Prognosis and factors related to anti-VEGF therapy in patients with retinal vein occlusion and concomitant carotid artery disease.

To evaluate the prognosis and influencing factors of retinal vein occlusion (RVO) in patients with concomitant carotid artery disease receiving anti-vascular endothelial growth factor (VEGF) treatment. Patients diagnosed with RVO and receiving anti-VEGF treatment were included. Eye and clinical data were collected. The patients were divided into a group with concomitant carotid artery disease (Group A) and a group without concomitant carotid artery disease (Group B). The risk factors affecting the visual prognosis of RVO patients with concomitant carotid artery disease were analyzed. Among 177 eligible patients with RVO, 101 had concomitant carotid artery disease (Group A), while 76 did not (Group B). Group A had a significantly lower treatment effectiveness rate than Group B (P < 0.001). The age and platelet distribution width of Group A were significantly higher than Group B (P < 0.001). Multivariate logistic regression analysis showed that baseline best-corrected visual acuity (BCVA), disorganization of retinal inner layers (DRIL), external limiting membrane (ELM) disruption, and red blood cell distribution width (RDW) were significantly associated with the posttreatment visual prognosis of RVO patients with concomitant carotid artery disease(P < 0.05). RVO patients with concomitant carotid artery disease had a significantly lower treatment effectiveness rate than RVO patients without carotid artery disease. The poor baseline BCVA, DRIL, ELM disruption, and a greater RDW are risk factors for low anti-VEGF treatment efficacy among RVO patients with concomitant carotid artery disease.

Treatment with APAC, a dual antiplatelet anticoagulant heparin proteoglycan mimetic, limits early collar-induced carotid atherosclerotic plaque development in Apoe-/- mice.

BACKGROUND AND AIMS: Mast cell-derived heparin proteoglycans (HEP-PG) can be mimicked by bioconjugates carrying antithrombotic and anti-inflammatory properties. The dual antiplatelet and anticoagulant (APAC) construct administered, either locally or intravenously (i.v.), targets activated endothelium, its adhesion molecules, and subendothelial matrix proteins, all relevant to atherogenesis. We hypothesized that APAC influences cellular interactions in atherosclerotic lesion development and studied APAC treatment during the initiation and progression of experimental atherosclerosis. METHODS: Male western-type diet-fed Apoe-/- mice were equipped with perivascular carotid artery collars to induce local atherosclerosis. In this model, mRNA expression of adhesion molecules including ICAM-1, VCAM-1, P-Selectin, and Platelet Factor 4 (PF4) are upregulated upon lesion development. From day 1 (prevention) or from 2.5 weeks after lesion initiation (treatment), mice were administered 0.2 mg/kg APAC i.v. or control vehicle three times weekly for 2.5 weeks. At week 5 after collar placement, mice were sacrificed, and lesion morphology was microscopically assessed. RESULTS: APAC treatment did not affect body weight or plasma total cholesterol levels during the experiments. In the prevention setting, APAC reduced carotid artery plaque size and volume by over 50 %, aligning with decreased plaque macrophage area and collagen content. During the treatment setting, APAC reduced macrophage accumulation and necrotic core content, and improved markers of plaque stability. CONCLUSIONS: APAC effectively reduced early atherosclerotic lesion development and improved markers of plaque inflammation in advanced atherosclerosis. Thus, APAC may have potential to alleviate the progression of atherosclerosis.

Effects of atorvastatin and ezetimibe on CD147, HIF-1, MMP-2 and VEGF in carotid atherosclerotic plaque under the guidance of IVUS.

