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BACKGROUND: Whereas the beneficial effect of antiplatelet therapy for recurrent stroke prevention has been well established, uncertainties remain regarding the optimal antithrombotic regimen for recently symptomatic carotid stenosis. We sought to explore the approaches of stroke physicians to antithrombotic management of patients with symptomatic carotid stenosis. METHODS: We employed a qualitative descriptive methodology to explore the decision-making approaches and opinions of physicians regarding antithrombotic regimens for symptomatic carotid stenosis. We conducted semi-structured interviews with a purposive sample of 22 stroke physicians (11 neurologists, 3 geriatricians, 5 interventional-neuroradiologists, and 3 neurosurgeons) from 16 centers on four continents to discuss symptomatic carotid stenosis management. We then conducted thematic analysis on the transcripts. RESULTS: Important themes revealed from our analysis included limitations of existing clinical trial evidence, competing surgeon versus neurologist/internist preferences, and the choice of antiplatelet therapy while awaiting revascularization. There was a greater concern for adverse events while using multiple antiplatelet agents (e.g., dual-antiplatelet therapy (DAPT)) in patients undergoing carotid endarterectomy compared to carotid artery stenting. Regional variations included more frequent use of single antiplatelet agents among European participants. Areas of uncertainty included antithrombotic management if already on an antiplatelet agent, implications of nonstenotic features of carotid disease, the role of newer antiplatelet agents or anticoagulants, platelet aggregation testing, and timing of DAPT. CONCLUSION: Our qualitative findings can help physicians critically examine the rationale underlying their own antithrombotic approaches to symptomatic carotid stenosis. Future clinical trials may wish to accommodate identified variations in practice patterns and areas of uncertainty to better inform clinical practice.

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Ischemic stroke (IS) is one of the most common causes of disability and death. Thrombolysis and neuroprotection are two current major therapeutic strategies to overcome ischemic and reperfusion damage. In this work, a novel peptide-templated manganese dioxide nanozyme (PNzyme/MnO2 ) is designed that integrates the thrombolytic activity of functional peptides with the reactive oxygen species scavenging ability of nanozymes. Through self-assembled polypeptides that contain multiple functional motifs, the novel peptide-templated nanozyme is able to bind fibrin in the thrombus, cross the blood-brain barrier, and finally accumulate in the ischemic neuronal tissues, where the thrombolytic motif is "switched-on" by the action of thrombin. In mice and rat IS models, the PNzyme/MnO2 prolongs the blood-circulation time and exhibits strong thrombolytic action, and reduces the ischemic damages in brain tissues. Moreover, this peptide-templated nanozyme also effectively inhibits the activation of astrocytes and the secretion of proinflammatory cytokines. These data indicate that the rationally designed PNzyme/MnO2 nanozyme exerts both thrombolytic and neuroprotective actions. Giving its long half-life in the blood and ability to target brain thrombi, the biocompatible nanozyme may serve as a novel therapeutic agent to improve the efficacy and prevent secondary thrombosis during the treatment of IS.

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The importance of Carotid Artery Perivascular Adipose Tissue Density (CAPATd), a parameter that can be readily evaluated on emergency computed tomographic angiography (CTA), in acute stroke has not been adequately clarified. We created exploratory logistic regression models to detect the interaction between the effect of CAPATd and intravenous (IV) tissue plasminogen activator (tPA) in 174 patients (mean age 71 ± 14 years, 94 women) with acute ischemic stroke treated with IV-tPA alone. The CAPATd-average mean (-60.6 ± 18.7 vs -89.8 ± 25.3 Hounsfield units (HU), P = .002) and CAPATd-maximum (14.8 ± 68.9 vs -20.5 ± 39.8 HU, P = .020) values were higher on the ipsilateral side of carotid artery stenosis >60%. CAPATd-maximum ipsilateral emerged as an independent predictor for both modified Rankin's Score 0-2 (52%) [exp(ß) = .984] and mRS 0-1 outcome (32%) [exp(ß) = .828] in addition to admission National Institutes of Health Stroke Scale, age and carotid plaque burden. CAPATd-maximum ipsilateral was acceptably accurate (Area under the Receiver operating characteristic Curve was .607, P = .0109 for mRS 0-2 and .613, P = .0102 for mRS 0-1). Ipsilateral CAPATd ≥ -25 HU predicted both mRS >3 and mRS >2 with usable sensitivity (59.8% and 66.07%) and specificity (63.6% and 59.68%). In conclusion, higher maximum CAPATd measured on emergency CTA indicates poorer functional prognosis in acute stroke patients treated with IV-tPA.

