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Öğe Continuing versus Stopping Prestroke Antihypertensive Therapy in Acute Intracerebral Hemorrhage: A Subgroup Analysis of the Efficacy of Nitric Oxide in Stroke Trial(ELSEVIER SCIENCE BV, 2016) Krishnan, Kailash; Scutt, Polly; Woodhouse, Lisa; Adami, Alessandro; Becker, Jennifer L.; Cala, Lesley A.; Casado, Ana M.Background and purpose: More than 50% of patients with acute intracerebral hemorrhage (ICH) are taking antihypertensive drugs before ictus. Although antihypertensive therapy should be given long term for secondary prevention, whether to continue or stop such treatment during the acute phase of ICH remains unclear, a question that was addressed in the Efficacy of Nitric Oxide in Stroke (ENOS) trial. Methods: ENOS was an international multicenter, prospective, randomized, blinded endpoint trial. Among 629 patients with ICH and systolic blood pressure between 140 and 220 mmHg, 246 patients who were taking antihypertensive drugs were assigned to continue (n = 119) or to stop (n = 127) taking drugs temporarily for 7 days. The primary outcome was the modified Rankin Score at 90 days. Secondary outcomes included death, length of stay in hospital, discharge destination, activities of daily living, mood, cognition, and quality of life. Results: Blood pressure level (baseline 171/92 mmHg) fell in both groups but was significantly lower at 7 days in those patients assigned to continue antihypertensive drugs (difference 9.4/3.5 mmHg, P < .01). At 90 days, the primary outcome did not differ between the groups; the adjusted common odds ratio (OR) for worse outcome with continue versus stop drugs was .92 (95% confidence interval, .45-1.89; P = .83). There was no difference between the treatment groups for any secondary outcome measure, or rates of death or serious adverse events. Conclusions: Among patients with acute ICH, immediate continuation of antihypertensive drugs during the first week did not reduce death or major disability in comparison to stopping treatment temporarily.Öğe Glyceryl Trinitrate for Acute Intracerebral Hemorrhage Results From the Efficacy of Nitric Oxide in Stroke (ENOS) Trial, a Subgroup Analysis(LIPPINCOTT WILLIAMS & WILKINS, 2016) Krishnan, Kailash; Scutt, Polly; Woodhouse, Lisa; Adami, Alessandro; Becker, Jennifer L.; Berge, Eivind; Cala, Lesley A.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 P0.05) 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.Öğe Infections Up to 76 Days After Stroke Increase Disability and Death(SPRINGER, 2017) Learoyd, Annastazia E.; Woodhouse, Lisa; Shaw, Laurence; Sprigg, Nikola; Bereczki, Daniel; Berge, Eivind; Caso, ValeriaEarly 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, Identifier, NCT00989716.Öğe Tranexamic acid to improve functional status in adults with spontaneous intracerebral haemorrhage: The TICH-2 RCT(NIHR JOURNALS LIBRARY, 2019) Sprigg, Nikola; Flaherty, Katie; Appleton, Jason P.; Al-Shahi Salman, Rustam; Bereczki, Daniel; Beridze, Maia; Ciccone, Alfonso; Collins, Ronan; Dineen, Robert A.; Duley, Lelia; Egea-Guerrero, Juan José; England, Timothy J.; Karlinski, Michal; Krishnan, Kailash; Laska, Ann Charlotte; Law, Zhe Kang; Ovesen, Christian; Öztürk, Şerefnur; Pocock, Stuart J.; Roberts, Ian; Robinson, Thompson G.; Roffe, Christine; Peters, Nils; Scutt, Polly; Thanabalan, Jegan; Werring, David; Whynes, David; Woodhouse, Lisa; Bath, Philip M.Background: Tranexamic acid reduces death due to bleeding after trauma and postpartum haemorrhage. Objective: The aim of the study was to assess if tranexamic acid is safe, reduces haematoma expansion and improves outcomes in adults with spontaneous intracerebral haemorrhage (ICH). Design: The TICH-2 (Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage) study was a pragmatic, Phase III, prospective, double-blind, randomised placebo-controlled trial. Setting: Acute stroke services at 124 hospitals in 12 countries (Denmark, Georgia, Hungary, Ireland, Italy, Malaysia, Poland, Spain, Sweden, Switzerland, Turkey and the UK). Participants: Adult patients (aged >= 18 years) with ICH within 8 hours of onset. Exclusion criteria: Exclusion criteria were ICH secondary to anticoagulation, thrombolysis, trauma or a known underlying structural abnormality; patients for whom tranexamic acid was thought to be contraindicated; prestroke dependence (i.e. patients with a modified Rankin Scale [mRS] score > 4); life expectancy < 3 months; and a Glasgow Coma Scale score of < 5. Interventions: Participants, allocated by randomisation, received 1 g of an intravenous tranexamic acid bolus followed by an 8-hour 1-g infusion or matching placebo (i.e. 0.9% saline). Main outcome measure: The primary outcome was functional status (death or dependency) at day 90, which was measured by the shift in the mRS score, using ordinal logistic regression, with adjustment for stratification and minimisation criteria. Results: A total of 2325 participants (tranexamic acid, n = 1161; placebo, n = 1164) were recruited from 124 hospitals in 12 countries between 2013 and 2017. Treatment groups were well balanced at baseline. The primary outcome was determined for 2307 participants (tranexamic acid, n = 1152; placebo, n = 1155). There was no statistically significant difference between the treatment groups for the primary outcome of functional status at day 90 [adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.76 to 1.03; p = 0.11]. Although there were fewer deaths by day 7 in the tranexamic acid group (aOR 0.73, 95% CI 0.53 to 0.99; p = 0.041), there was no difference in case fatality at 90 days (adjusted hazard ratio 0.92, 95% CI 0.77 to 1.10; p = 0.37). Fewer patients experienced serious adverse events (SAEs) after treatment with tranexamic acid than with placebo by days 2 (p = 0.027), 7 (p = 0.020) and 90 (p = 0.039). There was no increase in thromboembolic events or seizures. Limitations: Despite attempts to enrol patients rapidly, the majority of participants were enrolled and treated > 4.5 hours after stroke onset. Pragmatic inclusion criteria led to a heterogeneous population of participants, some of whom had very large strokes. Although 12 countries enrolled participants, the majority (82.1%) were from the UK. Conclusions: Tranexamic acid did not affect a patient's functional status at 90 days after ICH, despite there being significant modest reductions in early death (by 7 days), haematoma expansion and SAEs, which is consistent with an antifibrinolytic effect. Tranexamic acid was safe, with no increase in thromboembolic events. Future work: Future work should focus on enrolling and treating patients early after stroke and identify which participants are most likely to benefit from haemostatic therapy. Large randomised trials are needed.