Atherosclerosis (AS), as the main pathophysiological basis of coronary heart disease, can develop into carotid atherosclerotic plaque (CAP) through intimal inflammation, necrosis, fibrosis and calcification. However, there are few reports on the clinical drug selection of CAP. The aim of this study was to explore the effects of atorvastatin and ezetimibe on CD147, HIF-1, MMP-2 and VEGF in CAP under the guidance of IVUS, so as to provide basis for CAP of the best drug. 32 male New Zealand rabbits were divided into the control group, the model group, the atorvastatin group and the ezetimibe group randomly. The levels of serum LDL-C and MMP-2 have a significant decrease in atorvastatin group and ezetimibe group (P <0.05). The level of serum CD147 has a significant decrease in ezetimibe group (P <0.05). The average OD value of HIF-1 in atorvastatin group decreased significantly (P <0.05). The relative expression of CD147 and VEGF decreased significantly in atorvastatin group (P <0.05). There were different degrees of fibrous plaque and lipid plaque in model group, atorvastatin group and ezetimibe group. There exists a significant decline of CD147, HIF-1, MMP-2 and VEGF by atorvastatin in plaque, but the effect of ezetimibe is not obvious.

Pentoxifylline ameliorates subclinical atherosclerosis progression in patients with type 2 diabetes and chronic kidney disease: a randomized pilot trial.

BACKGROUND: Diabetic kidney disease (DKD) is associated with a higher risk of cardiovascular disease (CVD). Pentoxifylline (PTF), a nonselective phosphodiesterase inhibitor with anti-inflammatory, antiproliferative, and antifibrotic actions, has demonstrated renal benefits in both clinical trials and meta-analyses. The present work aimed to study the effects of PTF on the progression of subclinical atherosclerosis (SA) in a population of patients with diabetes and moderate to severe chronic kidney disease (CKD). METHODS: In this open-label, randomized controlled, prospective single-center pilot study the evolution of carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) were determined in 102 patients with type 2 diabetes mellitus and CKD assigned to PTF, aspirin or control groups during 18 months. We also determined the variations in the levels of inflammatory markers and Klotho (KL), a protein involved in maintaining cardiovascular health, and their relationship with the progression of SA. RESULTS: Patients treated with PTF presented a better evolution of CIMT, increased KL mRNA levels in peripheral blood cells (PBCs) and reduced the inflammatory state. The progression of CIMT values was inversely related to variations in KL both in serum and mRNA expression levels in PBCs. Multiple regression analysis demonstrated that PTF treatment and variations in mRNA KL expression in PBCs, together with changes in HDL, were significant determinants for the progression of CIMT (adjusted R2 = 0.24, P < 0.001) independently of traditional risk factors. Moreover, both variables constituted protective factors against a worst progression of CIMT [OR: 0.103 (P = 0.001) and 0.001 (P = 0.005), respectively]. CONCLUSIONS: PTF reduced SA progression assessed by CIMT variation, a beneficial effect related to KL gene expression in PBCs. TRIAL REGISTRATION: The study protocol code is PTF-AA-TR-2009 and the trial was registered on the European Union Drug Regulating Authorities Clinical Trials (EudraCT #2009-016595-77). The validation date was 2010-03-09.

Metabolomics and network pharmacology exploration of the effects of bile acids on carotid atherosclerosis and potential underlying mechanisms.

Background: Bile acids (BAs), products of gut microbiota metabolism, have long been implicated in atherosclerotic disease pathogenesis. Characterizing the serum bile acid profile and exploring its potential role in carotid atherosclerosis (CAS) development are crucial tasks. Methods: In this study, we recruited 73 patients with CAS as the disease group and 77 healthy individuals as the control group. We systematically measured the serum concentrations of 15 bile acids using ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression were applied to analyze the impact of bile acids on the disease and select the key BAs. The possible molecular mechanism was elucidated by network pharmacology. Results: (1) The BA profile of patients with CAS significantly differed. (2) Multifactorial logistic regression analysis identified elevated levels of GCDCA (OR: 1.01, P < 0.001), DCA (OR: 1.01, P = 0.005), and TDCA (OR: 1.05, P = 0.002) as independent risk factors for CAS development. Conversely, GCA (OR: 0.99, P = 0.020), LCA (OR: 0.83, P = 0.002), and GUDCA (OR: 0.99, P = 0.003) were associated with protective effects against the disease. GCA, DCA, LCA, and TDCA were identified as the four key BAs. (3) TNF, FXR, GPBAR1, ESR1 and ACE were predicted to be targets of BAs against AS. These four BAs potentially impact AS progression by triggering signaling pathways, including cAMP, PPAR, and PI3K-AKT pathways, via their targets. Conclusion: This study offers valuable insights into potential therapeutic strategies for atherosclerosis that target bile acids.

Efficacy, safety and mechanism of Simiaoyongan decoction in the treatment of carotid atherosclerotic plaque: a randomized, double-blind, placebo-controlled clinical trial protocol.

INTRODUCTION: Chronic inflammation is the major pathological feature of Atherosclerosis(As). Inflammation may accelerate plaque to develop, which is a key factor resulting in the thinning of the fibrous cap and the vulnerable rupture of plaque. Presently, clinical treatments are still lacking. It is necessary to find a safe and effective treatment for As inflammation. Simiaoyongan Decoction (SMYA) has potential anti-inflammatory and plaque protection effects. This protocol aims to evaluate the efficacy, safety, and mechanism of SMYA for patients with carotid atherosclerotic plaque. METHODS/DESIGN: The assessment of SMYA clinical trial is designed as a randomized, double-blind, placebo-controlled study. The sample size is 86 cases in total, with 43 participants in the intervention group and the control group respectively. The intervention group takes SMYA, while the control group takes SMYA placebo. The medication lasts for 14 days every 10 weeks, with a total of 50 weeks. We will use carotid artery high resolution magnetic resonance imaging (HR-MRI) to measure plaque. The plaque minimum fiber cap thickness (PMFCT) is adopted as the primary outcome. The secondary outcomes include plaque fiber cap volume, volume percentage of fiber cap, lipid-rich necrotic core (LRNC) volume, volume percentage of LRNC, internal bleeding volume of plaque, internal bleeding volume percentage of plaque, plaque calcification volume, volume percentage of plaque calcification, lumen stenosis rate, average and a maximum of vessel wall thickness, vessel wall volume, total vessel wall load, carotid atherosclerosis score, hs-CRP, IL-1ß and IL-6, the level of lipid profiles and blood glucose, blood pressure, and body weight. DISCUSSION: We anticipate that patients with As plaque will be improved from SMYA by inhibiting inflammation to enhance plaque stability. This study analyzes plaque by using HR-MRI to evaluate the clinical efficacy and safety of SMYA. Moreover, we conduct transcriptome analysis, proteomic analysis, and metagenomic analysis of blood and stool of participants to study the mechanism of SMYA against As plaque. This is the first prospective TCM trial to observe and treat As plaque by inhibiting inflammatory reaction directly. If successful, the finding will be valuable in the treatment of As plaque and drug development, especially in the "statin era". TRIAL REGISTRATION NUMBER: This trial is registered on Chinese Clinical Trials.gov with number ChiCTR2000039062 on October 15, 2020 ( http://www.chictr.org.cn ).

Effects of Xanthine Oxidase Inhibition by Febuxostat on Lipid Profiles of Patients with Hyperuricemia: Insights from Randomized PRIZE Study.

Although patients with hyperuricemia and gout often have dyslipidemia, the effects of febuxostat, a xanthine oxidase inhibitor, on their lipid profiles are unclear. Thus, we performed a sub-analysis of the randomized PRIZE study in which the effects of febuxostat on carotid atherosclerosis were investigated in patients with hyperuricemia. The participants were randomized to the febuxostat or control group. The primary endpoint of this sub-analysis was changes in the patients' non-high-density lipoprotein cholesterol (HDL-C) levels from baseline to 6-month follow-up. Correlations between the changes in lipid profiles and cardiometabolic parameters were also evaluated. In total, 456 patients were included. From baseline to 6 months, non-HDL-C levels were significantly reduced in the febuxostat group (-5.9 mg/dL, 95% confidence interval [CI]: -9.1 to -2.8 mg/dL, p < 0.001), but not in the control group (-1.3 mg/dL, 95% CI: -4.4 to 1.8, p = 0.348). The reduction in non-HDL-C levels was more pronounced in women and correlated with changes in serum uric acid and estimated glomerular filtration rate levels only in the febuxostat group. In patients with hyperuricemia, febuxostat treatment was associated with reduced non-HDL-C levels from baseline to the 6-month follow-up compared to the control treatment, suggesting that the lipid-lowering effect of febuxostat should be considered when targeting dyslipidemia.

Effect of lipid-lowering therapy on carotid plaque burden in older adults.

BACKGROUND: Little is known about the benefits of lipid-lowering medications in those age ≥ 75 years. We assessed the effect of lipid-lowering medications on progression to severe atherosclerosis in patients age > 75. METHODS: Data was retrospectively obtained from the Stroke Prevention & Atherosclerosis Research Centre, Canada. Atherosclerosis burden was measured as carotid total plaque area (TPA), a powerful predictor of cardiovascular risk. Survival time free of severe atherosclerosis (SFSA) was defined as the period when TPA remained <1.19 cm2. Kaplan-Meier, multiple Cox proportional hazard and hierarchical mixed-effect models were used to determine the effects of lipid-lowering medications on progression to severe atherosclerosis. RESULTS: In total 1404 cases (mean age 81 ± 4 years; women 52%) were included. Those taking lipid-lowering medications were more likely to have a history of diabetes and a higher burden of atherosclerosis at baseline. In Kaplan-Meier analysis, the SFSA was significantly longer in those receiving lipid-lowering therapy. In multivariable-adjusted analyses, those not receiving lipid lowering therapy (irrespective of their vascular disease at baseline) were more likely to have TPA > 1.19 cm2 (hazard ratio (HR) = 1.37, 95% confidence interval (CI): 1.09,0.71). Similar findings were observed in mixed effects models when plaque progression was defined as any change >0.05 cm2 per year (odds ratio (OR):2.17, 95% CI:1.38,3.57). CONCLUSION: Lipid-lowering therapy is effective in controlling the burden of atherosclerosis among older adults with and without vascular disease. The measurement of plaque burden can guide selection and follow-up of those who may benefit from treatment.

Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection.

BACKGROUND: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. RESULTS: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. CONCLUSIONS: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).

[Ultrasound examination of the carotid artery for improved prediction of cardiovascular events and the effect of statin treatment in advanced atherosclerosis : An observational study]. / Ultraschalluntersuchung der A. carotis zur verbesserten Vorhersage kardiovaskulärer Ereignisse und der Wirkung einer Statinbehandlung bei fortgeschrittener Atherosklerose : Eine Beobachtungsstudie.

BACKGROUND: Advanced atherosclerosis of the carotid artery is associated with a high risk of cardiovascular diseases. It was investigated whether ultrasound provides a better prediction of cardiovascular events compared to the prospective cardiovascular Münster study (PROCAM) score and whether treatment of subjects with advanced atherosclerosis with statins improves the prognosis. METHOD: Between 2009 and 2016 a total of 4482 subjects (41% women) aged 35-65 years with no signs of cardiovascular disease underwent carotid artery ultrasound examination. Total plaque area (TPA) and maximum plaque thickness were measured. The PROCAM score was used to determine the cardiovascular risk. RESULTS: The median follow-up time was 77 months (6.4 years) for the men and 74 months (6.2 years) for the women. Events, such as myocardial infarction, ischemic stroke, coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA), occurred in 131 (3.4%) of the 3833 subjects with complete follow-up data. The prediction of cardiovascular events was better with ultrasound than with the PROCAM score. Ultrasound predicted 79.4% of 131 events and the PROCAM score predicted 22.9%. Treatment of subjects with advanced atherosclerosis (types III, IV b) with a statin significantly improved the prognosis. The event rate was 12.6% in men and women in the treated group vs. 31.5% (p < 0.0001) in the untreated group. Mortality (from any cause) was significantly lower in men treated with statins (p = 0.0148). CONCLUSION: The prediction of cardiovascular events was better with plaque burden measurements than with the PROCAM score. Treatment with statins in subjects with advanced carotid atherosclerosis (types III-IV b findings on ultrasound) significantly improved the prognosis in a nonrandomized observational study.

Novel Therapeutic Approaches to Prevent Atherothrombotic Ischemic Stroke in Patients with Carotid Atherosclerosis.

Atherothrombotic stroke represents approximately 20% of all ischemic strokes. It is caused by large-artery atherosclerosis, mostly in the internal carotid artery, and it is associated with a high risk of early recurrence. After an ischemic stroke, tissue plasminogen activator is used in clinical practice, although it is not possible in all patients. In severe clinical situations, such as high carotid stenosis (≥70%), revascularization by carotid endarterectomy or by stent placement is carried out to avoid recurrences. In stroke prevention, the pharmacological recommendations are based on antithrombotic, lipid-lowering, and antihypertensive therapy. Inflammation is a promising target in stroke prevention, particularly in ischemic strokes associated with atherosclerosis. However, the use of anti-inflammatory strategies has been scarcely studied. No clinical trials are clearly successful and most preclinical studies are focused on protection after a stroke. The present review describes novel therapies addressed to counteract inflammation in the prevention of the first-ever or recurrent stroke. The putative clinical use of broad-spectrum and specific anti-inflammatory drugs, such as monoclonal antibodies and microRNAs (miRNAs) as regulators of atherosclerosis, will be outlined. Further studies are necessary to ascertain which patients may benefit from anti-inflammatory agents and how.

A Comparative Study on the Presence and Reversibility of Subclinical Arterial Damage in HCV-Infected Individuals and Matched Controls.

Background: The arterial pathology and mechanisms of increased cardiovascular disease (CVD) risk in HCV-infected individuals are not yet clear. The aim of this study was to identify types of arterial pathology in treatment-naive chronic HCV patients and to test their reversibility after successful treatment. Methods: Consecutive, never-treated, HCV-infected patients were compared with age and CVD-related risk factors, matched controls, healthy individuals (HI), patients with rheumatoid arthritis (RA) and people living with HIV (PLWH), in terms of arterial stiffening by pulse wave velocity, arterial atheromatosis/hypertrophy by carotid plaques/intima-media thickness and impaired pressure wave reflections by augmentation index. After three months of sustained virological response (SVR) administered using direct-acting antivirals, vascular examination was repeated in HCV-infected patients to test drug and viral-elimination effect in subclinical CVD. Results: Thirty HCV patients were examined at baseline; fourteen of them were re-examined post-SVR. Compared with HI, HCV patients had significantly more plaques, which is similar to that of RA patients and the PLWH group. No other differences were found in all other vascular biomarkers, and regression among HCV patients also revealed no differences 3 months post-SVR. Conclusions: Accelerated atheromatosis, rather than arterial stiffening, arterial remodeling and peripheral impaired hemodynamics is the underlying pathology leading to increased CVD risk in HCV patients.

Decline of thrombolysis rates before endovascular therapy in patients with acute anterior circulation large vessel occlusion ischemic stroke: A multicenter analysis from the German Stroke Registry.

