Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage: a randomised controlled clinical trial.

BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone. METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed. FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment. INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.

Advances in Prehospital Management of Intracerebral Hemorrhage.

BACKGROUND: Spontaneous acute intracerebral hemorrhage (ICH) is associated with greater stroke-related disability and mortality. Hematoma expansion (HME), an important treatment target in acute ICH, is time-dependent, with a greater probability of hematoma growth occurring <3 hours from ICH onset. SUMMARY: Promising treatment options to reduce HME include early intensive blood pressure (BP) reduction and the administration of hemostatic or anticoagulant reversal agents, yet large phase III clinical trials have so far failed to show overwhelming benefit for these interventions in acute ICH. Post-hoc analyses provide evidence, however, that the therapeutic benefit of such treatments is enhanced by rapid and ultra-early intervention, likely driven in large part by attenuation of early HME. Clinical trials assessing ultra-rapid treatments (<2 hours from ICH onset), including study procedures in the ambulance setting are currently underway, and demonstrate that the prehospital phase is a critical window for ICH management and an indispensable area of ICH research. Mobile stroke units, specialized ambulances equipped with imaging capabilities can provide confirmatory diagnosis and expedite treatments, as in acute ischemic stroke. Nevertheless, multiple barriers (financial, organisational, geographical among others) hinder worldwide implementation. Emerging portable technologies as well as point-of-care measures of blood biomarkers show promise as feasible adjunct tools to discriminate ICH from AIS in the field and have the potential for widespread accessibility. KEY MESSAGES: Ultra-early interventions in acute ICH are likely necessary to mitigate the risk of HME, and as such, the prehospital setting is ideal to initiate time-sensitive ICH therapies. As such, reliable prehospital acute ICH detection is essential to provide disease-specific treatments. Overall, it is imperative that "Time is brain" become the mantra not only for ischemic stroke but for ICH as well, and that the promise of ultra-early therapies for ICH be translated into concrete benefits for patients with this devastating condition.

Characteristics of Ischemic Stroke Despite Oral Anticoagulant Use For Atrial Fibrillation.

Oral anticoagulation (OAC) prevents stroke in atrial fibrillation, yet a residual stroke risk remains. In this single-center retrospective analysis of acute ischemic stroke patients despite OAC, suboptimal OAC treatment is common (30%: inappropriate dosing (17%); patient non-adherence (13%)). Other causes of stroke included OAC interruption (14.5%), a competing stroke mechanism (11.0%), and undetermined breakthrough stroke in 44.5%. Overall, easily modifiable causes of ischemic stroke despite OAC are common. Accordingly, strategies to improve treatment compliance, including appropriate dosing along with guideline-based risk factor and periprocedural OAC management, should be emphasized to improve secondary stroke prevention in this patient population.

Successful thrombectomy is beneficial in patients with pre-stroke disability: Results from an international multicenter cohort study.

BACKGROUND: Patients with pre-stroke disability, defined as a modified Rankin Scale (mRS) ≥3, were excluded from most trials of endovascular thrombectomy (EVT) for acute stroke. We sought to evaluate the prognostic factors associated with favorable outcome in stroke patients with known disability undergoing EVT, and the impact of successful reperfusion. METHODS: Consecutive acute stroke patients with pre-stroke disability, undergoing EVT, were retrospectively collected between 2016 to 2019 from a Canadian cohort and a multicenter French cohort (Endovascular Treatment in Ischemic Stroke registry-ETIS). Favorable outcome was defined as an mRS equal to pre-stroke mRS. Patients achieving successful reperfusion (defined as a modified Thrombolysis in Cerebral Infarction score of 2b/3) were compared with patients without successful reperfusion to determine if successful EVT was associated with better functional outcomes. RESULTS: Among 6220 patients treated with EVT, 280 (4.5%) patients with a pre-stroke mRS ≥3 were included. Sixty-one patients (21.8%) had a favorable outcome and 146 (52.1%) died at 3 months. Patients with successful reperfusion had a higher proportion of favorable 90-day mRS (27.6% versus 19.6%, p = 0.025) and a lower mortality (48.3% versus 69.6%, p = 0.008) than patients without successful reperfusion. After adjusting for baseline prognostic factors, successful reperfusion defined by TICI ≥2b was associated with favorable functional outcome (OR 3.16 CI95% [1.11-11.5]; p 0.048). CONCLUSION: In patients with pre-stroke disability, successful reperfusion is associated with a greater proportion of favorable outcome and lower mortality.