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INTRODUCTION: Acute ischemic stroke is a neurologic emergency, requiring rapid recognition and treatment with intravenous thrombolysis. Since the publication of the 2019 American Heart Association/American Stroke Association Guidelines that recommend tenecteplase as an alternative agent, several centers across the United States are transitioning from alteplase to tenecteplase as the agent of choice for thrombolysis in acute ischemic stroke. METHODS: Our health system transitioned to tenecteplase for the treatment of acute ischemic stroke in 2021 due to increasing evidence for efficacy and potential for improved door-to-needle time. Herein we describe our experience and provide guidance for other institutions to implement this change. CONCLUSION: Emergency nurses are vital to the care of acute ischemic stroke patients. There are several pharmacologic and logistical differences between alteplase and tenecteplase for this indication. This paper outlines these key differences.

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BACKGROUND: Intravenous thrombolysis with tissue plasminogen activator is used for off-label treatment of acute childhood stroke. Tenecteplase (TNK) is used to treat acute stroke in adults at many institutions, although there are extremely few data about TNK use in children. We aimed to characterize pediatric stroke experts' experience and preferences with regard to TNK use in children with stroke. METHODS: Online survey distributed to members of the International Pediatric Stroke Organization in April 2023. RESULTS: We received 33 responses. Most (81.2%) respondents reported only being "a little familiar" or "somewhat familiar" with TNK. Only six (18%) respondents reported being "familiar" or "very familiar" with TNK. Seventy percent of respondents were willing to treat pediatric stroke with TNK, at least in some situations. In a hypothetical scenario of a child in an outside emergency room with only TNK available, 81.8% would consider recommending treatment with TNK. However, only three (9.1%) respondents had TNK in their stroke protocol and seven (21.2%) had TNK on formulary at their hospital. Two respondents reported direct awareness of a child treated with TNK. CONCLUSIONS: The majority of pediatric stroke neurologists responding to this survey reported a willingness to consider TNK use in children. However, data on TNK use in children, provider experience, and pediatric hospital preparedness are limited.

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Administration of recombinant tPA (rtPA, or trade name Alteplase®) is an FDA-approved therapy for acute ischemic stroke (AIS), but poses the risk of hemorrhagic complications. Recombinant tPA can be rapidly inactivated by the endogenous inhibitor, plasminogen activator inhibitor 1 (PAI-1). In this work, we study a novel treatment approach that combines a PAI-1 inhibitor, PAItrap4, with a reduced dose of rtPA to address the hemorrhagic concern of rtPA. PAItrap4 is a highly specific and very potent protein-based inhibitor of PAI-1, comprising of a variant of uPA serine protease domain, human serum albumin, and a cyclic RGD peptide. PAItrap4 efficiently targets and inhibits PAI-1 on activated platelets, and also possesses a long half-life in vivo. Our results demonstrate that PAItrap4 effectively counteracts the inhibitory effects of PAI-1 on rtPA, preserving rtPA activity based on amidolytic and clot lysis assays. In an in vivo murine stroke model, PAItrap4, together with low-dose rtPA, enhances the blood perfusion in the stroke-affected areas, reduces infarct size, and promotes neurological recovery in mice. Importantly, such treatment does not increase the amount of cerebral hemorrhage, thus reducing the risk of cerebral hemorrhage. In addition, PAItrap4 does not compromise the normal blood coagulation function in mice, demonstrating its safety as a therapeutic agent. These findings highlight this combination therapy as a promising alternative for the treatment of ischemic stroke, offering improved safety and efficacy.

