Intensive Blood Pressure Reduction In Acute Cerebral Haemorrhage Trial Research Articles

Perihematomal Edema After Spontaneous Intracerebral Hemorrhage.

Perihematomal Edema After Spontaneous Intracerebral Hemorrhage.

Determinants of Early Versus Delayed Neurological Deterioration in Intracerebral Hemorrhage.

Background and Purpose- We investigated factors associated with early and delayed neurological deterioration (END and DND, respectively) after acute spontaneous intracerebral hemorrhage in the main INTERACT (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial)-2. Methods- INTERACT-2 was a randomized trial of early intensive versus guideline-recommended blood pressure lowering in hypertensive intracerebral hemorrhage (<6 hours from symptom onset) patients. END and DND were defined as a ≥4-point increase on the National Institutes of Health Stroke Scale or ≥2-point decrease on Glasgow Coma Scale, in periods baseline to 24 hours and 24 hours to 7 days, respectively. Multivariable logistic regression models were used to determine independent predictors of END and DND and 90-day outcomes (death and dependency on the modified Rankin Scale). Results- Of 2598 participants, 450 (17.3%) had either END or DND. Non-China recruitment, higher systolic blood pressure, larger baseline hematoma volume, left hemisphere hematoma location, intraventricular hemorrhage, subarachnoid extension, heterogeneous hematoma density, and cerebral white matter lesions, were predictors of END (all P≤0.045). Higher systolic blood pressure, lower diastolic blood pressure, higher glucose, larger baseline hematoma volume, intraventricular hemorrhage, lobar location, brain atrophy, and heterogeneous hematoma density were predictors of DND (all P≤0.042). END and DND were both related to death, and death or major disability (modified Rankin Scale scores of 3-6), in adjusted analyses ( P<0.001). Conclusions- Common variables, most directly related to the intracerebral hemorrhage morphology and underlying cerebral features, determine END and DND and their influence on poor outcomes of death and major disability. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT00716079.

Author response: Peak perihemorrhagic edema correlates with functional outcome in intracerebral hemorrhage.

We thank Drs. Lattanzi and Silvestrini for their comments on our article.1 Considering the pathophysiologic aspects, we agree that blood pressure (BP), BP lowering, and BP variability may represent relevant measures regarding perihemorrhagic edema (PHE) evolution. However, a possible association of BP and PHE is unclear in intracerebral hemorrhage (ICH) patients. Sansing et al.,2 nor pooled analysis of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) studies,3 nor data from the Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT)4 showed an independent association of BP values and edema volumes.

The systolic blood pressure sweet spot after intracerebral hemorrhage

Acute spontaneous intracerebral hemorrhage (ICH), the most severely disabling type of stroke, has few proven therapies. The mainstay of care remains acute blood pressure (BP)–lowering treatment, in order to mitigate hematoma expansion, perihematomal edema, and the attendant mass effects, each linked to early neurologic deterioration (END), death, and major disability.1,2 More than 5 randomized clinical trials (RCTs) have proven the safety and support the efficacy of early intensive BP-lowering treatment, as opposed to conservative BP control. These trials include the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 (INTERACT-2) and Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-2) trials, which were recently compared3 and compiled in a large meta-analysis.4 Mounting evidence,1 particularly ad hoc analyses of INTERACT-2,5,6 suggests that the earlier the treatment, the steeper the drop, and the lower the BP achieved, the better the outcome,1,6 halting radiologic or clinical deterioration2 and, more importantly, improving quality of life and shifting toward better functional physical outcome at 3 months.4–6 Furthermore, INTERACT-2 data revealed a dose effect with linear relationship between achieved systolic BP (SBP) and reducing hematoma growth5 and improved functional outcome.6

Author response: Blood pressure reduction and noncontrast CT markers of intracerebral hemorrhage expansion.

We thank Drs. Lattanzi and Silvestrini for their interest in our article.1 Increased blood pressure variability may lead to poor outcome after acute intracerebral hemorrhage (ICH) but a post hoc analysis of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 (INTERACT2) showed that this association was not mediated by an increased risk of ICH growth.2 Hematoma expansion is a very early event in the natural history of ICH and, therefore, we agree that time is a key factor. Ischemic stroke treatment in mobile stroke units reduces the time from symptom onset to treatment.3 Early identification and treatment of patients with ICH at high risk of hematoma growth may become feasible in the prehospital setting using mobile stroke units equipped with noncontrast CT (NCCT). In a previous analysis, we showed that intrahematoma hypodensities, timing of baseline NCCT, and presence of the CT angiography spot sign predicted ICH expansion independently from each other.4 Further studies are needed to investigate whether the integration of different imaging markers provides additional value in the identification of ICH patients at high risk of hemorrhage growth.

