Background: Children with chronic kidney disease, including those treated with kidney transplantation (KT), have an increased risk of cardiovascular disease. The aim of this study was to examine the cardiopulmonary exercise capacity after KT compared to matched controls, to relate the results to physical activity, blood pressure and biochemical findings and to follow exercise capacity over time.Methods: Patients with KT , with a mean time from transplantation of 3.7 years (0.9–13.0) and mean time in dialysis 0.8 years, were examined at inclusion and annually for up to three years. Healthy controls  were examined once. All subjects underwent a cardiopulmonary exercise test, resting blood pressure measurement, anthropometry and activity assessment. Patients also underwent echocardiography, dual-energy X-ray absorptiometry (DXA), 24-h ambulatory BP measurements (ABPM), assessment of glomerular filtration rate (GFR) and blood sampling annually.Results: As compared to healthy controls, KT patients showed decreased exercise capacity measured both as VO2peak  and maximal load , similarly as when results were converted to z-scores. No significant difference was found in weight, but the KT patients were shorter and had higher BMI z-score than controls, as well as increased resting SBP and DBP z-scores. The patient or parent reported physical activity was significantly lower in the KT group compared to controls (p < 0.001) In the combined group, the major determinants for exercise capacity z-scores were activity score and BMI z-score . Within the KT group, low exercise capacity was associated with high fat mass index (FMI), low activity score, low GFR and high blood lipids. In the multivariate analysis FMI and low GFR remained predictors of low exercise capacity. The longitudinal data for the KT patients showed no change in exercise capacity z-scores over time.Conclusion: Patients with KT showed decreased exercise capacity and increased BP as compared to healthy controls. Exercise capacity was associated to GFR, physical activity, FMI and blood lipids. It did not improve during follow-up. Kidney transplantation (KT) is an established treatment method and the treatment of choice for children as well as adults with chronic kidney disease and end-stage renal disease (ESRD) as it offers a dramatically better quality of life, improved survival and reduction in overall morbidity. Earlier transplantation, pre-emptive transplantation and improved routines during the last decades have further improved the prognosis  is still higher in the KT-group than in healthy children , if 3–5 h weekly exercise is achieved.Lubrano et al.  showed tThere is little or no information in the literature on the longitudinal evolvement of the exercise capacity in children after KT. As children with KT often are recommended to limit sports participation  was calculated as weight/heightAs part of their annual clinical visit, all children with KT monitored at The Queen Silvia Children's Hospital perform a CPET.2 (oxygen uptake) and VCO2 (carbon dioxide excretion) . A 12-lead ECG was collected simultaneously by Cardiolex EC sense  and monitored continuously. The test protocol consisted of a 3-min warm-up phase of pedaling without load, then incremental increase of load by 5–20 W/min, starting at 20 W, until peak exercise was reached, followed by 2-min rest   was performed using a portable oscillometric device  for all patients at baseline and at annual follow-up. Cuff size was selected according to the upper arm circumference. Blood pressure was measured for 24 h and daytime systolic and diastolic BP as well as nighttime systolic and diastolic BP were analyzed according to Elke Wühl et al. . All meaResting systolic (SBP) and diastolic blood pressure (DBP) was measured manually by an experienced examiner, with the subject in supine position after a 10 min rest.LVMI = LVM(g)/height(m)2,7  and low-density (LDL) lipoprotein cholesterol) were analyzed using an enzymatic calorimetric method and serum creatinine with an enzymatic method, all measured photometrically (Cobas 6000 Roche Diagnostica Scandinavia AB) at an accredited lab. The inter assay variation did not exceed 5% in any of the analyses.51Cr-EDTA) with a minimal dose of 0.074 MBq/kg and maximal dose 3.7 MBq. The clearance was calculated from the injected dose divided by the area under the curve, using the bi-exponential method , serum glucose > 5.6 mmol/L, triglycerides > 1.7 mmol/L and HDL cholesterol < 1.03 mmol/L , lean mass index (LMI) was calculated as LBM divided by height squared (kg/m2).All children with KT underwent a DXA scan for assessment of body composition, using Lunar iDXA . The normative healthy reference database, which uses sex, weight, ethnicity- and age-specific reference data, is provided by the DXA machine manufacturer LUNAR . Analyses of fat mass  and lean body mass  were made. Fat mass index (FMI) was calculated as FM divided by height squared .The distribution of continuous variables is given as mean, SD, median, minimum, and maximum and of categorical variables as number and percentages. For comparison between two groups with respect to continuous variables, the Mann–Whitney U-test was used, and for ordered categorical variables, Mantel-Haenszel test was used. Correlation was described by using Spearman correlation coefficients. Associations between VO2 peak/kg/min z-score and FMI, GFR, activity score, LMI and lipids were investigated using linear regression. The correlations between VO2peak and maximal load and lean body mass (LMI) were tested after log-transformation to ensure normal distribution, and to permit comparison with Sethna et al. . Stepwisn = 26) 0.8 years (range 4 days−5.4 years) were examined at inclusion and annually for up to 3 years. Seventeen matched healthy controls  with a median age of 11.7 years (range 7.3–18.6) were examined once , median age of 13.6 years (range 7.7–18), with a mean time from transplantation of 3.7 years (0.9–13.0) and mean time in dialysis , 17 children had GFR 30–59 (CKD stage 3) and one child had GFR 15–29 ml/min/1.73 m2 (CKD stage 4). All patients had B-Hemoglobin (Hb) >100 g/L. Cholesterol was high in 5%, LDL high in 8%, HDL low in 8% and triglycerides high in 16% , tacrolimus (34 patients) and mycophenolate (21 patients). Three patients received cyclosporine instead of tacrolimus and another three were given everolimus. Anti-hypertensive medication was given to 21 patients, of which 10 had single-therapy calcium blockers, three had single-therapy ACE-inhibitors, three had combination-therapy calcium blockers and beta blockers, and five had combination-therapy calcium blockers and ACE-inhibitors. Median GFR was 61 ml/min/1.73 mh in 16% . No chilOne of the KT patients had type 2 diabetes mellitus and was considered having metabolic syndrome, meeting 3 of 5 criteria. Ten patients had two criteria, 18 had one and nine patients had no criteria for metabolic syndrome .2peak  and maximal load , also when comparing z-scores (p = 0.0003 (p = 0.0107). Three of the KT patients were treated with beta blockers, in two of the patients this likely affected the maximum heart rate, which measured 151, 175, and 201/min in these patients. When comparing controls and KT patients categorized by activity score, there was a trend toward a significantly lower VO2peak z-score in the patients with KT in those with activity score 2  and a significantly lower VO2peak z-score in those with activity score 3 .The KT patients were significantly shorter than the healthy controls, had higher BMI z-score and higher resting SBP and DBP z-scores. The KT patients showed decreased exercise capacity measured both as VOz-scores . No diff= 0.0003 . The med2peak z-score were activity score and BMI z-score .In multiple regression analysis of both groups combined, the main determinants of VOr = 0.74, p < 0.0001 and r = 0.91, p < 0.0001, respectively).LMI and FMI were both associated with BMI in the KT patients  with SBP and/or DBP values above the 95th percentile, eight of whom had antihypertensive treatment. Four of the children with hypertension were classified as non-dippers, and six additional patients were non-dippers. Nine of the hypertensive children had nighttime DBP above the 95th percentile, of whom three also had nighttime SBP and three daytime BP above the 95th percentile. Three children were hypertensive only during daytime. There was no gender difference in day or night blood pressures. There were no correlations between day or night systolic or diastolic blood pressure z-scores and GFR, VO2,7 (range 20.8–45.2), LVM 98.3 g (51.7–206.2), LVd 4.5 cm (3.9–6.0), IVSd 7.0 mm (4.9–10.0), and PWd 6.7 mm (4.4–9.5). Three patients (10%) had LVMI above 95th percentile for height. There was no correlation between LVMI and blood pressure z-scores.Echocardiography was performed in 28 KT patients at baseline. Median LVMI was 31.4 g/m2 (range 35–88). There was an increase in night systolic blood pressure by 0.66 z-scores  after 3 years but no significant change in day blood pressures or night diastolic blood pressure. There was no correlation between blood pressure changes and GFR at start or after 3 years.The longitudinal data were captured for 1, 2, and 3 years in 33, 22, and 17 individuals, respectively. The KT patients showed no change in exercise capacity z-scores over time . Median We found a decreased exercise capacity and increased BP in children with KT compared to matched healthy controls. The exercise capacity was predicted by high activity score and low BMI z-score in the groups combined. In the multivariable logistic regression model within the KT-cohort, the main predictors for impaired exercise capacity were FMI, activity score and GFR .2peak and maximal load derived from Ten Harkel et al.  is preferred. None of the 38 children with KT in the study were on dialysis and the median time in dialysis before transplantation was relatively short. Nevertheless, children on PD have been shown to have a reduced exercise capacity, mainly due to decreased muscle strength . Indications of this difference between control subjects and KT patients were found in the difference in BMI z-score. However, this could not be confirmed in our study, as DXA was only performed in the children with KT. BMI z-score in this age group has its limitations, as it does not properly reflect body composition, and may lead to misclassification of overweight and obesity  for VO2peak in the univariate analysis, as opposed to the positive correlation between lean body mass and VO2peak. One reason for this may be that obesity is often associated with an increased muscle mass and an increased LMI, without the concurrent increase in exercise capacity otherwise seen in non-obese subjects with increased muscle mass.In our multiple regression analysis, the main determinant for exercise capacity was fat mass, measured as FMI. This may explain part of the decreased VO2peak z-score, suggesting a decreased exercise capacity with dyslipidemia. This may in part be a proxy for increased fat mass, which is indicated by the association with BMI z-score we found. It is also supported by the strong association between FMI and BMI in this group. However, only a few patients had dyslipidemia or obesity in our cohort using the Wilson criteria . In our cohort, the median Hb was 121 g/L, and we did not find any patient with Hb <100 g/L, suggesting that anemia was not an important factor decreasing oxygen consumption during exercise in our cohort. We did not find any association between VO2peak z-score and Hb, supporting this finding.Another metabolic factor that may affect the VO2peak z-score or maximal load z-score.The most common risk factor in our cohort was hypertension, frequently found in patients with KT  and 37.6% met the criteria for metabolic syndrome  did all the semi structured interviews for activity scoring.As this was an observational study of the cohort of KT children at our center, with a cross sectional design, the underlying kidney disease varied between the patients. They also had different duration of kidney failure and time in dialysis before transplantation and varying time interval between transplantation and inclusion in the study. Also, DXA and biochemistry data, ABPM data, as well as longitudinal data on exercise capacity, were not collected in the control group. The cardiac ultrasound had to be excluded in 11 children, as it was not performed in conjunction with the exercise test.The controls were fewer than the KT children. The groups were matched for age and sex ratio, but not on an individual basis. This is a weakness, potentially adding bias to the study. Despite the low number of children in the KT and control groups, we had significant results in many of the analyses, confirming the results from other studies.In this group of patients with KT showed decreased exercise capacity and increased BP as compared to age and gender-matched healthy controls. The lower exercise capacity could be explained by lower activity score, decreased GFR and high fat mass. The exercise capacity in patients with KT did not improve over time.The decreased exercise capacity in patients with KT did not improve over time. There were no intervention in terms of exercise program or the likes involved in the standard care program for these patients. Considering the results from this study, this may be a future priority, which potentially could improve not only the cardiorespiratory fitness, but also the metabolic state of these patients.