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BACKGROUND: Thromboembolic events are increasingly reported in the aging haemophilia population. The purpose of this study was to understand current practices and identify knowledge and research gaps in the management of persons with haemophilia requiring antithrombotic therapy for cardiovascular disorders (CVD) or venous thromboembolism (VTE). METHODS: We searched MEDLINE, EMBASE and Scopus for studies reporting on more than two patients with inherited haemophilia A or B, without inhibitors, requiring antithrombotic therapy for CVD or VTE. Data were extracted by two independent reviewers and analysed using descriptive statistics and narrative synthesis. RESULTS: We included 32 studies reporting on 432 persons with haemophilia. Three themes described the observed practice variation: (1) Difficulty weighing competing bleeding and thrombotic risks; (2) Tensions in providing standards of care and minimizing bleeding risk; (3) Advocacy for individualized strategies and multidisciplinary care. Different management strategies were used to treat persons with haemophilia in the setting of thromboembolic events, such as avoiding or choosing lower intensity antithrombotic therapy, or procedural alternatives to antithrombotic therapy. Initiation or alteration in haemostatic therapies along with antithrombotic therapy were common strategies and reported in 30 studies. However, data on target factor levels and bleeding and thrombotic events were largely missing. DISCUSSION: Our scoping review highlights unmet needs in the management of an aging population of persons with haemophilia with increasing prevalence of CVD and VTE. Management is inconsistent and divergent from those of non-haemophilic patients. Prospective data are needed to inform optimal and evidence-based management strategies of CVD and VTE in persons with haemophilia.

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BACKGROUND: Despite guidelines and strong evidence supporting intravenous thrombolysis and endovascular thrombectomy for acute stroke, access to these interventions remains a challenge. The objective of the IMPROVE stroke care program was to accelerate acute stroke care delivery by implementing best practices and improving the regional systems of care within comprehensive stroke networks. METHODS: The IMPROVE Stroke Care program was a prospective quality improvement program based on established models used in acute coronary care. Nine hub hospitals (comprehensive stroke centers), 52 regional/community referral hospitals (spokes), and over 100 emergency medical service agencies participated. Through 6 regional meetings, 49 best practices were chosen for improvement by the participating sites. Over 2 years, progress was tracked and discussed weekly and performance reviews were disseminated quarterly. RESULTS: Data were collected on 21,647 stroke code activations of which 8,502 (39.3%) activations had a final diagnosis of stroke. There were 7,226 (85.0%) ischemic strokes, and thrombolytic therapy was administered 2,814 times (38.9%). There was significant overall improvement in the proportion that received lytic therapy within 45 minutes (baseline of 44.6%-60.4%). The hubs were more frequently achieving this at baseline, but both site types improved. A total of 1,455 (17.1%) thrombectomies were included in the data of which 401 (27.6%) were transferred from a spoke. There was no clinically significant change in door-to-groin times for hub-presenting thrombectomy patients, however, significant improvement occurred for transferred cases, 46 minutes (interquartile range [IQR] 36, 115.5) at baseline to 27 minutes (IQR 10, 59). CONCLUSIONS: The IMPROVE program approach was successful at improving the delivery of thrombolytic intervention across the consortium at both spoke and hub sites through collaborative efforts to operationalize guideline-based care through iterative sharing of performance and best practices for implementation. Our approach allowed identification of both opportunities for improvement and operational best practices providing guidance on how best to create a regional stroke care network and operationalize the published acute stroke care guidelines.

