Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest.


BACKGROUND

Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever.

METHODS

In an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale.

RESULTS

In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar.

CONCLUSIONS

In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C.

Source: NEJM

 

CLOTBUST-Hands Free.


Pilot Safety Study of a Novel Operator-Independent Ultrasound Device in Patients With Acute Ischemic Stroke

Background and Purpose—The Combined Lysis of Thrombus in Brain Ischemia With Transcranial Ultrasound and Systemic T-PA-Hands-Free (CLOTBUST-HF) study is a first-in-human, National Institutes of Health–sponsored, multicenter, open-label, pilot safety trial of tissue-type plasminogen activator (tPA) plus a novel operator-independent ultrasound device in patients with ischemic stroke caused by proximal intracranial occlusion.

Methods—All patients received standard-dose intravenous tPA, and shortly after tPA bolus, the CLOTBUST-HF device delivered 2-hour therapeutic exposure to 2-MHz pulsed-wave ultrasound. Primary outcome was occurrence of symptomatic intracerebral hemorrhage. All patients underwent pretreatment and post-treatment transcranial Doppler ultrasound or CT angiography. National Institutes of Health Stroke Scale scores were collected at 2 hours and modified Rankin scale at 90 days.

Results—Summary characteristics of all 20 enrolled patients were 60% men, mean age of 63 (SD=14) years, and median National Institutes of Health Stroke Scale of 15. Sites of pretreatment occlusion were as follows: 14 of 20 (70%) middle cerebral artery, 3 of 20 (15%) terminal internal carotid artery, and 3 of 20 (15%) vertebral artery. The median (interquartile range) time to tPA at the beginning of sonothrombolysis was 22 (13.5–29.0) minutes. All patients tolerated the entire 2 hours of insonation, and none developed symptomatic intracerebral hemorrhage. No serious adverse events were related to the study device. Rates of 2-hour recanalization were as follows: 8 of 20 (40%; 95% confidence interval, 19%–64%) complete and 2 of 20 (10%; 95% confidence interval, 1%–32%) partial. Middle cerebral artery occlusions demonstrated the greatest complete recanalization rate: 8 of 14 (57%; 95% confidence interval, 29%–82%). At 90 days, 5 of 20 (25%, 95% confidence interval, 7%–49) patients had a modified Rankin scale of 0 to 1.

Conclusions—Sonothrombolysis using a novel, operator-independent device, in combination with systemic tPA, seems safe, and recanalization rates warrant evaluation in a phase III efficacy trial.

Source: Stroke

IV thrombolysis and renal function.


Abstract

Objective: To investigate the association of renal impairment on functional outcome and complications in stroke patients treated with IV thrombolysis (IVT).

Methods: In this observational study, we compared the estimated glomerular filtration rate (GFR) with poor 3-month outcome (modified Rankin Scale scores 3–6), death, and symptomatic intracranial hemorrhage (sICH) based on the criteria of the European Cooperative Acute Stroke Study II trial. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Patients without IVT treatment served as a comparison group.

Results: Among 4,780 IVT-treated patients, 1,217 (25.5%) had a low GFR (<60 mL/min/1.73 m2). A GFR decrease by 10 mL/min/1.73 m2 increased the risk of poor outcome (OR [95% CI]): (ORunadjusted 1.20 [1.17–1.24]; ORadjusted 1.05 [1.01–1.09]), death (ORunadjusted 1.33 [1.28–1.38]; ORadjusted 1.18 [1.11–1.249]), and sICH (ORunadjusted 1.15 [1.01–1.22]; ORadjusted 1.11 [1.04–1.20]). Low GFR was independently associated with poor 3-month outcome (ORadjusted 1.32 [1.10–1.58]), death (ORadjusted 1.73 [1.39–2.14]), and sICH (ORadjusted 1.64 [1.21–2.23]) compared with normal GFR (60–120 mL/min/1.73 m2). Low GFR (ORadjusted 1.64 [1.21–2.23]) and stroke severity (ORadjusted 1.05 [1.03–1.07]) independently determined sICH. Compared with patients who did not receive IVT, treatment with IVT in patients with low GFR was associated with poor outcome (ORadjusted 1.79 [1.41–2.25]), and with favorable outcome in those with normal GFR (ORadjusted 0.77 [0.63–0.94]).

Conclusion: Renal function significantly modified outcome and complication rates in IVT-treated stroke patients. Lower GFR might be a better risk indicator for sICH than age. A decrease of GFR by 10 mL/min/1.73 m2 seems to have a similar impact on the risk of death or sICH as a 1-point-higher NIH Stroke Scale score measuring stroke severity.

Rapid Blood-Pressure Lowering in Patients with Acute Intracerebral Hemorrhage.


BACKGROUND

Whether rapid lowering of elevated blood pressure would improve the outcome in patients with intracerebral hemorrhage is not known.

METHODS

We randomly assigned 2839 patients who had had a spontaneous intracerebral hemorrhage within the previous 6 hours and who had elevated systolic blood pressure to receive intensive treatment to lower their blood pressure (with a target systolic level of <140 mm Hg within 1 hour) or guideline-recommended treatment (with a target systolic level of <180 mm Hg) with the use of agents of the physician’s choosing. The primary outcome was death or major disability, which was defined as a score of 3 to 6 on the modified Rankin scale (in which a score of 0 indicates no symptoms, a score of 5 indicates severe disability, and a score of 6 indicates death) at 90 days. A prespecified ordinal analysis of the modified Rankin score was also performed. The rate of serious adverse events was compared between the two groups.

RESULTS

Among the 2794 participants for whom the primary outcome could be determined, 719 of 1382 participants (52.0%) receiving intensive treatment, as compared with 785 of 1412 (55.6%) receiving guideline-recommended treatment, had a primary outcome event (odds ratio with intensive treatment, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P=0.06). The ordinal analysis showed significantly lower modified Rankin scores with intensive treatment (odds ratio for greater disability, 0.87; 95% CI, 0.77 to 1.00; P=0.04). Mortality was 11.9% in the group receiving intensive treatment and 12.0% in the group receiving guideline-recommended treatment. Nonfatal serious adverse events occurred in 23.3% and 23.6% of the patients in the two groups, respectively.

CONCLUSIONS

In patients with intracerebral hemorrhage, intensive lowering of blood pressure did not result in a significant reduction in the rate of the primary outcome of death or severe disability. An ordinal analysis of modified Rankin scores indicated improved functional outcomes with intensive lowering of blood pressure.

Source: NEJM

 

Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial.


Background

Lowering of blood pressure prevents stroke but optimum target levels to prevent recurrent stroke are unknown. We investigated the effects of different blood-pressure targets on the rate of recurrent stroke in patients with recent lacunar stroke.

Methods

In this randomised open-label trial, eligible patients lived in North America, Latin America, and Spain and had recent, MRI-defined symptomatic lacunar infarctions. Patients were recruited between March, 2003, and April, 2011, and randomly assigned, according to a two-by-two multifactorial design, to a systolic-blood-pressure target of 130–149 mm Hg or less than 130 mm Hg. The primary endpoint was reduction in all stroke (including ischaemic strokes and intracranial haemorrhages). Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT 00059306.

Findings

3020 enrolled patients, 1519 in the higher-target group and 1501 in the lower-target group, were followed up for a mean of 3·7 (SD 2·0) years. Mean age was 63 (SD 11) years. After 1 year, mean systolic blood pressure was 138 mm Hg (95% CI 137–139) in the higher-target group and 127 mm Hg (95% CI 126–128) in the lower-target group. Non-significant rate reductions were seen for all stroke (hazard ratio 0·81, 95% CI 0·64–1·03, p=0·08), disabling or fatal stroke (0·81, 0·53–1·23, p=0·32), and the composite outcome of myocardial infarction or vascular death (0·84, 0·68–1·04, p=0·32) with the lower target. The rate of intracerebral haemorrhage was reduced significantly (0·37, 0·15–0·95, p=0·03). Treatment-related serious adverse events were infrequent.