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Regionala Etikprovningsnamnden in Gothenburg Medical Division Gothenburg, SWEDEN. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.SW, FD, SH, and TL were responsible for the planning and design of the study. TL, FD, SW, PB, and SH performed the examinations. EB, OH, and JK assisted in analyzing data. All authors assisted in interpreting the findings and writing the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Sex differences in blood pressure (BP) regulation at rest have been attributed to differences in vascular function. Further, arterial stiffness predicts an exaggerated blood pressure response to exercise (BPR) in healthy young adults. However, the relationship of vascular function to the workload-indexed BPR and potential sex differences in athletes are unknown.We examined 47 male (21.6 ± 1.7 years) and 25 female (21.1 ± 2 years) athletes in this single-center pilot study. We assessed vascular function at rest, including systolic blood pressure (SBP). Further, we determined the SBP/W slope, the SBP/MET slope, and the SBP/W ratio at peak exercise during cycling ergometry.p < 0.001) but a higher central pulse pressure , maximum SBP , and ΔSBP  than females. Total vascular resistance , pulse wave velocity , BP at rest , and the SBP/MET slope  were not different. The SBP/W slope (0.34 ± 0.12 vs. 0.53 ± 0.19 mmHg/W) and the peak SBP/W ratio (0.61 ± 0.12 vs. 0.95 ± 0.17 mmHg/W) were markedly lower in males than in females (p < 0.001).Male athletes had a lower central diastolic blood pressure (57 ± 9.5 vs. 67 ± 9.5 mmHg, Male athletes displayed a lower SBP/W slope and peak SBP/W ratio than females, whereas the SBP/MET slope was not different between the sexes. Vascular functional parameters were not able to predict the workload-indexed BPR in males and females. There is a wealth of evidence indicating a different blood pressure (BP) regulation at rest between women and men  during exercise is another controversial issue  was introduced . Only healthy individuals free of underlying cardiovascular diseases, risk factors, and medication  were included.The examination took place at noon between 12:00 and 14:00 o’clock and was scheduled in the first week of the new season after a 6-week competition-free interval. The last time athletes had trained was 36 h prior to the study beginning; the last allowed meal was breakfast up to 3 h before the investigation. There was no restriction of caffeine intake provided. Thus, alcohol consumption was prohibited the two days prior to the study beginning. The day before the examination was filled with commercial dates with no physical effort.The local ethics committee approved the study protocol. The study was performed in accordance with the ethical standards laid down in the Declaration of Helsinki and its later amendments. All subjects gave written informed consent to participate.The participants were 72 healthy professional athletes consisting of 47 male handball and 25 female soccer players. All participants included were Caucasian, non-smokers and none took medication  or multivitamin supplements. All female athletes were examined during the early follicular phase or in the placebo phase for those taking oral contraceptives to minimize hormonal effects. As age was found to influence the BPR to exercise in both sexes, only athletes aged 18–24 were included in the study.All individuals were subjected to a physical examination, 12-lead electrocardiogram (ECG), and progressive maximal cycling ergometer test. Age, height, weight, and body mass index were determined. Body surface area was calculated using the formula of DuBois.Resting brachial BP was measured before the exercise testing using a validated automatic device based on a standard sphygmomanometer technique . The cuff used for measurement was adjusted to the individual’s arm circumference. Measurements were performed by a trained research associate on both arms in a sitting position after a resting period of 5 min and repeated after 2 min. The average BP for each arm was calculated if both measurements were within 5 mmHg. The highest value was used for statistical analyses. Athletes with a resting SBP > 140 mmHg or diastolic BP (DBP) > 90 mmHg were excluded from the study.®, Switzerland). The exercise test protocol for male athletes started with a load level of 100 W after a 2-min warm-up period that was conducted with 50 W. Female athletes started with 75 W after a warm-up period conducted with 50 W. Loads were increased by 50 W in male athletes and 25 W in females every 2 min until exhaustion, which was defined as the participant’s inability to maintain the load for 2 min. Next, the load was decreased to 25 W for 3 min of active recovery that was followed by a 2-min cool-down period at rest. The test concluded with a final ECG recording and brachial BP measurement. BP was measured once a minute during test and recovery periods, including at the maximum workload, immediately after the maximum workload, immediately after the end of the test, and after 5 min of recovery. BP was measured at the right arm during the test, and the participant was instructed to let the right arm hang loosely during measurement, when possible. SBP was recorded at the appearance of the first Korotkoff sound. Each BP measurement was protocolled automatically with the corresponding time, heart rate, and workload.Athletes underwent a standardized progressive maximal cycling ergometer test with concurrent automatic brachial BP measurement and 12-lead ECG recording  values. Pulse pressure was calculated as SBP minus diastolic blood pressure (DBP) at rest and at maximum exercise. In addition, mean brachial BP was determined as: DBP + (SBP − DBP)/3. MET values were estimated using the standard equations of the ACSM for cycling ergometers  to acquire pulse pressure waveforms by means of oscillometry. The device uses a validated model , aortic pulse wave velocity (PWV), augmentation index (Aix), augmentation index at a heart rate of 75 bpm (Aix@75), resistance index (R), total vascular resistance, and ejection duration were calculated. CBP was determined using a transfer function that was based on the peripheral arterial waveform. Calculation of Aix@75 was also based on the pulse waveform.p < 0.05 (two-tailed) for all measurements. All statistical analyses were performed using the statistical software SPSS 25.0 for Mac .Descriptive analyses were carried out on all study variables for the total sample and separated by sex. All data are presented as mean ± standard deviation (SD). The Shapiro–Wilk test was used to determine normal distribution. If the data were determined to have a skewed distribution, all analyses were performed on normalized data. Between-group comparisons were made using independent sample t tests. Bivariate relations were analyzed using the Spearman correlation coefficient. Pearson’s product-moment correlation coefficient was used to determine linear correlations between vascular functional parameters and exercise test results. We also performed multivariate stepwise regression analyses to explore possible linear associations across the vascular functional parameters measured at rest in both sexes, using separately the SBP/MET slope, the peak SBP/W ratio and SBP/W slope as continuous dependent variable. Statistical significance was set at p = 0.365) and history of professional training were not different between groups (p = 0.112). The clinical characteristics, anthropometric data, and specific training data are displayed in detail in Table A total of 72 participants, consisting of 47 male and 25 female athletes, were included in the study. Male athletes were taller and heavier and displayed a greater body mass index and a higher body surface area than females. Further, the training amount per week was higher than that of females. However, age  took oral contraceptives. The used hormonal contraceptives have a monophasic effect and are assigned to the fourth generation of hormonal contraceptives. They contained 3 mg drospirenone and 0.03 mg estradiol. In one case, the oral contraceptive contained 3 mg drospirenone and 0.02 mg estradiol. These combined oral contraceptive pills supply 21 days of pills with hormones followed by 7 days of hormone-free pills. This regimen is called the 21/7 regimen.r = 0.959, p < 0.001) in all athletes. Further, age was positively correlated with training per week , height , weight  and BMI (r = 0.314 p < 0.001). Height, weight, body surface area, and BMI all correlated positively with each other (p < 0.05) and with the training history and the training duration per week (p < 0.05).As expected, we found a significant correlation of age with history of professional training (p > 0.05). None of the participants displayed a BP > 140/90 mmHg. Further, heart rate at rest and central SBP were not different between the groups (p > 0.05). Male athletes had a significantly lower central diastolic BP (< 0.001) and mean CBP (p = 0.003) compared with female athletes. In contrast, the central pulse pressure (p < 0.001) was higher in males than in females. Detailed data are presented in Table Resting brachial BP, mean brachial BP, and brachial pulse pressure at rest were not different between male and female athletes . Further, the augmentation index at a heart rate of 75 bpm (Aix@75) (p = 0.203), the resistance index (R) (p = 0.148) and total vascular resistance (p = 0.369) were not different between the groups. In addition, none of the measured parameters of vascular function at rest were correlated to sex (p > 0.05). In contrast, PWV was correlated to age (p < 0.001) and BMI (p = 0.044), but not to height or weight (p > 0.05).The aortic pulse wave velocity (PWV) was not different between male and female athletes . Male athletes achieved a significantly higher absolute workload than female athletes with a correspondingly higher relative workload and MET.p < 0.001) and the peak SBP/W ratio  were significantly lower in male athletes than in female athletes. However, the SBP/MET slope was not different between males and females   and the peak SBP/W ratio  were correlated with sex, but the SBP/MET slope  was not.The SBP/W slope , weight , and BMI  but not with age .The SBP/MET slope was positively correlated with height , height , weight , and BMI .In contrast, the SBP/W slope was negatively correlated with age , weight , and BMI  were found.Further, negative correlations of the peak SBP/W ratio with height . In another study a median of 6.4 mmHg/MET in a male cohort of a general population  of the fourth generation that were taken by four athletes seems unlikely, as these OCP are currently seen not to affect peripheral vasculature  and a moderate static component (10–20%) (Levine et al. Our study has a few limitations. The number of participants limited its power to uncover potential correlations between the workload-indexed BPR parameters measured and markers of cardiac and vascular function other than CBP, PWV, total vascular resistance, brachial BP, and the BPR to a maximum exercise test. The focus on professional soccer and handball athletes may limit extrapolation of the results to other sport disciplines; however, as these team sports expose athletes to the hemodynamic stress of frequent interval sprints, it is representative of other sports with a high dynamic component (> 75% In our cohort of professional athletes, we detected sex differences in the SBP/W slope and the peak SBP/W ratio, with a steeper BP increase in females. In contrast, we identified the SBP/MET slope as a sex-independent marker of workload-indexed BPR. Despite sex differences in central hemodynamics and vascular function measured at rest, these parameters were not able to predict any of the workload-indexed markers of BPR in males and females. These findings emphasize the link between vascular function, total vascular resistance, BPR, and physical performance during exercise in athletes. Further, a sex-specific consideration of BPR to exercise testing, which is frequently performed in the cardiovascular evaluation of competitive athletes, is encouraged to identify athletes at risk.


The optimal blood pressure (BP) management in acute ischaemic stroke (AIS) and acute intracerebral haemorrhage (ICH) remains controversial. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist physicians in their clinical decisions regarding BP management in acute stroke.The guidelines were developed according to the ESO standard operating procedure and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations based on the GRADE approach. Despite several large randomised-controlled clinical trials, quality of evidence is generally low due to inconsistent results of the effect of blood pressure lowering in AIS. We recommend early and modest blood pressure control (avoiding blood pressure levels >180/105 mm Hg) in AIS patients undergoing reperfusion therapies. There is more high-quality randomised evidence for BP lowering in acute ICH, where intensive blood pressure lowering is recommended rapidly after hospital presentation with the intent to improve recovery by reducing haematoma expansion. These guidelines provide further recommendations on blood pressure thresholds and for specific patient subgroups.There is ongoing uncertainty regarding the most appropriate blood pressure management in AIS and ICH. Future randomised-controlled clinical trials are needed to inform decision making on thresholds, timing and strategy of blood pressure lowering in different acute stroke patient subgroups. As randomised-controlled clinical trials (RCTs) of this topic are limited and challenging, clinical decisions are often made on the basis of observational studies that are prone to bias, confounding and random error.25 Theoretical concepts and pathophysiological arguments are used to defend arguments for and against alteration of blood pressure in the setting of acute stroke; to reduce the risk of stroke recurrence, cerebral oedema, reperfusion haemorrhage for AIS patients after reperfusion therapies, and reduce haematoma expansion and cerebral oedema in ICH; to avoid impairment of cerebral perfusion to viable ischaemic tissue in the presence of altered autoregulation.7 Whilst most attention has been focused on the avoidance of hypertension, drug-induced hypertension has been proposed as a potential therapeutic strategy to increase cerebral perfusion in some AIS patients.8Elevated blood pressure levels (systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg) are common in patients with acute ischaemic stroke (AIS) and acute intracerebral haemorrhage (ICH), but the pathophysiology of the hypertensive response is poorly understood.912 there has been inconsistency in results from multiple RCTs of different antihypertensive strategies for acute stroke subtypes.Although numerous observational studies have shown that both extremely low and high blood pressure levels are associated with worse outcomes in AIS and ICH patients,13 and ICH,14 this including new RCTs and individual patient data meta-analyses (IPDM) that have been published since 200813 and 201414 respectively. We review current evidence and provide recommendations for blood pressure management (both blood pressure reduction and augmentation) in patients with acute stroke; including recommendations for blood pressure management in the pre-hospital setting, according to eligibility for reperfusion treatment in AIS and separately for patients with acute ICH. Our goal was to facilitate decision-making in these patient groups where there is considerable ongoing uncertainty over optimal post-stroke blood pressure management.Here, we update previous guidelines from the European Stroke Organisation (ESO) on the management of acute blood pressure in AIS15 which are based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system.16 The ESO Guidelines Board and Executive Committee reviewed the intellectual and financial disclosures of the module working group (MWG) members , and in children with acute stroke.Eight Patient Intervention Comparator Outcome (PICO) were developed and agreed upon within the MWG following a teleconference and e-mail correspondence.Produced a list of relevant outcomes for which the MWG used the Delphi method to score their importance .The MWG undertook the following steps:Mortality (90 days or end of follow-up)    Mean score: 8.8/9Functional outcome (90 days or the end of follow-up) Mean score: 8.8/9Recurrent ischaemic stroke   Mean score: 7.0/9Symptomatic ICH        Mean score: 6.9/9Quality of life (90 days)     Mean score: 6.4/9Neurological deterioration    Mean score 5.5/9 (48 hours) Acute kidney injury       Mean score 4.0/9The list of outcomes in the AIS subgroup were:Mortality (90 days or      Mean score: 8.9/9 end of follow-up)Functional outcome (90 days or end of follow-up)  Mean score: 8.9/9Haematoma expansion     Mean score: 6.9/9Quality of life (90 days)     Mean score: 5.4/9Neurological deterioration    Mean score 6.4/9 (48 hours)   Incident ischaemic stroke    Mean score: 5.4/9Recurrent ICH          Mean score: 5.2/9Acute kidney injury      Mean score 4.2/9The list of outcomes in ICH subgroup were: 4.The main recommendations were based on a systematic review of RCTs evaluating different blood pressure management strategies in AIS and ICH patients. The literature search was completed on September 30, 2020. We conducted a systematic review in all PICOs resulting in 35 different sets of analyses. Details regarding the search strategies are provided in the Supplement. We also included relevant literature published to February 27, 2021 in the final manuscript. 5.For each PICO question, a group consisting of three to four MWG members was formed. 6. MWG members assigned to each PICO independently screened the titles and abstracts of the publications identified by the electronic search and assessed the full text of potentially relevant RCTs. Where there were no RCT data available for a certain topic, systematic reviews of non-randomised studies or key observational studies were identified and considered.2 statistic, and heterogeneity was classified as moderate (I2 ≥ 30%), substantial (I2 ≥ 50%), or considerable (I2 ≥ 75%).17 The Cochrane Collaboration risk of bias tool was used for the risk of bias assessment.7.Where appropriate, a random-effects meta-analysis was conducted using Stata software version 11.0 (Statacorp), with results summarised as odds ratios (ORs) and 95% confidence interval (CI). Any heterogeneity across studies was assessed using the I16 GRADE evidence profiles/summary of findings tables were generated using GRADEPro. 8.The results of data analysis were imported into the GRADEpro Guideline Development Tool . For each PICO question and each outcome, the risk of bias was assessed and quality of evidence rated as high, moderate, low or very low based on the type of available evidence  and considerations on inconsistency of results, indirectness of evidence, imprecision of results, and risk of bias.Analysis of current evidence summarised current pathophysiological considerations and relative recommendations from other scientific societies related to that specific question, followed by a summary and discussion of the results of the identified RCTs. Where there was no RCT, the paragraph described the results of systematic reviews of non-randomised studies. Second, Additional information was added when more details on RCTs referred to in the first section were needed, to summarise results of observational studies, or to provide information on key subgroup analyses of the included RCTs and on ongoing or future RCTs. Third, Evidence-based Recommendations were provided, these based on the GRADE methodology. The direction, strength and formulation of the recommendation were determined according to the GRADE evidence profiles and the ESO-SOP.18 These recommendations do not apply to planned or ongoing trials. Finally, according to the first addendum to the ESO SOP, Expert Consensus Statements were added whenever the PICO group considered that there was insufficient evidence available to provide Evidence-based Recommendations where practical guidance is needed for routine clinical practice. In that case, a pragmatic suggestion was provided, with the results of the votes of all MWG members  on this proposal. Importantly, the suggestions provided in this paragraph should not be mistaken as evidence-based recommendations but rather as the opinion of the MWG members. 