Use of the Win Ratio for Analysis of Stroke Trials: Description, Illustration, and Planned Use in the Second European Carotid Surgery Trial (ECST-2).

Randomized trials in stroke often focus on outcomes beyond a single clinical event. Trials of stroke prevention commonly use composite outcomes that include multiple components (eg, death, stroke, or myocardial infarction). A major limitation is that all events count equally but may differ markedly in terms of clinical severity. Trials in acute stroke often use ordinal outcomes or scale scores. Limitations include the requirement for statistical assumptions and the difficulty of handling the competing risk of death. We introduce the win ratio as an alternative method. It works by placing components of a composite into a hierarchy, whereby clinically more important outcomes take priority over less important ones. We illustrate how it works using data from 2 major stroke trials: the ICSS (International Carotid Stenting Study, a trial in stroke prevention) and the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Potential benefits of the win ratio approach include the possibility to (1) emphasize the clinically most important outcomes, (2) combine components of different outcome types into a composite (eg, a mixture of time-to-event, continuous, and categorical), and (3) naturally handle the competing risk of death in analyses of quantitative outcomes. The win ratio will be used in the upcoming analysis of the ECST-2 (Second European Carotid Surgery Trial), which has a hierarchical primary outcome of (1) time to perioperative death, fatal stroke, or fatal myocardial infarction (most important); (2) time to nonfatal stroke; (3) time to nonfatal myocardial infarction (excluding silent infarcts); and (4) new silent cerebral infarct on brain imaging (least important). The win ratio provides a useful clinically relevant method for analyzing trial outcomes. It has some advantages over conventional methods, and we recommend its wider application in future stroke trials.

Similar long-term outcomes for venous, bovine pericardial, and polyester patches for primary carotid endarterectomy.

BACKGROUND: Currently, the type of patch used for carotid endarterectomy closure depends on the preference of the operating surgeon. Various materials are available, including autologous venous patches, bovine pericardial patches (BPP), and synthetic patches. The purpose of this study was to compare the long-term outcomes. METHODS: All patients who underwent primary carotid endarterectomy with patch angioplasty using a venous, bovine, or polyester patch between 2010 and 2020 at two high-volume medical centers were included in this retrospective analysis on largely prospectively collected data. Study endpoints included long-term ipsilateral transient ischemic attack or cerebrovascular accident, restenosis, reintervention, and all-cause mortality. Cox proportional hazard models were fitted to assess the effect of patch type to each outcome. RESULTS: In total, 1481 CEAs were performed with a follow-up of 32 (13-65) months. Venous patch was used in 309 patients (20.9%), BPP in 1000 patients (67.5%), and polyester patch in 172 patients (11.6%). A preoperative symptomatic carotid artery stenosis of >50% was observed in 91.9% (n = 284) of the patients who received a venous patch, 92.1% (n = 921) of the patients who received BPP, and 90.7% (n = 156) of the patients who received a polyester patch (p = 0.799). Only in selected patients with an asymptomatic stenosis of >70% surgery was considered. Multivariable analyses showed no significant differences between the three patch types regarding long-term outcomes after adjusting for confounders. CONCLUSIONS: In patients undergoing primary carotid endarterectomy, the use of venous, bovine pericardial, or polyester patches seems equally safe and durable in terms of comparability in long-term outcomes.

Stronger pinch strength at long-term follow-up after pyrocarbon disc interposition arthroplasty compared to trapeziectomy with ligament reconstruction and tendon interposition for CMC-1 osteoarthritis.

BACKGROUND/INTRODUCTION: In this study, we wanted to compare the pyrocarbon disc interposition arthroplasty (PDI) with trapeziectomy plus ligament reconstruction tendon interposition (LRTI). Primarily, we tested whether PDI resulted in a higher pinch strength. Secondarily, we compared the grip strength, range of motion (ROM), patient reported outcomes, satisfaction and complications. METHODS: Due to scarcity of preoperative hand measurements, we performed a descriptional cross-sectional cohort study of patients operated between 2006 and 2014, with a minimum of 5 years of follow-up. Patients were treated with PDI or LRTI. We determined key pinch strength as primary outcome, followed by tip- and tripod pinch, grip strength, palmar abduction and opposition; the Michigan Hand Outcome Questionnaire (MHQ), Patient Reported hand and Wrist evaluation (PRWHE), satisfaction and complications. Propensity score matching was used to match both study groups on demographic variables. A ratio of 2:1 was used resulting in inclusion of 62 (of 154) PDI and 31 (of 31) LRTI thumbs. RESULTS: The PDI-group patients showed stronger key and tip pinch strength than the LRTI group (p=0.027 and p=0.036 respectively). Tripod pinch, grip strength and ROM were equal for both groups. MHQ and PRWHE were comparable, with higher satisfaction for the PDI group. Eight PDI patients were converted to LRTI due to pain. CONCLUSION/DISCUSSION: This study confirmed our hypothesis that key and tip pinch strength is stronger after PDI compared to LRTI for CMC-1 joint osteoarthritis. Both techniques have comparable outcomes considering patient reported outcome (MHQ and PRWHE), ROM and complications.

Long-Term Stroke Risk in Patients With New Ischemic Brain Lesions on MRI After Carotid Revascularization.

BACKGROUND: Carotid artery revascularization can result in new ischemic brain lesions on diffusion-weighted magnetic resonance imaging. This study aimed to investigate the relationship between periprocedural ischemic diffusion-weighted imaging (DWI) lesions after carotid artery revascularization and recurrent long-term cerebrovascular events. METHODS: A secondary observational prospective cohort analysis of existing clinical trial data was performed on 162 patients with symptomatic carotid stenosis that were previously randomized to carotid artery stenting or carotid endarterectomy in the ICSS (International Carotid Stenting Study) and included in the magnetic resonance imaging substudy. Magnetic resonance imagings were performed 1 to 7 days before and 1 to 3 days after treatment. The primary composite clinical outcome was the time to any stroke or transient ischemic attack during follow-up. Patients with new diffusion-weighted imaging (DWI) lesions on posttreatment magnetic resonance imaging scan (DWI+) were compared with patients without new lesions (DWI-). RESULTS: The median time of follow-up was 8.6 years (interquartile range, 5.0-12.5). Kaplan-Meier cumulative incidence for the primary outcome after 12.5-year follow-up was 35.3% (SE, 8.9%) in DWI+ patients and 31.1% (SE, 5.6%) in DWI- patients. Uni- and multivariable regression analyses did not show significant differences (hazard ratio, 1.50 [95% CI, 0.76-2.94] and hazard ratio, 1.30 [95% CI, 0.10-1.02], respectively). Higher event rate of the primary outcome in DWI+ patients in the overall cohort was mainly caused by events in the carotid artery stenting group. CONCLUSIONS: Based on our outcome analysis within the ICSS magnetic resonance imaging substudy, DWI lesions following carotid revascularization did not seem to have a relationship with long-term stroke risk. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: ISRCTN 25337470.

Patch angioplasty during carotid endarterectomy using different materials has similar clinical outcomes.

OBJECTIVE: Patch angioplasty during carotid endarterectomy (CEA) is commonly used to treat carotid artery stenosis. However, the choice of which patch to use remains a matter of debate. Autologous venous material has disadvantages such as wound-related problems at the harvest site and a prolonged intervention time. These limitations can be bypassed when synthetic or biological patches are used. Both materials have been associated with divergent advantages and disadvantages. Therefore, the aim of our study was to compare the long-term follow-up outcomes in patients who underwent CEA and closure with either a bovine pericardial patch (BPP) or polyester patch. METHODS: A retrospective cohort study was conducted including all patients who underwent primary CEA and closure with a BPP or a polyester patch between January 2010 and December 2020 at our tertiary referral center. In 2015, the BPP was introduced as an alternative for polyester. The primary outcome was the occurrence of transient ischemic attack (TIA) or cerebrovascular accident (CVA) during follow-up and secondary outcomes included restenosis, reintervention, all-cause mortality, and patch infection. Cox proportional hazard models were used and hazard ratios with 95% confidence intervals were used to predict these outcomes. RESULTS: We included 417 CEA patients; 254 patients (61%) received a BPP and 163 received (39%) a polyester patch. The mean age was 70.2 ± 8.7 years and 67% were male. The median follow-up time was 15 months (range, 12-27 months) for BPP and 42 months (range, 16-60 months) for polyester (P < .001). Postoperative hematoma (≤30 days) was significantly lower in the BPP cohort (2% BPP vs 6% polyester; P = .047). No other significant differences on short-term outcomes were found. Univariable Cox regression analyses showed no significant differences between the effect estimates of polyester and BPP on TIA or CVA (P = .106), restenosis (P = .211), reintervention (P = .549), or all-cause mortality (P = .158). No significant differences were found after adjusting for confounders in the multivariable analyses: TIA or CVA (P = .939), restenosis (P = .057), reintervention (P = .193) and all-cause mortality (P = .742). Three patients with a polyester patch had patch infection compared with none of the patients in the group who received a BPP. CONCLUSIONS: This large retrospective study showed comparable safety and durability of both BPP and polyester suggesting that both patch types can be safely applied for CEA with patch angioplasty. Patch infection was rare and was absent in the BPP group.