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BACKGROUND: Debates persist when using intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO). This systematic review and meta-analysis synthesized evidence on outcomes in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO), comparing bridging therapy (BT) with MT alone. METHOD: We conducted searches of PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to July 2023 to identify pertinent clinical trials and observational studies. RESULT: 76 studies, involving 37,658 patients, revealed no significant difference in 90-day functional independence between DEVT and BT. However, a trend favoring BT for achieving functional independence with a modified Rankin Scale (mRS) of 0-1 was observed, having Odds ratio (OR) of 0.75 (95% CI 0.66-0.86; p < 0.001). DEVT was associated with higher postprocedural mortality (OR 1.44;95% CI 1.25-1.65; p < 0.001), but a lower risk of symptomatic intracranial hemorrhage compared to BT (OR 0.855; 95% CI 0.621-1.177; p = 0.327). Successful recanalization rates favored BT, emphasizing the importance of individualized treatment decisions (OR 0.759; 95% CI 0.594-0.969; p = 0.027). Sensitivity analyses were conducted to identify key contributors to heterogeneity. CONCLUSION: Our meta-analysis underscores the intricate equilibrium between functional efficacy and safety in the evaluation of DEVT and BT for ACS-LVO. Fundamentally, while BT appears more efficacious, concerns about safety arise due to the superior safety profile demonstrated by DEVT. Individualized treatment decisions are imperative, and further trials are warranted to enhance precision in clinical guidance.

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BACKGROUND: Systemic thrombolysis (ST) is the guideline-recommended treatment for high-risk pulmonary embolism (PE), although catheter-directed thrombolysis (CDT) may provide a treatment alternative associated with lower rates of bleeding. Furthermore, the treatment trends and outcomes among those with high-risk PE according to treatment assignments of no lytic therapy (NLT), ST, and CDT are underreported. METHODS: Patients hospitalized for high-risk PE between 2016 and 2019 were identified by administrative claims codes from the National Readmission Database. Therapy assignment was similarly defined by administrative codes, then stratified into NLT, ST, and CDT cohorts to report patient characteristics, care settings, and clinical outcomes. The primary outcome was in-hospital mortality with rates adjusted for patient and hospital characteristics using multivariable logistic regression. Secondary outcomes included intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), and 90-day readmission. Over the years of interest, trends in lytic treatment along with concomitant use of mechanical or surgical thrombectomy were reported. RESULTS: Among 74,516 patients with high-risk PE, 61,569 (82.6%) received NLT, 8445 (11.3%) received ST, and 4502 (6.04%) received CDT. The NLT subgroup, relative to ST and CDT, tended to be older (66.1 ± 15.4, 62.8 ± 15.3, and 63.4 ± 14.4; p < 0.001) and more frequently women (56.0%, 54.4%, and 51.3%; p < 0.001), respectively. The unadjusted in-hospital mortality rate was highest for ST (18.8%, 34.1%, and 18.3% for NLT, ST, and CDT, respectively; p < 0.001) and persisted after multivariable adjustment (adjusted odds ratio (aOR) 0.43; 95% CI 0.38-0.49; p < 0.0001) of in-hospital mortality for CDT relative to ST. The unadjusted rate of ICH or GIB was lowest for NLT (1.0%, 2.0%, and 0.6% for NLT, ST, and CDT, respectively; p < 0.001). CDT, relative to ST, was associated with reduced odds of ICH (aOR 0.32; 95% CI 0.18-0.55; p < 0.0001) and GIB (aOR 0.78; 95% CI 0.62-0.98; p < 0.0001). Readmissions were highest for NLT (21.7%, 9.6%, and 12.1% for NLT, ST, and CDT, respectively; p < 0.001). CDT was associated with a higher incidence of 90-day readmission relative to ST (aOR 1.32; 95% CI 1.10-1.57; p < 0.001). From 2016 to 2019, individual treatment trends were not significantly different, although NLT tended to be offered among smaller and rural hospitals. Rates of concomitant thrombectomy were low in all three treatment groups. CONCLUSIONS: Among a large, contemporary, US cohort with high-risk PE, over 80% of patients did not receive any form of thrombolysis. High-risk PE that did receive systemic thrombolysis was associated with the highest rates of in-hospital mortality, suggesting opportunities to study the implementation of lytic and nonlytic-based treatments to improve outcomes for those presenting with high-risk PE.

