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      Elevated Blood Pressure in the Acute Phase of Stroke and the Role of Angiotensin Receptor Blockers

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          Abstract

          Raised blood pressure (BP) is common after stroke but its causes, effects, and management still remain uncertain. We performed a systematic review of randomized controlled trials that investigated the effects of the angiotensin receptor blockers (ARBs) administered in the acute phase (≤72 hours) of stroke on death and dependency. Trials were identified from searching three electronic databases (Medline, Cochrane Library and Web of Science Database). Three trials involving 3728 patients were included. Significant difference in BP values between treatment and placebo was found in two studies. No effect of the treatment was seen on dependency, death and vascular events at one, three or six months; the cumulative mortality and the number of vascular events at 12 months differed significantly in favour of treatment in one small trial which stopped prematurely. Evidence raises doubts over the hypothesis of a specific effect of ARBs on short- and medium-term outcomes of stroke. It is not possible to rule out that different drugs might have different effects. Further trials are desirable to clarify whether current findings are generalizable or there are subgroups of patients or different approaches to BP management for which a treatment benefit can be obtained.

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          Most cited references41

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          Telmisartan to prevent recurrent stroke and cardiovascular events.

          Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke. In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes. The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P=0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10). Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062.) 2008 Massachusetts Medical Society
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            Blood pressure and clinical outcomes in the International Stroke Trial.

            Among patients with acute stroke, high blood pressure is often associated with poor outcome, although the reason is unclear. We analyzed data from the International Stroke Trial (IST) to explore the relationship between systolic blood pressure (SBP), subsequent clinical events over the next 2 weeks, and functional outcome at 6 months in patients with acute stroke. We included in the analysis 17 398 patients from IST with confirmed ischemic stroke. A single measurement of SBP was made immediately before randomization. Clinical events within 14 days of randomization were recorded: recurrent ischemic stroke, symptomatic intracranial hemorrhage, death resulting from presumed cerebral edema, fatal coronary heart disease, and death. Survival and dependency were assessed at 6 months. Outcomes were adjusted for age, sex, clinical stroke syndrome, time to randomization, consciousness level, atrial fibrillation, and treatment allocation (aspirin, unfractionated heparin, both, or neither). A U-shaped relationship was found between baseline SBP and both early death and late death or dependency: early death increased by 17.9% for every 10 mm Hg below 150 mm Hg (P<0.0001) and by 3.8% for every 10 mm Hg above 150 mm Hg (P=0.016). The rate of recurrent ischemic stroke within 14 days increased by 4.2% for every 10-mm Hg increase in SBP (P=0.023); this association was present in both fatal and nonfatal recurrence. Death resulting from presumed cerebral edema was independently associated with high SBP (P=0.004). No relationship between symptomatic intracranial hemorrhage and SBP was seen. Low SBP was associated with a severe clinical stroke (total anterior circulation syndrome) and an excess of deaths from coronary heart disease (P=0.002). Both high blood pressure and low blood pressure were independent prognostic factors for poor outcome, relationships that appear to be mediated in part by increased rates of early recurrence and death resulting from presumed cerebral edema in patients with high blood pressure and increased coronary heart disease events in those with low blood pressure. The occurrence of symptomatic intracranial hemorrhage within 14 days was independent of SBP.
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              Blood pressure decrease during the acute phase of ischemic stroke is associated with brain injury and poor stroke outcome.

              Studies on the relation between blood pressure (BP) and stroke outcome have shown contradictory results. We explored the association of systolic (SBP) and diastolic (DBP) BP during acute stroke with early neurological deterioration, infarct volume, neurological outcome, and mortality at 3 months. We included 304 patients with acute ischemic stroke. SBP and DBP on admission and on the first day were the average values of all readings obtained in the emergency department and during a 24-hour period after patient allocation in the stroke unit. A U-shaped effect was observed: for every 10 mm Hg 180 mm Hg, the risk of early neurological deterioration increased by 40% and the risk of poor outcome increased by 23%, with no effect on mortality. Mean infarct volume increased 7.3 and 5.5 cm(3) for every 10 mm Hg 180 mm Hg. A similar pattern was found in patients with DBP 100 mm Hg. These effects disappeared after adjustment for the use of antihypertensive drugs and BP drop >20 mm Hg within the first day, with the latter being the more important prognostic factor of poor outcome. High and low SBP and DBP, as well as a relevant drop in BP, are associated with poor prognosis in patients with ischemic stroke.
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                Author and article information

                Journal
                Int J Hypertens
                Int J Hypertens
                IJHT
                International Journal of Hypertension
                Hindawi Publishing Corporation
                2090-0384
                2090-0392
                2013
                31 January 2013
                : 2013
                : 941783
                Affiliations
                Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Via Conca 71, 60020 Ancona, Italy
                Author notes

                Academic Editor: Marc de Gasparo

                Article
                10.1155/2013/941783
                3574652
                23431423
                0dd63e17-be6f-4b52-b95a-c5288f754b36
                Copyright © 2013 Simona Lattanzi et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 October 2012
                : 31 December 2012
                : 2 January 2013
                Categories
                Review Article

                Cardiovascular Medicine
                Cardiovascular Medicine

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