Predictors of Outcome After Mechanical Thrombectomy in Stroke Patients Aged ≥85 Years.

BACKGROUND: The effectiveness of mechanical thrombectomy (MT) in elderly stroke patients remains debated. We aimed to describe outcomes and their predictors in a cohort of patients aged ≥ 85 years treated with MT. METHODS: Data from consecutive patients aged ≥ 85 years undergoing MT at two stroke centers between January 2016 and November 2019 were reviewed. Admission National Institutes of Health Stroke Scale (NIHSS), pre-stroke, and 3-month modified Rankin scale (mRS) were collected. Successful recanalization was defined as modified thrombolysis in cerebral ischemia score ≥ 2b. Good outcome was defined as mRS 0-3 or equal to pre-stroke mRS at 3 months. RESULTS: Of 151 included patients, successful recanalization was achieved in 74.2%. At 3 months, 44.7% of patients had a good outcome and 39% had died. Any intracranial hemorrhage (ICH) and symptomatic ICH occurred in 20.3% and 3.6%, respectively. Logistic regression analysis identified lower pre-stroke mRS score (adjusted odds ratio [aOR], 0.52; 95% CI, 0.36-0.76), lower admission NIHSS score (aOR, 0.90; 95% CI, 0.83-0.97), successful recanalization (aOR, 3.65; 95% CI, 1.32-10.09), and absence of ICH on follow-up imaging (aOR, 0.42; 95% CI, 0.08-0.75), to be independent predictors of good outcome. Patients with successful recanalization had a higher proportion of good outcome (45.3% vs 34.3%, p = 0.013) and lower mortality at 3 months (35.8% vs 48.6%, p = 0.006) compared to patients with unsuccessful recanalization. CONCLUSIONS: Among patients aged ≥ 85 years, successful recanalization with MT is relatively common and associated with better 3-month outcome and lower mortality than failed recanalization. Attempting to achieve recanalization in elderly patients using MT appears reasonable.

Prospective Evaluation of a Two-Scale Protocol for Prehospital Large Vessel Occlusion Detection.

Background and purposes: Stroke severity scales may expedite prehospital large vessel occlusion (LVO) stroke detection, but few are validated for paramedic use. We evaluated the feasibility of introducing the Cincinnati Stroke Triage Assessment Tool (C-STAT) in the field and its capacity to detect LVO stroke.Methods: We performed a prospective paramedic-based study assessing C-STAT in the field on patients currently redirected to two comprehensive stroke centers (CSC), based on a Cincinnati Prehospital Stroke Scale (CPSS) score of 3/3. C-STAT was administered by on-site paramedics with telephone guidance from trained centralized clinical support paramedics.Results: Between October 2018 and November 2019, C-STAT scores were obtained in 188/218 (86.2%) patients, among which 118/188 (62.8%) were positive. Paramedics reported performing the C-STAT in less than 5 minutes on 170/188 (90.4%) patients and noted no difficulties administering the scale in 151/188 (80.3%). A positive C-STAT identified 51/68 (75%) LVO strokes in the cohort, demonstrating a 43% (95% CI: 38%-48%) positive and 76% (95% CI: 66%-83%) negative predictive value for LVO stroke diagnosis. In a cohort of 100 patients with CPSS 3/3, requiring a positive C-STAT for redirection would decrease CSC patient volume by 37 but miss 9 of 36 LVO strokes.Conclusion: Prehospital administration of the C-STAT was feasible, using a model of minimal paramedic training and real-time telephone guidance. A protocol based on both a CPSS 3/3 and a positive C-STAT would decrease CSC redirected patient volume by one-third but would miss one-quarter of LVO strokes when compared to a CPSS-based protocol.

Early Impact of the COVID-19 Pandemic on Acute Stroke Treatment Delays.

This is an observational cohort study comparing 156 patients evaluated for acute stroke between March 30 and May 31, 2020 at a comprehensive stroke center with 138 patients evaluated during the corresponding time period in 2019. During the pandemic, the proportion of COVID-19 positive patients was low (3%), the time from symptom onset to hospital presentation was significantly longer, and a smaller proportion of patients underwent reperfusion therapy. Among patients directly evaluated at our institution, door-to-needle and door-to-recanalization metrics were significantly longer. Our findings support concerns that the current pandemic may have a negative impact on the management of acute stroke.