William M. Feinberg Award for Excellence in Clinical Stroke: High Explosive Treatment for Ultra-Acute Stroke: Hype of Hope.

Proven treatments for acute stroke can be categorized by target population (ischemic stroke [IS], intracerebral hemorrhage [ICH], or both), utility (proportion of patients who can be treated), magnitude of efficacy, and cost. In general, high-cost interventions need to have high efficacy for health economic reasons; examples include intravenous alteplase, mechanical thrombectomy, and hemicraniectomy. Conversely, low-cost interventions, such as aspirin, typically have low efficacy. Having a medium-to-high efficacy intervention that was inexpensive and could be used worldwide in both IS and ICH would be a major advantage. High blood pressure (BP) is common in acute stroke and associated independently with poor functional outcome, increased death, and early recurrence (IS) and hematoma expansion (ICH).1,2 Although debated since 1985,3 it was only recently demonstrated in the INTERACT-2 (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial-2) trial that intensive BP lowering was beneficial,4 as now promoted in international guidelines.5,6 In contrast, whether BP should be lowered acutely in IS remains unclear.7–9 Nitric oxide (NO) is a diatomic gaseous molecule of nitrogen and oxygen that is highly reactive and short lived. However, it is a fundamental physiological control and defense molecule that may have been used by early organisms as far back as 3 billion years.10 In human physiology, it has vascular regulatory, neurotransmitter, anti-infection, and reproductive roles. NO is synthesized from the amino acid L-arginine by 3 enzymes: endothelial, inducible, and neuronal NO synthase. Many effects of NO are mediated through the second messenger cGMP, which is catalyzed by guanylate cyclase from guanylate triphosphate. cGMP levels may be maintained by phosphodiesterase-5 inhibitors such as dipyridamole. NO is inactivated through oxidation to nitrite then nitrate; this reaction may be reversed and it now appears that NO may be synthesized from nitrate …

Degree and Timing of Intensive Blood Pressure Lowering on Hematoma Growth in Intracerebral Hemorrhage: Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial-2 Results.

Degree and timing of blood pressure (BP) lowering treatment in relation to hematoma growth were investigated in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial-2 (INTERACT2). INTERACT2 was an international clinical trial of intensive (target systolic BP [SBP], <140 mm Hg) versus guideline-recommended (SBP, <180 mm Hg) BP lowering in 2839 patients within 6 hours of spontaneous intracerebral hemorrhage and elevated SBP (150-220 mm Hg), in which 964 had repeat cranial computed tomography at 24 hours. ANCOVA models assessed categories of SBP reduction and time to target SBP on 24-hour hematoma growth. Greater SBP reduction was associated with reduced hematoma growth (13.3, 5.0, and 3.0 mL for <10, 10-20, and ≥20 mm Hg, respectively; P trend<0.001). In the intensive treatment group (n=491), the least mean hematoma growth was in patients who achieved target SBP <1 hour (2.6 mL) versus to those in target at 1 to 6 (4.7 mL) and >6 hours (5.4 mL). The smallest mean absolute hematoma growth (2.0 mL) was in those achieving target SBP 5 to 8 times versus 3 to 4 (3.1 mL) and 0 to 2 times (5.2 mL). Intensive BP lowering with greater SBP reduction, which is achieved quickly and maintained consistently, seems to provide protection against hematoma growth for 24 hours. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00716079.

New Insights into Blood Pressure Control for Intracerebral Haemorrhage.

Although blood pressure (BP) levels may rise in the weeks preceding intracerebral haemorrhage (ICH), in contrast to findings in the ischaemic stroke population, the initial post-ICH BP is often much higher than the last pre-morbid level. Elevated BP is therefore common in acute ICH, often with markedly elevated levels, and is associated with poor outcomes, though the exact pathophysiological mechanisms remain unclear. The Antihypertensive Treatment of Acute Cerebral Haemorrhage (ATACH) trial and the INTEnsive blood pressure Reduction in Acute Cerebral haemorrhage Trial (INTERACT) demonstrated that early and intensive lowering of elevated BP in the acute ICH period is feasible and safe. Importantly, recent CT perfusion studies have shown that early, intense BP reduction does not reduce cerebral blood flow or promote cerebral ischaemia. The recent, large INTERACT2 trial confirmed the safety of early BP lowering in ICH and suggested that intensive target-driven BP reduction may improve outcomes, with a non-significant trend towards reduced death and major disability and a significant favourable shift of scores on the modified Rankin scale compared with guideline-based treatment. BP lowering in acute ICH may reduce haematoma growth, particularly when target levels are achieved early and are sustained, though the evidence is partly conflicting. Other aspects of BP may also be important following acute ICH, with maximum systolic BP and systolic BP variability being independent predictors of poor outcomes in a recent study. This chapter gives an overview of the current evidence regarding BP in ICH and covers the following topics: the incidence of elevated BP in acute ICH and the patterns of BP observed before and after the event; the effect of elevated BP on outcomes in ICH and the potential underlying pathophysiological mechanisms; the safety and feasibility of BP lowering; the effects of BP lowering on clinical and radiological outcomes; other important aspects of BP in ICH; and the choice of antihypertensive agent.

Intensive blood pressure reduction in acute intracerebral hemorrhage: A meta-analysis.

Editors' Note: This week's WriteClick correspondence examines the article “Intensive blood pressure reduction in acute intracerebral hemorrhage: A meta-analysis.” First, authors Tsivgoulis and Katsanos issue an erratum describing their data translocation and provide an updated figure comparing the association with mortality of intensive vs conservative blood pressure lowering. Drs. Behrouz et al. point out that a post hoc analysis of INTERACT II would better confirm the trial's conclusions than a meta-analysis, since the subjects from INTERACT II made up the majority of the meta-analysis's data. The authors respond. The erratum appears on page 2466. —Megan Alcauskas, MD, and Robert C. Griggs, MD Following personal communication with Dr. William Powers, we realized that the 3-month rates of mortality and death/dependency of Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) I in figure 2, A and B, respectively, are reversed.1 This typing mistake happened after transferring the extracted study values from our data sheet to the software program used for this meta-analysis. After correcting this error, we provided a new …

Rapid Blood Pressure Lowering According to Recovery at Different Time Intervals after Acute Intracerebral Hemorrhage: Pooled Analysis of the INTERACT Studies

Background and Purpose: Early intensive blood pressure (BP) lowering has been shown to improve functional outcome in acute intracerebral hemorrhage (ICH), but the treatment effect is modest and without a clearly defined underlying explanatory mechanism. We aimed at more reliably quantifying the benefits of this treatment according to different time periods in the recovery of participants in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) studies. Methods: Pooled analysis of the pilot INTERACT1 (n = 404) and main INTERACT2 (n = 2,839) involving patients with spontaneous ICH (<6 h) and elevated systolic BP (SBP 150-220 mm Hg) who were randomized to intensive (target SBP <140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) BP lowering treatment. Treatment effects were examined according to repeated measures analysis of an ordinal (‘shift') across all 7 levels of the modified Rankin Scale (mRS) assessed during follow-up at 7, 28, and 90 days, post-randomization. Clinical trial registration information: http://www.clinicaltrials.gov, NCT00226096 and NCT00716079. Results: Intensive BP lowering resulted in a significant favorable distribution of mRS scores for better functioning (odds ratio 1.13, 95% confidence interval 1.00-1.26; p = 0.042) over 7, 28 and 90 days, and the effect was consistency for early (7-28 days) and later (28-90 days) time periods (p homogeneity 0.353). Treatment effects were also consistent across several pre-specified patient characteristic subgroups, with trends favoring those randomized early, and with higher SBP and milder neurological severity at baseline. Conclusions: Intensive BP lowering provides beneficial effects on physical functioning that manifests consistently through the early and later phases of recovery from ICH.

Prognostic significance of perihematomal edema in acute intracerebral hemorrhage: pooled analysis from the intensive blood pressure reduction in acute cerebral hemorrhage trial studies.

Controversy exists over the prognostic significance of perihematomal edema (PHE) in intracerebral hemorrhage. We aimed to determine the association of early PHE and clinical outcome among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) studies. Pooled analyses of computed tomographic substudies in the pilot phase (INTERACT1) and main phase (INTERACT2), both international, prospective, open, blinded end point, randomized controlled trials, of patients with spontaneous intracerebral hemorrhage (<6 hours) and elevated systolic blood pressure, randomly assigned to intensive (target systolic blood pressure, <140 mm Hg) or guideline-based (systolic blood pressure, <180 mm Hg) blood-pressure management. Substudy participants (n=1310; 346 INTERACT1, 964 INTERACT2) had blinded central analyses of digital images from standardized baseline and 24-hour computed tomography. Predictors of death or dependency (modified Rankin scale scores, ≥3) at 90 days were assessed in logistic regression models and reported with odds ratios and 95% confidence intervals. INTERACT studies are registered at ClinicalTrials.gov (NCT00226096 and NCT00716079). Of 1138 (87%) patients with 2 CTs available for edema analysis and outcome information, time from intracerebral hemorrhage onset to baseline computed tomography, baseline hematoma volume, 24-hour hematoma growth, and intraventricular extension were independent predictors of 24-hour PHE growth. Absolute growth in PHE volume was significantly associated with death or dependency (adjusted odds ratio, 1.17; 95% confidence interval, 1.02-1.33 per 5 mL increase from baseline; P=0.025) at 90 days after adjustment for demographic, clinical, and hematoma parameter prognostic factors. Associations were consistent across various sensitivity analyses. PHE growth is an independent prognostic factor in intracerebral hemorrhage. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00226096 and NCT00716079.

The speed of ultraearly hematoma growth in acute intracerebral hemorrhage.

The prognostic importance of the speed of early hematoma growth in acute intracerebral hemorrhage (ICH) has not been well established. We aimed to determine the association between the rate of increase in hematoma volume and major clinical outcomes in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) studies. The effects of early intensive blood pressure (BP) lowering according to the speed of hematoma growth were also investigated. Pooled analyses of the INTERACT1 (n = 404) and INTERACT2 (n = 2,839) studies-randomized controlled trials of patients with spontaneous ICH with elevated systolic BP, randomly assigned to intensive (target systolic BP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. The speed of ultraearly hematoma growth (UHG) was defined as hematoma volume (mL)/onset-to-CT time (hours). Primary outcome was death or major disability (modified Rankin Scale score of 3-6) at 90 days. Among a total of 2,909 patients (90%) with information on UHG and outcome, median speed of UHG was 6.2 mL/h. There was a linear association between UHG and outcome: multivariable-adjusted odd ratios 1.90 (95% confidence interval 1.50-2.39) for 5-10 mL/h and 2.96 (2.36-3.71) for >10 mL/h vs the <5 mL/h group. There were no clear differences in the effects of intensive BP lowering according to 3 speeds of UHG on outcome (p = 0.75 for homogeneity). The speed of UHG in patients with ICH was continuously associated with increased risks of death or major disability, and from lower levels than previously reported (≥5 mL/h). The benefits of intensive BP lowering appear to be independent of the speed of bleeding.

Blood pressure variability on antihypertensive therapy in acute intracerebral hemorrhage: the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-intracerebral hemorrhage study.

The associations between early blood pressure (BP) variability and clinical outcomes in patients with intracerebral hemorrhage after antihypertensive therapy, recently clarified by a post hoc analysis of Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 (INTERACT2), were confirmed using the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-intracerebral hemorrhage study cohort. Patients with hyperacute (<3 hours from onset) intracerebral hemorrhage with initial systolic BP (SBP) >180 mm Hg were registered in a prospective, multicenter, observational study. All patients received antihypertensive therapy based on a predefined standardized protocol to lower and maintain SBP between 120 and 160 mm Hg using intravenous nicardipine. BPs were measured hourly during the initial 24 hours. BP variability was determined as SD and successive variation. The associations between BP variability and hematoma expansion (>33%), neurological deterioration within 72 hours, and unfavorable outcome (modified Rankin Scale, 4-6) at 3 months were assessed. Of the 205 patients, 33 (16%) showed hematoma expansion, 14 (7%) showed neurological deterioration, and 81 (39%) had unfavorable outcomes. The SD and successive variation of SBP were 13.8 (interquartile range, 11.5-16.8) and 14.9 (11.7-17.7) mm Hg, respectively, and those of diastolic BP were 9.4 (7.5-11.2) and 13.1 (11.2-15.9) mm Hg, respectively. On multivariate regression analyses, neurological deterioration was associated with the SD of SBP (odds ratio, 2.75; 95% confidence interval, 1.45-6.12 per quartile) and the successive variation of SBP (2.37; 1.32-4.83), and unfavorable outcome was associated with successive variation of SBP (1.42; 1.04-1.97). Hematoma expansion was not associated with any BP variability. SBP variability during the initial 24 hours of acute intracerebral hemorrhage was independently associated with neurological deterioration and unfavorable outcomes. Stability of antihypertensive therapy may improve clinical outcomes.