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OBJECTIVE: To evaluate the non-inferiority of endovascular treatment (EVT) alone versus intravenous thrombolysis (IVT) followed by EVT and to assess its heterogeneity across prespecified subgroups. METHODS: We pooled data from two trials (SKIP in Japan; DEVT in China). Individual patient data were pooled to assess outcomes and heterogeneity of treatment effect. The primary outcome was functional independence (modified Rankin Scale score 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS: We included 438 patients (217 EVT alone; 221 combined IVT+EVT). The meta-analysis failed to demonstrate the non-inferiority of EVT alone over combined IVT+EVT in achieving 90-day functional independence (56.7% vs 51.6%; adjusted common odds ratio (cOR)=1.27, 95% CI 0.84 to 1.92, pnon-inferiority=0.06). Effect sizes favoring EVT alone were present with stroke onset to puncture time longer than 180 min (cOR=2.28, 95% CI 1.18 to 4.38, pinteraction ≤180 vs >180 min=0.02) and intracranial internal carotid artery ICA occlusions (for ICA cOR=3.04, 95% CI 1.10 to 8.43, pinteraction ICA vs MCA=0.08). The rates of sICH (6.5% vs 9.0%; cOR=0.77, 95% CI 0.37 to 1.61) and 90-day mortality (12.9% vs 13.6%; cOR=1.05, 95% CI 0.58 to 1.89) were comparable. CONCLUSIONS: The cumulative data of these two recent Asian trials failed to unequivocally demonstrate the non-inferiority of EVT alone over combined IVT+EVT. However, our study suggests a potential role for more individualized decision-making. Specifically, Asian patients with stroke onset to EVT longer than 180 min, as well as those with intracranial ICA occlusions and those with atrial fibrillation might have better outcomes with EVT alone than with combined IVT+EVT.

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Current guideline recommendations for primary prophylaxis of venous thromboembolism (VTE) are based on randomized clinical trials that usually exclude subjects at a potentially high risk of bleeding complications. For this reason, no specific guideline is available for thromboprophylaxis in hospitalized patients with thrombocytopenia and/or platelet dysfunction. However, except in patients with absolute contraindications to anticoagulant drugs, antithrombotic prophylaxis should always be considered, for example, in hospitalized cancer patients with thrombocytopenia, especially in those with multiple VTE risk factors. Low platelet number, platelet dysfunction, and clotting abnormalities are also very common in patients with liver cirrhosis, but these patients have a high incidence of portal venous thrombosis, implying that cirrhotic coagulopathy does not fully protect against thrombosis. These patients may benefit from antithrombotic prophylaxis during hospitalization. Patients hospitalized for COVID-19 need prophylaxis, but frequently experience thrombocytopenia or coagulopathy. In patients with antiphospholipid antibodies, a high thrombotic risk is usually present, even in the presence of thrombocytopenia. VTE prophylaxis in high-risk conditions is thus suggested in these patients. At variance with severe thrombocytopenia (< 50,000/mm3), mild/moderate thrombocytopenia (≥ 50,000/mm3) should not interfere with VTE prevention decisions. In patients with severe thrombocytopenia, pharmacological prophylaxis should be considered on an individual basis. Aspirin is not as effective as heparins in lowering the risk of VTE. Studies in patients with ischemic stroke demonstrated that thromboprophylaxis with heparins is safe in these patients also during antiplatelet treatment. The use of direct oral anticoagulants in the prophylaxis of VTE in internal medicine patients has been recently evaluated, but no specific recommendation exists for patients with thrombocytopenia. The need for VTE prophylaxis in patients on chronic treatment with antiplatelet agents should be evaluated after assessing the individual risk of bleeding complications. Finally, the selection of patients who require post-discharge pharmacological prophylaxis remains debated. New molecules currently under development (such as the inhibitors of factor XI) may contribute to improve the risk/benefit ratio of VTE primary prevention in this setting of patients.

