Effects of Blood Pressure–Lowering Treatment in Different Subtypes of Acute Ischemic Stroke

Sandset, Else Charlotte; Jusufovic, Mirza; Sandset, Per Morten; Bath, Philip M; Berge, Eivind

doi:10.1161/strokeaha.114.008512

Cited by 31 publications

(39 citation statements)

References 14 publications

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“…In a subgroup analysis of the Scandinavian Candesartan Acute Stroke Trial, there was a significant trend toward a better effect of candesartan on the functional outcome in patients with larger infarcts (total anterior circulation or partial anterior circulation) than in patients with smaller infarcts (lacunar infarction) [13] . In contrast, there was a trend suggesting a beneficial effect of antihypertensive treatment in lacunar stroke and a detrimental effect in embolic stroke in the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) [8] .…”

confidence: 95%

Early Blood Pressure Reduction in Acute Ischemic Stroke with Various Severities: A Subgroup Analysis of the CATIS Trial

Li²,

Zhang³

et al. 2016

Cerebrovasc Dis

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Background: Clinical trials have generally showed a neutral effect of blood pressure (BP) reduction on clinical outcomes among acute ischemic stroke patients. We conducted a prespecified subgroup analysis to assess whether disease severity modifies the effect of early antihypertensive treatment on death and disability among patients with acute ischemic stroke. Methods: In the China Antihypertensive Trial in Acute Ischemic Stroke, 4,071 patients with acute ischemic stroke and elevated BP were randomly assigned to receive antihypertensive treatment or to discontinue all hypertension medications within 48 h of symptom onset. The primary outcome was a combination of death and major disability at 14 days or hospital discharge. In this subgroup analysis, participants were categorized into 3 groups according to their baseline NIH Stroke Scale (NIHSS) scores (0-4, 5-15, or ≥16). Results: At 24 h after randomization, mean systolic BP differences (95% CIs) were -8.5 (-10.0 to -7.1), -9.8 (-11.4 to -8.3), and -9.1 (-14.4 to -3.8) mm Hg between the treatment and control groups (all p values <0.001) for patients with a baseline NIHSS score of 0-4, 5-15, and ≥16, respectively. At day 7 after randomization, the corresponding mean systolic BP differences were -9.3 (-10.5 to -8.2), -9.1 (-10.3 to -7.8), and -10.1 (-15.1 to -5.1) mm Hg between the treatment and control groups (all p values <0.001). The primary outcome was not significantly different between the treatment and control groups at day 14 or hospital discharge among all NIHSS subgroups (p value for homogeneity = 0.66). ORs (95% CI) associated with treatment were 1.14 (0.87-1.49, p = 0.33), 1.04 (0.86-1.25, p = 0.70), and 0.67 (0.18-2.44, p = 0.54) for patients with a baseline NIHSS score of 0-4, 5-15, and ≥16, respectively. The composite outcome of death and major disability at 3-month follow-up did not differ between the 2 comparison groups for all NIHSS subgroups. In addition, vascular events and recurrent stroke were not significantly different between the 2 comparison groups at the 3-month follow-up visit among all NIHSS subgroups except that there was a suggestive risk reduction for recurrent stroke among those with an NIHSS score of 5-15 (OR 0.45, 95% CI 0.20-0.99, p = 0.05). Conclusion: Early BP reduction with antihypertensive medications did not reduce or increase the risk of death, major disabilities, recurrent instances of stroke, and vascular events in acute ischemic stroke patients with a variety of disease severities.

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confidence: 95%

Early Blood Pressure Reduction in Acute Ischemic Stroke with Various Severities: A Subgroup Analysis of the CATIS Trial

Li²,

Zhang³

et al. 2016

Cerebrovasc Dis

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“…The classification of strokes according to pathogenic mechanisms and the vascular territories involved is important to investigate the effects of risk factor management, including arterial hypertension, in different subtypes of acute ischemic stroke. In this respect, a recent study suggested that the effect of blood pressure-lowering treatment may differ according to different types of acute ischaemic stroke, with antihypertensive therapy having a better effect in patients with larger infarcts (TACI or PACI) than in patients with smaller infarcts (LACI) [33]. The observed trend may be the consequence of long-standing hypertension in patients with LACI resulting in the aforementioned rightward shift of the autoregulatory curve and the occurrence of perfusion deficits following a blood pressure lowering toward normal values [33].…”

Section: Definition and Classification Of Strokementioning

confidence: 99%

“…In this respect, a recent study suggested that the effect of blood pressure-lowering treatment may differ according to different types of acute ischaemic stroke, with antihypertensive therapy having a better effect in patients with larger infarcts (TACI or PACI) than in patients with smaller infarcts (LACI) [33]. The observed trend may be the consequence of long-standing hypertension in patients with LACI resulting in the aforementioned rightward shift of the autoregulatory curve and the occurrence of perfusion deficits following a blood pressure lowering toward normal values [33]. Moreover, cerebral autoregulation seems to be impaired, in patients with LACI, not only in the affected hemisphere but also in the opposite one: this would lead to a disproportionate fall in cerebral perfusion after blood pressure lowering [33].…”

