Background and purpose
The Blood Pressure Target in Acute Ischemic Stroke to Reduce Hemorrhage After Endovascular Therapy (BP TARGET) trial evaluated whether an intensive systolic blood pressure ...(SBP) target resulted in reduced rates of intracranial hemorrhage (ICH) after successful endovascular therapy (EVT) but did not assess the effect of blood pressure variability (BPV) on functional outcomes and ICH occurrence. We sought to evaluate this question in the BP TARGET trial.
Methods
We performed a post hoc analysis of the BP TARGET trial and included patients with at least 50% of blood pressure (BP) recordings during the first 24 h after EVT. BPV parameters were SBP and diastolic BP (DBP) coefficient of variation (CV), standard deviation (SD), maximum–minimum (max–min), successive variation (SV), and time rate. The primary outcome was favorable functional outcome (3‐month modified Rankin Scale between 0 and 2); the secondary outcome was the rate of ICH at 24 h.
Results
We included 290 patients (mean number of BP measures = 30.4, SD = 8.0). BPV parameters (SBPSD, SBPmax–min, SBPCV) were higher in the intensive SBP target group. Only DBP BPV parameters were associated with worse functional outcomes in the unadjusted model (DBPSD, DBPmax–min, DBPCV, and DBPSV), but not after adjustment. Higher SBPmax–min was associated with worse functional outcomes in Thrombolysis in Cerebral Infarction 2B patients (odds ratio OR = 0.62, 95% confidence interval CI = 0.38–1.02), but not in patients with complete reperfusion (OR = 1.27, 95% CI = 0.80–2.02, p for heterogeneity (phet=0.037). None of the BPV parameters was associated with ICH, regardless of the randomization group or the reperfusion grade.
Conclusions
BPV was significantly higher in the intensive SBP target group but was not associated with functional outcome or ICH.
To date, current European guidelines suggest that neurologists should monitor blood pressure (BP) noninvasively and not actively reduce systolic BP to <130 mmHg during the first 24 h after successful endovascular therapy (EVT). The present findings also suggest against BP fluctuation, notably by the intermittent use of bolus, discontinuation, and reinitiation of intravenous antihypertensive treatments such as nicardipine. Finally, further analyses are needed to clarify the impact of BP management according to the reperfusion status. Current guidelines do not suggest a distinction based on the specific reperfusion status (i.e., Thrombolysis in Cerebral Infarction 2B vs. 3) regarding BP management after successful EVT.
High systolic blood pressure after successful endovascular therapy for acute ischaemic stroke is associated with increased risk of intraparenchymal haemorrhage. However, no randomised controlled ...trials are available to guide optimal management. We therefore aimed to assess whether an intensive systolic blood pressure target resulted in reduced rates of intraparenchymal haemorrhage compared with a standard systolic blood pressure target.
We did a multicentre, open-label, randomised controlled trial at four academic hospital centres in France. Eligible individuals were adults (aged ≥18 years) with an acute ischaemic stroke due to a large-vessel occlusion that was successfully treated with endovascular therapy. Patients were randomly assigned (1:1) to either an intensive systolic blood pressure target group (100–129 mm Hg) or a standard care systolic blood pressure target group (130–185 mm Hg), by means of a central web-based procedure, stratified by centre and intravenous thrombolysis use before endovascular therapy. In both groups, the target systolic blood pressure had to be achieved within 1 h after randomisation and maintained for 24 h with intravenous blood pressure lowering treatments. The primary outcome was the rate of radiographic intraparenchymal haemorrhage at 24–36 h and the primary safety outcome was the occurrence of hypotension. Analyses were done on an intention-to-treat basis. BP-TARGET is registered with ClinicalTrials.gov, number NCT03160677, and the trial is closed at all participating sites.
Between June 21, 2017, and Sept 27, 2019, 324 patients were enrolled in the four participating stroke centres: 162 patients were randomly assigned to the intensive target group and 162 to the standard target group. Four (2%) of 162 patients were excluded from the intensive target group and two (1%) of 162 from the standard target group for withdrawal of consent or legal reasons. The mean systolic blood pressure during the first 24 h after reperfusion was 128 mm Hg (SD 11) in the intensive target group and 138 mm Hg (17) in the standard target group. The primary outcome was observed in 65 (42%) of 154 patients in the intensive target group and 68 (43%) of 157 in the standard target group on brain CT within 24–36 h after reperfusion (adjusted odds ratio 0·96, 95% CI 0·60–1·51; p=0·84). Hypotensive events were not significantly different between both groups and occurred in 12 (8%) of 158 patients in the intensive target and five (3%) of 160 in the standard target group. Mortality within the first week after randomisation occurred in 11 (7%) of 158 patients in the intensive target group and in seven (4%) of 160 in the standard target group.
An intensive systolic blood pressure target of 100–129 mm Hg after successful endovascular therapy did not reduce radiographic intraparenchymal haemorrhage rates at 24–36 h as compared with a standard care systolic blood pressure target of 130–185 mm Hg. Notably, these results are applicable to patients with successful reperfusion and systolic blood pressures of more than 130 mm Hg at the end of procedure. Further studies are needed to understand the association between blood pressure and outcomes after reperfusion.
