EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.

PURPOSE The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry. PARTICIPANTS All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS). FINDINGS TO DATE Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups. FUTURE PLANS This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements

Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage

Background: Rebleeding is an important cause of death and disability in people with aneurysmal subarachnoid haemorrhage. Rebleeding is probably related to the dissolution of the blood clot at the site of the aneurysm rupture by natural fibrinolytic activity. This review is an update of previously published Cochrane Reviews. Objectives: To assess the effects of antifibrinolytic treatment in people with aneurysmal subarachnoid haemorrhage. Search methods: We searched the Cochrane Stroke Group Trials Register (May 2022), CENTRAL (in the Cochrane Library 2021, Issue 1), MEDLINE (December 2012 to May 2022), and Embase (December 2012 to May 2022). In an effort to identify further published, unpublished, and ongoing studies, we searched reference lists and trial registers, performed forward tracking of relevant references, and contacted drug companies (the latter in previous versions of this review). Selection criteria: Randomised trials comparing oral or intravenous antifibrinolytic drugs (tranexamic acid, epsilon amino-caproic acid, or an equivalent) with control in people with subarachnoid haemorrhage of suspected or proven aneurysmal cause. Data collection and analysis: Two review authors (MRG & WJD) independently selected trials for inclusion, and extracted the data for the current update. In total, three review authors (MIB & MRG in the previous update; MRG & WJD in the current update) assessed risk of bias. For the primary outcome, we dichotomised the outcome scales into good and poor outcome, with poor outcome defined as death, vegetative state, or (moderate) severe disability, assessed with either the Glasgow Outcome Scale or the Modified Rankin Scale. We assessed death from any cause, rates of rebleeding, delayed cerebral ischaemia, and hydrocephalus per treatment group. We expressed effects as risk ratios (RR) with 95% confidence intervals (CI). We used random-effects models for all analyses. We assessed the quality of the evidence with GRADE. Main results: We included one new trial in this update, for a total of 11 included trials involving 2717 participants. The risk of bias was low in six studies. Five studies were open label, and we rated them at high risk of performance bias. We also rated one of these studies at high risk for attrition and reporting bias. Five trials reported on poor outcome (death, vegetative state, or (moderate) severe disability), with a pooled risk ratio (RR) of 1.03 (95% confidence interval (CI) 0.94 to 1.13; P = 0.53; 5 trials, 2359 participants; high-quality evidence), which showed no difference between groups. All trials reported on death from all causes, which showed no difference between groups, with a pooled RR of 1.02 (95% CI 0.90 to 1.16; P = 0.77; 11 trials, 2717 participants; high-quality evidence). In trials that combined short-term antifibrinolytic treatment (< 72 hours) with preventative measures for delayed cerebral ischaemia, the RR for poor outcome was 0.98 (95% CI 0.81 to 1.18; P = 0.83; 2 trials, 1318 participants; high-quality evidence). Antifibrinolytic treatment reduced the risk of rebleeding, reported at the end of follow-up (RR 0.65, 95% CI 0.47 to 0.91; P = 0.01; 11 trials, 2717 participants; absolute risk reduction 7%, 95% CI 3 to 12%; moderate-quality evidence), but there was heterogeneity (I² = 59%) between the trials. The pooled RR for delayed cerebral ischaemia was 1.27 (95% CI 1.00 to 1.62; P = 0.05; 7 trials, 2484 participants; moderate-quality evidence). However, this effect was less extreme after the implementation of ischaemia preventative measures and < 72 hours of treatment (RR 1.10, 95% CI 0.83 to 1.46; P = 0.49; 2 trials, 1318 participants; high-quality evidence). Antifibrinolytic treatment showed no effect on the reported rate of hydrocephalus (RR 1.09, 95% CI 0.99 to 1.20; P = 0.09; 6 trials, 1992 participants; high-quality evidence). Authors' conclusions: The current evidence does not support the routine use of antifibrinolytic drugs in the treatment of people with aneurysmal subarachnoid haemorrhage. More specifically, early administration with concomitant treatment strategies to prevent delayed cerebral ischaemia does not improve clinical outcome. There is sufficient evidence from multiple randomised controlled trials to incorporate this conclusion in treatment guideline

Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage

Background: Rebleeding is an important cause of death and disability in people with aneurysmal subarachnoid haemorrhage. Rebleeding is probably related to the dissolution of the blood clot at the site of the aneurysm rupture by natural fibrinolytic activity. This review is an update of previously published Cochrane Reviews. Objectives: To assess the effects of antifibrinolytic treatment in people with aneurysmal subarachnoid haemorrhage. Search methods: We searched the Cochrane Stroke Group Trials Register (May 2022), CENTRAL (in the Cochrane Library 2021, Issue 1), MEDLINE (December 2012 to May 2022), and Embase (December 2012 to May 2022). In an effort to identify further published, unpublished, and ongoing studies, we searched reference lists and trial registers, performed forward tracking of relevant references, and contacted drug companies (the latter in previous versions of this review). Selection criteria: Randomised trials comparing oral or intravenous antifibrinolytic drugs (tranexamic acid, epsilon amino-caproic acid, or an equivalent) with control in people with subarachnoid haemorrhage of suspected or proven aneurysmal cause. Data collection and analysis: Two review authors (MRG & WJD) independently selected trials for inclusion, and extracted the data for the current update. In total, three review authors (MIB & MRG in the previous update; MRG & WJD in the current update) assessed risk of bias. For the primary outcome, we dichotomised the outcome scales into good and poor outcome, with poor outcome defined as death, vegetative state, or (moderate) severe disability, assessed with either the Glasgow Outcome Scale or the Modified Rankin Scale. We assessed death from any cause, rates of rebleeding, delayed cerebral ischaemia, and hydrocephalus per treatment group. We expressed effects as risk ratios (RR) with 95% confidence intervals (CI). We used random-effects models for all analyses. We assessed the quality of the evidence with GRADE. Main results: We included one new trial in this update, for a total of 11 included trials involving 2717 participants. The risk of bias was low in six studies. Five studies were open label, and we rated them at high risk of performance bias. We also rated one of these studies at high risk for attrition and reporting bias. Five trials reported on poor outcome (death, vegetative state, or (moderate) severe disability), with a pooled risk ratio (RR) of 1.03 (95% confidence interval (CI) 0.94 to 1.13; P = 0.53; 5 trials, 2359 participants; high-quality evidence), which showed no difference between groups. All trials reported on death from all causes, which showed no difference between groups, with a pooled RR of 1.02 (95% CI 0.90 to 1.16; P = 0.77; 11 trials, 2717 participants; high-quality evidence). In trials that combined short-term antifibrinolytic treatment (< 72 hours) with preventative measures for delayed cerebral ischaemia, the RR for poor outcome was 0.98 (95% CI 0.81 to 1.18; P = 0.83; 2 trials, 1318 participants; high-quality evidence). Antifibrinolytic treatment reduced the risk of rebleeding, reported at the end of follow-up (RR 0.65, 95% CI 0.47 to 0.91; P = 0.01; 11 trials, 2717 participants; absolute risk reduction 7%, 95% CI 3 to 12%; moderate-quality evidence), but there was heterogeneity (I² = 59%) between the trials. The pooled RR for delayed cerebral ischaemia was 1.27 (95% CI 1.00 to 1.62; P = 0.05; 7 trials, 2484 participants; moderate-quality evidence). However, this effect was less extreme after the implementation of ischaemia preventative measures and < 72 hours of treatment (RR 1.10, 95% CI 0.83 to 1.46; P = 0.49; 2 trials, 1318 participants; high-quality evidence). Antifibrinolytic treatment showed no effect on the reported rate of hydrocephalus (RR 1.09, 95% CI 0.99 to 1.20; P = 0.09; 6 trials, 1992 participants; high-quality evidence). Authors' conclusions: The current evidence does not support the routine use of antifibrinolytic drugs in the treatment of people with aneurysmal subarachnoid haemorrhage. More specifically, early administration with concomitant treatment strategies to prevent delayed cerebral ischaemia does not improve clinical outcome. There is sufficient evidence from multiple randomised controlled trials to incorporate this conclusion in treatment guidelines

Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage

Rebleeding is an important cause of death and disability in people with aneurysmal subarachnoid haemorrhage. Rebleeding is probably related to dissolution of the blood clot at the site of aneurysm rupture by natural fibrinolytic activity. This review is an update of a previously published Cochrane review. To assess the effects of antifibrinolytic treatment in people with aneurysmal subarachnoid haemorrhage. We searched the Cochrane Stroke Group Trials Register (February 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 1), MEDLINE (1948 to December 2012), and EMBASE (1947 to December 2012). In an effort to identify further published, unpublished, and ongoing studies we searched reference lists and trial registers, performed forward tracking of relevant references and contacted drug companies. Randomised trials comparing oral or intravenous antifibrinolytic drugs (tranexamic acid, epsilon amino-caproic acid, or an equivalent) with control in people with subarachnoid haemorrhage of suspected or proven aneurysmal cause. Two review authors independently selected trials for inclusion and extracted the data. Three review authors assessed trial quality. For the primary outcome we converted the outcome scales between good and poor outcome for the analysis. We scored death from any cause and rates of rebleeding, cerebral ischaemia, and hydrocephalus per treatment group. We expressed effects as risk ratios (RR) with 95% confidence intervals (CI). We used random-effects models for all analyses. We included 10 trials involving 1904 participants. The risk of bias was low in six studies. Four studies were open label and were rated as high risk of performance bias. One of these studies was also rated as high risk for attrition bias. Four trials reported on poor outcome (death, vegetative state, or severe disability) with a pooled risk ratio (RR) of 1.02 (95% confidence interval (CI) 0.91 to 1.15). All trials reported on death from all causes with a pooled RR of 1.00 (95% CI 0.85 to 1.18). In a trial that combined short-term antifibrinolytic treatment ( <72 hours) with preventative measures for cerebral ischaemia the RR for poor outcome was 0.85 (95% CI 0.64 to 1.14). Antifibrinolytic treatment reduced the risk of re-bleeding reported at the end of follow-up (RR 0.65, 95% CI 0.44 to 0.97; 78 per 1000 participants), but there was heterogeneity (I^2 = 62%) between the trials. The pooled RR for reported cerebral ischaemia was 1.41 (95% CI 1.04 to 1.91, 83 per 1000 participants), again with heterogeneity between the trials (I^2 = 52%). Antifibrinolytic treatment showed no effect on the reported rate of hydrocephalus in five trials (RR 1.11, 95% CI 0.90 to 1.36). The current evidence does not support the use of antifibrinolytic drugs in the treatment of people with aneurysmal subarachnoid haemorrhage, even in those who have concomitant treatment strategies to prevent cerebral ischaemia. Results on short-term treatment are promising, but not conclusive. Further randomised trials evaluating short-term antifibrinolytic treatment are needed to evaluate its effectivenes

Variation in restarting antithrombotic drugs at hospital discharge after intracerebral hemorrhage

Whether intracerebral hemorrhage (ICH) survivors should restart antithrombotic drugs is unknown. We analyzed the frequency of restarting antithrombotic drugs in ICH survivors who had taken prophylactic antithrombotic drugs in atrial fibrillation or after thromboembolic disease in 5 cohorts and explored factors associated with doing so. We compared the characteristics and proportions of patients taking antithrombotic drugs at ICH onset and discharge in 4 hospital-based cohorts (Lille, France, n=542; Utrecht, The Netherlands, n=389; multicenter Clinical Relevance of Microbleeds in Stroke-2 (CROMIS-2) ICH, United Kingdom, n=667; and Amsterdam, The Netherlands, n=403) and 1 community-based study (Lothian, Scotland, n=137), using bivariate analyses. We sought characteristics associated with restarting using bivariate and multivariable logistic regression analyses. A total of 942 (44%) patients with ICH took antithrombotic drugs at hospital admission (no difference between cohorts). Antithrombotic drugs were restarted in 96 (20%) of the 469 survivors who had taken antithrombotic drugs for secondary prevention or atrial fibrillation, but this proportion differed when stratified by the cohort of origin (Lille, 18%; Utrecht, 45%; Lothian, 15%; CROMIS-2 ICH, 11%; Amsterdam, 20%; P <0.001) and by type of antithrombotic drug pre-ICH (14% in patients with previous antiplatelet drugs versus 26% in patients with previous vitamin K antagonists and 41% in patients with both drugs; P <0.001). We did not find other consistent, independent associations with restarting antithrombotic drugs. The variation in clinical practice and lack of consistent associations with restarting antithrombotic drugs after ICH reflect current knowledge and support the need for randomized controlled trials to resolve this dilemm

EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: Basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry

Purpose The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry. Participants All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS). Findings to date Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups. Future plans This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements