Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS): a partial-factorial randomised controlled trial

Bath, Philip M.W.

Abstract

Background

High blood pressure is associated with poor outcome after stroke. Whether blood pressure should be lowered early after stroke, and whether to continue or temporarily withdraw existing antihypertensive drugs, is not known. We assessed outcomes after stroke in patients given drugs to lower their blood pressure.
Methods

In our multicentre, partial-factorial trial, we randomly assigned patients admitted to hospital with an acute ischaemic or haemorrhagic stroke and raised systolic blood pressure (systolic 140–220 mm Hg) to 7 days of transdermal glyceryl trinitrate (5 mg per day), started within 48 h of stroke onset, or to no glyceryl trinitrate (control group). A subset of patients who were taking antihypertensive drugs before their stroke were also randomly assigned to continue or stop taking these drugs. The primary outcome was function, assessed with the modified Rankin Scale at 90 days by observers masked to treatment assignment. This study is registered, number ISRCTN99414122.
Findings

Between July 20, 2001, and Oct 14, 2013, we enrolled 4011 patients. Mean blood pressure was 167 (SD 19) mm Hg/90 (13) mm Hg at baseline (median 26 h [16–37] after stroke onset), and was significantly reduced on day 1 in 2000 patients allocated to glyceryl trinitrate compared with 2011 controls (difference −7·0 [95% CI −8·5 to −5·6] mm Hg/–3·5 [–4·4 to −2·6] mm Hg; both p<0·0001), and on day 7 in 1053 patients allocated to continue antihypertensive drugs compared with 1044 patients randomised to stop them (difference −9·5 [95% CI −11·8 to −7·2] mm Hg/–5·0 [–6·4 to −3·7] mm Hg; both p<0·0001). Functional outcome at day 90 did not differ in either treatment comparison—the adjusted common odds ratio (OR) for worse outcome with glyceryl trinitrate versus no glyceryl trinitrate was 1·01 (95% CI 0·91–1·13; p=0·83), and with continue versus stop antihypertensive drugs OR was 1·05 (0·90–1·22; p=0·55).
Interpretation

In patients with acute stroke and high blood pressure, transdermal glyceryl trinitrate lowered blood pressure and had acceptable safety but did not improve functional outcome. We show no evidence to support continuing prestroke antihypertensive drugs in patients in the first few days after acute stroke.

Citation

Bath, P. M. (2015). Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS): a partial-factorial randomised controlled trial. Lancet, 385(9968), https://doi.org/10.1016/S0140-6736%2814%2961121-1

• Journal Article Type: Article
• Acceptance Date: Oct 1, 2014
• Online Publication Date: Oct 22, 2014
• Publication Date: Feb 14, 2015
• Deposit Date: Aug 5, 2016
• Publicly Available Date: Aug 5, 2016
• Journal: The Lancet
• Print ISSN: 0140-6736
• Electronic ISSN: 1474-547X
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 385
• Issue: 9968
• DOI: https://doi.org/10.1016/S0140-6736%2814%2961121-1
• Public URL: https://nottingham-repository.worktribe.com/output/745001
• Publisher URL: http://www.sciencedirect.com/science/article/pii/S0140673614611211
• Additional Information: Acceptance date is estimated. :: Article attributed to ENOS Trial Investigators. Writing committee: Philip M W Bath, Lisa Woodhouse, Polly Scutt, Kailash Krishnan, Joanna M Wardlaw, Daniel Bereczki, Nikola Sprigg, Eivind Berge, Maia Beridze, Valeria Caso, Christopher Chen, Hanne Christensen, Ronan Collins, Anwar El Etribi, Ann Charlotte Laska, Kennedy R Lees, Serefnur Ozturk, Steve Phillips, Stuart Pocock, H Asita de Silva, Szabolcs Szatmari, Sally Utton.
• Contract Date: Aug 5, 2016