Interpretation

Although the reduction in stroke was not significant, our results support that in patients with recent lacunar stroke, the use of a systolic-blood-pressure target of less than 130 mm Hg is likely to be beneficial.

Funding

National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS)


Introduction

Hypertension is the most relevant and prevalent risk factor for stroke, particularly for stroke associated with cerebral small-vessel disease. Reduction in blood pressure is the most effective intervention to prevent stroke.12 and 3

Small subcortical brain infarcts, commonly known as lacunar strokes, comprise about 25% of ischaemic strokes.4 and 5 Most result from disease of the small penetrating arteries. Despite the frequency and importance of these strokes, randomised trials have not focused on prevention of recurrent stroke in patients with MRI-defined lacunar stroke. Whether there are optimum blood-pressure targets to prevent stroke recurrence in patients with cerebral small-artery disease is unknown.6

In the Secondary Prevention of Small Subcortical Strokes (SPS3) trial we tested two interventions in patients with recent, symptomatic, MRI-confirmed lacunar stroke: two antiplatelet regimens and two target ranges of systolic blood pressure. The results of the antiplatelet component have been published previously.7 We present here the results of the blood-pressure component of the trial, in which we tested the hypothesis that assignment to a lower target range for systolic blood pressure would lessen the rate of stroke recurrence compared with a higher target range.

Methods

Patients

Details of the rationale, study design, and characteristics of the participants in SPS3 have been described elsewhere.8 and 9 Briefly, SPS3 was a randomised, multicentre, clinical trial undertaken in 81 centres in North America, Latin America, and Spain between March, 2003, and April, 2011. Eligible patients were aged 30 years or older, were normotensive or hypertensive, had had a recent (within 180 days), symptomatic, MRI-confirmed lacunar stroke, and were without surgically amenable ipsilateral carotid artery stenosis or high-risk cardioembolic sources. Main exclusion criteria included disabling stroke (modified Rankin score of 4 or higher), previous intracranial haemorrhage from non-traumatic causes, or cortical ischaemic stroke.7 and 8Participation required written informed consent and approval was provided by local ethics committees for human research.

Randomisation and masking

Patients were randomised, according to a two-by-two factorial design, to two blood-pressure-control groups with targets of 130–149 mm Hg or less than 130 mm Hg.10 Treatment was open label. To avoid lowering of blood pressure soon after an acute stroke, participants were randomised at least 2 weeks after the index stroke. Randomisation was stratified by clinical centre and baseline hypertensive status. The schedule was computer generated with a permuted-block design (variable block size). Treatment assignments were stored electronically on the study servers at the SPS3 statistical centre, University of Alabama at Birmingham, AL, USA, as well as locally for each study site on an SPS3-designated computer. Upon patients’ eligibility being established, study coordinators ransomised patients via their data entry systems.

Management of blood pressure

Baseline hypertensive status was determined by measurement of blood pressure taken at two consecutive visits before randomisation. Patients taking medications to control blood pressure were allowed to continue doing so. Blood pressure was measured three times at every visit and the average measurement was used to decide hypertensive status.8910 and 11 Patients were classified as being hypertensive if either or both of the following features were noted: average systolic blood pressure 140 mm Hg or higher or diastolic blood pressure 90 mm Hg or higher on two consecutive visits, and confirmed history of hypertension before the index stroke and taking antihypertensive medication at the time of visit. After randomisation, if patients had blood pressures outside the assigned target range, they were initially seen at least monthly for measurement of blood pressure and adjustment of medications. Patients whose blood pressure was in the relevant range for two consecutive visits were seen every 3 months. If at any point during the study a patient’s systolic blood pressure was outside the assigned target range, he or she was asked to return within 1 month.