Editor's Choice - Risk of Bleeding Complications With Different Peri-Operative Antithrombotic Regimens During Carotid Endarterectomy: a National Registry Analysis.

OBJECTIVE: Antithrombotic therapy is one of the cornerstones of the prevention of (recurrent) ocular or cerebral ischaemic events in patients with carotid artery stenosis. Randomised controlled trials on antithrombotic therapy for patients with minor ischaemic stroke and transient ischaemic attack (TIA) have recommended dual antiplatelet therapy (DAPT) in the three weeks following the index event. However, these trials excluded patients undergoing carotid revascularisation. To date, the optimal antithrombotic therapy during the peri-operative period of carotid endarterectomy (CEA) remains unclear. METHODS: Symptomatic and asymptomatic patients with carotid artery stenosis undergoing primary CEA from the Dutch Audit for Carotid Interventions registry between June 2013 and December 2020 were eligible for inclusion. The primary outcome was defined as post-operative cervical bleeding needing re-intervention or intracranial haemorrhage during the first 30 days following CEA. The secondary outcomes were ischaemic stroke or TIA or all cause mortality during the first 30 days following CEA. Descriptive statistics and multiple logistic regressions analyses were applied, with acetylsalicylic acid (ASA) as the reference value. RESULTS: A total of 12 317 patients were included. In the peri-operative phase, 31.0% of patients were treated with ASA, 32.4% with clopidogrel, 11.1% with ASA plus clopidogrel, 10.4% with ASA plus dipyridamole, 10.3% with vitamin K antagonist, and 4.8% with direct acting oral anticoagulants therapy. After multiple logistic regression analysis, no association was seen with the primary outcome in ASA plus clopidogrel (odds ratio [OR] 0.81; confidence interval [CI] 0.58 - 1.13; p = .23), and ASA plus dipyridamole (OR 0.69; CI 0.47 - 1.00; p = .059). Both the DAPT therapies were not associated with the secondary outcome. CONCLUSION: The effectiveness and safety of DAPT did not differ from single antiplatelet therapy (SAPT) in patients undergoing CEA and further evaluation is needed in prospective studies. Considering additional data from the literature and guideline recommendations, DAPT should be started immediately after stroke until 30 days after CEA followed by SAPT, due to a possible reduction in the risk of recurrence.

A narrative review of plaque and brain imaging biomarkers for stroke risk stratification in patients with atherosclerotic carotid artery disease.

OBJECTIVE: In this narrative review, we aim to review imaging biomarkers that carry the potential to non-invasively guide stroke risk stratification for treatment optimization. BACKGROUND: Carotid atherosclerosis plays a fundamental part in the occurrence of ischemic stroke. International guidelines select the optimal treatment strategy still mainly based on the presence of clinical symptoms and the degree of stenosis for stroke prevention in patients with atherosclerotic carotid plaques. These guidelines, based on randomized controlled trials that were conducted three decades ago, recommend carotid revascularization in symptomatic patients with high degree of stenosis versus a conservative approach for most asymptomatic patients. Due to optimization of best medical therapy and risk factor control, it is suggested that a subgroup of symptomatic patients is at lower risk of stroke and may not benefit from revascularization, whereas a selective subgroup of high-risk asymptomatic patients would benefit from this procedure. METHODS: A literature search was performed for articles published up to December 2020 using PubMed, EMBASE and Scopus. Based on the literature found, change in stenosis degree and volume, plaque echolucency, plaque surface, intraplaque haemorrhage, lipid-rich necrotic core, thin fibrous cap, inflammation, neovascularization, microembolic signals, cerebrovascular reserve, intracranial collaterals, silent brain infarcts, diffusion weighted imaging lesions and white matters lesions have the potential to predict stroke risk. CONCLUSIONS: The applicability of imaging biomarkers needs to be further improved before the potential synergistic prognostic ability of imaging biomarkers can be verified on top of the clinical biomarkers. In the future, the routine and combined assessment of both plaque and brain imaging biomarkers might help to improve optimization of treatment strategies in individual patients with atherosclerotic carotid artery disease.