9.Each PICO group addressed their respective question by providing distinct sections. First, 10.The Guideline document was subsequently reviewed several times by all MWG members and revised until a consensus was reached. Finally, the Guideline document was reviewed and approved by external reviewers and members of the ESO Guidelines Board and Executive Committee.Based on voting scores, functional outcome and mortality were allocated highest priority for both AIS and ICH and were the only outcomes considered in the meta-analyses. The outcome of recurrent ischaemic stroke was also of interest in the AIS subgroup, while haematoma expansion was the outcome considered important in the ICH subgroup. Unless specified otherwise, ‘excellent’ and ‘good’ outcome were defined as 3-month modified Rankin Scale (mRS) scores of 0–1 and 0–2, respectively. Unless specified otherwise, ‘any better’ functional outcome corresponded to an ordinal shift analysis of the mRS score at 3 months. For the subgroup of patients with suspected stroke in the prehospital setting we used the outcomes favoured in the AIS subgroup since the aetiology in the majority (≈80%-85%) of these patients is ischaemic. The MWG formulated a list of PICO questions according to the ESO Guideline SOP, which were reviewed and subsequently approved by the ESO Guidelines Board and Executive Committee.19 High blood pressure is associated with poor short- and long-term functional outcome both patients with AIS and ICH. Treatment-resistant very high blood pressure (>185/110 mm Hg) is a contraindication to intravenous thrombolysis (IVT),20 whereas blood pressure lowering in acute ICH has been associated with improved functional outcome and reduced haematoma expansion.22 Blood pressure management is a relatively low-cost treatment option feasible in the pre-hospital setting, and may contribute to improved outcomes in patients with suspected stroke.23 Current ESO and European Academy of Neurology (EAN) guidelines do not recommend blood pressure lowering in the pre-hospital setting24 and the American Heart Association (AHA)/American Stroke Association (ASA) have no specific recommendations for blood pressure management for patients with suspected stroke in this setting.25High blood pressure in patients with suspect stroke in the ambulance is common, and blood pressure may vary according to stroke subtype.26The Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke trial (RIGHT) randomised 41 patients with suspected stroke (Face Arm Speech Test score of 2 or 3) and systolic blood pressure ≥140 mm Hg within 4 hours of symptom onset. The intervention, transdermal glyceryl trinitrate (GTN), was administered in the ambulance by trained paramedics. At 90 days, there was a significant improvement in the mRS with a shift of 1 point in favour of treatment with GTN (p = 0.04), but no significant difference in mortality .27The RIGHT-2 trial recruited 1149 patients with suspected stroke (Fast Arm Speech Test scores 2 or 3) and systolic blood pressure ≥120 mm Hg) within 4 hours of symptom onset, according to a similar intervention as the pilot trial. There were no differences in mRS scores (mRS > 2) in patients with a final diagnosis of stroke  nor in all included patients , nor in mortality.26,27 with no difference detected between any vasodepressor drug compared to control  (2 = 46%)  . There w2 = 46%) .28The Field Administration of Stroke Therapy-Magnesium (FAST-MAG) randomised 1700 patients in the ambulance with suspected stroke to intravenous magnesium or placebo within 2 hours of symptom onset. The trial evaluated the potential neuroprotective effect of magnesium, which also has mild vasoactive activities. There were no differences between the two groups in the rates of good functional outcome (mRS scores (0-2) at 3 months (magnesium 449/857 [52%) vs placebo 445/843 [53%]; p = 0.88) nor in mortality .23 Since the trial did not report mortality beyond 1 week, we did not include the trial in the meta-analysis.The Paramedic Initiated Lisinopril for Acute Stroke Treatment (PIL-FAST) trial randomised 14 patients with unilateral arm weakness, systolic blood pressure ≥160 mm Hg within 3 hours of symptom onset to sublingual lisinopril or control. Blood pressure was lower in the lisinopril group on hospital admission. There was no difference in 1-week mortality between the two groups (lisinopril 1/6 [17%] vs placebo 1/8 [13%]).29 Prehospital blood pressure lowering in the ambulance in patients with suspected stroke is currently being tested in two RCTs.31In the subgroup of 145 patients included in the RIGHT-2 trial with confirmed ICH after admission to hospital, GTN was associated with a worse shift in the mRS scores . There was no difference in death at days 4 or 90.Expert consensus statementDue to the potential harm in patients with intracerebral haemorrhage prehospital treatment with glyceryl trinitrate should be avoided. Vote 9 of 10.32 Based on pathophysiology, optimal blood pressure management may be different in patients who are not eligible for reperfusion treatment with either IVT or MT; lowering blood pressure may reduce the risk of haemorrhagic transformation and oedema, whereas high blood pressure may protect the brain by maintaining cerebral perfusion when autoregulation is partially impaired. Current European13 and AHA/ASA25 guidelines suggest a cautious approach to hypertension management in those with AIS not eligible for IVT or MT, recommending against aggressive blood pressure lowering in most patients during the initial 24 hours unless blood pressure levels are extreme, or there is a concomitant specific situation that necessitated rapid lowering.Only a minority of patients with AIS receive reperfusion therapy  in Europe: the percentage ranges from 1% to 20% (mean 7.3%), with even less receiving mechanical thrombectomy (MT) (mean 1.9%).3350,51,52 Seven included patients with ICH but reported results separately for ICH and AIS subgroups.51,52 One trial did not discriminate between AIS and ICH34 but was included based on the assumption that AIS contributed to the majority of patients. Three trials included patients who received IVT, but the proportion receiving IVT was low, and the results were available separately for subgroups according to IVT either in the main paper, or in subsequent post hoc analyses.45 Notably, the majority of studies excluded patients with extremely high systolic blood pressure levels (>220 mm Hg) and many included patients up to 72 hours of symptom onset.Data from 18 RCTs were considered in the analysis of the effect of blood pressure lowering treatment on death and/or disability.Most of the patients were recruited from the three RCTs described below:45 Eight percent of patients with AIS received IVT. Blood pressure was lower in the treatment group at day 7 (−5/−2 mm Hg difference in systolic and diastolic blood pressures). There were neutral effects on the two co-primary endpoints: 1) poor functional outcome at six months  and 2) composite outcome of vascular death, myocardial infarction or stroke during the six months follow-up period. There were no significant differences between the candesartan and placebo groups in mortality, functional outcome or recurrent ischaemic stroke in the subgroup of 1733 patient with AIS.52The Scandinavian Candesartan Acute Stroke Trial (SCAST) recruited 2029 patients with AIS (n = 1733) and ICH (n = 274) and systolic blood pressure ≥140 mm Hg within 30 hours of onset and compared treatment with candesartan for seven days with placebo on co-primary end points at six months.37 In a partial factorial design, those on pre-existing anti-hypertensive drugs were randomised to stop or continue their medication. Blood pressure was significantly lower in the GTN treatment group at 24 hours (-7/-3 mm Hg difference) but there was no significant difference after day 3. In the overall patient population (AIS and ICH combined) the primary outcome  was neutral for GTN versus placebo , with no significant interaction between stroke type (AIS versus ICH) and effect of treatment on outcome in a pre-specified subgroup analysis.The Efficacy of Nitric Oxide in Stroke trial (ENOS) randomised 4011 patients with AIS (n = 3342), including 225 who received IVT, or ICH (n = 629) and systolic blood pressure 140–220 mm Hg to transdermal GTN patches (5 mg) or placebo within 48 hours of onset for 7 days.35 The study compared targeted blood pressure lowering (10 to 25% systolic blood pressure reduction in 24 hours) with either intravenous angiotensin receptor inhibitors (ACEi) (first line), oral calcium channel antagonists (CCB) (second line), or oral diuretics to control. Mean systolic blood pressure was lower in the treatment group (−9.1 mm Hg at 24 hours). There was no significant effect on functional outcome (mRS ≥3) at 14 days or at 90 days.The China Antihypertensive Trial in Acute Ischaemic Stroke (CATIS) recruited 4071 patients with AIS (not treated with IVT) and a systolic blood pressure ranging between 140–220 mm Hg within 48 hours of symptom onset.All the other included studies reported similarly neutral results.27In analyses of RIGHT-2 limited to 580 patients with AIS, there was no evidence of an effect of GTN on functional outcome at 90 days compared with sham ; adjusted common OR .43A post hoc subgroup analysis of the Prevention Regime for Effectively Avoiding Second Strokes (PRoFESS) trial examined the effect of adding the angiotensin receptor blocker telmisartan versus placebo to standard antihypertensive treatment in 1360 patients with mild AIS within 72 hours of onset. Telmisartan produced a modest lowering of blood pressure, without increase in adverse events, but there was no effect on poor functional outcome, mortality, stroke recurrence or cardiovascular events. Again, the cohort had mild neurological severity  score 3), and treatment initiated rather late (average 58 hours after symptom onset).42 Conversely, Intravenous Nimodipine West European Stroke Trial (INWEST), comparing the effect of nimodipine  to placebo in 265 AIS patients reported poorer functional (according to Barthel Index) and neurological outcomes  in the 2 mg treatment group versus placebo at 21 days (primary efficacy time point) and at 24 weeks.40In a comparison of amlodipine or irbesartan versus control in 320 AIS patients < 48 hours of onset, the results for effect on poor functional outcome (mRS ≥3) favoured treatment .27,33--40,42--50,52, 53 No statistically significant effect was found; OR 1.00 (95%CI: 0.84–1.19), p = 0.98, I2 = 35% (2 = 35%).27,35,38,41-47,50,53Eighteen trials were included in the meta-analysis for the effect of blood pressure lowering on mortality at 3–6 months following symptom onset.I2 = 35% . Twelve I2 = 35% . There w51 RCTs using ARBs for blood pressure reduction report conflicting results.48 Candesartan showed promising effects in a pilot trial,48 but SCAST was neutral and if anything, favoured placebo;45 the Valsartan Efficacy oN modesT blood pressure Reduction in acute ischaemic stroke (VENTURE) trial was neutral for functional outcome but reported significantly more early neurological deterioration among patients in the valsartan group;46 the low dose BEta blockade in acute Stroke Trial (BEST) reported increased early death in those randomised to beta-blocker versus control ,34 and in the Controlling Hypertension and Hypotension Immediately Post Stroke (CHHIPS) trial,51 labetalol was safe. Results from small RCTs of CCBs have produced mixed results: some favoured placebo,41 but others have been neutral.33 Small and larger RCTs in Nitric Oxide (NO) donors have reported safety with GTN but no significant effect on functional outcome.47We hypothesise that factors other than blood pressure may influence the treatment effect on outcomes, these including drug class, blood pressure target, timing of treatment, underlying stroke aetiology, premorbid blood pressure levels, and magnitude and rate of blood pressure lowering. Data from the included studies regarding these variables are conflicting. When considering drug class: ACEi appear safe but did not influence outcomes;1 Most RCTs excluded AIS patients with extremely elevated systolic blood pressure (>220 mm Hg), and thus the effects of blood pressure lowering in this group are unknown. Owing to heterogeneity in terms of blood pressure targets among studies, no robust conclusions can be drawn as to the optimal blood pressure target, though avoiding large drops in blood pressure during the first 24 hours seems reasonable given the negative effects reported on some outcomes in trials of intravenous CCBs with large (>20%) reduction in blood pressure.53 Time to treatment may have an effect and has varied considerably across RCTs (<4 hours to 5 days). In the ENOS patient subgroup treated within 6 hours54 treatment with GTN was associated with significantly improved functional outcome, and among a similar group of participants in SCAST there was a non-significant benefit on the composite vascular endpoint in those treated < 6 hours.55 In CATIS, subgroup analysis showed a reduction in poor functional outcome in those randomised later (>24 hours) from stroke symptom onset.35 In RIGHT-2, where treatment was initiated within 4 hours of onset, GTN was associated with a non-significant trend for a worse functional outcome;27 this tendency towards harm was more evident in patients with very early stroke (<1 hour), and severe stroke .27Premorbid and initial blood pressure level and blood pressure targets may also be of importance.52 as shown in another study.56 The presence of large vessel occlusion and significant carotid artery stenosis may influence the effect of blood pressure lowering treatment, although data are partly conflicting: a pre-specified subgroup analysis from SCAST of AIS patients with carotid imaging (n = 993) showed that those with severe stenosis (≥70%) treated with candesartan had a trend towards increased risk of stroke progression and poor functional outcome .57 Conversely, in ENOS, GTN was shown to be safe across all levels of ipsilateral carotid stenosis among participants with carotid imaging data (n = 2038).58Neurological severity and subtype may alter the effect of treatment. In a secondary subgroup analysis of patients with AIS included in SCAST there was a benefit of treatment with candesartan in larger , but not smaller (lacunar) AIS,6 In the subgroup of 11,015 patients with AIS there was no benefit of any vasodepressor drug compared with control on the outcome of death and dependency : OR = 1.00 (95%CI: 0.92–1.08). Furthermore, no differences in treatment effect were observed in subgroups according to drug class, stroke location , or blood pressure target used. CCBs, ACEi, ARB, beta-blockers and NO donors all lowered blood pressure.6We considered a 2014 Cochrane review relevant to this topic.Expert consensus statementIn patients with acute ischaemic stroke not treated with intravenous thrombolysis or mechanical thrombectomy and blood pressure >220/120 mm Hg, careful blood pressure reduction (<15% systolic blood pressure reduction in 24 hours) is reasonable and likely to be safe. No specific blood pressure lowering agent can be recommended. Vote 10 of 10.5961 elevated systolic and diastolic blood pressure levels before (>185/110 mm Hg) and during (>180/105 mm Hg) alteplase infusion of AIS patients are contraindications to IVT based upon the protocol for the original National Institute of Neurological Diseases and Stroke (NINDS)-recombinant tissue plasminogen activator (rt-PA) Stroke Study.62 AHA/ASA and ESO guidelines endorse these thresholds and advocate against treating AIS patients with intravenous IVT, when blood pressure is uncontrolled before or during thrombolysis treatment.25Based on data from small, uncontrolled, non-randomised pilot studies,63 IVT can be delayed or even denied in a substantial number of patients whose blood pressure is above this threshold and unresponsive to antihypertensive treatment.64 In addition, there is appropriate concern that aggressive blood pressure reduction, may reduce viable penumbral tissue, result in expansion of the cerebral infarction and contribute to neurological deterioration.6466There are no randomised data to support these recommended blood pressure thresholds, and since elevated blood pressure is common in patients with AIS,6772 Additionally, in a post-hoc analysis of the second European Cooperative Acute Stroke Study (ECASS), increasing baseline, maximum and mean (per 10 mm Hg) systolic blood pressure levels were associated with a higher risk of parenchymal haemorrhage during the 7 first days after symptom onset in AIS.73 Similarly, in a post-hoc analysis of third International Stroke Trial, the odds of sICH increased by 10% (95%CI: 2–19%) for each 10 mm Hg increase in baseline systolic blood pressure, after adjustment for baseline stroke severity.74 Many of these have studies illustrated a linear relationship between increasing systolic or diastolic blood pressure levels and the likelihood of sICH and of death or dependency.7074 They have also indicated that intensive blood pressure control (below the recommended levels of 180/105 mm Hg) during or after alteplase is safe, and may further improve clinical outcomes and reduce the rates of any or symptomatic intracranial bleeding.76Conversely, evidence from large, non-randomised real world evidence studies and meta-analyses suggest that elevated blood pressure levels before or during IVT may be related to adverse clinical and imaging outcomes including a higher risk of symptomatic intracranial haemorrhage (sICH), a lower likelihood of complete recanalisation and three-month good functional outcome (mRS scores of 0–2) or three-month functional improvement .25 However, there is considerable observational data showing that blood pressure protocol violations are common among AIS patients treated with IVT.78 In particular, a single-centre observational study reported that pre-treatment blood pressure violations (>185/110 mm Hg) occurred in 12% of AIS treated with IVT in everyday clinical practice and were independently associated with higher likelihood of sICH .79 Moreover, in a recent retrospective analysis of the Safe Implementation of Treatments in Stroke (SITS) thrombolysis registry in regard to 11 off-label criteria related to the European license for alteplase, elevated pre-treatment blood pressure levels represented the only off-label criterion that was independently associated with a higher odds of sICH .77 Finally, a post-hoc analysis of a phase III RCT of sono-thrombolysis that implemented a robust blood pressure control protocol using serial blood pressure recordings before during and after alteplase infusions reported a high rate (34%) of blood pressure excursions above the prespecified thresholds among AIS patients treated with IVT. Most notable was that blood pressure excursions above guideline thresholds were associated with adverse clinical  and imaging (any ICH at 24 hours) outcomes.78 The heterogeneity of the study populations needs to be considered when interpreting these results: patients had different AIS subtypes (large vessel occlusion vs. lacunar stroke), different medical histories (with or without history of hypertension) and received different blood-pressure lowering therapies . Finally, no specific antihypertensive agent has been tested for controlling elevated blood pressure levels (exceeding the recommended thresholds before or during IVT for AIS).There is no randomised evidence of the safety and efficacy of blood pressure lowering therapies in AIS patients treated with IVT that exceed guideline-recommended blood pressure thresholds .80 2196 patients with systolic blood pressure > 150 mm Hg who were eligible for IVT with alteplase were randomised to intensive blood pressure lowering (target systolic blood pressure 130–140 mm Hg within 1 hour) or to a standard target systolic blood pressure (<180 mm Hg), and for maintenance of such levels over 72 hours. Mean systolic blood pressure over 24 hours was 144 ± 10 mm Hg in the intensive group and 150 ± 12 mm Hg in the control group.80 Functional outcome at 90 days did not differ between groups . However, fewer patients in the intensive group (14.8%) than in the control group (18.7%) had any ICH . Blood pressure reduction was also associated with a non-significant decrease in type 2 parenchymal haemorrhage .80 The health-related quality of life was assessed as an overall health utility score (EQ-5D) and no differences were observed between the two treatment groups.80The Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) investigated the safety and efficacy of blood pressure lowering strategies in AIS patients treated with IVT according to guideline criteria (blood pressure levels < 185/110 mm Hg).81 First, the study design was open-label and blinded-endpoint adjudication. Second, the mean difference in systolic blood pressure levels during the first 24 hours between the active and control treatment group was modest differing by < 7 mm Hg rather than the planned 15 mm Hg; this may have limited the possibility to detect significant treatment effects between groups. Third, included patients already had blood pressure controlled below the 185/110 mm Hg thresholds and may have received blood pressure lowering treatment prior to inclusion. Fourth, almost three quarters of randomised patients were from Asia where the pattern of cerebrovascular disease differs from the West. Finally, advanced imaging was not included in the selection of patients, and thus the potential of exclusion of patients with higher risk of sICH who may have benefited the most from intensive blood pressure lowering treatment strategies.Certain methodological concerns need to be taken into account when interpreting ENCHANTED findings.82 Notably, in the prespecified subgroup analysis of severe stroke defined by computed tomography or magnetic resonance angiogram confirmation of large vessel occlusion, receipt of endovascular therapy, final diagnosis of large artery atherosclerotic disease, or high (>10) baseline NIHSS score there was no significant difference in the primary outcome of death or disability at three months in the two treatment arms. However, intensive blood pressure lowering significantly increased three-month mortality  compared with guideline blood pressure lowering, despite significantly lower clinician-reported ICH .83 The findings of the aforementioned post-hoc analysis may only serve for hypothesis generation and deserve further validation in future RCTs.The ENCHANTED trial observed no significant heterogeneity of the treatment effect (shift on 3-month mRS score) in subgroups including demographics , pre-treatment with antiplatelets, dose of alteplase (low vs. standard), stroke severity stratified by NIHSS scores and stroke subgroups where large vessel occlusion might be anticipated, AIS subtypes classified on the basis of clinician diagnosis of large vessel atherosclerosis, cardioembolism or lacunar stroke.37 A total of 204 and 221 patients were randomised to active and control groups respectively. GTN was not associated with improved three-month functional outcome compared to placebo .37A subgroup analysis of the ENOS trial within 48 hours of stroke onset compared GTN to no GTN in 425 AIS patients presenting with elevated systolic blood pressure levels (140–220 mm Hg) who also received treatment with intravenous alteplase.84 However, this was not confirmed in the RIGHT-2 trial, although the GTN group had a trend towards less haemorrhagic transformation .29An individual patient data meta-analysis of different RCTs evaluating the safety and efficacy of NO for blood pressure management in acute stroke has reported that among 98 AIS patients treated with IVT, GTN was associated with improved functional outcomes at three months compared to placebo .8587 approximately 46% of patients with successful reperfusion die or are left disabled following the procedure.88 Blood pressure management in the acute/subacute setting following recanalisation is a potential modifiable determinant of functional improvement in this population. However, data regarding the optimal blood pressure management for AIS undergoing successful MT is scarce89 and there is no clear consensus over the intensity of blood pressure (lowering or enhancement) before, during or after the MT.Despite MT becoming standard of care for patients with AIS due to large vessel occlusion of the anterior circulation over the last year,25 which have been arbitrarily adopted based on evidence regarding blood pressure management in the setting of IVT for AIS. The rationale of this recommendation is to avoid reperfusion haemorrhages associated with elevated blood pressure levels before, during and after MT for large vessel occlusion.Current AHA/ASA guidelines advocate thresholds of systolic blood pressure ≤180 mm Hg and diastolic blood pressure ≤105 mm Hg during and for the first 24 hours following MT,18 No specific blood pressure-lowering drug has been recommended. The quality of evidence is graded as low/very low and strength of recommendation is weak in both American25 and European18 recommendations.Current MT guidelines from the ESO and European Society for Minimally Invasive Neurological Therapy (ESMINT) recommend