Section: Definition and Classification Of Strokementioning

confidence: 99%

“…The observed trend may be the consequence of long-standing hypertension in patients with LACI resulting in the aforementioned rightward shift of the autoregulatory curve and the occurrence of perfusion deficits following a blood pressure lowering toward normal values [33]. Moreover, cerebral autoregulation seems to be impaired, in patients with LACI, not only in the affected hemisphere but also in the opposite one: this would lead to a disproportionate fall in cerebral perfusion after blood pressure lowering [33]. This is not the case for patients with TACI and PACI, whose pathogenesis is mainly atherothrombotic or cardioembolic: these infarcts are more likely to be complicated by oedema development or hemorrhagic transformation and real benefit may be obtained from a moderate lowering of blood pressure [33].…”

Section: Definition and Classification Of Strokementioning

confidence: 99%

“…Moreover, cerebral autoregulation seems to be impaired, in patients with LACI, not only in the affected hemisphere but also in the opposite one: this would lead to a disproportionate fall in cerebral perfusion after blood pressure lowering [33]. This is not the case for patients with TACI and PACI, whose pathogenesis is mainly atherothrombotic or cardioembolic: these infarcts are more likely to be complicated by oedema development or hemorrhagic transformation and real benefit may be obtained from a moderate lowering of blood pressure [33]. In daily clinical practice antihypertensive medications are more likely prescribed in ischemic patients with small vessel diseases that in patients with large arteries stenosis [34].…”

Section: Definition and Classification Of Strokementioning

confidence: 99%

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Hypertension and Stroke: Epidemiological Aspects and Clinical Evaluation

Pistoia

Sacco

Degan

et al. 2015

High Blood Press Cardiovasc Prev

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The strong relationship between stroke and hypertension has been the object of several studies and trials. These studies addressed the epidemiology of stroke and hypertension, in order to estimate their worldwide distribution and time evolution, and investigated the effects of the management of hypertension on stroke outcomes. Evidences coming from these studies are essential to plan proper health services, optimise economic resources, and estimate the effectiveness of therapeutic strategies in primary and secondary prevention. Additional suggestions are needed to tailor the pharmacologic management of hypertension on the individual needs of patients and to select the most appropriate treatment to avoid stroke recurrences on the basis of the first-ever stroke subtype. Moreover, an increasing attention has been given, over the last years, to the relationship between the presence of hypertension and the development of an end-organ brain damage leading to early cognitive dysfunctions. A better understanding of this relationship is the prerequisite to promote successful aging and well-being.

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The Hazard of Negative (Not Neutral) Trials on Treatment of Acute Stroke

2020

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cute stroke has multiple treatment interventions, including strokeunitsforallpatients 1 ;reperfusiontherapies(eg,thrombolysis, thrombectomy), 2-4 aspirin, 5 and hemicraniectomy 6 for acute ischemic stroke; and blood pressure (BP) lowering for hyperacute hemorrhagic stroke. 7 In contrast, other classes of interventions have failed to show efficacy, notably anticoagulation, neuroprotection, and BP lowering for acute ischemic stroke. Although most acute stroke randomized clinical trials (RCTs) have neutral findings (ie, the intervention did not show a significant effect on its primary outcome), a significant proportion have negative outcomes, with the intervention apparently being hazardous. It is inevitable that trials with negative findings will exist; the uncertainty principle that should underpin all RCTs means that although we start with a plausible and defendable idea, unknown factors may lead to a trial having neutral or negative findings. Nevertheless, the number of RCTs with negative outcomes could be limited through improved preclinical study design, delivery, and clinical oversight during trials. By examining acute stroke RCTs with negative outcomes,thesubjectofthisreview,wehopefullycanreducetheirnumber. MethodsIn this review, negative is used in the broad sense that the experimental treatment was associated with 1 or more statistically nega-tive clinical outcomes, whether or not these included the primary outcome. Hence, the intervention may have been associated with more impairment, disability, dependency, death, or serious adverse events (SAEs). In some cases, data monitoring committees (DMCs) or sponsors stopped trials early for hazard on the basis of interim analysis, in which case the relevant outcome may not still be negative once all final outcomes have been collected. Where trials studied 2 or more doses, hazard was more likely to be present at the highest dose, and the following comments tend to relate to this dose.The negative trials referenced here are those known to the authors through their own libraries of references. 8,9 A formal systematic search was not performed, largely because many authors refer to trials with neutral findings as being negative (ie, not positive), which massively reduces the specificity of any electronic search. The distinction between neutral and negative is important both to explain trial results and to assess potential reasons, and the common verbal and written use of negative to mean not positive should be resisted. Interventions cover drugs, biologics, cells, and devices. The review does not cover the large number of acute stroke RCTs with neutral findings and an explanation for these, but often, neutral findings reflect lack of efficacy or small sample size. No tabulated data or statistical analyses were performed.IMPORTANCE While there are a limited number of beneficial treatments for acute stroke (eg, stroke units, reperfusion, aspirin, hemicraniectomy), there are more negative (as opposed to neutral) interventions spanning multiple different mechanisms of act...

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Effects of Blood Pressure–Lowering Treatment in Different Subtypes of Acute Ischemic Stroke

Cited by 31 publications

References 14 publications

Early Blood Pressure Reduction in Acute Ischemic Stroke with Various Severities: A Subgroup Analysis of the CATIS Trial

Early Blood Pressure Reduction in Acute Ischemic Stroke with Various Severities: A Subgroup Analysis of the CATIS Trial

Hypertension and Stroke: Epidemiological Aspects and Clinical Evaluation

The Hazard of Negative (Not Neutral) Trials on Treatment of Acute Stroke

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