All study sites were provided with automated Colin Press-Mate BP-8800C sphygmomanometers (Colin Medical Instruments, San Antonio, TX, USA).11 Blood-pressure management was overseen at each site by a physician with special expertise in blood-pressure control. If systolic blood pressure in patients assigned to the higher-target group (130–149 mm Hg) dropped to below the lower limit of the target range, the protocol required that patients taking antihypertensive medications stop taking them or have the doses reduced, unless prescribed for reasons other than blood pressure control; patients taking no antihypertensive medications continued to be followed up every 3 months. If systolic blood pressure increased to within the target range, patients were managed according to their originally assigned target. If patients or primary-care physicians refused to titrate blood pressure to the assigned target range per protocol, patients were classified as inactive. Patients whose blood pressure could not be kept within the assigned target range for medical reasons or because of intolerable side-effects of antihypertensive drugs after trying different agents were classified as failure to achieve assigned target. All participants were followed up to a common end-of-study date, irrespective of activity status.

Antihypertensive medications were prescribed by the local study physician and supplied via the study formularies. At least one drug from each of the major classes of antihypertensive medications was available. They were obtained and distributed to study centres by the Veterans Administration Cooperative Studies Program Clinical Research Coordinating Center, Drug Distribution Center, Albuquerque, NM, USA.

Statistical analysis

The primary endpoint was reduction in all stroke. Ischaemic stroke was clinically defined as a focal neurological deficit persisting for longer than 24 h, with an absence of haemorrhage confirmed by neuroimaging. Intracranial haemorrhages included intracerebral, subdural or epidural, and subarachnoid locations defined by neuroimaging. Disabling strokes were classified as those with modified Rankin scores of 3 or higher after 3–6 months. Strokes were deemed fatal if death occurred within 30 days or if death after 30 days could be attributed to the stroke. Secondary endpoints were reductions in acute myocardial infarction, defined by standard criteria (compatible clinical history with changes on ECG or in cardiac enzyme concentrations), need for acute admission to hospital for a major vascular event, and death, classified as vascular, non-vascular, or unknown. All reported efficacy outcomes were confirmed by a central adjudication committee that was unaware of treatment assignment. Safety outcomes were serious adverse events related to hypotension and blood-pressure management. The trial was monitored by an independent data and safety monitoring committee selected by the sponsor.

The initial sample size of 2500 patients was calculated assuming an average follow-up of 3 years, an estimated 3-year recurrent stroke rate of 21%, a 25% relative-risk reduction in stroke by intensive control of blood pressure, a type I error of α=0·05, and 90% power. Sample-size estimation was reassessed midway through the trial to check the power of the study on the basis of the observed overall event rate. This assessment resulted in the final sample size being increased from 2500 to 3000 patients.12

We did two prespecified subgroup analyses. The first was in patients who were hypertensive at baseline. Thus, we excluded from this analysis patients who were non-hypertensive at baseline (systolic blood pressure lower than 130 mm Hg without taking antihypertensive medications) and who received no antihypertensive therapy during the study unless blood pressure exceeded the assigned target range during follow-up. The second included data after censoring at 6 months of follow-up. This analysis was undertaken because the maximum separation of the baseline and achieved blood pressures requires an average of 6 months of medication titration. All participants who did not die or withdraw from the study during the first 6 months, irrespective of whether or not they had an event during this time, were included in this subgroup. We also assessed outcomes in various demographic and clinical subgroups.

We did standard time-to-event analyses of the primary endpoint with the log-rank test and used Cox’s proportional hazards models to compute hazard ratios (HRs) and 95% CIs in each treatment group. If multiple events of the same type occurred, time to event was calculated as time to first event. Data for patients with no events were censored at the end of study participation or death, whichever occurred first. The proportional hazards assumption was verified by assessment of the interaction between time and blood-pressure-intervention group, and we used Cox’s models to investigate whether the effect of intervention differed by specific subgroups. Odds ratios and 95% CIs were computed by logistic regression for orthostatic symptoms, as these were measured as whether or not the patient had at least one symptom during the follow-up period All analyses were based on the intention-to-treat principle and were done with SAS (version 9.2). The study is registered with ClinicalTrials.gov, number NCT00059306.

