BACKGROUND: Symptomatic intracranial hemorrhage (sICH) is a serious complication after endovascular treatment for ischemic stroke. We aimed to identify determinants of its occurrence and location... Show moreBACKGROUND: Symptomatic intracranial hemorrhage (sICH) is a serious complication after endovascular treatment for ischemic stroke. We aimed to identify determinants of its occurrence and location.METHODS: We retrospectively analyzed data from the Dutch MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and MR CLEAN registry. We included adult patients with a large vessel occlusion in the anterior circulation who underwent endovascular treatment within 6.5 hours of stroke onset. We used univariable and multivariable logistic regression analyses to identify determinants of overall sICH occurrence, sICH within infarcted brain tissue, and sICH outside infarcted brain tissue.RESULTS: SICH occurred in 203 (6%) of 3313 included patients and was located within infarcted brain tissue in 50 (25%), outside infarcted brain tissue in 23 (11%), and both within and outside infarcted brain tissue in 116 (57%) patients. In 14 patients (7%), data on location were missing. Prior antiplatelet use, baseline systolic blood pressure, baseline plasma glucose levels, post-endovascular treatment modified treatment in cerebral ischemia score, and duration of procedure were associated with all outcome parameters. In addition, determinants of sICH within infarcted brain tissue included history of myocardial infarction (adjusted odds ratio, 1.65 [95% CI, 1.06-2.56]) and poor collateral score (adjusted odds ratio, 1.42 [95% CI, 1.02-1.95]), whereas determinants of sICH outside infarcted brain tissue included level of occlusion on computed tomography angiography (internal carotid artery or internal carotid artery terminus compared with M1: adjusted odds ratio, 1.79 [95% CI 1.16-2.78]).CONCLUSIONS: Several factors, some potentially modifiable, are associated with sICH occurrence. Further studies should investigate whether modification of baseline systolic blood pressure or plasma glucose level could reduce the risk of sICH. In addition, determinants differ per location of sICH, supporting the hypothesis of varying underlying mechanisms.[GRAPHICS]. Show less
Steen, W. van der; Sluijs, P.M. van der; Graaf, R.A. van de; Su, R.S.; Wolff, L.; Voorst, H. van; ... ; MR CLEAN-MED Investigators 2022
Objectives: We aimed to evaluate whether the overall harmful effect of periprocedural treatment with aspirin or heparin during endovascular stroke treatment is different in patients with a... Show moreObjectives: We aimed to evaluate whether the overall harmful effect of periprocedural treatment with aspirin or heparin during endovascular stroke treatment is different in patients with a successful reperfusion after the procedure. Materials and methods: We performed a post-hoc analysis of the MR CLEAN-MED trial, including adult patients with a large vessel occlusion in the anterior circulation eligible for endovascular treatment (EVT). In this trial, patients were randomized for periprocedural intravenous treatment with aspirin or no aspirin (1:1 ratio), and for moderatedose unfractionated heparin, low-dose unfractionated heparin or no unfractionated heparin (1:1:1 ratio). We tested for interaction between the post-EVT extended thrombolysis in cerebral infarction (eTICI) score and treatment with periprocedural medication with multivariable regression analyses. The primary outcome was the modified Rankin Scale score at 90 days. Secondary outcomes were final infarct volume, intracranial hemorrhage, and symptomatic intracranial hemorrhage. Results: Of 534 included patients, 93 (17%) had a post-EVT eTICI score of 0-2a, 115 (22%) a score of 2b, 73 (14%) a score of 2c, and 253 (47%) a score of 3. For both aspirin and heparin, we found no interaction between post-EVT eTICI score and treatment on the modified Rankin Scale score (p=0.76 and p=0.47, respectively). We found an interaction between post-EVT eTICI score and treatment with heparin on the final infarct volume (p=0.01). Of note, this interaction showed a biologically implausible distribution over the subgroups. Conclusions: The overall harmful effect of periprocedural aspirin and unfractionated heparin is not different in patients with a successful reperfusion after EVT. Show less
Steen, W. van der; Ende, N.A.M. van der; Kranendonk, K.R. van; Chalos, V.; Brouwer, J.; Oostenbrugge, R.J. van; ... ; MR Clean Registry Investigators 2022
