Glyceryl Trinitrate for Acute Intracerebral Hemorrhage

Abstract

Background and Purpose-The Efficacy of Nitric Oxide in Stroke (ENOS) trial found that transdermal glyceryl trinitrate (GTN, a nitric oxide donor) lowered blood pressure but did not improve functional outcome in patients with acute stroke. However, GTN was associated with improved outcome if patients were randomized within 6 hours of stroke onset. Methods-In this prespecified subgroup analysis, the effect of GTN (5 mg/d for 7 days) versus no GTN was studied in 629 patients with intracerebral hemorrhage presenting within 48 hours and with systolic blood pressure ≥140 mm Hg. The primary outcome was the modified Rankin Scale at 90 days. Results-Mean blood pressure at baseline was 172/93 mm Hg and significantly lower (difference −7.5/−4.2 mm Hg; both P≤0.05) on day 1 in 310 patients allocated to GTN when compared with 319 randomized to no GTN. No difference in the modified Rankin Scale was observed between those receiving GTN versus no GTN (adjusted odds ratio for worse outcome with GTN, 1.04; 95% confidence interval, 0.78-1.37; P=0.84). In the subgroup of 61 patients randomized within 6 hours, GTN improved functional outcome with a shift in the modified Rankin Scale (odds ratio, 0.22; 95% confidence interval, 0.07-0.69; P=0.001). There was no significant difference in the rates of serious adverse events between GTN and no GTN. Conclusions-In patients with intracerebral hemorrhage within 48 hours of onset, GTN lowered blood pressure was safe but did not improve functional outcome. Very early treatment might be beneficial but needs assessment in further studies. Clinical Trial Registration-URL: http://www.isrctn.com/ISRCTN99414122. Unique identifier: 99414122.

Effects of Intensive Blood Pressure Reduction on Acute Intracerebral Hemorrhage: A Systematic Review and Meta-analysis

“…The acute hypertensive response in ICH is highly prevalent and is an important prognostic factor 4 . To date, management of blood pressure (BP) has been proven to be safe, but remains uncertain as a method for improving clinical outcomes 5 – 7 .…”

Angeli's Salt, a nitroxyl anion donor, reverses endothelin-1 mediated vascular dysfunction in murine aorta

“…The use of nitrosovasodilators, such as Gtn, for the treatment of cardiovascular conditions is well established and has been used for decades (Boden et al , 2015; Investigators et al , 2015; Woodhouse et al , 2015; Krishnan et al , 2016 ). Although nitrosovasodilators mediate rapid and pronounced vasodilation, they are limited clinically due to the development of tolerance and reported increases in ROS generation (Sage et al , 2000; Schulz et al , 2002; Munzel et al , 2005).…”

Therapeutic Potential of Transdermal Glyceryl Trinitrate in the Management of Acute Stroke

“…The time-dependent effect on functional outcome was seen in both IS and ICH; a finding supported by a subgroup analysis of participants with ICH from the ENOS trial [51]. Those with ICH who received GTN within 6 h of onset had significant improvements in functional outcome, cognition, disability, mood and quality of life at 90 days compared with those who did not receive GTN [51].…”