French Health Ministry.
30% more strokes are expected by 2030. To face this incoming huge public health challenge, large-scale projects for primary, secondary and tertiary prevention of neurovascular risk have to be ...developed. French new advanced nursing practices will be most promising if they are based on the timeliness of pathology follow-up but also on leadership in training, research and innovation in the care pathway for stroke victims.
Cerebral infarction (CI) is caused by intracranial artery occlusion. The main treatment approach is recanalisation, which is performed either medically, by intravenous thrombolysis within 4 hours and ...a half of the event, or by mechanical thrombectomy, which is possible up to 24 hours after CI.
Acute ischemic stroke (AIS) patients with a history of hypertension experience worse outcomes, which may be explained by a deleterious impact of the renin-angiotensin system (RAS) overactivation. We ...sought to investigate whether prestroke antihypertensive treatments (AHT) influenced baseline stroke severity and neurological outcomes, in patients with AIS successfully treated by endovascular therapy.
We performed a post hoc analysis of the BP TARGET trial (Blood Pressure Target in Acute Stroke to Reduce Hemorrhage After Endovascular Therapy) and included hypertensive patients with available data regarding AHT at admission, categorized as RAS inhibitors (ACE angiotensin-converting enzyme inhibitors, ARBs angiotensin 2 receptor blockers, and β-blockers) and non-RAS inhibitors (calcium channel blockers and diuretics). Associations of each AHT with National Institutes of Health Stroke Scale (NIHSS) score at baseline were investigated in linear mixed model adjusted for the number of treatments and center. Associations of each AHT with 24-hour NIHSS change, intracranial hemorrhage were performed using linear mixed model adjusted for baseline NIHSS, the number of treatments, center, age, and sex and adjusted for age, sex, diabetes, and current smoking for favorable outcome. All analyses were performed on cases-available data regarding the low number of missing data.
Overall, 203 patients with at least one AHT were included. Patients under non-RAS inhibitor treatments had a higher NIHSS score at baseline (adjusted mean difference=3.28 95% CI, 1.33-5.22;
=0.001). Conversely, patients under RAS inhibitor treatments had a lower baseline NIHSS score (adjusted mean difference=-2.81 95% CI, -5.37 to -0.25;
=0.031). Intracranial hemorrhage occurrence was significantly more frequent in patients under non-RAS inhibitor treatments (adjusted odds ratio of 2.48 95% CI, 1.12-5.47;
=0.025). Conversely, the use of RAS inhibitor treatments before AIS was not associated with higher odds of radiographic intracranial hemorrhage. Patients with non-RAS inhibitor treatments had less improvement of NIHSS at 24 hours compared with patients without (adjusted mean difference, 2.83 95% CI, -0.16 to 5.81;
=0.063). Baseline RAS inhibitor or noninhibitor treatments were not associated with favorable outcome.
We showed an opposite effect of baseline AHT, based on their effect on the RAS. Patients treated with RAS inhibitor agents before AIS exhibited less severe AIS compared with patients under non-RAS inhibitor treatments, developed less intracranial hemorrhage at 24 hours and had a trend toward better NIHSS score at 24 hours.
URL: https://www.
gov; Unique identifier: NCT03160677.
To assess the association between systolic blood pressure change (ΔSBP) at different time intervals after successful reperfusion with radiographic and clinical outcomes.
This is a post hoc analysis ...of the BP-TARGET multicenter trial (Blood Pressure Target in Acute Stroke to Reduce Hemorrhage After Endovascular Therapy). ΔSBP was defined as end of procedure SBP minus mean SBP at different time intervals (15-60 minutes, 1-6 hours, and 6-24 hours postprocedure). The primary outcome was the poor functional outcome (90-day modified Rankin Scale score 3-6).
We included a total of 267 patients (130 in the intensive treatment group). Compared with patients with favorable outcome, patients with poor outcome had lower ΔSBP (less SBP reduction) at all times intervals. After adjusting for potential confounders including baseline SBP, both ΔSBP
and ΔSBP
were associated with lower odds of poor outcome (adjusted odds ratio per 5 mm Hg SBP reduction, 0.89 95% CI, 0.81-0.99, and adjusted odds ratio 0.82 95% CI, 0.73-0.92, respectively). Concerning safety outcomes, patients with intraparenchymal hemorrhage had lower ΔSBP at all time intervals. ΔSBP
was associated with lower odds of any intraparenchymal hemorrhage (adjusted odds ratio per 5 mm Hg SBP reduction 0.91 95% CI, 0.83-0.99). Conversely, ΔSBP was not associated with mortality or neurological deterioration at any time interval.
After successful reperfusion, ΔSBP had a linear relationship with poor outcome and the risk of poor outcome was higher with less reduction from the baseline SBP. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03160677.
Background and purpose
Acute ischaemic stroke patients with cerebral small vessel disease (CSVD), including cerebral microbleeds (CMBs) and white matter hyperintensities (WMHs), have worse outcomes. ...The effect was investigated of two blood pressure strategies (intensive vs. standard) and blood pressure variability (BPV) after reperfusion according to CSVD burden in the BP TARGET trial.