Blood Pressure Lowering and Acute Perihematomal Brain Edema After Intracerebral Hemorrhage

See related article, p 1292. Intracerebral hemorrhage (ICH) is a common and often fatal subtype of stroke that produces severe neurological deficits in survivors.1 There are still no proven therapeutic interventions for ICH, but there has been much interest in the potential use of acutely reducing blood pressure to limit hematoma expansion. A key factor affecting ICH outcome is hematoma size, and hematoma expansion occurs in about one third of patients with ICH.2 This has led to 3 clinical trials: Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT), Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH), and The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT).3–5 INTERACT 2 reported last year6 and suggested an improvement in outcome although this did not reach statistical significance. Understanding the importance of those results requires determination of whether acute blood pressure reductions may have detrimental and beneficial effects in patients with ICH. In this …

Is BP Lowering During Acute Intracerebral Hemorrhage Safe?

One of the most devastating consequences of hypertension is stroke resulting from brain hemorrhage. These acute situations generate some of the highest blood pressure (BP) readings. Despite impressive levels of BP, we are often reluctant to treat these patients with BPlowering drugs for three reasons. First is the concern that the area around the hemorrhage, called the penumbra, is in jeopardy of ischemia, and BP reduction might tip it more towards ischemia and extend the consequences of the stroke. Second, thrombolytic therapy, which requires a systolic BP <185 mm Hg to be given safely, is not an issue since that would worsen this presentation. Finally, there simply wasn’t evidence to demonstrate benefit in this situation until recently, when the pilot study Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT), which assessed the effectiveness of early intensive BP-lowering targeting lower systolic BP (SBP) levels of <140 mm Hg in patients with acute intracerebral hemorrhage (ICH), showed less growth in the size of the brain hematoma at 72 hours in patients assigned to a lower (<140 mm Hg) compared with a higher (<180 mm Hg) in-hospital BP goal. Building on this original study, the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 (INTERACT2) was recently conducted. INTERACT2 was a large multicenter international prospective randomized open treatment trial. Patients with spontaneous acute ICH within the previous 6 hours were randomized to receive either intensive treatment to lower BP to a target SBP of <140 mm Hg within 1 hour vs guideline-recommended treatment of SBP <180 mm Hg. The BP level was maintained for the next 7 days after randomization. The agents used to lower BP were left to the discretion of the treating physician. The main outcome at 90 days was death or major disability using a Rankin scale, where a score of 0 indicates no symptoms/disabilities, 5 indicates severe disability, and 6 indicates death. A prespecified ordinal analysis of a modified Rankin score was also performed. The analysis showed a 13% improvement in the modified Rankin score with intensive treatment (odds ratio for greater disability, 0.87; 95% confidence interval, 0.77–1.00; P=.04). Rate of 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. Episodes of severe hypotension were similar in both groups and occurred in <1% of participants. The difference in hematoma growth between groups was not significant. What this says to us is that (1) it appears to be safe to lower the systolic BP within about 6 hours of an ICH, and (2) there may be a small benefit to doing so in terms of symptoms and disabilities following stroke, bearing in mind that many (two thirds) of the participants were Chinese and that the main drug used was urapidil (an a1 adrenoceptor and serotonin blocker), which is not available in the United States. It will be important to frame INTERACT2 findings in the light of the ongoing trial being conducted in the United States—Antihypertensive Treatment of Acute Cerebral Hemorrhage Trial II (ATACH)—which will compare treating the SBP to <140 mm Hg vs <180 mm Hg in patients with acute ICH using nicardipine as the agent of choice to lower BP. Some patience will be needed as the results are expected in 2016. In the meantime, there is some encouragement that managing high systolic pressures in the presence of an acute brain hemorrhage does not cause harm and may have some benefit.

INTERACT-2

Blood pressure (BP) lowering after spontaneous intracerebral hemorrhage (ICH) is intuitively attractive as a means to prevent continued bleeding or perihematomal edema. Concerns about potential reduction of cerebral perfusion pressure with concomitant risk of ischemia, particularly among patients with a recalibrated autoregulatory curve as a consequence of chronic hypertension, were largely mitigated by imaging studies that found no significant reduction of cerebral blood flow in the face of pharmacological BP lowering,1–3 and the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) pilot study.4 The INTERACT investigators have now formally put the concept to test and have shown that if there is a clinical effect of BP lowering, it is fairly muted and smaller than anticipated. Of 2794 patients with spontaneous ICH, the relative risk for poor outcome was 0.94 (0.87–1.002), P =0.063, in the intensive BP-lowering group (to target systolic pressure ≤140 mm Hg) compared with the control guideline group aiming for systolic pressure ≤180 mm Hg. Various permutations of modified Rankin Scale dichotomization were also nonsignificant when adjusted for baseline factors. The Rankin shift analysis using ordinal logistic regression was marginally significant in favor of the intensive BP-lowering group ( P =0.04). Importantly, no differences in mortality and major safety …