systolic and diastolic blood pressure levels < 180/105 mm Hg during and 24 hours after MT and specify the importance of avoiding drops in systolic blood pressure during the procedure.90The Society for Neuroscience in Anesthesiology and Critical Care Expert Consensus Statement, recommend that systolic blood pressure should be maintained >140 mm Hg (fluids and vasopressors) and < 180 mm Hg (with or without IVT), and diastolic blood pressure < 105 mm Hg  during endovascular treatment for AIS.There is a paucity of RCT data regarding the potential safety and efficacy of blood pressure lowering therapies in MT-treated AIS patients with large vessel occlusion that receive endovascular reperfusion therapies. Most large vessel occlusion patients enrolled in the RCTs within 6 hours of symptom onset had received IVT before MT and the trial protocols stipulated management according to local guidelines with systolic or diastolic blood pressure levels ≤180/105 mm Hg during and for 24 hours after the procedure.9194Nevertheless, there are observational data indicating that extremely high systolic and/or diastolic blood pressure levels (>220/120 mm Hg) before MT for large vessel occlusion stroke are associated with worse clinical and imaging outcomes including higher rates of sICH, mortality and functional dependence.95 An analysis of individual patient data from 3 RCTs (SAGA Collaborators) reported that both low (<70 mm Hg) and high (>90 mm Hg) mean arterial blood pressure levels during MT were associated with worse functional outcomes at three months.96 Also, a 10% mean arterial blood pressure drop from baseline during MT for AIS has been related to worse 3-month functional outcomes regardless of sedation modality.97 Other observational studies and meta-analysis also showed that mean arterial blood pressure falls ≥10% during the endovascular procedure, intra-procedural mean arterial blood pressure levels < 70 mm Hg for a duration of ≥10 min and mean arterial blood pressure < 100 mm Hg before recanalisation are associated with adverse clinical outcomes in MT-treated patients.98100 These observations support the hypothesis that a decrease in systemic blood pressure may lead to hypoperfusion of ischaemic penumbra and cause an increase in final infarction sizes.100There are also observational data indicating that hypotension is frequent during MT, can mainly be explained by sedation modality  and appears to be associated with infarct expansion and worse functional outcomes at three months..101104There are accruing observational evidence that extremely elevated systolic and/or diastolic blood pressure levels after MT for large vessel occlusion stroke appear also to be associated with worse clinical and imaging outcomes including higher rates of sICH, mortality and functional dependence and this association may be mediated by recanalisation status following MT105Moreover, increased systolic blood pressure variability appears to be associated with adverse clinical outcomes in large vessel occlusion patients treated with MT independent of blood pressure levels.However, the heterogeneity of study populations needs to be considered when interpreting these results according to recanalisation status , different blood pressure parameters , medical history , reperfusion strategy (direct thrombectomy vs. bridging therapy with IVT and MT) and different blood pressure lowering agents .106 There were no safety concerns with trial procedures and all feasibility targets were achieved.There is one pilot RCT assessing the feasibility of differential systolic blood pressure targeting during MT for anterior circulation ischaemic stroke. This trial randomly assigned 51 patients to receive either standard or augmented systolic blood pressure management from the start of anaesthesia to recanalisation of the target vessel.107 In the control group, intraprocedural systolic blood pressure target range is 140–180 mm Hg. The intervention group is the individualised approach, which is maintaining the intraprocedural systolic blood pressure at the level on presentation (±10 mm Hg). The primary endpoint is the 90-day mRS score dichotomised by 0–2  to 3–6 . Secondary endpoints include early neurological improvement, infarction size, and systemic physiology monitor parameters. Another ongoing multicentre RCT in France will use PROBE design to assess the individualised approach of blood pressure management during MT.108 Patients randomised to the intervention group will be treated with an individualised approach, which is maintaining mean arterial blood pressure during MT within 10% of the first mean arterial blood pressure measurement before MT. In the control group, the intraprocedural systolic blood pressure target range will range between 140–180 mm Hg. The primary endpoint is good functional outcome at 90 days (mRS scores of 0–2). Secondary endpoints include early neurological improvement, excellent outcome, infarct size, systemic physiology monitor parameter, sICH rates and mortality at 3 months.Further randomised evidence on the intra-procedural management of blood pressure during MT will be provided by an ongoing explorative single-centre RCT with a PROBE  design.109112 The only completed RCT is the Blood Pressure Target in Acute Stroke to Reduce Haemorrhage After Endovascular Therapy (BP-TARGET) trial, a multicentre, prospective, randomised, controlled, open-label, blinded endpoint clinical trial conducted in France.114 The study enrolled AIS patients with large vessel occlusion in the anterior circulation who had successful reperfusion  grades of 2 b or 3) following MT. The enrolled patients were randomly assigned, in a 1:1 ratio, to have intensive (systolic blood pressure target 100–129 mm Hg) or a conservative (systolic blood pressure target 130–185 mm Hg) blood pressure control in the following 24 hours, with the primary efficacy endpoint of radiographic intraparenchymal haemorrhage at 24–36 hours and the primary safety endpoint of hypotension occurrence. Secondary endpoints included the rate of the sICH, the overall distribution of the mRS scores at 90 days, good functional outcome (90–day mRS scores of 0–2), functional improvement , infarct volume at follow-up CT scan at 24–36 h, change in NIHSS-scores at 24 hours, and all-cause mortality at 90 days. A total of 158 and 160 patients were randomised to the intensive and conservative systolic blood pressure groups respectively, with similar proportions of the primary endpoint (any ICH: 42% in the intensive group vs. 43% in the conservative group) and hypotension in the two treatment groups (8% in the intensive group vs. 3% in the conservative group). All secondary endpoints including three-month functional improvement , three-month good functional outcome  and three-month mortality (19% vs. 14%) were similar in the two treatment groups.113 The main methodological shortcoming of this RCT included: (i) modest systolic blood pressure difference (10 mm Hg) between the randomised groups; (ii) one third of the individuals in the conservative arm having systolic blood pressure measurements < 130 mm Hg; (iii) moderate sample size; (iv) primary endpoint being imaging, rather than clinical, (v) non-invasive modality of blood pressure assessment every 15 minutes for the first 2 hours, then every 30 minutes for 6 hours and every 1 hour for the remaining 16 hours.115 Labetalol or an intravenous beta-blocker such as metoprolol in low doses were recommended for post-procedural blood pressure management.115 The DAWN  trial protocol recommended maintaining systolic blood pressure < 140 mm Hg in the first 24 hours in subjects who were reperfused after MT.116Two protocols of RCTs evaluating the safety and efficacy of MT compared to standard therapy in AIS patients with anterior circulation large vessel occlusion have provided additional recommendations regarding optimal blood pressure management before and after the endovascular procedure. The ESCAPE  trial protocol stated that systolic blood pressure ≥150 mm Hg is probably useful in promoting and keeping collateral flow adequate, while the artery remained occluded, and that controlling blood pressure once reperfusion has been achieved and aiming for a normal blood pressure for that individual was sensible.117119 The advocated intraprocedural systolic blood pressure range until reperfusion was 140–160 mm Hg in SIESTA (Sedation vs. Intubation for Endovascular Stroke TreAtment) trial,117 140–180 mm Hg in ANSTROKE (Anaesthesia During Stroke) trial118 and >140 mm Hg in GOLIATH  trial.119Three RCTs investigating the optimal anaesthesia management  of large vessel occlusion patients treated with MT have suggested specific systolic blood pressure ranges during the procedures.121 In addition, different observational studies have evaluated blood pressure levels following successful recanalisation in AIS patients due to large vessel occlusion and have consistently reported an inverse association between increasing post-reperfusion blood pressures and good functional outcomes at three months.122124 They also highlight, that systolic blood pressure levels < 140 mm Hg post MT are related to the higher odds of good functional outcome. Also, a single-centre study has recently documented that spontaneous systolic blood pressure drop after MT is an early predictor of dramatic neurological recovery  in large vessel occlusion patients that receive endovascular treatment.125 There is no randomised data regarding the safety and efficacy of induced hypertension in large vessel occlusion patients who achieve successful reperfusion following endovascular therapy. Nevertheless, there are theoretical concerns against drug-induced hypertension in large vessel occlusion with complete recanalisation  following endovascular therapy. In particular, transcranial Doppler studies monitoring cerebral haemodynamics of AIS patients in real-time have shown that elevated flow velocities following complete recanalisation of large vessel occlusion may lead to hyperperfusion haemorrhage within the area of infarcted brain tissue in large vessel occlusion patients achieving mTICI 2 b/2c/3 grades following MT.126128Large vessel occlusion patients who undergo successful reperfusion documented as mTICI grades ≥2 b following endovascular therapy display spontaneous blood pressure drop due to potential earlier reperfusion of the ischaemic penumbra leading to earlier haemodynamic normalisation.129Dynamic autoregulation-based blood pressure targets instead of fixed blood pressure thresholds hold promise as a guide for individualising haemodynamic management in AIS due to large vessel occlusion. In a small observational study, a novel approach to define the limits of autoregulation using near-infrared spectroscopy (NIRS) was proposed. Continuous non-invasive NIRS monitoring in response to changes in mean arterial pressure was found to identify and track the patient-specific blood pressure range at which autoregulation was optimally functioning in individual patients after large vessel AIS.Expert consensus statementIn patients with acute ischaemic stroke due to large vessel occlusion who achieve successful reperfusion defined as modified Thrombolysis in Cerebral Infarction grade of 3 following mechanical thrombectomy we suggest against induced hypertension. Vote 10 of 10The hypertensive response seen in patients with AIS has traditionally been viewed as a pathophysiological response to ensure adequate cerebral perfusion in patients with compromised cerebral circulation. The rationale for pharmacologically inducing hypertension is to maintain adequate cerebral perfusion especially in patients with large vessel occlusion, fluctuating symptoms and low blood pressure who are not eligible for reperfusion or where reperfusion has failed.130 Patients with systolic blood pressure >170 mm Hg at baseline were excluded. The