Streamlined Poststroke Treatment Order Sets During the SARS-CoV-2 Pandemic: Simplifying While Not Compromising Care.

BACKGROUND AND PURPOSE: Standard poststroke treatment monitoring protocols are made problematic during the coronavirus disease 2019 (COVID-19) pandemic by the frequency of patient assessments, requiring repeated donning and doffing procedures in a short interval of time. METHODS: A streamlined poststroke treatment protocol was developed to limit frequency of patient encounters while maximizing the yield of each encounter by grouping together different components of poststroke care into single bedside visits. RESULTS: Streamlined order sets were developed late March 2020. During the first 6 weeks following implementation, 70 patients were admitted to a geographically defined designated warm COVID-19 unit with modified poststroke care order sets. Of these, 33 (47.1%) patients received acute reperfusion therapy. All but 3 patients evolved favorably with either stable or improving National Institutes of Health Stroke Scale at 24 hours. In the 3 patients who experienced early neurological deterioration, none were found to be attributable to insufficient patient monitoring. CONCLUSIONS: Adapting preexisting poststroke care protocols may be necessary while the risk of COVID-19 infection remains high. We propose a streamlined approach to facilitate poststroke monitoring in patients with stroke with unknown COVID status.

Non-Contrast CT and CT-Angiogram for Late Window Ischemic Stroke Treatment Selection.

INTRODUCTION: The benefit of late window endovascular treatment (EVT) for anterior circulation ischemic stroke has been demonstrated using perfusion-based neuroimaging. We evaluated whether non-contrast CT (NCCT) and CT-angiogram (CTA) alone can select late-presenting patients for EVT. METHODS: We performed a retrospective comparison of all patients undergoing EVT at a single comprehensive stroke center from January 2016 to April 2017. Patients planned for EVT were divided into early (<6 hours from onset) and late (≥6 hours from onset or last time seen normal) window groups. Incidence of symptomatic hemorrhagic transformations (sHTs) at 24 hours and 3-month modified Rankin scores (mRSs) were compared. RESULTS: During the study period, 204 (82%) patients underwent EVT in the early and 44 (18%) in the late window. Median (interquartile range) NIH Stroke Scale Score was similar between groups (early: 18 [15-23] vs. late: 17 [13-21]), as were median ASPECT scores (early: 9 [8-10] vs. late: 9 [7-9]). In the late window, 42 (95%) strokes were of unknown onset. Similar proportions of sHT occurred at 24 hours (early: 12 [6%] vs. late: 4 [9%], p = 0.43). At 3 months, the proportion of patients achieving functional independence (mRS 0-2) were comparable in the early (80/192 [42%]) and late (16/41 [39%]) windows (p = 0.76). CONCLUSION: NCCT- and CTA-based patient selection led to similar functional independence outcomes and low proportions of sHT in the early and late windows. In centers without access to perfusion-based neuroimaging, this pragmatic approach could be safe, particularly for strokes of unknown onset.

A randomized pilot study of patients with tandem carotid lesions undergoing thrombectomy.

BACKGROUND AND PURPOSE: The optimal management of patients with tandem lesions (TL), or cervical internal carotid artery (c-ICA) steno-occlusive pathology and ipsilateral intracranial occlusion, who are undergoing endovascular thrombectomy (EVT) remains unknown. We sought to establish the feasibility of a trial designed to address this question. MATERIALS AND METHODS: The Endovascular Acute Stroke Intervention (EASI) study was a single-centre randomized trial comparing EVT to medical therapy for large-vessel occlusion stroke. Patients with TL receiving EVT were randomly allocated to acute c-ICA stenting or no stenting. The primary outcome was the proportion of patients with a modified Rankin Scale (mRS) score of 0-2 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage (sICH) at 24hours and mortality at 90 days. RESULTS: Of 301 patients included in EASI between 2013 and 2018, 24 (8.0%) with TL were randomly allocated to acute stenting (n=13) or no stenting (n=11). Baseline characteristics were balanced. Eight (61.5%; 95% CI 35.5%-82.3%) and 7 (63.6%; 95% CI 35.4%-84.9%) patients, respectively, had a favorable outcome (mRS 0-2; P=1.0). One non-stented patient had a symptomatic intracerebral hemorrhage. CONCLUSIONS: This pilot trial of patients with TL undergoing EVT suggests that a sufficiently powered larger TL trial comparing acute c-ICA stenting to no stenting is feasible. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02157532.