INTRODUCTION: In recent years, the role of intravenous thrombolysis (IVT) before endovascular stroke treatment (EVT) has been discussed intensively. Whether the discussion was accompanied by changing rates of bridging IVT is unknown. METHODS: Data were extracted from the prospectively maintained German Stroke Registry, including patients treated with EVT at one of 28 stroke centers in Germany between 2016 and 2021. Primary outcome parameters were the rate of bridging IVT (a) in the entire registry cohort and (b) in patients without formal contraindications to IVT (i.e. recent oral anticoagulants, time window ⩾4.5 h, extensive early ischemic changes) adjusted for demographic and clinical confounders. RESULTS: 10,162 patients (52.8% women, median age 77 years, median National Institutes of Health Stroke Scale score 14) were analyzed. In the entire cohort, the rate of bridging IVT decreased from 63.8% in 2016 to 43.6% in 2021 (average absolute annual decrease 3.1%, 95% CI 2.4%-3.8%), while the proportion of patients with at least one formal contraindication increased by only 1.2% annually (95% CI 0.6%-1.9%). Among 5460 patients without record of formal contraindications, the rate of bridging IVT decreased from 75.5% in 2016 to 63.2% in 2021 and was significantly associated with admission date in a multivariable model (average absolute annual decrease 1.4%, 95% CI 0.6%-2.2%). Clinical factors associated with lower odds of bridging IVT included diabetes mellitus, carotid-T-occlusion, dual antiplatelet therapy, and direct admission to a thrombectomy center. CONCLUSION: We observed a substantial decline in bridging IVT rates independent of demographic confounders and not explained by an increase in contraindications. This observation deserves further exploration in independent populations.

Effect of pharmacologic anti-atherosclerotic therapy on carotid intraplaque neovascularization: A systematic review.

Intraplaque neovascularization (IPN), a key feature of vulnerable carotid plaque, is associated with adverse cardiovascular (CV) events. Statin therapy has been shown to diminish and stabilize atherosclerotic plaque, but its effect on IPN is uncertain. This review investigated the effects of common pharmacologic anti-atherosclerotic therapies on carotid IPN. Electronic databases (MEDLINE, EMBASE and Cochrane Library) were searched from inception until July 13, 2022. Studies evaluating the effect of anti-atherosclerotic therapy on carotid IPN among adults with carotid atherosclerosis were included. Sixteen studies were eligible for inclusion. Contrast-enhanced ultrasound (CEUS) was the most common IPN assessment modality (n=8), followed by dynamic contrast-enhanced MRI (DCE-MRI) (n=4), excised plaque histology (n=3) and superb microvascular imaging (n=2). In fifteen studies, statins were the therapy of interest and one study assessed PCSK9 inhibitors. Among CEUS studies, baseline statin use was associated with a lower frequency of carotid IPN (median OR = 0.45). Prospective studies showed regression of IPN after 6-12 months of lipid-lowering therapy, with more regression observed in treated participants compared to untreated controls. Our findings suggest that lipid-lowering therapy with statins or PCSK9 inhibitors is associated with IPN regression. However, there was no correlation between change in IPN parameters and change in serum lipids and inflammatory markers in statin-treated participants, so it is unclear whether these factors are mediators in the observed IPN changes. Lastly, this review was limited by study heterogeneity and small sample sizes, so larger trials are needed to validate findings.

Proanthocyanidins may be potential therapeutic agents for the treatment of carotid atherosclerosis: A review.

Atherosclerotic cerebrovascular disease is one of the major causes of death in China, with associated serious risk of disability and burden on society and families. Therefore, the development of active and effective therapeutic drugs for this disease is of great significance. Proanthocyanidins are a class of naturally occurring active substances, rich in hydroxyl groups and from a wide range of sources. Studies have suggested that they have a strong potential for anti-atherosclerosis activity. In this paper, we review published evidence regarding anti-atherosclerotic effects of proanthocyanidins in different atherosclerotic research models.

Tenecteplase Treatment and Thrombus Characteristics Associated With Early Reperfusion: An EXTEND-IA TNK Trials Analysis.