Stroke Progress Review Group

The Stroke Progress Review Group (PRG) was formed in 2001 to produce research recommendations to the National Institute of Neurological Disorders and Stroke (NINDS) for the next 10 years. The PRG produced a progress report in 2006, and a final report in 2012. The PRG process used expert study groups covering 16 areas of research. Each group was tasked to summarize progress in their field and then come up with research priorities. The proceedings were published in the journal Stroke and online.1,2 For planning the next decade, NINDS has reconfigured the PRG process with the intention of identifying a narrowed focus on the most critically important priorities, and obtaining more input from the wider community of healthcare workers involved with stroke and from the public using a dedicated web page: http://www.ninds.nih.gov/strokerfi Eventually, work-groups will be configured on stroke treatment, stroke prevention, and stroke recovery with the intention to narrow down priorities to 2 to 3 per area. I will describe progress on the basis of current decision to of NINDS to divide the field into 3 broad topics: acute stroke treatment, stroke prevention, and stroke repair/recovery/rehabilitation. Other aspects of stroke research that were considered priorities by the PRG between 2001 and 2012 will be covered in a fourth category (Other). ### Acute Stroke Treatment 1. Improve reperfusion therapy: the first priority in the area of acute stroke treatment that was identified in the reports of 2001, 2006, and 2012 was to improve reperfusion therapy. The following is a list of research progress in this area: 1. Enhanced thrombolysis—randomized trials: Study of Tenecteplase in Acute Ischemic Stroke (TNK), Ancrod, …

Stroke: Highlights of Selected Articles

<i>Stroke:</i> Highlights of Selected Articles

Targeting hematoma expansion in ICH

> And the greatest artist of ancient Greece would be determined in a contest between Zeuxis and Parrhasius. Zeuxis painted grapes so naturalistically that birds flew to peck at them. Victory seeming to be Zeuxis', he called on Parrhasius to draw back the curtain concealing his drawing. Only, the curtain was the painting itself! Zeuxis yielded the prize: he had deceived the birds, but Parrhasius had deceived him. > > — Plinii, Naturalis Historiae Several variables are associated with poor outcome and mortality after intracerebral hemorrhage (ICH).1 Among modifiable factors, hematoma expansion may have a predominant role, and has been the target of recent therapeutic trials in ICH. The Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) and Antihypertensive Treatment of Acute Cerebral Hemorrhage Study (ATACH-1) showed that intensive blood pressure (BP) lowering is associated with reduced hematoma expansion during the first 24 hours of …

Earlier Blood Pressure-Lowering and Greater Attenuation of Hematoma Growth in Acute Intracerebral Hemorrhage

The INTEnsive blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT) pilot study showed that early intensive blood pressure-lowering can attenuate hematoma growth in acute intracerebral hemorrhage. The present analysis aimed to determine the treatment effects on hematoma growth by time from intracerebral hemorrhage onset to randomization. Patients (N=404) with acute intracerebral hemorrhage and elevated systolic blood pressure were randomly assigned to intensive or guideline-based blood pressure management. Baseline and repeat CT (24 and 72 hours) were performed and changes in hematoma volume were assessed using generalized estimating equations. Among 296 patients with all 3 CT scans available for analysis, reductions in proportional hematoma growth produced by randomized intensive blood pressure-lowering treatment over 72 hours decreased progressively with delays in initiation of study treatment: 22%, 17%, 9%, and 3% for quartile groups defined by time from onset to randomization of <2.9, 2.9 to 3.6, 3.7 to 4.8, and ≥4.9 hours, respectively (P trend=0.001). There were also smaller absolute reductions in hematoma growth with delays in initiation of study treatment (6.5 mL, 3.3 mL, 0.9 mL, and 0.6 mL), although the trend did not reach statistical significance (P trend=0.12). Earlier initiation of intensive blood pressure-lowering treatment is likely to provide greater protection against hematoma growth in acute intracerebral hemorrhage. http://www.clinicaltrials.gov, NCT002226096.