Role of the funding source

The sponsor of the study participated in study design, data collection, data analysis, data interpretation, and writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Results

3020 participants were enrolled from North America (n=1960 [65%]), Latin America (n=694 [23%]), and Spain (n=366 [12%]) and were followed up for a mean of 3·7 (range 0–8·6, SD 2·0) years (appendix p 1). Baseline characteristics did not differ substantially between target groups (table 1). The median time from qualifying stroke to randomisation was 62 days. Blood-pressure therapy was permanently discontinued in similar numbers of patients in the higher-target and lower-target groups (258 [17%] vs 240 [16%]). 90 (3%) participants were lost to follow-up and an additional 465 (15%) ended follow-up early for the following reasons: withdrawn consent (n=242), site closure (n=151), physician request (n=12), and other reasons (n=60).

Table 1. Patients’ characteristics

Higher-target group (n=1519) Lower-target group (n=1501)
Age (years) 63 (10·8) 63 (10·7)
Men 990 (65%) 912 (61%)
Blood pressure at entry (mm Hg)
Systolic 144 (19) 142 (19)
Diastolic 79 (11) 78 (10)
Body-mass index (kg/m2) 29·2 (7·5) 29·0 (6·1)
History of hypertension 1137 (75%) 1127 (75%)
Diabetes mellitus 553 (36%) 553 (37%)
Ischaemic heart disease 173 (11%) 144 (10%)
Previous clinical stroke or TIA 211 (14%) 237 (16%)
Current tobacco smoker 308 (20%) 309 (21%)
Qualifying event
Ischaemic stroke 1506 (99%) 1473 (98%)
TIA 13 (1%) 28 (2%)
Ethnic origin
White 760 (50%) 778 (52%)
Hispanic 468 (31%) 448 (30%)
Black 251 (17%) 241 (16%)
Other 40 (3%) 34 (2%)
Region
North America 987 (65%) 976 (65%)
Latin America 352 (23%) 342 (23%)
Spain 183 (12%) 183 (12%)
Number of antihypertensive medications at study entry 1·7 (1·2) 1·7 (1·2)
Mean number of antihypertensive medications at 1 year* 1·8 (1.4) 2·4 (1.3)
Types of antihypertensive medications at 1 year
Thiazides 576 (43%) 774 (58%)
ACE inhibitor/ARB 835 (63%) 1064 (80%)
Calcium-channel blockers 398 (30%) 571 (43%)
β blockers 333 (25%) 408 (31%)
Other 117 (9%) 146 (11%)
Mean number of antihypertensive medication at last visit 1·8 (1·4) 2·4 (1·4)
Types of antihypertensive medications at last visit§
Thiazides 569 (38%) 804 (54%)
ACE inhibitor/ARB 894 (60%) 1156 (78%)
Calcium-channel blockers 438 (39%) 637 (43%)
β blockers 424 (28%) 521 (35%)
Other 168 (11%) 204 (14%)
Statins used during follow-up 1248 (84%) 1254 (85%)

Data are mean (SD) or number (%). TIA=transient ischaemic attack. ACE=angiotensin-converting enzyme. ARB=antiotensin-II-receptor blocker.

*

Difference between groups p<0·0001.

Difference between groups p<0·0001 for all types, except β blockers (p=0·0008) and other (p=0·051).

Difference between groups p<0·0001.

§

Difference between groups p<0·0001 for all types, except other (p=0·042).

iscussion

Lowering of systolic blood pressure to a target of less than 130 mm Hg in patients with recent lacunar stroke resulted in non-significant reductions in all stroke, disabling or fatal stroke, and major vascular events, and a significant reduction in intracerebral stroke. These effects were associated with few serious side-effects, and were consistent across major subgroups, including patients with diabetes and Hispanic patients, and irrespective of blood pressure at study entry. Exclusion of normotensive patients at entry showed a reduction in the rate of recurrent stroke of 20% in the lower–target group, although this reduction was not significant. Blood-pressure lowering offered a similar effect on stroke recurrence irrespective of stroke subtype.

