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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
Scopus
Open Access Toplam 299 atıf DOI
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. Funding UK Medical Research Council.
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Infections Up to 76 Days After Stroke Increase Disability and Death
Scopus
Havuzumuzda Open Access 33 atıf almış
Early infection after stroke is associated with a poor outcome. We aimed to determine whether delayed infections (up to 76 days post-stroke) are associated with poor outcome at 90 days. Data came from the international Efficacy of Nitric Oxide Stroke (ENOS, ISRCTN99414122) trial. Post hoc data on infections were obtained from serious adverse events reports between 1 and 76 days following stroke in this large cohort of patients. Regression models accounting for baseline covariates were used to analyse fatalities and functional outcomes (modified Rankin Scale (mRS), Barthel Index, Euro-Qol-5D) at 90 days, in patients with infection compared to those without infection. Of 4011 patients, 242 (6.0%) developed one or more serious infections. Infections were associated with an increased risk of death (p < 0.001) and an increased likelihood of dependency (measured by mRS) compared to those of all other patients (p < 0.001). This remained when only surviving patients were analysed, indicating that the worsening of functional outcome is not due to mortality (p < 0.001). In addition, the timing of the infection after stroke did not alter its detrimental association with fatality (p = 0.14) or functional outcome (p = 0.47). In conclusion, severe post-stroke infections, whether occurring early or late after stroke, are associated with an increased risk of death and poorer functional outcome, independent of differences in baseline characteristics or treatment. Not only are strategies needed for reducing the risk of infection immediately after stroke, but also during the first 3 months following a stroke. This study is registered: ISRCTN registry, number ISRCTN99414122, ClinicalTrials.gov Identifier, NCT00989716.
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Kurumlar (16)
Ain Shams University
Cairo, Egypt
All India Institute of Medical Sciences, New Delhi
New Delhi, India
Általános Orvostudományi Kar
Budapest, Hungary
Bispebjerg Hospital
Copenhagen, Denmark
Danderyds Sjukhus
Danderyd, Sweden
Hawke's Bay Hospital
Hastings, New Zealand
Institute of Psychiatry and Neurology, Warszawa
Warsaw, Poland
London School of Hygiene & Tropical Medicine
London, United Kingdom
Oslo Universitetssykehus
Oslo, Norway
Selçuk Üniversitesi
Selçuklu, Turkey