BACKGROUND: Intracranial occlusion site, contrast permeability, and clot burden are thrombus characteristics that influence alteplase-associated reperfusion. In this study, we assessed the reperfusion efficacy of tenecteplase and alteplase in subgroups based on these characteristics in a pooled analysis of the EXTEND-IA TNK trial (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke). METHODS: Patients with large vessel occlusion were randomized to treatment with tenecteplase (0.25 or 0.4 mg/kg) or alteplase before thrombectomy in hospitals across Australia and New Zealand (2015-2019). The primary outcome, early reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion on first-pass angiogram. We compared the effect of tenecteplase versus alteplase overall, and in subgroups, based on the following measured with computed tomography angiography: intracranial occlusion site, contrast permeability (measured via residual flow grades), and clot burden (measured via clot burden scores). We adjusted for covariates using mixed effects logistic regression models. RESULTS: Tenecteplase was associated with higher odds of early reperfusion (75/369 [20%] versus alteplase: 9/96 [9%], adjusted odds ratio [aOR], 2.18 [95% CI, 1.03-4.63]). The difference between thrombolytics was notable in occlusions with low clot burden (tenecteplase: 66/261 [25%] versus alteplase: 5/67 [7%], aOR, 3.93 [95% CI, 1.50-10.33]) when compared to high clot burden lesions (tenecteplase: 9/108 [8%] versus alteplase: 4/29 [14%], aOR, 0.58 [95% CI, 0.16-2.06]; Pinteraction=0.01). We did not observe an association between contrast permeability and tenecteplase treatment effect (permeability present: aOR, 2.83 [95% CI, 1.00-8.05] versus absent: aOR, 1.98 [95% CI, 0.65-6.03]; Pinteraction=0.62). Tenecteplase treatment effect was superior with distal M1 or M2 occlusions (53/176 [30%] versus alteplase: 4/42 [10%], aOR, 3.73 [95% CI, 1.25-11.11]), but both thrombolytics had limited efficacy with internal carotid artery occlusions (tenecteplase 1/73 [1%] versus alteplase 1/19 [5%], aOR, 0.22 [95% CI, 0.01-3.83]; Pinteraction=0.16). CONCLUSIONS: Tenecteplase demonstrates superior early reperfusion versus alteplase in lesions with low clot burden. Reperfusion efficacy remains limited in internal carotid artery occlusions and lesions with high clot burden. Further innovation in thrombolytic therapies are required.

Nonvalvular atrial fibrillation and retinal vein occlusion: The Valdecilla Cohort.

INTRODUCTION AND OBJECTIVES: Retinal vein occlusion (RVO) and nonvalvular atrial fibrillation (NVAF) are associated with vascular risk factors (VRF) and aging. The aim of this study is to analyze differences in the prevalence of VRF, vascular events, glaucoma, and anticoagulant treatment in patients with NVAF and RVO compared to a control group of the general population from the same geographic area. METHODS: This is a prospective, single-center, case-control study. All patients diagnosed with RVO from December 2008 to March 2020 as well as a control group were included. Clinical, laboratory, electrocardiographic, and carotid ultrasound variables were analyzed. RESULTS: A total of 386 patients with RVO and 343 controls were studied. Patients with RVO and NVAF were older and more of them had hypertension, a history of vascular events, and carotid atheromatosis than subjects with RVO without NVAF. In patients with NVAF who were on anticoagulants, those who had RVO differed from the controls with NVAF in that they had a higher prevalence of glaucoma (32 vs. 5.3%; p<0.034), with no significant differences regarding age, VRF, vascular events, or type of anticoagulant therapy (acenocumarol or direct-acting oral anticoagulants). CONCLUSIONS: Patients with RVO and NVAF were older and had a higher prevalence of hypertension and carotid atheromatosis than subjects with RVO without NVAF. Patients with NVAF and RVO had higher prevalence of glaucoma than subjects with NVAF without RVO. In patients with NVAF, it is recommended to optimized VRF treatment and glaucoma control to prevent the development of RVO.