Introduction: Little is known about the timing of occurrence of symptomatic intracranial hemorrhage (sICH) after endovascular therapy (EVT) for acute ischemic stroke. A better understanding could... Show moreIntroduction: Little is known about the timing of occurrence of symptomatic intracranial hemorrhage (sICH) after endovascular therapy (EVT) for acute ischemic stroke. A better understanding could optimize in-hospital surveillance time points and duration. The aim of this study was to delineate the probability of sICH over time and to identify factors associated with its timing. Patients and methods: We retrospectively analyzed data from the Dutch MR CLEAN trial and MR CLEAN Registry. We included adult patients who underwent EVT for an anterior circulation large vessel occlusion within 6.5 h of stroke onset. In patients with sICH (defined as ICH causing an increase of > 4 points on the National Institutes of Health Stroke Scale [NIHSS]), univariable and multivariable linear regression analysis was used to identify factors associated with the timing of sICH. This was defined as the time between end of EVT and the time of first CT-scan on which ICH was seen as a proxy. Results: SICH occurred in 205 (6%) of 3391 included patients. Median time from end of EVT procedure to sICH detection on NCCT was 9.0 [IQR 2.9-22.5] hours, with a rapidly decreasing incidence after 24 h. None of the analyzed factors, including baseline NIHSS, intravenous alteplase treatment, and poor reperfusion at the end of the procedure were associated with the timing of sICH. Conclusion: SICHs primarily occur in the first hours after EVT, and less frequently beyond 24 h. Guidelines that recommend to perform frequent neurological assessments for at least 24 h after intravenous alteplase treatment can be applied to ischemic stroke patients treated with EVT. Show less
Background Aspirin and unfractionated heparin are often used during endovascular stroke treatment to improve reperfusion and outcomes. However, the effects and risks of anti-thrombotics for this... Show moreBackground Aspirin and unfractionated heparin are often used during endovascular stroke treatment to improve reperfusion and outcomes. However, the effects and risks of anti-thrombotics for this indication are unknown. We therefore aimed to assess the safety and efficacy of intravenous aspirin, unfractionated heparin, both, or neither started during endovascular treatment in patients with ischaemic stroke.Methods We did an open-label, multicentre, randomised controlled trial with a 2 x 3 factorial design in 15 centres in the Netherlands. We enrolled adult patients (ie, >= 18 years) with ischaemic stroke due to an intracranial large-vessel occlusion in the anterior circulation in whom endovascular treatment could be initiated within 6 h of symptom onset. Eligible patients had a score of 2 or more on the National Institutes of Health Stroke Scale, and a CT or MRI ruling out intracranial haemorrhage. Randomisation was done using a web-based procedure with permuted blocks and stratified by centre. Patients were randomly assigned (1:1) to receive either periprocedural intravenous aspirin (300 mg bolus) or no aspirin, and randomly assigned (1:1:1) to receive moderate-dose unfractionated heparin (5000 IU bolus followed by 1250 IU/h for 6 h), low-dose unfractionated heparin (5000 IU bolus followed by 500 IU/h for 6 h), or no unfractionated heparin. The primary outcome was the score on the modified Rankin Scale at 90 days. Symptomatic intracranial haemorrhage was the main safety outcome. Analyses were based on intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. This trial is registered with the International Standard Randomised Controlled Trial Number, ISRCTN76741621.Findings Between Jan 22, 2018, and Jan 27, 2021, we randomly assigned 663 patients; of whom, 628 (95%) provided deferred consent or died before consent could be asked and were included in the modified intention-to-treat population. On Feb 4, 2021, after unblinding and analysis of the data, the trial steering committee permanently stopped patient recruitment and the trial was stopped for safety concerns. The risk of symptomatic intracranial haemorrhage was higher in patients allocated to receive aspirin than in those not receiving aspirin (43 [14%] of 310 vs 23 [7%] of 318; adjusted OR 1.95 [95% CI 1.13-3.35]) as well as in patients allocated to receive unfractionated heparin than in those not receiving unfractionated heparin (44 [13%] of 332 vs 22 [7%] of 296; 1.98 [1.14-3.46]). Both aspirin (adjusted common OR 0.91 [95% CI 0.69-1.21]) and unfractionated heparin (0.81 [0.61-1.08]) led to a non-significant shift towards worse modified Rankin Scale scores.Interpretation Periprocedural intravenous aspirin and unfractionated heparin during endovascular stroke treatment are both associated with an increased risk of symptomatic intracranial haemorrhage without evidence for a beneficial effect on functional outcome. Copyright (C) 2022 Published by Elsevier Ltd. All rights reserved. Show less