That lower is better is a general construct for chronic blood-pressure management after stroke, but optimum clinical practice requires that benefits and risks associated with specific targets be defined. The PROGRESS trial2 showed that lowering of blood pressure in stroke survivors was associated with a reduction of 28% in stroke recurrence. The mean achieved systolic blood pressure at the end of the study was 138 mm Hg, but the optimum target for blood-pressure control was not established. Similarly to the ACCORD trial,19 we explored the efficacy and safety of setting systolic-blood-pressure targets lower than 130 mm Hg, but our assessment was extended to patients with MRI-defined lacunar stroke attributed to small-vessel disease.

Our results are best viewed in the context of previous trials of long-term lowering of blood pressure in patients who have had brain ischaemia (table 5figure 4).1, 2, 3, 13, 14, 15, 16, 17 and 20 We tested target blood pressure rather than specific antihypertensive agents and explored effects in patients with well defined ischaemic-stroke subtypes. Although the magnitude of the reduction in rate was not significant, the findings are strongly supported by those of previous trials.1, 2 and 3

The trial protocol was based on the assigned target of systolic blood pressure being achieved and, therefore, we did not require specific antihypertensive agents to be used. Patients assigned to the lower-target group used an average of 2·4 antihypertensive medications and the distribution of medication categories differed from that in the higher-target group (table 1). The mean difference in systolic blood pressure at the end of the trial was 11 mm Hg. On the basis of previous studies, this difference should have resulted in about a 30% reduction in recurrent stroke. The observed reduction of 19% (95% CI −3 to 36), however, was smaller even than the hypothesised 25%. This finding could be due to chance or the specific population of patients assessed.2 and 21 The 95% CI for the 19% reduction does include the hypothesised 25% reduction, but it also spans zero and, therefore, is not significant. The rate of intracerebral haemorrhage was reduced by 63% in the lower-target group, which is consistent with the known sensitivity of this stroke subtype to strict blood-pressure control.14 This result indicates that the number needed to treat to prevent one intracerebral haemorrhage at 4 years (roughly the average follow-up in SPS3) would be 175.

The SPS3 trial had limitations. First, the observed rate of recurrent stroke was much lower than that anticipated. This low rate is similar to that seen in other trials that have assessed prevention of recurrent stroke.22, 23 and 24 It might, therefore, be the result of good blood-pressure control in both treatment groups, the frequent use of statins, and high adherence to antiplatelet therapy. Second, the assignment to blood-pressure targets was not masked, which could have potentially introduced bias. Stroke endpoints were, however, confirmed by a central adjudication committee that was unaware of patients’ group allocations, as is frequently done in large hypertension trials.25 Third, we tested treatment targets and not the effect of specific blood-pressure agents. Finally, some patients did not achieve blood pressures within the target ranges at any point during follow-up (70 [4·6%] in the higher-target group and 74 [4·9%] in the lower-target group). These proportions, however, are similar to those reported in other trials of blood-pressure targets and, therefore, probably reflect the clinical realities of blood-pressure management.19 and 25 An important strength of the SPS3 trial is that blood-pressure lowering was tested in a well defined and homogeneous cohort of stroke patients.

In conclusion, although our results do not show a significant reduction in the rate of recurrent stroke, the findings are congruent with those of previous trials of blood-pressure lowering after stroke and support a treatment target of less than 130 mm Hg systolic blood pressure for most patients with recent lacunar stroke (panel). As our study cohort comprised patients with recent lacunar strokes due mainly to cerebral small-vessel disease, whether our findings are applicable to patients with strokes from other mechanisms warrants additional research.

Panel. Research in context

Systematic review

We searched PubMed and Cochrane Library for randomised clinical trials of secondary stroke prevention with blood-pressure reduction as an intervention, published before April, 2013, in all languages. We used the search terms “blood pressure”, “reduction”, hypertension”, “secondary”, “stroke”, “prevention”, and “clinical trial”. Eight randomised clinical trials2, 13, 14, 15, 16, 17 and 18 and one pooled analysis1 were identified. Aggregate results showed consistently that reduced blood pressure in stroke survivors lessened the risk of stroke recurrence.

