroke to randomization 70 (45, 115) min; face-arm-speech scale score 2.6 (0.5); and blood pressure 162 (25)/92 (18) mmHg. The final diagnosis was ischemic stroke 52%, hemorrhagic stroke 13%, Transient Ischemic Attack (TIA) 9%, and mimic 25%. The main trial results will be presented in quarter 4 2018. The results will also be included in updated Cochrane systematic reviews, and individual patient data meta-analyses of all relevant randomized controlled trials. Conclusion It was feasible to perform a multicenter ambulance-based ultra-acute stroke trial in the UK and to treat with glyceryl trinitrate versus sham. The relatively unselected cohort of stroke patients is broadly representative of those admitted to hospital in the UK. Trial registration ISRCTN26986053.

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Effect of Treatment Delay, Stroke Type, and Thrombolysis on the Effect of Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome after Acute Stroke: A Systematic Review and Meta-Analysis of Individual Patient from Randomised Trials

Stroke Research and Treatment ◽

10.1155/2016/9706720 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Philip M. Bath ◽

Lisa Woodhouse ◽

Kailash Krishnan ◽

Craig Anderson ◽

Eivind Berge ◽

...

Keyword(s):

Nitric Oxide ◽

Glyceryl Trinitrate ◽

Acute Stroke ◽

Meta Analysis ◽

Haemorrhagic Stroke ◽

Stroke Onset ◽

Nitric Oxide Donor ◽

No Donor ◽

No Donors ◽

Subacute Stroke

Background.Nitric oxide (NO) donors are a candidate treatment for acute stroke and two trials have suggested that they might improve outcome if administered within 4–6 hours of stroke onset. We assessed the safety and efficacy of NO donors using individual patient data (IPD) from completed trials.Methods.Randomised controlled trials of NO donors in patients with acute or subacute stroke were identified and IPD sought from the trialists. The effect of NO donor versus control on functional outcome was assessed using the modified Rankin scale (mRS) and death, by time to randomisation. Secondary outcomes included measures of disability, mood, and quality of life.Results.Five trials (4,197 participants) were identified, all involving glyceryl trinitrate (GTN). Compared with control, GTN lowered blood pressure by 7.4/3.3 mmHg. At day 90, GTN did not alter any clinical measures. However, in 312 patients randomised within 6 hours of stroke onset, GTN was associated with beneficial shifts in the mRS (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.34–0.78) and reduced death (OR 0.32, 95% CI 0.14–0.78).Conclusions.NO donors do not alter outcome in patients with recent stroke. However, when administered within 6 hours, NO donors might improve outcomes in both ischaemic and haemorrhagic stroke.

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Faculty Opinions recommendation of Effect of hyperacute administration (within 6 hours) of transdermal glyceryl trinitrate, a nitric oxide donor, on outcome after stroke: subgroup analysis of the efficacy of nitric oxide in stroke (ENOS) trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725850686.793510844 ◽

2015 ◽

Author(s):

Andrea Semplicini

Keyword(s):

Nitric Oxide ◽

Glyceryl Trinitrate ◽

Subgroup Analysis ◽

Nitric Oxide Donor

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Glyceryl trinitrate, a nitric oxide donor, abrogates ferric nitrilotriacetate-induced oxidative stress and renal damage

Archives of Biochemistry and Biophysics ◽

10.1016/s0003-9861(03)00365-5 ◽

2003 ◽

Vol 418 (1) ◽

pp. 71-79 ◽

Cited By ~ 13

Author(s):

Ayesha Rahman ◽

Salahuddin Ahmed ◽

Shaista M Vasenwala ◽

Mohammad Athar

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Glyceryl Trinitrate ◽

Renal Damage ◽

Nitric Oxide Donor ◽

Ferric Nitrilotriacetate

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Nicorandil as a novel therapy for advanced diabetic nephropathy in the eNOS-deficient mouse

AJP Renal Physiology ◽

10.1152/ajprenal.00596.2011 ◽

2012 ◽

Vol 302 (9) ◽

pp. F1151-F1160 ◽

Cited By ~ 37

Author(s):

Katsuyuki Tanabe ◽

Miguel A. Lanaspa ◽

Wataru Kitagawa ◽

Christopher J. Rivard ◽

Makoto Miyazaki ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Diabetic Nephropathy ◽

Oxidant Stress ◽

Nitric Oxide Donor ◽

K Channel ◽

Glomerular Injury ◽

Novel Therapy ◽

Glucose Levels ◽

Stress Studies

Nicorandil is an orally available drug that can act as a nitric oxide donor, an antioxidant, and an ATP-dependent K channel activator. We hypothesized that it may have a beneficial role in treating diabetic nephropathy. We administered nicorandil to a model of advanced diabetic nephropathy (the streptozotocin-induced diabetes in mice lacking endothelial nitric oxide synthase, eNOSKO); controls included diabetic eNOS KO mice without nicorandil and nondiabetic eNOS KO mice treated with either nicorandil or vehicle. Mice were treated for 8 wk. Histology, blood pressure, and renal function were determined. Additional studies involved examining the effects of nicorandil on cultured human podocytes. Here, we found that nicorandil did not affect blood glucose levels, blood pressure, or systemic endothelial function, but significantly reduced proteinuria and glomerular injury (mesangiolysis and glomerulosclerosis). Nicorandil protected against podocyte loss and podocyte oxidative stress. Studies in cultured podocytes showed that nicorandil likely protects against glucose-mediated oxidant stress via the ATP-dependent K channel as opposed to its NO-stimulating effects. In conclusion, nicorandil may be beneficial in diabetic nephropathy by preserving podocyte function. We recommend clinical trials to determine whether nicorandil may benefit diabetic nephropathy or other conditions associated with podocyte dysfunction.

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