Glyceryl Trinitrate for Acute Intracerebral Hemorrhage: Results From the Efficacy of Nitric Oxide in Stroke (ENOS) Trial, a Subgroup Analysis

Krishnan, Kailash; Scutt, Polly; Woodhouse, Lisa J.; Adami, Alessandro; Becker, Jennifer L.; Berge, Eivind; Cala, Lesley A.; Casado, Ana M.; Caso, Valeria; Chen, Christopher; Christensen, Hanna; Collins, Ronan; Czlonkowska, Anna; Dineen, Robert A.; Gommans, John; Koumellis, Panos; Lees, Kennedy R.; Ntaios, George; Ozturk, Serefnur; Phillips, Stephen J.; Pocock, Stuart J.; de Silva, Asita; Sprigg, Nikola; Szatmari, Szabolcs; Wardlaw, Joanna M.; Bath, Philip M.W.

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 randomised within 6 hours of stroke onset.

Methods: In this pre-specified subgroup analysis, the effect of GTN (5 mg/day for 7 days) versus no GTN was studied in 629 patients with intracerebral haemorrhage presenting within 48 hours and with systolic blood pressure >140 mmHg. The primary outcome was the modified Rankin Scale (mRS) at 90 days.

Results: Mean blood pressure at baseline was 172/93 mmHg and significantly lower (difference -7.5/-4.2 mmHg; both p< 0.05) on day 1 in 310 patients allocated to GTN as compared with 319 randomised to no GTN. No difference in the mRS was observed between those receiving GTN versus no GTN (adjusted odds ratio, OR for worse outcome with GTN 1.04, 95% confidence interval (CI) 0.78-1.37; p=0.84). In the subgroup of 61 patients randomised within 6 hours, GTN improved functional outcome with a shift in the modified Rankin Scale (OR 0.22, 95% CI 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 haemorrhage 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.

Citation

Krishnan, K., Scutt, P., Woodhouse, L. J., Adami, A., Becker, J. L., Berge, E., Cala, L. A., Casado, A. M., Caso, V., Chen, C., Christensen, H., Collins, R., Czlonkowska, A., Dineen, R. A., Gommans, J., Koumellis, P., Lees, K. R., Ntaios, G., Ozturk, S., Phillips, S. J., …Bath, P. M. (in press). Glyceryl Trinitrate for Acute Intracerebral Hemorrhage: Results From the Efficacy of Nitric Oxide in Stroke (ENOS) Trial, a Subgroup Analysis. Stroke, 47(1), 44-52. https://doi.org/10.1161/strokeaha.115.010368

• Journal Article Type: Article
• Acceptance Date: Oct 26, 2015
• Online Publication Date: Dec 8, 2015
• Deposit Date: Aug 1, 2016
• Publicly Available Date: Aug 1, 2016
• Journal: Stroke
• Print ISSN: 0039-2499
• Electronic ISSN: 1524-4628
• Publisher: American Heart Association
• Peer Reviewed: Peer Reviewed
• Volume: 47
• Issue: 1
• Pages: 44-52
• DOI: https://doi.org/10.1161/strokeaha.115.010368
• Keywords: Acute stroke ; Antihypertensive therapy ; Blood pressure ; Glyceryl trinitrate ; Intracerebral haemorrhage ; Randomised controlled trial
• Public URL: https://nottingham-repository.worktribe.com/output/769801
• Publisher URL: http://dx.doi.org/10.1161/STROKEAHA.115.010368
• Contract Date: Aug 1, 2016