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BACKGROUND: A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI. METHODS: In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints. RESULTS: From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a -15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: -3.4%; 95% confidence interval [CI]: -11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: -0.5%; 95% CI: -5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. CONCLUSION: rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI. TRIAL REGISTRATION: www.ClinicalTrials.gov (No. NCT02835534).

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BACKGROUND: Risks and benefits of intravenous thrombolysis (IVT) in patients undergoing mechanical thrombectomy (MT) have been a topic of interest. However, IVT's specific effects on stent retriever (SR) and aspiration thrombectomy (ASP) outcomes remain largely unexplored. In this meta-analysis, we aimed to investigate the effects of IVT on SR and ASP thrombectomy outcomes. METHODS: In accordance with PRISMA guidelines, a systematic literature review was conducted using Medline, Embase, Scopus, Web of Science, and Cochrane Center of Clinical Trials databases. Outcomes of interest included successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b), modified first pass efficacy (mFPE), functional independence (modified Rankin Scale (mRS) ≤2), symptomatic intracranial hemorrhage (sICH), and embolization to new territories (ENT). RESULTS: Four randomized controlled trials with 1176 patients were included. SR and ASP resulted in similar mTICI ≥2b, mFPE, and mRS 0-2 rates in patients with and without IVT administration. SR without IVT was associated with a significantly lower rate of mFPE compared with the SR+IVT (RR 0.85, 95% CI 0.74 to 0.97). Furthermore, ASP without IVT resulted in a lower rate of mRS 0-2 than the ASP+IVT with a strong trend towards significance (RR 0.78, 95% CI 0.60 to 1.01). Finally, bridging therapy did not increase sICH and ENT rates after ASP or SR thrombectomy. CONCLUSIONS: Our findings suggest that SR and ASP thrombectomy have comparable safety and efficacy profiles, regardless of prior IVT administration. Additionally, our results indicate that the addition of IVT may improve certain efficacy outcomes based on the employed first-line MT technique.

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The last 10 years have seen a major shift in management of large vessel ischemic stroke with changes towards ever-expanding use of reperfusion therapies (intravenous thrombolysis and mechanical thrombectomy). These strategies 'open the door' to acute therapeutics for ischemic tissue, and we should investigate novel therapeutic approaches to enhance survival of recently reperfused brain. Key insights into new approaches have been provided through translational research models and preclinical paradigms, and through detailed research on ischemic mechanisms. Additional recent clinical trials offer exciting salvos into this new strategy of pairing reperfusion with neuroprotective therapy. This pairing strategy can be employed using drugs that have shown neuroprotective efficacy; neurointerventionalists can administer these during or immediately after reperfusion therapy. This represents a crucial moment when we emphasize reperfusion, and have the technological capability along with the clinical trial experience to lead the way in multiprong approaches to stroke treatment.

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Best medical therapy (BMT) for peripheral arterial disease (PAD), carotid artery stenosis (CAS) and abdominal aortic aneurysm (AAA) involving concomitant use of antiplatelets, lipid-lowering agents, and blood pressure control, improves patient survival and prevents clinical cardiovascular disease (CVD). We performed a single-center cross-sectional study, over a 4-year period, describing BMT use in Western Australian patients with symptomatic PAD, CAS and AAA in the community. Overall, 45.3% of our cohort (n = 1689) were on appropriate BMT (CAS, 58.1%; PAD, 43.1%; AAA, 41.1%). There was highest uptake of blood pressure control at 93.0% (lipid-lowering agents, 65.3%; antithrombotics 63.5%). PAD was associated with highest uptake of blood pressure control (PAD 93.9%; CAS, 91.4%; AAA, 91.1%, P = .092) whilst CAS had highest uptake of antithrombotics (CAS 76.3%; PAD, 61.0%; AAA 60.4%, P < .001) and lipid-lowering agents (CAS 78.7%; PAD, 63.1%; AAA, 60.4%, P < .001). Our study indicates suboptimal use of BMT in patients with vascular disease in the community. The risk of CVD in CAS is likely misperceived as higher than PAD and AAA.

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BACKGROUND: The DIRECT-MT trial showed that endovascular thrombectomy (EVT) alone was noninferior to EVT preceded by intravenous alteplase. However, the infusion of intravenous alteplase was uncompleted before the initiation of EVT in most cases of this trial. Therefore, the additional benefit and risk of over 2/3-dose intravenous alteplase pretreatment remain to be assessed. METHODS: We assessed patients with acute anterior circulation ischemic stroke who received EVT alone or with over 2/3-dose intravenous alteplase pretreatment from the DIRECT-MT trial. Patients were assigned to the thrombectomy-alone group and the alteplase pretreatment group. The primary outcome was the distribution of modified Rankin Scale (mRS) at 90 days. The interaction of treatment allocation and collateral capacity was assessed. RESULTS: A total of 393 patients (thrombectomy alone: 315; alteplase pretreatment: 78) were identified. The thrombectomy alone was comparable with alteplase pretreatment prior to the thrombectomy on the distribution of mRS at 90 days without significant effect modification by collateral capacity (adjusted common odds ratio (acOR), 1.12; 95% CI, 0.72-1.74; adjusted P for interaction = 0.83). Successful reperfusion before thrombectomy and the number of passes in the thrombectomy alone group differed significantly from the alteplase pretreatment group (2.6% vs. 11.5%; corrected P = 0.02 and 2 vs. 1; corrected P = 0.003). There was no interaction between treatment allocation and collateral capacity on all outcomes. CONCLUSIONS: EVT alone and EVT preceded by over 2/3-dose intravenous alteplase might have equal efficacy and safety for patients with acute anterior circulation large vessel occlusion, except for successful perfusion before thrombectomy and the number of passes.

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BACKGROUND: The SAMe-TT2R2 score identifies patients on vitamin K antagonists (VKAs) who are more likely to have poor time in therapeutic range (TTR); however, the association between SAMe-TT2R2 and clinical outcomes remains controversial. OBJECTIVES: The objective is to assess the association of SAMe-TT2R2 score with clinical outcomes and poor TTR in patients on VKAs. METHODS: We searched using the term "SAMe-TT2R2." Original articles reporting clinical outcomes and SAMe-TT2R2 scores before October 2021 were included. Odds ratios (ORs) of clinical outcomes, diagnostic accuracy parameters of poor TTR (<60%-70%), and mean TTR were extracted. Meta-analysis was performed using random-effects models. RESULTS: Ten studies were included (N = 22 894); 4 showed pooled changes in TTR of -3.61% (95% CI:-4.88% to -2.35%) and -3.98% (95% CI: -6.08% to -1.87%) at SAMe-TT2R2 scores ≥2 and ≥3, respectively, compared with lower scores. The diagnostic accuracy parameters for poor TTR were too heterogeneous to conclude. SAMe-TT2R2 ≥3 significantly correlated with all adverse events (OR = 1.43 [95% CI: 1.29-1.54; P < 0.001]), composite thromboembolism (OR = 1.53 [95% CI: 1.19-1.97; P = 0.001]), and composite bleeding (OR = 1.33 [95% CI: 1.12-1.59; P = 0.001] regardless of the indication, while an SAMe-TT2R2 ≥2 significantly correlated with mortality (OR = 1.32 [95% CI: 1.02-1.70; P = 0.033]). We found no relationship between an SAMe-TT2R2 ≥3 and mortality or between a score ≥2 and clinical outcomes. CONCLUSIONS AND RELEVANCE: Patients on VKAs with SAMe-TT2R2 ≥3 experienced more adverse events, bleeding, and thromboembolism compared with patients who had an SAMe-TT2R2 <3. However, the score had limited and inconclusive predictability for poor TTR in the study.

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