Effects of Blood Pressure and Blood Pressure-Lowering Treatment During the First 24 Hours Among Patients in the Third International Stroke Trial of Thrombolytic Treatment for Acute Ischemic Stroke.
OBJECTIVE
In patients with acute ischemic stroke, a high blood pressure or a highly variable blood pressure is a common reason for withholding thrombolytic treatment, but guidelines recommend a conservative approach to active blood pressure lowering in this setting. We have performed exploratory analyses to study the clinical effects of blood pressure and early blood pressure-lowering treatment in patients included in a randomized-controlled trial of thrombolytic treatment for acute ischemic stroke.


METHODS
The Third International Stroke Trial (IST-3) randomized 3035 patients with ischemic stroke to recombinant tissue-type plasminogen activator 0.9 mg/kg or open control within 6 hours of symptom onset. Blood pressure was measured at randomization, at start of treatment, and at 30 minutes and 1 and 24 hours after start of treatment, and the use of blood pressure-lowering treatment during the first 24 hours was recorded. We have characterized blood pressure by mean systolic blood pressure at baseline, by variability of systolic blood pressure (expressed by the standard deviation and the range between the lowest and the highest pressure), and by the change in systolic blood pressure from baseline to 24 hours. We used logistic regression analysis to explore the associations of blood pressure characteristics or blood pressure-lowering treatment with early adverse events, early death, and functional outcome at 6 months, after adjustment for key prognostic variables.


RESULTS
High baseline blood pressure and high blood pressure variability during the first 24 hours were associated with higher numbers of early adverse events and early deaths, and for several analyses, the differences were statistically significant. A larger decline in blood pressure and the use of blood pressure-lowering treatment during the first 24 hours were associated with a reduced risk of poor outcome at 6 months (odds ratio, 0.93; 95% confidence interval, 0.89-0.97; P=0.001 and odds ratio, 0.78; 95% confidence interval, 0.65-0.93; P=0.007, respectively), irrespective of whether the patient was given recombinant tissue-type plasminogen activator (P values for interaction >0.05).


CONCLUSIONS
Among patients with ischemic stroke who are candidates for thrombolytic treatment, high baseline blood pressure and a large pressure variability during the first 24 hours may be associated with a poor prognosis, whereas a large reduction in blood pressure and the use of blood pressure-lowering treatment during the first 24 hours may be associated with a favorable prognosis. These data support the rationale for further trials of agents that lower blood pressure or reduce blood pressure variability in the acute phase of ischemic stroke.


BACKGROUND
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00120003.
From the Departments of Internal Medicine (E.B.) and Neurology (E.C.S.), Oslo University Hospital, Oslo, Norway; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, Scotland (G.C., P.S., J.M.W., W.W.); and George Institute for Global Health and Discipline of Medicine, University of Sydney, Sydney, New South Wales, Australia (R.I.L.). eivind.berge@medisin.uio.no.
Eivind
E
Berge
From the Departments of Internal Medicine (E.B.) and Neurology (E.C.S.), Oslo University Hospital, Oslo, Norway; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, Scotland (G.C., P.S., J.M.W., W.W.); and George Institute for Global Health and Discipline of Medicine, University of Sydney, Sydney, New South Wales, Australia (R.I.L.).
Geoffrey
G
Cohen
From the Departments of Internal Medicine (E.B.) and Neurology (E.C.S.), Oslo University Hospital, Oslo, Norway; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, Scotland (G.C., P.S., J.M.W., W.W.); and George Institute for Global Health and Discipline of Medicine, University of Sydney, Sydney, New South Wales, Australia (R.I.L.).
Richard I
RI
Lindley
From the Departments of Internal Medicine (E.B.) and Neurology (E.C.S.), Oslo University Hospital, Oslo, Norway; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, Scotland (G.C., P.S., J.M.W., W.W.); and George Institute for Global Health and Discipline of Medicine, University of Sydney, Sydney, New South Wales, Australia (R.I.L.).
Peter
P
Sandercock
From the Departments of Internal Medicine (E.B.) and Neurology (E.C.S.), Oslo University Hospital, Oslo, Norway; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, Scotland (G.C., P.S., J.M.W., W.W.); and George Institute for Global Health and Discipline of Medicine, University of Sydney, Sydney, New South Wales, Australia (R.I.L.).
Joanna M
JM
Wardlaw
From the Departments of Internal Medicine (E.B.) and Neurology (E.C.S.), Oslo University Hospital, Oslo, Norway; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, Scotland (G.C., P.S., J.M.W., W.W.); and George Institute for Global Health and Discipline of Medicine, University of Sydney, Sydney, New South Wales, Australia (R.I.L.).
Else C
EC
Sandset
From the Departments of Internal Medicine (E.B.) and Neurology (E.C.S.), Oslo University Hospital, Oslo, Norway; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, Scotland (G.C., P.S., J.M.W., W.W.); and George Institute for Global Health and Discipline of Medicine, University of Sydney, Sydney, New South Wales, Australia (R.I.L.).
William
W
Whiteley
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002545:Brain Ischemia / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D038622:Internationality; D008297:Male; D020521:Stroke / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
antihypertensive agents; blood pressure; cerebral hemorrhage; cerebral infarction; hypertension; stroke; thrombolytic therapy