Safety and efficacy of intensive blood pressure lowering after successful endovascular therapy in acute ischaemic stroke (BP-TARGET): a multicentre, open-label, randomised controlled trial

International audienceBACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: French Health Ministry. Copyrigh

Effect of emergent carotid stenting during endovascular therapy for acute anterior circulation stroke patients with tandem occlusion: A multicenter, randomized, clinical trial (TITAN) protocol

International audienceBackground and hypothesis: There is no consensus on the optimal endovascular management of the extracranial internal carotid artery steno-occlusive lesion in patients with acute ischemic stroke due to tandem occlusion. We hypothesized that intracranial mechanical thrombectomy plus emergent internal carotid artery stenting (and at least one antiplatelet therapy) is superior to intracranial mechanical thrombectomy alone in patients with acute tandem occlusion. Study design: TITAN is an investigator-initiated, multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) study. Eligibility requires a diagnosis of acute ischemic stroke, pre-stroke modified Rankin Scale (mRS)≤2 (no upper age limit), National Institutes of Health Stroke Scale (NIHSS)≥6, Alberta Stroke Program Early Computed Tomography Score (ASPECTS)≥6, and tandem occlusion on the initial catheter angiogram. Tandem occlusion is defined as large vessel occlusion (intracranial internal carotid artery, M1 and/or M2 segment) and extracranial severe internal carotid artery stenosis ≥90% (NASCET) or complete occlusion. Patients are randomized in two balanced parallel groups (1:1) to receive either intracranial mechanical thrombectomy plus internal carotid artery stenting (and at least one antiplatelet therapy) or intracranial mechanical thrombectomy alone within 8 h of stroke onset. Up to 432 patients are randomized after tandem occlusion confirmation on angiogram. Study outcomes: The primary outcome measure is complete reperfusion rate at the end of endovascular procedure, assessed as a modified Thrombolysis in Cerebral Infarction (mTICI) 3, and ≥4 point decrease in NIHSS at 24 h. Secondary outcomes include infarct growth, recurrent clinical ischemic event in the ipsilateral carotid territory, type and dose of antiplatelet therapy used, mRS at 90 (±15) days and 12 (±1) months. Safety outcomes are procedural complications, stent patency, intracerebral hemorrhage, and death. Economics analysis includes health-related quality of life, and costs utility comparison, especially with the need or not of endarterectomy. Discussion: TITAN is the first randomized trial directly comparing two types of treatment in patients with acute ischemic stroke due to anterior circulation tandem occlusion, and especially assessing the safety and efficacy of emergent internal carotid artery stenting associated with at least one antiplatelet therapy in the acute phase of stroke reperfusion. Trial registration: ClinicalTrials.gov NCT0397898

Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Background: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. Methods: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. Findings: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09–2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75–3·10, p<0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14–2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons