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The ENOS trial protocol, statistical analysis plan, baseline characteristics and main trial results have been published elsewhere 4, 14- 16. The aim of the present planned substudy was to assess the impact of dehydration on haemodynamic changes, effect of blood pressure reduction on clinical outcomes, and prognosis after stroke. Overall, GTN did not alter clinical outcomes, despite lowering BP by 7/3.5 mmHg at day 1 4, but when administered within 6 h of stroke onset, GTN improved multiple clinical outcomes at day 90 13. The Efficacy of Nitric Oxide in Stroke (ENOS) trial assessed the effect of transdermal glyceryl trinitrate (GTN) on outcome in 4011 patients 4. As a consequence, dehydration has been associated with poor clinical outcomes following acute stroke 10- 12, and adequate hydration after stroke is recommended in clinical guidelines 8. It may also lead to renal impairment and is associated with venous thromboembolism 8, 9. Hypovolaemia may reduce cerebral perfusion and increase the infarct core in ischaemic stroke 6 and the perihaematomal ischaemia in intracerebral haemorrhage 7. Reduced circulating volume is also common in stroke, especially if admission to hospital is delayed, thereby allowing dehydration to develop. Most drug classes that might be useful for lowering BP (including angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists and nitrates) have accentuated vasodepressant effects when patients are dehydrated or hypovolaemic 5. Lowering elevated BP is recommended in acute intracerebral haemorrhage 2, and is safe in ischaemic stroke 3, 4.
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High blood pressure (BP) is common in acute stroke and associated independently with a poor outcome in both ischaemic stroke and intracerebral haemorrhage 1. BP-lowering treatment was safe in dehydrated patients, with no precipitous changes in BP, thus supporting its use in acute stroke prior to blood markers of dehydration becoming available.
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Increased baseline urea was associated with poor prognosis after stroke. Conclusionsīlood pressure-lowering treatment was safe in dehydrated patients, with no precipitous changes in BP, thus supporting its use in acute stroke prior to blood markers of dehydration becoming available. Overall, increasing urea was associated with an unfavourable shift in mRS and increased risk of death at day 90 (hazard ratio 4.55, 95% CI 1.51, 13.66 P = 0.007). There were no significant associations between dehydration markers and fall in blood pressure from baseline to day 1, and no significant interaction with allocated treatment.
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Blood markers of dehydration at baseline were collected at two sites ( n = 310) and their relationship with haemodynamics and outcome was assessed. The primary outcome was functional outcome (modified Rankin Scale, mRS) at day 90.
#MONIT GTN 2.6 USED FOR PATCH#
MethodsĮNOS randomized 4011 patients with acute stroke and raised systolic BP to a glyceryl trinitrate (GTN) patch or no GTN patch, and to continue or to stop existing antihypertensive treatment within 48 h of onset. We assessed the impact of dehydration on haemodynamics, the effects of antihypertensive treatment, and prognosis in the ENOS trial. Antihypertensive agents have accentuated effects in dehydrated patients. Although high blood pressure (BP) is common in acute stroke and associated with poor outcome, the Efficacy of Nitric Oxide in Stroke (ENOS) trial showed no beneficial effect of antihypertensive treatment in this situation.