The effects of transdermal glyceryl trinitrate, a nitric oxide donor, on blood pressure, cerebral and cardiac hemodynamics, and plasma nitric oxide levels in acute stroke
Section snippets
Design
A prospective single-center dose-comparison, open-label blinded-endpoint randomized controlled trial was performed. The primary outcome measure was 24 hour mean arterial blood pressure (MAP) on day 1 (ie, reflecting the first 24 hours of treatment); day 1 was also the main timing of interest for other hemodynamic measures to avoid the potentially confounding effects of tolerance. A sample size of 21 patients per group was calculated assuming the following: difference in blood pressure, 10 mmHg17
Results
Consent or assent was given by 93 patients, 3 of whom withdrew from the study prior to randomisation (Fig 1). The patients in the control and GTN groups were well matched for age, gender, history of hypertension, and stroke severity and type (Table 1); a non-significant trend to less total anterior circulation syndrome was present in patients randomized to GTN (Table 1). The average time from stroke onset to randomization was 50 hours.
Conclusions
This trial confirms the finding of our previous study17 that GTN lowers systolic, diastolic, and mean arterial blood pressure in patients with acute stroke. Importantly, the study extends this information in three ways. First, GTN lowered blood pressure in a dose-dependent manner: as compared with control, GTN at doses of 5 mg and 10 mg reduced blood pressure by 7.0% and 7.8% respectively. Second, we studied approaches which might delay the appearance of tolerance, a known pharmacological
Acknowledgements
We thank the patients for taking part in this trial and Mrs. Bev Whysall for performing some of the 3 month follow-up assessments. No pharmaceutical company was involved in the conception, design, execution, analysis, interpretation, or funding of this trial. P.B. is the Stroke Association Professor of Stroke Medicine; the Division of Stroke Medicine receives core funding from The Stroke Association. This work was presented in part at the American Stroke Association meeting, San Antonio, TX,
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Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial
2019, The LancetCitation Excerpt :Five randomised trials7–11 of an NO donor, transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), in acute stroke showed that GTN lowered peripheral and central blood pressure, 24 h blood pressure, pulse pressure, and augmentation index. Conversely, GTN had no effect on middle cerebral artery blood flow velocity, cerebral blood flow, intracranial pressure, or platelet function.7–9 Although four of the trials7–9,11 were neutral for functional outcome, GTN improved functional outcome in the phase 2 Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial (RIGHT),10 with randomisation by paramedics within 4 h of stroke, and in a prespecified subgroup analysis of the phase 3 hospital-based Efficacy of Nitric Oxide in Stroke trial (ENOS),11,12 with randomisation within 6 h of stroke.
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