Lack of Consensus Among Stroke Experts on the Optimal Management of Patients With Acute Tandem Occlusion.

Background and Purpose- In patients with acute stroke caused by tandem occlusion, the benefit of immediate revascularization (stenting) of the cervical internal carotid artery lesion during endovascular thrombectomy is uncertain. We sought to determine current practice patterns and whether consensus existed among physicians with stroke expertise. Methods- We distributed an online survey to stroke experts affiliated with the Canadian Stroke Consortium, the Canadian Interventional Neuro Group, the Society of Vascular and Interventional Neurology, and international ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times) collaborators. Questions were based on clinical scenarios, and multiple choice responses across a Likert-type scale were provided. The survey was sent out in September 2017. After 2 months, data were extracted and then analyzed using descriptive statistics. Results- Responses from 162 stroke experts were analyzed; most were stroke physicians (n=65, 40.1%) and neurointerventionalists (n=74, 45.7%), from Canada (n=95, 58.6%), the United States (n=42, 25.9%), and other countries (n=25, 15.4%). Over half (n=96, 59.3%) of respondents consider acute stenting of the cervical internal carotid artery as a treatment option, whereas 40.7% (n=66) would never use it. Most respondents (n=113, 69.8%) agree that there exists uncertainty about the optimal acute management of patients with tandem occlusion. A majority (n=88, 54.3%) of physicians surveyed would include patients in a randomized trial addressing this question. Conclusions- This survey shows high variability in practice about acute management of tandem occlusion. The existence of community equipoise underscores the importance of a randomized trial evaluating the benefit of acute internal carotid artery stenting in patients with tandem occlusion undergoing endovascular thrombectomy.

Cincinnati Prehospital Stroke Scale for EMS Redirection of Large Vessel Occlusion Stroke.

INTRODUCTION: Prehospital identification of large vessel occlusion (LVO) stroke may expedite treatment by direct transport to comprehensive stroke centers (CSCs) with endovascular capabilities. The Cincinnati Prehospital Stroke Scale (CPSS) is commonly used for prehospital stroke detection. We aimed to assess whether (1) a high CPSS score can identify LVO and (2) an Emergency Medical Service (EMS) redirection protocol based on high CPSS accelerated endovascular treatment (EVT). METHODS: A retrospective comparison of patients transported by EMSs for suspected stroke to a high-volume CSC over a 16-month period, before and after implementation of an EMS redirection protocol based on high CPSS score (3/3). Charts were reviewed to determine the presence of LVO. Time to EVT and 3-month outcomes were compared before and after implementation. RESULTS: A prehospital CPSS 3/3 score was found in 223 (59%) patients, demonstrating positive and negative predictive values for LVO of 29% and 94%, respectively. CPSS-based EMS redirection increased the proportion of EVT performed after direct transport to CSC [before: 21 (36%), after: 45 (63%), p < 0.01] and decreased median first door-to-groin puncture time by 28 minutes [109 (interquartile range (IQR) 64-116) versus 81 (IQR 56-130), p = 0.03]. At 3 months, the proportion of patients achieving functional independence (modified Rankin score 0-2) went from 20/57 (35%) to 29/68 (43%) (p = 0.39) following implementation. CONCLUSIONS: CPSS-based EMS redirection accelerated identification of LVO strokes in the out-of-hospital setting and decreased time to EVT. Nevertheless, this protocol was also associated with high rates of non-LVO stroke. Impact on clinical outcomes should be evaluated in a larger cohort.

Utilité de l'échelle de Cincinnati pour la redirection des occlusions artérielles cérébrales proximales par les services médicaux d'urgence. Introduction : Dans un contexte pré-hospitalier, le fait de pouvoir identifier l'occlusion de vaisseaux sanguins cérébraux proximaux peut accélérer l'amorce d'un traitement en favorisant un transfert direct vers un centre complet de prise en charge des AVC (comprehensive stroke centers) doté de moyens d'intervention endovasculaire. L'échelle de Cincinnati (Cincinnati Prehospital Stroke Scale ou CPSS) est couramment utilisée afin de détecter les signes d'un AVC dans un contexte pré-hospitalier. Notre intention est double ici : 1) évaluer dans quelle mesure un score élevé à la CPSS peut permettre d'identifier l'occlusion de vaisseaux sanguins cérébraux proximaux ; 2) évaluer dans quelle mesure un protocole des services médicaux d'urgence consistant à rediriger des patients en fonction d'un score élevé à la CPSS a permis d'accélérer l'offre d'un traitement endovasculaire. Méthodes : Au cours d'une période de 16 mois, soit avant et après la mise sur pied de ce protocole en fonction d'un score élevé à la CPSS (3/3), nous avons effectué une comparaison rétrospective des dossiers de patients transportés vers des centres complets de prise en charge des AVC en raison de soupçons d'AVC. Ces dossiers ont été analysés afin de pouvoir identifier les cas d'occlusion proximales. Enfin, les délais permettant d'obtenir un traitement endovasculaire et l'évolution de l'état de santé des patients au bout de 3 mois ont été comparés avant et après la mise sur pied de ce protocole. Résultats : En fonction d'un score de 3/3 à la CPSS obtenu en contexte pré-hospitalier a été observé chez 223 patients (59 %), la valeur prédictive positive et négative pour des cas d'occlusion de vaisseaux sanguins cérébraux proximaux étant respectivement de 29 % et de 94 %. Le fait que les services médicaux d'urgence redirigent des patients en fonction d'un certain score à la CPSS a fini par augmenter le nombre de traitements endovasculaires prodigués à la suite d'un transfert direct vers un centre complet de prise en charge des AVC (avant le protocole : 21 (36 %) ; après le protocole : 45 (63 %) ; p < 0,01) et par diminuer de 28 minutes les délais entre la prise en charge à l'arrivée et la ponction artérielle (109 [intervalle interquartile de 64-116] contre 81 [intervalle interquartile de 56-130] ; p = 0,03). Au bout de 3 mois, à la suite de la mise sur pied du protocole, la proportion de patients autonomes sur le plan fonctionnel (échelle de Rankin modifiée : 0-2) est passée de 20/57 (35 %) à 29/68 (43 %) (p = 0,39). Conclusion : Le fait de rediriger des patients en fonction d'un certain score à la CPSS a permis d'accélérer la détection de cas d'AVC survenus à la suite de l'occlusion de vaisseaux sanguins cérébraux proximaux et donc de réduire les temps d'intervention. Cela dit, ce protocole a aussi été associé à un taux élevé de détection d'AVC non produits par l'occlusion de vaisseaux sanguins cérébraux proximaux. L'impact de cette constatation en ce qui regarde l'évolution de l'état de santé des patients devrait être évalué dans une plus vaste cohorte.

Prognostic significance of delayed intraventricular haemorrhage in the INTERACT studies.

BACKGROUND AND PURPOSE: Intraventricular extension of intracerebral haemorrhage (ICH) predicts poor outcome, but the significance of delayed intraventricular haemorrhage (dIVH) is less well defined. We determined the prognostic significance of dIVH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT 1 and 2). METHODS: Pooled analyses of the INTERACT CT substudies-international, multicentre, prospective, open, blinded end point, randomised controlled trials of patients with acute spontaneous ICH and elevated systolic blood pressure (SBP)-randomly assigned to intensive (<140 mm Hg) or guideline-based (<180 mm Hg) SBP management. Participants had blinded central analyses of baseline and 24 h CTs, with dIVH defined as new intraventricular haemorrhage (IVH) on the latter scan. Outcomes of death and major disability were defined by modified Rankin Scale scores at 90 days. RESULTS: There were 349 (27%) of 1310 patients with baseline IVH, and 107 (11%) of 961 initially IVH-free patients who developed dIVH. Significant associations of dIVH were prior warfarin anticoagulation, high (≥15) baseline National Institutes of Health Stroke Scale score, larger (≥15 mL) ICH volume, greater ICH growth and higher achieved SBP over 24 h. Compared with those who were IVH-free, dIVH had greater odds of 90-day death or major disability versus initial IVH (adjusted ORs 2.84 (95% CI 1.52 to 5.28) and 1.87 (1.36 to 2.56), respectively (p trend <0.0001)). CONCLUSIONS: Although linked to factors determining greater ICH growth including poor SBP control, dIVH is independently associated with poor outcome in acute small to moderate-size ICH. TRIAL REGISTRATION NUMBERS: NCT00226096 and NCT00716079.

Associations with health-related quality of life after intracerebral haemorrhage: pooled analysis of INTERACT studies.

BACKGROUND AND PURPOSE: Limited data exist on health-related quality of life (HRQoL) after intracerebral haemorrhage (ICH). We aimed to determine baseline factors associated with HRQoL among participants of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT 1 and 2). METHODS: The INTERACT studies were randomised controlled trials of early intensive blood pressure (BP) lowering in patients with ICH (<6 hours) and elevated systolic BP (150-220 mm Hg). HRQoL was determined using the European Quality of Life Scale (EQ-5D) at 90 days, completed by patients or proxy responders. Binary logistic regression analyses were performed to identify factors associated with poor overall HRQoL. RESULTS: 2756 patients were included. Demographic, clinical and radiological factors associated with lower EQ-5D utility score were age, randomisation outside of China, antithrombotic use, high baseline National Institutes of Health Stroke Scale (NIHSS) score, larger ICH, presence of intraventricular extension and use of proxy responders. High (≥14) NIHSS score, larger ICH and proxy responders were associated with low scores in all five dimensions of the EQ-5D. The NIHSS score had a strong association with poor HRQoL (p<0.001). Female gender and antithrombotic use were associated with decreased scores in dimensions of pain/discomfort and usual activity, respectively. CONCLUSIONS: Poor HRQoL was associated with age, comorbidities, proxy source of assessment, clinical severity and ICH characteristics. The strongest association was with initial clinical severity defined by high NIHSS score. TRIAL REGISTRATION NUMBERS: NCT00226096 and NCT00716079; Post-results.

Withdrawal of active treatment after intracerebral haemorrhage in the INTERACT2 study.

Background: in the second Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2), a minority of patients received withdrawal of active treatment (WAT). We wished to determine the characteristics of these patients, and the relation of this decision-making to subsequent management and final outcome. Methods: the INTERACT2 cohort of acute intracerebral haemorrhage (ICH) patients had a decision of WAT within 7 days after hospital admission recorded. Multivariable logistic regression was used to identify the determinants of WAT and poor outcome at 90 days, defined by modified Rankin scale (mRS) scores 3-6. Results: of 2,779 participants with available data, WAT occurred in 121 (4%) and this was significantly associated with increasing age, greater neurological severity, larger haematoma volume, intraventricular extension and randomisation to intensive BP lowering. Compared to other patients, those with WAT had greater mortality (81/121 [67%] versus 205/2624 [8%]; P < 0.001) and survivors were more likely to be severely disabled (mRS score 4-5, 19/39 [49%] versus 695/2419 [29%]; P = 0.006). Conclusions: WAT was undertaken in patients with recognised predictors of poor prognosis, who subsequently were more likely to die or be left with severe disability. Improved understanding of specific factors determining WAT in ICH patients might improve care delivery and outcomes. Clinical Trial Registration: the INTERACT2 study is registered with ClinicalTrials.gov (NCT00716079).

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.

BACKGROUND AND PURPOSE: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: Intensive BP lowering with greater SBP reduction, which is achieved quickly and maintained consistently, seems to provide protection against hematoma growth for 24 hours. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00716079.

Significance of Hematoma Shape and Density in Intracerebral Hemorrhage: The Intensive Blood Pressure Reduction in Acute Intracerebral Hemorrhage Trial Study.