Interpretation

We assessed blood-pressure targets in survivors of MRI-defined lacunar stroke. A reduced rate of all stroke was observed in patients with a target systolic blood pressure lower than 130 mm Hg compared with a target of 130–149 mm Hg, but this difference was not significant. The intervention was safe and well tolerated. Interpreted in the context of previous randomised, controlled trials of blood-pressure lowering after stroke, our results suggest that management of systolic to levels lower than 130 mm Hg is likely to reduce the risk of recurrent stroke in patients with recent lacunar stroke.

Source: http://www.sciencedirect.com

 

Rapid Blood-Pressure Lowering in Patients with Acute Intracerebral Hemorrhage..


Whether rapid lowering of elevated blood pressure would improve the outcome in patients with intracerebral hemorrhage is not known. Methods We randomly assigned 2839 patients who had had a spontaneous intracerebral hemorrhage within the previous 6 hours and who had elevated systolic blood pressure to receive intensive treatment to lower their blood pressure (with a target systolic level of <140 mm Hg within 1 hour) or guideline-recommended treatment (with a target systolic level of <180 mm Hg) with the use of agents of the physician`s choosing. The primary outcome was death or major disability, which was defined as a score of 3 to 6 on the modified Rankin scale (in which a score of 0 indicates no symptoms, a score of 5 indicates severe disability, and a score of 6 indicates death) at 90 days. A prespecified ordinal analysis of the modified Rankin score was also performed. The rate of serious adverse events was compared between the two groups. Results Among the 2794 participants for whom the primary outcome could be determined, 719 of 1382 participants (52.0%) receiving intensive treatment, as compared with 785 of 1412 (55.6%) receiving guideline-recommended treatment, had a primary outcome event (odds ratio with intensive treatment, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P=0.06). The ordinal analysis showed significantly lower modified Rankin scores with intensive treatment (odds ratio for greater disability, 0.87; 95% CI, 0.77 to 1.00; P=0.04). Mortality was 11.9% in the group receiving intensive treatment and 12.0% in the group receiving guideline-recommended treatment. Nonfatal serious adverse events occurred in 23.3% and 23.6% of the patients in the two groups, respectively. Conclusions In patients with intracerebral hemorrhage, intensive lowering of blood pressure did not result in a significant reduction in the rate of the primary outcome of death or severe disability. An ordinal analysis of modified Rankin scores indicated improved functional outcomes with intensive lowering of blood pressure.

Source: NEJM

 

 

Impact of global cerebral atrophy on clinical outcome after subarachnoid hemorrhage.


Abstract

OBJECT

Atrophy in specific brain areas correlates with poor neuropsychological outcome after subarachnoid hemorrhage (SAH). Few studies have compared global atrophy in SAH with outcome. The authors examined the relationship between global brain atrophy, clinical factors, and outcome after SAH.

METHODS

This study was a post hoc exploratory analysis of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) trial, a randomized, double-blind, placebo-controlled trial of 413 patients with aneurysmal SAH. Patients with infarctions or areas of encephalomalacia on CT, and those with large clip/coil artifacts, were excluded. The 97 remaining patients underwent CT at baseline and 6 weeks, which was analyzed using voxel-based volumetric measurements. The percentage difference in volume between time points was compared against clinical variables. The relationship with clinical outcome was modeled using univariate and multivariate analysis.

RESULTS

Older age, male sex, and systemic inflammatory response syndrome (SIRS) during intensive care stay were significantly associated with brain atrophy. Greater brain atrophy was significantly associated with poor outcome on the modified Rankin scale (mRS), severity of deficits on the National Institutes of Health Stroke Scale (NIHSS), worse executive functioning, and lower EuroQol Group–5D (EQ-5D) score. Adjusted for confounders, brain atrophy was not significantly associated with Mini-Mental State Examination and Functional Status Examination scores. Brain atrophy was not associated with angiographic vasospasm or delayed ischemic neurological deficit.

CONCLUSIONS

Worse mRS score, NIHSS score, executive functioning, and EQ-5D scores were associated with greater brain atrophy and older age, male sex, and SIRS burden. These data suggest outcome is associated with factors that cause global brain injury independent of focal brain injury.

Source: JNS