intervention group received treatment with intravenous phenylephrine with a target of 20% increase in systolic blood pressure from baseline. Induced hypertension was associated with early neurologic improvement at 7 days  though, this did not translate into functional improvement at 90 days : unadjusted common OR 1.27, 95%CI: 0.72–2.22, p = 0.422). Mortality at 90 days did not differ between the intervention group (1.3%) and the control group . The rates of patients with good functional outcome at 90 days tended to be higher in the intervention group . ICH on follow-up MRI was more prevalent in the induced hypertension group , however the rates of sICH were similar in the two groups .130 There are several limitations to the SETIN-HYPERTENSION trial. First, patients in the induced hypertension group were younger, were more often included due to stroke progression, had higher NIHSS scores and a higher rate of large vessel occlusions. Second, the small sample size and that the trial was conducted in Korea, generalisability is questionable.The Safety and Efficacy of Therapeutic Induced HYPERTENSION (SETIN-HYPERTENSION) randomised 153 patients with major neurological deficit (NIHSS-score 4–18) from non-cardioembolic stroke aetiology, ineligibility for reperfusion therapy or progressive stroke. Progressive stroke was defined as 2-point increase in the NIHSS score, including an increase in the motor score for the affected upper or lower limbs during hospitalisation and the presence of new lesions or infarct growth on DWI performed within 24 hour of aggravation.131 There was more improvement in NIHSS scores in the induced hypertension group compared to the control group on day 3 and on day 90.131 Since functional outcome was not assessed with mRS at 90 days the study was not included in our meta-analysis.In a pilot trial, 15 patients recruited within 7 days of symptom onset, with > 20% diffusion – perfusion mismatch on MRI and quantifiable, stable or worsening of aphasia, hemispatial neglect and/or hemiparesis were randomly assigned to induced hypertension with phenylephrine or control.132 Overall, systolic blood pressure was increased in 41% of the patients. Norepinephrine was used to increase blood pressure in 17% of patients in Group 1, 48% of patients in Group 2 and 62% of patients in Group 3. There was no difference between the groups in functional outcome at 90 days. Adverse events (acute coronary syndrome and bradycardia) were limited to group 2 (4%) and Group 3 (7.6%) and were associated with norepinephrine infusion. There was also a significantly higher sICH rate in Group 3.132The Early Manipulation of Arterial Blood Pressure in Acute Ischaemic Stroke (MAPAS) trial randomised 218 patients within 12 hours of acute ischaemic stroke to maintain systolic blood pressure during 24 hours within three ranges; Group 1: SBP target 140–160 mm Hg, Group 2: SBP target 161–180 mm Hg, and Group 3: SBP target 181–200 mm Hg.133137In addition, observational data from small pilot studies indicate that phenylephrine induced hypertension may be associated with neurological improvement in patients with AIS due to large artery atherosclerotic steno-occlusive disease or small vessel occlusion.Expert consensus statementIn patients with acute ischaemic stroke not treated with reperfusion therapies  and with clinical deterioration where a haemodynamic mechanism is suspected or shown to be directly responsible for the deterioration, we suggest:• stopping existing blood pressure lowering therapy,• administering intravenous fluids and• introducing non-pharmacological procedures to raise blood pressurebefore considering• careful use of vasopressor agents to increase blood pressure with close monitoring of blood pressure values. Vote 10 of 10.Blood pressure lowering therapy is a key strategy for the primary and secondary prevention of AIS and other serious cardiovascular events. However, it is unclear if continuing or stopping previous oral antihypertensive agents is beneficial in the AIS setting. Continuing prior antihypertensive agents may improve blood pressure control, however, may also lower blood pressure and worsen the perfusion of the critical hypoperfused brain tissue.138 In this study 763 patients who had acute stroke and were taking antihypertensive drugs were enrolled within 48 h of stroke onset. Among the overall group, 444 patients were included with AIS. In the predetermined subgroup analysis of AIS patients in COSSACS there was a benefit in death or dependency at three months (mRS scores ≥3) in the continue group versus the stop group .138One RCT examined the effect of continuing or stopping previous blood pressure lowering therapy in AIS. The Continue Or Stop post-Stroke Antihypertensives Collaborative Study (COSSACS) was a UK multicentre, prospective, randomised, open, blinded-endpoint trial.37ENOS was a multicentre, partial-factorial, randomised trial. In this study, 4011 patients who had stroke were enrolled within 48 h of stroke onset. Among the overall group, 928 patients with AIS were randomised to continue and 904 to stop antihypertensive treatment.139 Two trials138 were included in the meta-analysis on continuing versus stopping previous blood pressure lowering therapy. There were no significant differences of continuing versus stopping previous blood pressure lowering therapy on mortality  nor good functional outcome (mRS 0 – 2) .A meta-analysis of individual patient data from the COSSACS and Efficacy of Nitric Oxide in Stroke (ENOS) trial evaluated the effect of continuing versus stopping previous blood pressure-lowering therapy on death or dependency and included 2335 patients with AIS. There were no significant associations between continuing versus stopping previous blood pressure lowering therapy and the odds of death or improved functional outcome at 3–6 months in the AIS subgroup.139When deciding to continue or stop previous antihypertensive agents whether the patient has received reperfusion treatment, premorbid blood pressure values and the need for antihypertensive agents to maintain blood pressure within the recommended thresholds need to be considered. In case an antihypertensive is needed to maintain blood pressure values within the recommended range, continuation of previous antihypertensive agents may favour more stable blood pressure control. However, the continuation of oral antihypertensive agents may be challenging in patients with dysphagia and impaired consciousness. The route of application depends on the ability to swallow and/or the degree of consciousness.Expert consensus statementIn patients with acute ischaemic stroke we suggest stopping previous oral blood pressure lowering therapy in patients with dysphagia until swallowing is restored or a nasogastric tube is in place. Vote 10 of 10140The rationale behind decreasing blood pressure in acute spontaneous ICH is to reduce the driving force of haematoma expansion and thereby to prevent further clinical deterioration. Most haematoma expansion takes place within the first three hours.141 The trial recruited 404 patients. Blood pressure lowering drugs were administered according to a “stepped intravenous protocol to lower blood pressure” which was “established before the start of the study based on which drugs were available in that country” with urapidil being the most frequently used agent (47%). The primary efficacy endpoint  was significantly smaller in the intensive lowering group (13.7%) compared to the standard group .141 There was no difference in the risk of adverse events.141The INTensive blood pressure reduction in Acute Cerebral Haemorrhage trial (INTERACT); compared intensive lowering with a target systolic blood pressure of <140 mm Hg within 1 hour (intensive group) with a moderate lowering with a target systolic blood pressure of <180 mm Hg within 6 hours (standard group) after spontaneous ICH.21 However, the pre-defined secondary endpoint  showed significantly lower mRS scores with intensive treatment . The rates of non-fatal serious adverse events did not differ between the groups.21INTERACT-2 recruited 2839 patients using the identical treatment protocol as the INTERACT trial. There was no signficant difference in the primary outcome (death or dependency at 90 days defined as mRS scores of 3–6) .(ATACH-II) trial compared intensive (target systolic blood pressure 111–140 mm Hg) with moderate (target systolic blood pressure 140–180 mm Hg) blood pressure lowering with intravenous nicardipine in patients with spontaneous ICH within 4.5 hours of symptom onset.142 The trial recruited 1000 patients and there were no differences between the intensive and moderate groups in primary endpoint (death or disability at three months defined as mRS-scores of 4–6): adjusted relative risk (RR): 1.04; 95% CI: 0.85–1.27. There was a significantly higher rate of renal adverse events within 7 days after randomisation in the intensive treatment group .142 A post-hoc-analysis of ATACH-II showed a significant reduction on haematoma expansion within 24 hours and a significantly better functional outcome at three months when blood pressure lowering was initiated within 2 hours of symptom onset.143The Antihypertensive Treatment of Acute Cerebral Haemorrhage-II 50 The trial compared an individualised blood pressure lowering strategy with standard blood pressure lowering. In the subgroup of ICH (n = 242), the rates of the primary endpoint  were similar in the standard blood pressure lowering group  and in the individualised blood pressure lowering group .50 There was no difference in mortality rates (12% vs. 13%).The Controlling Hypertension After Severe Cerebrovascular Event (CHASE) trial included a mixed population with either severe AIS or ICH patients presenting with systolic blood pressure levels ranging between 150 mm Hg and 210 mm Hg.51The Controlling Hypertension and Hypotension Immediately Post Stroke (CHHIPS) included a mixed population of patients with AIS (n = 154) and ICH (n = 25) presenting with systolic blood pressure higher than 160 mm Hg on admission who were treated with labetalol (n = 58), lisinopril (n = 58) or placebo (n = 63). The primary endpoint (death or dependency at 2 weeks) occurred in 14 of 18 patients treated with labetalol or lisinopril (“active treatment”) and 3 of 7 placebo patients in the ICH subgroup. Death occurred in 2 and 0 patients in the active and placebo arms, respectively.144 In the subgroup of 61 ICH patients treated within 6 hours, GTN was associated with lower odds of functional worsening at three months  and lower 3-month mortality rates .144In the subgroup of 629 patients with ICH included in ENOS, GTN was not associated with functional worsening : adjusted common OR: 1.04; 95%CI: 0.78–1.38). There was no association between GTN and three-month mortality .29 Since treatment with GTN was initiated in the ambulance prior to imaging whether these results are due to chance, confounding or the true effect of GTN remains uncertain.In the subgroup of 145 patients with confirmed ICH included in the RIGHT-2 trial, patients in the GTN group tended to have worse functional outcomes at three months . More patients in the GTN died in hospital , but there was no difference in death at 90 days .145 There was no difference in the primary endpoint (mRS-scores of 3–6 at 90 days) between the two treatment groups .145Gupta and co-workers randomised 118 patients with ICH within 72 hours of symptom onset to tight blood pressure control if mean arterial pressure exceeded 115 mm Hg or to conventional blood pressure control if mean arterial pressure ≥130 mm Hg. Patients were randomised within 1 hour of admission and treatment was continued for 72 hours.146 Treatment duration was 48 hours. The rates of the primary endpoint  were similar in the aggressive (1/21) and standard (2/21) treatment groups. There were also no differences in 3-month mortality or haematoma expansion .146Koch and co-workers randomised 42 patients with ICH within 8 hours of symptom onset to either aggressive  or standard treatment .147In the subgroup analysis of 274 patients with ICH in the SCAST trial, patients in the candesartan group had significantly worse functional outcome , adjusted common OR 1.61, 95% CI: 1.03–2.50.149 At 2 hours, the mean systolic blood pressure was significantly lower in the <150 mm Hg group. However, the primary endpoint  was not different between the two treatment groups. There were no significant differences in mortality rates at day 30: 18% in the <150 mm Hg group and 11% in the <180 mm Hg group, and no difference in functional outcomes at 90 days.149The Intracerebral Haemorrhage Acutely Decreasing Arterial Pressure Trial (ICH-ADAPT) evaluated the influence of systolic blood pressure lowering on cerebral blood flow (CBF). Patients with acute ICH and systolic blood pressure >150 mm Hg on admission, brain CT within 24 hours after symptom onset and no contraindication to CT angiography were randomised to systolic blood pressure target of <150 mm Hg (n = 39) compared to a systolic blood pressure target of <180 mm Hg (n = 36) to be reached within 1 hour of randomisation.150 The primary endpoint was the incidence of re-haemorrhage within 7 days after randomisation “defined as a greater postoperative haematoma volume, a difference of ≤5 mL between the pre- and postoperative haematoma volumes or a difference of ≥5 mL in haematoma volumes between the first postoperative computed tomography and the subsequent computed tomography”. The re-haemorrhage rates did not differ between the intensive (11%) and conservative (14%) groups. The mortality rates at 90 days were also similar.150The Perioperative Antihypertensive Treatment in Patients With Spontaneous Intracerebral Haemorrhage (PATICH) was a single centre, assessor-blinded RCT that investigated the effect of peri-operative anti-hypertensive therapy. Adult patients with imaging-proven (brain CT or MRI) acute ICH, elevated systolic blood pressure (150–220 mm Hg) and the need for surgery within 24 hours after onset were randomised within 1 hour of admission to an intensive treatment group  or conservative treatment group .2 = 0%; 144,145150 Treatment time window varied between 3 and 72 hours. Subgroup analyses of mortality according to time to treatment revealed no significant associations between blood pressure lowering and mortality at three to six months at different time windows .In order to achieve rapid and controlled blood pressure lowering, drugs used need to be fast-acting with a short half-life time to reduce the risk of excessive blood pressure lowering. Most of the currently used antihypertensives  do only partially fulfil these criteria. Clevidipine is a calcium channel antagonist with a half-life time of 1.5 minutes that may be effective in blood pressure control of patients with acute ICH. Graffagnino and co-workers published a very small prospective case-series of 35 patients with acute ICH treated with clevidipine.153 The question remains: Why does reduction of haematoma expansion not translate into a clinical benefit? Our hypothesis is as follows: The clinical benefit in ICH is primarily derived by preventing lesion increase ( = haematoma expansion). An individual patient data meta-analysis of 5435 acute ICH patients identified two strong predictors of haematoma expansion. First, the time from onset to first brain CT and second, the volume of baseline ICH.140 Most haematoma expansion occurred within the first three hours after onset of ICH. The probability of haematoma expansion increased with the volume of the initial lesion up to 75 ml.140 In the five RCTs on blood pressure lowering for hyperacute ICH, the mean time from ICH onset to treatment in was 5.7 hours. This timeframe is at least 2 hours longer than the time period where haematoma expansion most commonly occurs.21,141,142,146,149In conclusion, early (<6 hours from symptom) lowering of blood pressure leads to a reduction of haematoma expansion in acute ICH patients. Haematoma expansion is strongly and independently associated with adverse functional outcome at three months in acute ICH.21,141,142,146,149 Since the evidence available is primarily from patients with small haematoma volume, uncertainty remains regarding the effect of blood pressure lowering in patients with large initial haematoma volumes. Also, it should be noted that in addition to haematoma expansion there are other factors impacting 3-month functional outcome in acute ICH including neurocritical care, location of baseline haematoma volume, end-of-life health policies across different countries and these factors may have moderated or diluted the potential association of early (<6 h) intensive blood pressure lowering and functional outcome at three months.The mean volume of the initial lesion in the five RCTs was 14 ml, which may be too small to show a clinically meaningful change by preventing haematoma expansion.154 The spot sign is commonly assumed to represent continued bleeding  from ruptured vessels surrounding the initial haematoma. The spot sign has been associated with both haematoma expansion and poor clinical outcomes in acute ICH patients.155 SCORE-IT (Spot Sign Score in Restricting ICH Growth) is a preplanned prospective observational study nested in the ATACH-II RCT including consecutive patients with primary ICH who underwent a CT angiography within 8 hours from onset.156 A total of 133 patients were included in this preplanned analysis. Of these, 40% had a spot sign, and 20% experienced haematoma expansion. After adjustment for potential confounders, intensive blood pressure treatment was not associated with a significant reduction of haematoma expansion  or functional outcome  in spot sign–positive patients.A robust marker of ongoing bleeding, studied extensively over the past years, is the CT angiography spot sign.Expert consensus statementIn patients with acute intracerebral haemorrhage, we suggest initiating antihypertensive treatment as early as possible and ideally within 2 hours of symptom onset. The decrease of systolic blood pressure should not exceed 90 mm Hg from baseline values. Vote 10 of 10.In patients with acute intracerebral haemorrhage, we suggest lowering blood pressure according to recommended levels beyond 6 hours after onset of treatment for at least 24 hours and up to 72 hours to reduce haematoma expansion. Vote 10 of 10.Blood pressure lowering therapy is a key strategy for the primary and secondary prevention of ICH and other serious cardiovascular events. However, it is unclear if it is better to continue or temporarily stop prior ongoing antihypertensive agent(s) in the setting of an acute ICH. One theoretical argument in favour of continuing blood pressure lowering therapy in acute ICH is related to more effective blood pressure control that in turn may limit haematoma expansion. On the other hand, it may be argued that continuing oral antihypertensive agents may worsen functional outcome due to compromise in cerebral blood flow and perihaematomal perfusion; furthermore, it may increase the risk of aspiration pneumonia.157 There was no difference in mRS scores between the treatment groups at day 90 . There was no significant difference in mortality between the 2 groups at day 90 .157 There was no information on haematoma expansion.One RCT, ENOS, included 246 patients with acute ICH and elevated systolic blood pressure (140–220 mm Hg) who were previously on antihypertensive therapy. The patients were randomised to continue or stop previous blood pressure lowering treatment for seven days.139 The meta-analysis indicated no significant association of continuing versus stopping previous blood pressure lowering therapy with the odds of death or the improved functional outcome in the subgroup of patients with ICH  among the group members.Many questions regarding blood pressure management in acute stroke remain unanswered. First, in both patients with AIS and ICH blood pressure is a highly individual parameter and the association between blood pressure and outcome is likely to be multifactorial. The “one-target fits all” may not be appropriate in acute stroke settings, and future trials should consider premorbid hypertension, baseline blood pressure values and relative reductions in baseline blood pressure rather than arbitrary absolute blood pressure targets. As shown in the evidence presented in these guidelines, the detrimental effect of high blood pressure on both short- and long-term outcome in AIS is not altered by blood pressure lowering. There are also multiple stroke related factors contributing to elevated blood pressure levels in AIS including ischaemic stroke subtype, recanalisation status and collateral flow that should be considered in the design of future trials. In addition, future trials should differentiate between the different blood pressure management strategies before, during and after successful reperfusion evaluating personalised autoregulation-oriented blood pressure thresholds.For patients with acute ICH we have shown effects of blood pressure lowering on haematoma growth within a narrow time window of 6 hours but not on functional outcome. Overall, haematoma size in the patients included in the trials was small and treatment was in some of the trials initiated treatment up to 48 hours after symptom onset, which is likely too late to influence outcome. There is also the possibility that manipulating blood pressure is not effective enough alone to influence functional outcome but may work synergistically as part of a bundle of care that can carry a greater impact on functional outcome. Future trials should investigate the efficacy of blood pressure lowering therapies in the hyperacute time window of first 6 hours following symptom onset in patients with acute ICH and evaluate blood pressure lowering agents that reduce blood pressure variability in addition to absolute blood pressure levels.Blood pressure in patients with suspected stroke should not be treated in the ambulanceIf the stroke is due to a blood clot in the arteries:Blood pressure should not be treated unless the blood pressure is very high (systolic blood pressure >220 mm Hg) or if the patients can receive treatment with clot-busting drugs (thrombolytics) or clot-fishing (endovascular treatment).Giving drugs to increase blood pressure should be avoided in the majority of patientsIf the patient is already under treatment with blood pressure lowering drugs at the time of admission these should be stopped in patients who cannot swallowIf the stroke is caused by a brain bleed:Elevated blood pressure should be treated as early as possible after symptom onsetIf patients are already under treatment with blood pressure drugs these should be continued during the hospital stayThe majority of patients with stroke either due to blood clots (ischaemic stroke) or brain bleeds  have high blood pressure both in the ambulance and on admission to the hospital. We know that high blood pressure in the acute phase of stroke can lead to death, new strokes and poor functional outcome. Despite this, we don’t know whether we should treat high blood pressure as the damaged brain might need higher blood pressure to ensure adequate blood flow. The guideline authors provide ten recommendation, the most important being:Click here for additional data file.Supplemental material, sj-pdf-1-eso-10.1177_23969873211012133 for European Stroke Organisation (ESO) guidelines on blood pressure management in acute ischaemic stroke and intracerebral haemorrhage by Else Charlotte Sandset, Craig S Anderson, Philip M Bath, Hanne Christensen, Urs Fischer, Dariusz Gąsecki, Avtar Lal, Lisa S Manning, Simona Sacco, Thorsten Steiner and Georgios Tsivgoulis in European Stroke Journal