BACKGROUND AND PURPOSE: In patients with acute intracerebral hemorrhage (ICH), the shape and density of the hematoma are associated with its subsequent growth, but the impact of these parameters on clinical outcome is uncertain. METHODS: Baseline computed tomographic scans and clinical data were obtained in the Intensive Blood Pressure Reduction in Acute Intracerebral Hemorrhage Trial (INTERACT2). Three independent neurologists blind to clinical data assessed ICH for shape and density using a previously described scale. Shape was defined as irregular when the ICH had ≥2 extra lesions added to the ellipsoid-shaped ICH. Density was heterogeneous when there were ≥3 low-density lesions within the ICH. Outcome measures were death and major disability (modified Rankin scale score of 3-5), combined and separate at 90-day postrandomization. Multivariable logistic regression models were used to determine the significance of hematoma characteristics on outcome. RESULTS: There were 2066 patient computed tomographic scans included in the analysis, with 46% and 38% having irregular and heterogeneous ICH, respectively. Irregular shape was independently associated with death/major disability (adjusted odds ratio, 1.60; 95% confidence interval [CI], 1.29-1.98) and major disability alone (adjusted odds ratio, 1.60; 95% CI, 1.31-1.95), but not with death alone (adjusted odds ratio, 0.97; 95% CI, 0.68-1.39). Heterogeneous density was not associated with clinical outcomes (adjusted odds ratio, 1.06; 95% CI, 0.85-1.33), 1.04 (95% CI, 0.73-1.48), and 1.14 (95% CI, 0.93-1.39), respectively, for death/major disability, death alone, and disability alone). CONCLUSIONS: Irregular shape, but not heterogeneous density, is independently associated with poor outcome after ICH. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00716079.

Prognostic Significance of Hyperglycemia in Acute Intracerebral Hemorrhage: The INTERACT2 Study.

BACKGROUND AND PURPOSE: We aimed to determine associations of baseline blood glucose and diabetes mellitus with clinical outcomes in participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). METHODS: INTERACT2 was an international prospective, open, blinded end point, randomized controlled trial of 2839 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) BP management. Associations of hyperglycemia at presentation (>6.5 mmol/L) and combined and separate poor outcomes of death and major disability (scores of 3-6, 3-5, and 6, respectively, on the modified Rankin scale) at 90 days were determined in logistic regression models. RESULTS: In 2653 patients with available data, there were 1348 (61%) with hyperglycemia and 292 (11%) with diabetes mellitus. Associations of baseline blood glucose and poor outcome were strong and near continuous. After adjustment for baseline variables, the highest fourth (7.9-25.0 mmol/L) of blood glucose was significantly associated with combined poor outcome (adjusted odds ratio 1.35, 95% confidence interval 1.01-1.80; P trend 0.015). Diabetes mellitus also predicted poor outcome (adjusted odds ratio 1.46, 95% confidence interval 1.05-2.02; P=0.023), though more important for residual disability than death on separate analysis. CONCLUSIONS: Hyperglycemia and diabetes mellitus are independent predictors of poor outcome in patients with predominantly mild to moderate severity of intracerebral hemorrhage. These data support guideline recommendations for good glycemic control in patients with intracerebral hemorrhage. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00716079.

Significance of Cerebral Small-Vessel Disease in Acute Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: The significance of structural changes associated with cerebral small-vessel disease (SVD), including white matter lesions (WML), lacunes, and brain atrophy, to outcome from acute intracerebral hemorrhage is uncertain. We determined associations of computed tomographic radiological manifestations of cerebral SVD and outcomes, and in terms of any differential effect of early intensive blood pressure-lowering treatment, in the large-scale Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). METHODS: We graded WML (van Swieten scale), the presence of lacunes, and brain atrophy (2 linear measurements and visual rating) for 2069 of 2839 patients with available baseline brain computed tomography (<6 hours of intracerebral hemorrhage onset) by 3 independent neurologists blind to clinical data. RESULTS: WML grade and 2 linear measurements of brain atrophy were associated with death or major disability at 90 days: multivariable-adjusted odds ratios for WML (grade 3 and 4 versus 0), frontal ratio, and third ventricle Sylvian fissure distance (most versus least severe atrophy quartile) were 1.42 (95% confidence interval, 1.02-1.98), 1.47 (1.08-1.99), and 1.64 (1.21-2.22), respectively (all P for trend <0.05). There was no association between lacunes and outcomes. There were no significant differences in the effects of intensive blood pressure-lowering across subgroups of cerebral SVD. CONCLUSIONS: Preexisting cerebral SVD manifestations of WML and brain atrophy predict poor outcome in acute intracerebral hemorrhage. There is no apparent hazard of early intensive lowering of blood pressure according to the INTERACT2 protocol, in patients with underlying cerebral SVD. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00716079.

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. (Funded by the National Health and Medical Research Council of Australia; INTERACT2 ClinicalTrials.gov number, NCT00716079.).