Methods
Patients with available magnetic resonance imaging at baseline were included. CMBs were described as absent or present and WMH severity was described according to the Fazekas classification (0–1, absent–mild; 2–3, moderate to severe). Outcomes consisted of any intracerebral hemorrhage (ICH) at 24 h and favorable outcome at 90 days (modified Rankin Scale score between 0 and 2).
Results
In all, 246 patients were included. The intensive systolic blood pressure target was not associated with lower rates of ICH or favorable outcome according to CSVD subgroups (all p values >0.35). Several BPV parameters were associated with increased odds of ICH in patients with CMBs but not in patients without CMBs (diastolic blood pressure coefficient of variation, odds ratio 2.06, 95% confidence interval CI 1.13–3.77, in patients with ≥1 CMB vs. 0.94, 95% CI 0.68–1.31, in patients without CMBs, phet = 0.026). Several diastolic BPV parameters were associated with worse outcomes in patients with severe WMHs but not in patients without WMHs (diastolic blood pressure coefficient of variation, odds ratio 0.32, 95% CI 0.17–0.61, in patients with severe WMHs vs. 1.09, 95% CI 0.67–1.79, in patients without WMHs; phet = 0.003).
Conclusion
No effect of the intensive systolic blood pressure management strategy was found on ICH occurrence or functional outcome according to CSVD burden. BPV was associated with higher odds of ICH in patients with CMBs and worse outcome in patients with moderate‐to‐severe WMHs.
Stroke is a cerebrovascular disorder characterised by the sudden onset of symptoms and clinical signs. Each year, an estimated 140,000 people in France are hospitalised for stroke. Ischemic stroke is ...the most common kind of stroke, accounting for 80% of all cases. Haemorrhagic stroke accounts for about 20% of all strokes.
Accumulating evidence indicates that neutrophil activation (NA) contributes to microvascular thromboinflammation in acute ischemic stroke (AIS) due to a large vessel occlusion. Preclinical data have ...suggested that intravenous thrombolysis (IVT) before endovascular therapy (EVT) could dampen microvascular thromboinflammation. In this study we investigated the association between NA dynamics and stroke outcome, and the impact of IVT on NA in patients with AIS treated with EVT.
A single-center prospective study was carried out, including patients treated with EVT for whom three blood samples (before, within 1 hour, 24 hours post-EVT) were drawn to measure plasma myeloperoxidase (MPO) concentration as a marker of NA. Unfavorable outcome was defined as a modified Rankin score of 3-6 at 3 months.
Between 2016 and 2020, 179 patients were included. The plasma MPO concentration peaked significantly 1 hour post-EVT (median increase 21.0 ng/mL (IQR -2.1-150)) and returned to pre-EVT baseline values 24 hours after EVT (median change from baseline -0.8 ng/mL (IQR -7.6-6.7)). This peak was strongly associated with unfavorable outcomes at 3 months (aOR 0.53 (95% CI 0.34 to 0.84), P=0.007). IVT before EVT abolished this 1 hour post-EVT MPO peak. Changes in plasma MPO concentration (baseline to 1 hour post-EVT) were associated with unfavorable outcomes only in patients not treated with IVT before EVT (aOR 0.54 (95% CI 0.33 to 0.88, P=0.013). However, we found no significant heterogeneity in the associations between changes in plasma MPO concentration and outcomes.
A peak in plasma MPO concentration occurs early after EVT and is associated with unfavorable outcomes. IVT abolished the post-EVT MPO peak and may modulate the association between NA and outcomes.
Abstract
Background
Hypotension and blood pressure (BP) variability during endovascular therapy (EVT) for acute ischemic stroke (AIS) due to an anterior large vessel occlusion (LVO) is associated ...with worse outcomes. However, the optimal BP threshold during EVT is still unknown given the lack of randomized controlled evidence. We designed the DETERMINE trial to assess whether an individualized BP management during EVT could achieve better functional outcomes compared to a standard BP management.
Methods
The DETERMINE trial is a multicenter, prospective, randomized, controlled, open-label, blinded endpoint clinical trial (PROBE design). AIS patients with a proximal anterior LVO are randomly assigned, in a 1:1 ratio, to an experimental arm in which mean arterial pressure (MAP) is maintained within 10% of the first MAP measured before EVT, or a control arm in which systolic BP (SBP) is maintained within 140–180 mm Hg until reperfusion is achieved or artery closure in case of EVT failure. The primary outcome is the rate of favorable functional outcomes, defined by a modified Rankin Scale (mRS) between 0 and 2 at 90 days. Secondary outcomes include excellent outcome and ordinal analysis of the mRS at 90 days, early neurological improvement at 24 h (National Institutes of Health Stroke Scale), final infarct volume, symptomatic intracranial hemorrhage rates, and all-cause mortality at 90 days. Overall, 432 patients will be included.
Discussion
DETERMINE will assess the clinical relevance of an individualized BP management before reperfusion compared to the one size fits all approach currently recommended by international guidelines.
Trial registration
ClinicalTrials.gov
,
NCT04352296.
Registered on 20th April 2020.