Background Aspirin and unfractionated heparin are often used during endovascular stroke treatment to improve reperfusion and outcomes. However, the effects and risks of anti-thrombotics for this... Show moreBackground Aspirin and unfractionated heparin are often used during endovascular stroke treatment to improve reperfusion and outcomes. However, the effects and risks of anti-thrombotics for this indication are unknown. We therefore aimed to assess the safety and efficacy of intravenous aspirin, unfractionated heparin, both, or neither started during endovascular treatment in patients with ischaemic stroke.Methods We did an open-label, multicentre, randomised controlled trial with a 2 x 3 factorial design in 15 centres in the Netherlands. We enrolled adult patients (ie, >= 18 years) with ischaemic stroke due to an intracranial large-vessel occlusion in the anterior circulation in whom endovascular treatment could be initiated within 6 h of symptom onset. Eligible patients had a score of 2 or more on the National Institutes of Health Stroke Scale, and a CT or MRI ruling out intracranial haemorrhage. Randomisation was done using a web-based procedure with permuted blocks and stratified by centre. Patients were randomly assigned (1:1) to receive either periprocedural intravenous aspirin (300 mg bolus) or no aspirin, and randomly assigned (1:1:1) to receive moderate-dose unfractionated heparin (5000 IU bolus followed by 1250 IU/h for 6 h), low-dose unfractionated heparin (5000 IU bolus followed by 500 IU/h for 6 h), or no unfractionated heparin. The primary outcome was the score on the modified Rankin Scale at 90 days. Symptomatic intracranial haemorrhage was the main safety outcome. Analyses were based on intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. This trial is registered with the International Standard Randomised Controlled Trial Number, ISRCTN76741621.Findings Between Jan 22, 2018, and Jan 27, 2021, we randomly assigned 663 patients; of whom, 628 (95%) provided deferred consent or died before consent could be asked and were included in the modified intention-to-treat population. On Feb 4, 2021, after unblinding and analysis of the data, the trial steering committee permanently stopped patient recruitment and the trial was stopped for safety concerns. The risk of symptomatic intracranial haemorrhage was higher in patients allocated to receive aspirin than in those not receiving aspirin (43 [14%] of 310 vs 23 [7%] of 318; adjusted OR 1.95 [95% CI 1.13-3.35]) as well as in patients allocated to receive unfractionated heparin than in those not receiving unfractionated heparin (44 [13%] of 332 vs 22 [7%] of 296; 1.98 [1.14-3.46]). Both aspirin (adjusted common OR 0.91 [95% CI 0.69-1.21]) and unfractionated heparin (0.81 [0.61-1.08]) led to a non-significant shift towards worse modified Rankin Scale scores.Interpretation Periprocedural intravenous aspirin and unfractionated heparin during endovascular stroke treatment are both associated with an increased risk of symptomatic intracranial haemorrhage without evidence for a beneficial effect on functional outcome. Copyright (C) 2022 Published by Elsevier Ltd. All rights reserved. Show less
Samuels, N.; Graaf, R.A. van de; Berg, C.A.L. van den; Venema, S.M.U.; Bala, K.; Doormaal, P.J. van; ... ; MR CLEAN Registry Investigators 2021
Background and Purpose: Optimal blood pressure (BP) management in the acute phase of ischemic stroke remains an unresolved issue. It is uncertain whether guidelines for BP management during and... Show moreBackground and Purpose: Optimal blood pressure (BP) management in the acute phase of ischemic stroke remains an unresolved issue. It is uncertain whether guidelines for BP management during and after intravenous alteplase can be extrapolated to endovascular treatment (EVT) for stroke due to large artery occlusion in the anterior circulation. We evaluated the associations between systolic BP (SBP) in the first 6 hours following EVT and functional outcome as well as symptomatic intracranial hemorrhage. Methods: Patients of 8 MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry centers, with available data on SBP in the 6 hours following EVT, were analyzed. We evaluated maximum, minimum, and mean SBP. Study outcomes were functional outcome (modified Rankin Scale) at 90 days and symptomatic intracranial hemorrhage. We used multivariable ordinal and binary regression analysis to adjust for important prognostic factors and studied possible effect modification by successful reperfusion. Results: Post-EVT SBP data were available for 1161/1796 patients. Higher maximum SBP (per 10 mm Hg increments) was associated with worse functional outcome (adjusted common odds ratio, 0.93 [95% CI, 0.88-0.98]) and a higher rate of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.17 [95% CI, 1.02-1.36]). The association between minimum SBP and functional outcome was nonlinear with an inflection point at 124 mm Hg. Minimum SBP lower and higher than the inflection point were associated with worse functional outcomes (adjusted common odds ratio, 0.85 per 10 mm Hg decrements [95% CI, 0.76-0.95] and adjusted common odds ratio, 0.81 per 10 mm Hg increments [95% CI, 0.71-0.92]). No association between mean SBP and functional outcome was observed. Successful reperfusion did not modify the relation of SBP with any of the outcomes. Conclusions: Maximum SBP in the first 6 hours following EVT is positively associated with worse functional outcome and an increased risk of symptomatic intracranial hemorrhage. Both lower and higher minimum SBP are associated with worse outcomes. A randomized trial to evaluate whether modifying post-intervention SBP results in better outcomes after EVT for ischemic stroke seems justified. Show less
