Therapy For Stroke Prevention Research Articles

Predictive value of total atrial conduction time for developing cerebrovascular stroke in patients with sinus rhythm and normal left ventricular systolic function, a case-control study

Abstract Background Stroke is the second leading cause of death worldwide. Recently, atrial cardiopathy has become recognized as a substantial risk factor for cerebrovascular stroke. Greater LA size is linked to stroke in AF patients, but few data linking LA size to stroke in population with sinus rhythm. Purpose To investigate the value of total atrial conduction time (TACT) measured non-invasively by assessing PA-TDI duration as a predictor of stroke in patients who initially presented with sinus rhythm and have normal LV systolic function. Methods In our case-control study, we included 156 patients with acute ischemic stroke and 50 control subjects all presented in sinus rhythm and normal LV systolic function. All participants underwent echocardiography. The bi-plane modified Simpson's approach was used to determine the LV-EF. The left atrial (LA) diameter was measured also left atrial volume index (LAVI) was assessed. The PA-TDI interval was used to estimate the TACT. In the apical four-chamber view, the pulsed-wave tissue Doppler sample was positioned on the lateral and septal walls of the LA above the mitral annulus. The time between the onset of the P wave (lead II) and the peak of the A' wave was called the PA-TDI interval. Also, speckle tracking indices of LA strain were measured. Results LA volume index was larger in the stroke group (39.24±4 versus 33.6±2.8, p: 0.01), PA-TDI duration showed statistical highly significant difference between both groups (165.94±21.695 versus 99.4±22.960, p: <0.001). There were significantly impaired LAS parameters in the stroke group (LA reservoir, contraction & conduit strain, 22.7%, -6.6% & -16.1% versus 40%, -12%, and − 27% in the control group with P < 0.000). ROC curve showed the best cutoff point for LA volume index is >42.2 ml/m2 for prediction of stroke with area under the curve (AUC): 0.7, p value is 0.005. ROC curve showed the best cutoff point for PA-TDI is >155.5 ms. with AUC: 0.9, 90% sensitivity, 91% specificity, p value: <0.001. ROC curve showed that LA reservoir strain and LA stiffness can independently predict stroke at cut-off values of 30% & 24.5% respectively, P < 0.001. Multivariate logistic regression analysis showed that hypertension, LA volume index, LA stiffness and PA-TDI duration are independent predictors of stroke (p: < 0.05, < 0.05, < 0.01 and < 0.001 respectively). Conclusions The assessment of electromechanical asynchrony by measuring the PA-TDI duration may help to predict patients at risk for stroke. It is easy to measure without the need for special software like speckle tracking indices. We also advise patients who exceed the cutoff points of LA volume index and PA-TDI duration to receive antithrombotic therapy for better stroke prevention. Also we recommend adding PA-TDI to CHA2DS2-VASC-HSF score to assess stroke risk in patients with sinus rhythm and paroxysmal AF during their sinus rhythm intervals.

Efficacy and Safety of Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke: A Systematic Review and Meta-analysis

Introduction: Stroke remains a major cause of morbidity and mortality after cardiac surgery. One factor associated with stroke occurrence is postoperative AF (pAF), which predisposes to the formation of atrial thrombus. As most thrombi form in the left atrial appendage (LAA), there is significant interest in LAA as a potential therapeutic target. While guidelines recommend direct oral anticoagulants (DOACs) as the preferred therapy for stroke prevention in patients with AF and a CHA2DS2-VASc score of ≥2, they cannot be administered to all patients who are poor candidates for long-term oral anticoagulation because of the high risk of bleeding, drug compliance and drug tolerance. There are limited data on the efficacy and safety of LAA occlusion (LAAO) during cardiac surgery for stroke prevention. Methods: A comprehensive and relevant search of randomised controlled trials, cohort and case–control studies was conducted. Outcome measures for ischaemic stroke events, all-cause mortality and pAF were extracted and analysed using a random-effects model. Results: Twelve studies were included and 18,982 subjects were analysed. There were 231 ischaemic stroke events in 9,473 patients who received LAAO compared with 371 ischaemic stroke events in 9,509 patients who did not receive LAAO. Concomitant LAAO showed a significant difference in ischaemic event rate (risk ratio [RR] 0.65; [95% CI: 0.55–0.77]; p<0.00001, I2=0%) and all-cause mortality (RR 0.74; 95% CI [0.57–0.97]; p=0.03; I2=68%). For pAF, there was no difference between the two groups (RR 1.08; 95% CI [0.95–1.22]; p=0.24; I2=72). Conclusion: Concomitant LAAO was more effective in preventing ischaemic stroke events and all-cause mortality, with an overall moderate certainty of evidence. However, pAF rates were similar between LAAO and non-LAAO groups.

Lipid-lowering therapies and long-term stroke prevention in East Asians: A systematic review and meta-analysis of randomized controlled trials.

Stroke prevention is a pressing global health priority, with reducing elevated lipids recognized as a key strategy. East Asians, constituting more than 1.6 billion individuals and the largest racial group worldwide, are a key demographic in this effort. Yet, the effectiveness of lipid-lowering therapies for stroke prevention in this population remains uncertain. We conducted a systematic review and meta-analysis of large-scale randomized controlled trials (RCTs) with at least 3 years of follow-up to evaluate the long-term impact of lipid-lowering therapies on stroke incidence in East Asians. We systematically searched four electronic databases up to 11 January 2024. The association was quantified using relative risk (RR) with a 95% confidence interval (CI), and between-study heterogeneity was evaluated using the I2 statistic. In addition, we utilized the Cochrane Risk of Bias Tool to assess the risk of bias in each included RCT and applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to evaluate the certainty of the evidence. This study incorporated data from nine large-scale RCTs involving 54,354 participants. Our findings of overall analyses revealed that lipid-lowering therapies did not significantly affect the long-term incidence of all strokes (9 RCTs; 54,354 participants; RR = 0.98 (95% CI = 0.87-1.10); P = 0.75), ischemic stroke (7 RCTs; 52,059 participants; RR = 0.91 (95% CI, = 0.79-1.04); P = 0.16), or hemorrhage stroke (7 RCTs; 52,059 participants; RR = 1.24 (95% CI = 0.97-1.59); P = 0.09) in East Asians. Notably, there was no evidence of heterogeneity or publication bias, and the quality of evidence assessed using GRADE methodologies was rated as high. Sensitivity analyses confirmed the robustness of our results, with no single study significantly affecting the overall findings. Furthermore, subgroup analyses consistently supported the conclusions, further bolstering the reliability of our study. Lipid-lowering therapies did not demonstrate any beneficial effects on long-term stroke prevention among East Asians.

Oral anticoagulation with Edoxaban for stroke prevention in patients with atrial fibrillation: Analysis of 1-year follow-up data of routine clinical practice in Germany, Austria and Switzerland (DACH) from the ETNA-AF registry

Non-vitamin-K oral anticoagulants (NOACs) are safe and effective for stroke prevention in patients with atrial fibrillation (AF). Data on the safety and efficacy of Edoxaban in routine care in Germany, Austria and Switzerland (DACH) are limited. We report one-year outcomes in patients with AF treated with Edoxaban in routine care. The ETNA-AF-Europe study (Clinicaltrials.gov:NCT02 944 019) is a multicenter, prospective, observational study that enrolled 13 092 patients with AF treated with Edoxaban from 852 sites across 10 European countries (Austria, Belgium, Germany, Ireland, Italy, the Netherlands, Portugal, Spain, Switzerland, and the United Kingdom). The DACH-cohort consists of 5457 (41,7 %) patients of sites in Germany, Austria and Switzerland. Patients had a mean age of 74 years (2384 [44 %]women) and a mean CHA2DS2-VASc-score of 3.2 ± 1.4. A label-conform dosing of Edoxaban was administered to 4309 patients (78,9 %). At the one-year-follow-up a stroke or systemic embolism occurred in 42 patients (0,8 %/year), and severe bleeding was reported in 36 patients (0,7 %/year). Ten patients (0,2 %/year) suffered intracranial and 13 patients (0,3 %/year)gastrointestinal bleeding. Numbers of death from all causes and cardiovascular death occurred in 179 patients (3,4 %/year) and 85 patients (1,6 %/year), respectively. Age > 75 years, frailty and a CHA2DS2-VASc score ≥ 4 were associated with a higher all-cause mortality - and those patients were more likely to suffer a stroke or a major bleeding event. In Germany, Austria and Switzerland in patients with AF on Edoxaban therapy for stroke prevention the number of stroke and major bleeding events is low. Increasing morbidity is associated with a higher number of important clinical events.

Management and outcomes of cerebrovascular injuries after gunshot wounds to the cervical spine

Study designThis study was a multicenter retrospective analysis of cervical spine gunshot wound (GSW) patients. ObjectiveThe present study was conducted to evaluate the management and outcomes of vascular injuries following GSW involving the cervical spine. Summary of background dataGunshot wounds (GSW) injuring the cervical spine are associated with high rates of vascular injury. MethodsCharts of patients with GSW involving the cervical spine at two Level 1 trauma centers were reviewed from 2010 to 2021 for demographics, injury characteristics, management and follow-up. Statistical analysis included T tests and ANOVA for comparisons of continuous variables and chi-square testing for categorical variables, non-parametric tests were used when indicated. Beta-binomial models were used to estimate the probabilities outcomes. Bayesian regression models were utilized to compute risk ratios (RR) and their 95 % confidence intervals (CI) to enhance the inferential robustness. Results40 patients with cervical spine GSW and associated cerebrovascular injury were included in our analysis. 15 % of patients had Biffl grade (BG) V injuries, 50 % grade IV, and 35 % grade III–I. Angiography was performed in 35 % of patients. 5 of these patients (BG V–III) required endovascular treatment for pseudoaneurysm obliteration or parent vessel sacrifice. 7 patients (22 %) showed evidence of progression. 70 % of patients were placed on antiplatelet therapy for stroke prevention. Bayesian regression models with a skeptical prior for cerebral ischemia revealed a mean RR of 4.82 (95 % CI 1.02–14.48) in the BG V group, 0.75 (95 % CI 0.13–2.26) in the BG IV group, and 0.61 (95 % CI 0.06–2.01) in the combined BG III-I group. For demise the mean RR was 3.41 (95 % CI 0.58–10.65) in the BG V group and 1.69 (95 % CI 0.29–5.97) in the BG IV group. In the high BG (V, IV) group, 54.55 % of patients treated with antiplatelet therapy had complications. None of the patients that were treated with antiplatelet therapy in the low BG (III–I) group had complications. ConclusionsCervical spine GSWs are associated with high-grade vascular injuries and may require early endovascular intervention. Additionally, a high rate of injury progression was seen on follow up imaging, requiring subsequent intervention. Reintervention and demise were common and observed in high BG (V, IV) groups. The incidence of stroke was low, especially in low BG (I–III) groups, suggesting that daily aspirin prophylaxis is adequate for long-term stroke prevention.

One-year effectiveness and safety outcomes of edoxaban treatment in Chinese patients with atrial fibrillation: First snapshot of more than 4,800 patients from the ETNA-AF-China study

Abstract Background Direct oral anticoagulants (DOACs) have become the first-line therapy for ischaemic stroke prevention in atrial fibrillation (AF) patients. Data on the effectiveness and safety of single DOAC in large Chinese populations are scarce. Purpose We firstly present the one-year outcome data of edoxaban treatment in 5001 Chinese AF patients. Methods This is a multi-centre, prospective, observational study, ETNA-AF-China, conducted in 89 centres from four economic regions in Mainland of China with a follow-up of two years. Primary endpoint of safety [bleeding events including intracranial hemorrhage (ICH), all-cause and cardiovascular (CV) mortality] and efficacy endpoints [stroke, systemic embolic events (SEE), transient ischemic attack (TIA)] were adjudicated. Annualised event rates and Kaplan­Meier (KM) survival curves are given. Results A total of 4822 patients (57.1% male) using edoxaban (60 mg OD: n=2614, 30 mg OD: n=2208) who completed one-year follow-up were included in the full analysis set. The mean (SD) age of the overall patient population was 70.3 (9.5) years, CHA2DS2-VASc and HAS-BLED scores were 2.9 (1.4), 1.7 (1.0), with creatinine clearance (CrCl) of 71.2 (27.7) mL/min. Patients receiving 30 mg OD edoxaban at baseline were older (73.4 vs 67.7 years), with higher CHA2DS2-VASc score (3.3 vs 2.6), larger percentage of frail (9.9% vs 3.4%), and higher renal impairment (defined as CrCl ≤80 mL/min, 70.3% vs 42.9%). Annualised rates for all-cause and cardiovascular death in the overall population were very low with 2.22%/year and 0.41%/year, respectively. (Figure 1) The death rates were nearly three times lower in those receiving standard dose (60 mg) than reduction dose (30 mg) of edoxaban. Annualised event rates for all stroke/SEE (1.03%/year) and ischemic stroke (0.60%/year) were similar between two dose groups. Overall, annualised rates for major bleeding (1.03%/year), ICH (0.18%/year), major gastrointestinal (GI) bleeding (0.48%/year) events were relatively low, and those on 60 mg dose experienced less above bleeding events. Cumulative survival analysis demonstrated a slow increase in time-to-first event curve of all-cause death; and from baseline to 1-year follow-up, significant lower events of all-cause death (log-rank p<0.001), major bleeding (p=0.002) in 60 mg vs 30 mg edoxaban groups. (Figure 2). Conclusion Low incidences of major bleeding, notably ICH, major GI bleeding, and CV death were observed in unselected 4822 patients with AF during 1-year of edoxaban treatment. These findings confirm the effectiveness and safety of routine edoxaban use in China, consistent with other countries, and reinforce the results of the ENGAGE AF-TIMI 48 trial.Figure 1Figure 2

Diabetes and Stroke: Impact of Novel Therapies for the Treatment of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a significant risk factor for stroke. Nevertheless, the evidence supporting stringent glycemic control to reduce macrovascular complications, particularly stroke, is not as clear as for microvascular complications. Presently, risk reduction strategies are based on controlling multiple risk factors, including hypertension, dyslipidemia, glycemia, smoking, and weight. Since 2008, new pharmacological therapies for treating T2DM have been required to undergo trials to ensure their cardiovascular safety. Remarkably, several novel therapies have exhibited protective effects against the combined endpoint of major cardiovascular events. Evidence from these trials, with stroke as a secondary endpoint, along with real-world data, suggests potential benefits in stroke prevention, particularly with glucagon-like peptide 1 receptor agonists. Conversely, the data on sodium-glucose cotransporter type 2 inhibitors remains more controversial. Dipeptidyl peptidase 4 inhibitors appear neutral in stroke prevention. More recent pharmacological therapies still lack significant data on this particular outcome. This article provides a comprehensive review of the evidence on the most recent T2DM therapies for stroke prevention and their impact on clinical practice.

Long-term combined antiplatelet therapy for secondary prevention of noncardioembolic stroke

Introduction. The high risk of recurrent ischemic events after non-cardioembolic ischemic stroke(IS), the prevalence of which is 25% of all strokes in the Russian Federation, determines the need to search for effective and safe secondary prevention strategies.Аim. The study was to evaluate the efficacy and safety of a combination of ADP receptor inhibitors (dipyridamole) with acetylsalicylic acid in patients with ischemic stroke (IS) in the secondary prevention of noncardioembolic stroke.Materials and methods. 229 patients in the early recovery period of noncardioembolic IS (139 women, 90 men), with an average age of 59.0 ± 5.7 years were included in the study. The duration of IS was 54.4 ± 6.1 days. All patients received a multimodal medical rehabilitation (MMR) program. Long-term double antiplatelet therapy with acetylsalicylic acid (ASA) 75 mg per day and dipyridamole at a daily dose of 225 mg divided into 3 doses were prescribed to all the patients. The neurological and neuropsychological status of the patient, quality of life and hemorheological parameters were assessed initially (T0), after MMR (T1, 6 weeks) and 12 months after IS(T2).Results. Motor and coordination indicators of patients as well as the cognitive and emotional parameters were significantly (p < 0,05) improved due to MMR technology. These were confirmed by the dynamics of the corresponding scales. The prescribed double antiplatelet therapy did not cause significant adverse events and worsening of the patients’ well-being both during the MMR process and during the observation period. The combination of ASA with dipyridamole was well tolerated. At the end of the study, recurrent IS, myocardial infarctions, and fatal bleeding were not recorded. In 5.2% patients with severe risks of cardiovascular complications there was occurred TIA. The effectiveness of the dual antiplatelet therapy was confirmed by a decrease in the level of platelet aggregation (p < 0,05).Conclusions. The high effectiveness of secondary prevention of IS with a combination of ASA and dipyridamole with good tolerability and safety in patients after IS has been shown.

Computerized clinical decision support to improve stroke prevention therapy in primary care management of atrial fibrillation: a cluster randomized trial

Despite guidelines supporting antithrombotic therapy use in atrial fibrillation (AF), under-prescribing persists. We assessed whether computerized clinical decision support (CDS) would enable guideline-based antithrombotic therapy for AF patients in primary care. This cluster randomized trial of CDS versus usual care (UC) recruited participants from primary care practices across Nova Scotia, following them for 12 months. The CDS tool calculated bleeding and stroke risk scores and provided recommendations for using oral anticoagulants (OAC) per Canadian guidelines. From June 14, 2014 to December 15, 2016, 203 primary care providers (99 UC, 104 CDS) with access to high-speed Internet were recruited, enrolling 1,145 eligible patients (543 UC, 590 CDS) assigned to the same treatment arm as their provider. Patient mean age was 72.3 years; most were male (350, 64.5% UC, 351, 59.5% CDS) and from a rural area (298, 54.9% UC, 315, 53.4% CDS). At baseline, a higher than anticipated proportion of patients were receiving guideline-based OAC therapy (373, 68.7% UC, 442, 74.9% CDS; relative risk [RR] 0.97 (95% confidence interval [CI], 0.87-1.07; P = .511)). At 12 months, prescription data were available for 538 usual care and 570 CDS patients, and significantly more CDS patients were managed according to guidelines (415, 77.1% UC, 479, 84.0% CDS; RR 1.08 (95% CI, 1.01-1.15; P = .024)). Notwithstanding high baseline rates, primary care provider access to the CDS over 12 months further optimized the prescribing of OAC therapy per national guidelines to AF patients potentially eligible to receive it. This suggests that CDS can be effective in improving clinical process of care. Clinical Trials NCT01927367. https://clinicaltrials.gov/ct2/show/NCT01927367?term=NCT01927367&draw=2&rank=1.

Effectiveness of Statin Therapy for Primary and Secondary Prevention of Stroke: A Literature Review

Effectiveness of Statin Therapy for Primary and Secondary Prevention of Stroke: A Literature Review

Magnetic Resonance Imaging Assists With Determining Etiology After Transient Ischemic Attack or Minor Stroke.

Magnetic resonance imaging infarct topography may assist with determining stroke etiology. The influence of diffusion-weighted imaging (DWI)-positive lesions on etiology determination in patients with transient ischemic attack or minor stroke is not well studied. We prospectively enrolled patients between 2010 and 2017 in 2 studies; participants with a final diagnosis of probable or definite transient ischemic attack or stroke were pooled for analysis. The primary outcome was the adjudicated ischemic etiology. We compared proportion of each etiology (cardioembolic, large-vessel, small-vessel disease, other) in patients who had DWI positivity compared with DWI negativity. We used logistic regression to determine the adjusted odds ratio (OR) for each etiology compared with undetermined by DWI positivity. The final analysis included 1498 patients: 832 (55.5%) were DWI-positive. DWI-positive patients were more likely to be diagnosed with small-vessel disease (19.1% versus 5.3%) and less likely with undetermined etiology (36.9% versus 53.0%; P<0.001). After adjustment, the presence of any DWI lesion was associated with increased odds of assigning any etiology (OR, 1.8 [95% CI, 1.3-2.5]). A single DWI lesion was associated with increased odds of small-vessel disease diagnosis (OR, 9.5 [95% CI, 6.4-14.0]), and multiple DWI lesions with reduced odds of small-vessel disease (OR, 0.2 [95% CI, 0.1-0.4]) but increased odds of all other etiologies compared with undetermined etiology. Any DWI-positive lesion after suspected transient ischemic attack or minor stroke was associated with increased odds of assigning a etiology. Presence and topography of DWI lesions on magnetic resonance imaging may assist with etiology determination and may impact stroke prevention therapies.

Minimally invasive left atrial appendage occlusion plus reduced dose direct oral anticoagulant to prevent stroke in patients with atrial fibrillation-the LAAO-PlusRE.

The onset of atrial fibrillation (AF) has a direct association with left atrial appendage (LAA) function, as demonstrated by recent studies demonstrating the link between left atrial (LA) wall fibrosis, impaired contractility, and the development of AF. Non-valvular AF (NVAF) affects almost 30 million people worldwide, with this number expected to increase in the next 20 years. It is the main cause of ischemic stroke, with significant subsequent economic and social impact. Currently, the mainstay of stroke prevention in patients with NVAF is oral anticoagulation (OAC), which reduces the incidence of ischemic events at the stake of increased hemorrhagic events. Despite the introduction and widespread use of direct oral anticoagulants (DOACs), which almost completely replaced vitamin K antagonists (VKAs), the adherence to OAC is still low, hindering the efficacy of stroke prevention. Percutaneous LAA occlusion (LAAO) is now indicated (class IIB) in patients with NVAF at increased ischemic risk who cannot undergo OAC. Recently published data demonstrated that a reduced dose of DOAC after percutaneous LAAO is superior to long-term dual antiplatelet therapy (DAPT) for stroke prevention in the mid-term. One of the possible pitfalls of percutaneous LAAO is postprocedural peri-device leaks (PDLs) that have been associated with increased thromboembolic events. According to LAAOS III results, surgical LAAO during cardiac surgery brings a 33% reduction in risk of stroke at five years, independently from the OAC regimen with a high rate of complete appendage occlusion. The combination of surgical LAAO and reduced dose DOAC might ensure adequate embolic prevention, lowering the hemorrhagic risk. The present manuscript aims to describe the rationale and design of the Minimally Invasive Left Atrial Appendage Occlusion Plus REduced Dose DOAC To Prevent Stroke In Patients With Atrial Fibrillation Randomized Clinical Trial (LAAO-PlusRE).

Patient Characteristics Associated With Using Transcatheter Left Atrial Appendage Occlusion Versus Oral Anticoagulants for Atrial Fibrillation.

Transcatheter left atrial appendage occlusion (LAAO) is an alternative to oral anticoagulants (OACs) for stroke prevention in patients with atrial fibrillation, but the predictors of LAAO use in routine care are unclear. We aimed to assess the utilization trends of LAAO and compare the change in characteristics of LAAO users versus OACs since its marketing. Using the US Medicare claims database (March 15, 2015, to December 31, 2020), we identified patients with atrial fibrillation, ≥65 years, and CHA2DS2-VASc score ≥2 (men) or ≥3 (women), with either first implantation of an LAAO device or initiation of OACs, including apixaban, dabigatran, rivaroxaban, edoxaban, or warfarin. Patient characteristics, measured 365 days before the first LAAO or OAC use date, were compared using logistic regression. There were 30 058 LAAO recipients (mean age, 77.74 years; female, 42.1%) and 792 600 OAC initiators (mean age, 78.48; female, 53.3%). In 2020, patients had higher odds of initiating LAAO use than in 2015 (0.52 versus 9.32%; adjusted odds ratio [aOR], 13.64 [95% CI, 12.56-14.81]). Old age (ie, >85 versus 65-75 years; aOR, 0.84 [95% CI, 0.80-0.88]), female sex (aOR, 0.74 [95% CI, 0.71-0.76]), Black race (aOR, 0.63 [95% CI, 0.58-0.68]) versus White race, and Medicaid eligibility (aOR, 0.61 [95% CI, 0.58-0.64]) were associated with lower odds of receiving LAAO. Among clinical characteristics, frailty, cancer, fractures, and venous thromboembolism were associated with lower odds of LAAO use, while history of intracranial and extracranial bleeding, coagulopathy, and falls were associated with higher odds of receiving LAAO. Among patients with atrial fibrillation receiving stroke-preventive therapy, LAAO use increased rapidly from 2015 to 2020 and was positively associated with the risk factors for OAC complications but negatively associated with old age, advanced frailty, and cancer. Black race and female sex were associated with a lower likelihood of receiving LAAO.

Protocol for a randomised controlled trial comparing warfarin with no oral anticoagulation in patients with atrial fibrillation on chronic dialysis: the Danish Warfarin-Dialysis (DANWARD) trial

IntroductionAtrial fibrillation is highly prevalent in patients on chronic dialysis. It is unclear whether anticoagulant therapy for stroke prevention is beneficial in these patients. Vitamin K-antagonists (VKA) remain the predominant...

Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy

Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation. To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 μV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium. Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508). The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage. With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52]). In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin. ClinicalTrials.gov Identifier: NCT03192215.

Genetic insights into the relationship between immune cell characteristics and ischemic stroke: A bidirectional Mendelian randomization study.

Ischemic stroke, a major contributor to global disability and mortality, is underpinned by intricate pathophysiological mechanisms, notably neuroinflammation and immune cell dynamics. Prior research has identified a nuanced and often paradoxical link between immune cell phenotypes and ischemic stroke susceptibility. The aim of this study was to elucidate the potential causal links between the median fluorescence intensity (MFI) and morphological parameters (MP) of 731 immune cell types and ischemic stroke risk. By analyzing extensive genetic datasets, we conducted comprehensive Mendelian randomization (MR) analyses to discern the genetic correlations between diverse immune cell attributes (MFI and MP) and ischemic stroke risk. Our study identified key immune cell signatures linked to ischemic stroke risk. Both B cells and T cells, among other immune cell types, have a bidirectional influence on stroke risk. Notably, the regulatory T-cell phenotype demonstrates significant neuroprotective properties, with all odds ratio (OR) values and confidence intervals (CIs) being less than 1. Furthermore, CD39 phenotype immune cells, particularly CD39+ CD8+ T cells (inverse variance weighting [IVW] OR 0.92, 95% CI 0.87-0.97; p = 0.002) and CD39+ activated CD4 regulatory T cells (IVW OR 0.93, 95% CI 0.90-0.97; p < 0.001), show notable neuroprotection against ischemic stroke. This investigation provides new genetic insights into the interplay between various immune cells and ischemic stroke, underscoring the complex role of immune processes in stroke pathogenesis. These findings lay a foundation for future research, which may confirm and expand upon these links, potentially leading to innovative immune-targeted therapies for stroke prevention and management.

Abstract WP238: Efficacy of Dual Antiplatelet Therapy After Lacunar versus Non-Lacunar Syndromes in the POINT Trial

Introduction: About 20% of ischemic strokes are lacunar infarcts, the pathophysiology of which differs from that of other stroke etiological subtypes. The POINT trial demonstrated the efficacy of dual antiplatelet therapy (DAPT) for secondary stroke prevention in patients with minor ischemic stroke and high-risk TIA, but it remains unknown whether this benefit differed in lacunar versus non-lacunar strokes. Method: In a secondary analysis of POINT trial data, we compared the efficacy of DAPT in patients with an index lacunar syndrome versus not. A lacunar syndrome was defined based on common classic lacunar syndromes (e.g., pure motor hemiparesis, clumsy-hand dysarthria) and ascertained using subcomponents of the National Institutes of Health Stroke Scale documented at baseline. Our primary efficacy outcome was ischemic stroke and the safety outcome was intracranial hemorrhage. We used survival analysis and tests of interaction to compare the effect of DAPT between the lacunar and non-lacunar subgroups. Result: Among 4,881 patients enrolled in the study, 1,083 (22.1%) were classified as having an index lacunar syndrome. The effect of DAPT on the risk of ischemic stroke did not vary significantly after a lacunar syndrome (HR, 0.76; 95% CI, 0.52-1.09) versus after a non-lacunar syndrome (HR, 0.69; 95% CI, 0.50-0.95) (P value for interaction, 0.70). Similarly, the effect of DAPT on the risk of intracranial hemorrhage did not vary significantly after a lacunar syndrome (HR, 2.82; 95% CI, 0.29-27.1) versus after a non-lacunar syndrome (HR, 2.10; 95% CI, 0.63-6.99) (P for interaction, 0.82). Conclusion: In a post hoc secondary analysis of the POINT trial, we found no evidence of a lesser benefit of DAPT after a minor ischemic stroke or TIA in patients presenting with a lacunar syndrome compared to other stroke subtypes.

C-Reactive Protein, Interleukin-6, and Vascular Recurrence According to Stroke Subtype: An Individual Participant Data Meta-Analysis

Anti-inflammatory therapies reduce major adverse cardiovascular events (MACE) in coronary artery disease but remain unproven after stroke. Establishing the subtype-specific association between inflammatory markers and recurrence risk is essential for optimal selection of patients in randomized trials (RCTs) of anti-inflammatory therapies for secondary stroke prevention. Using individual participant data (IPD) identified from a systematic review, we analyzed the association between high-sensitivity C-reactive protein, interleukin-6 (IL-6), and vascular recurrence after ischemic stroke or transient ischemic attack. The prespecified coprimary end points were (1) any recurrent MACE (first major coronary event, recurrent stroke, or vascular death) and (2) any recurrent stroke (ischemic, hemorrhagic, or unspecified) after sample measurement. Analyses were performed stratified by stroke mechanism, per quarter and per biomarker unit increase after loge transformation. We then did study-level meta-analysis with comparable published studies not providing IPD. Preferred Reporting Items for Systematic Review and Meta-Analyses IPD guidelines were followed. IPD was obtained from 10 studies (8,420 patients). After adjustment for vascular risk factors and statins/antithrombotic therapy, IL-6 was associated with recurrent MACE in stroke caused by large artery atherosclerosis (LAA) (risk ratio [RR] 2.30, 95% CI 1.21-4.36, p = 0.01), stroke of undetermined cause (UND) (RR 1.78, 1.19-2.66, p = 0.005), and small vessel occlusion (SVO) (RR 1.71, 0.99-2.96, p = 0.053) (quarter 4 [Q4] vs quarter 1 [Q1]). No association was observed for stroke due to cardioembolism or other determined cause. Similar results were seen for recurrent stroke and when analyzed per loge unit increase for MACE (LAA, RR 1.26 [1.06-1.50], p = 0.009; SVO, RR 1.22 [1.01-1.47], p = 0.04; UND, RR 1.18 [1.04-1.34], p = 0.01). High-sensitivity CRP was associated with recurrent MACE in UND stroke only (Q4 vs Q1 RR 1.45 [1.04-2.03], p = 0.03). Findings were consistent on study-level meta-analysis of the IPD results with 2 other comparable studies (20,136 patients). Our data provide new evidence for the selection of patients in future RCTs of anti-inflammatory therapy in stroke due to large artery atherosclerosis, small vessel occlusion, and undetermined etiology according to inflammatory marker profile.

Central American and Caribbean Consensus Document for the Optimal Management of Oral Anticoagulation in Patients with Non-Valvular Atrial Fibrillation Endorsed by the Central American and Caribbean Society of Arterial Hypertension and Cardiovascular Prevention.

Atrial fibrillation (AF) is the most common arrhythmia in adults. Prevention of the ischaemic risk with oral anticoagulants (OACs) is widely recommended, and current clinical guidelines recommend direct oral anticoagulants (DOACs) as preference therapy for stroke prevention. However, there are currently no clinical practice guidelines or recommendation documents on the optimal management of OACs in patients with AF that specifically address and adapt to the Central American and Caribbean context. The aim of this Delphi-like study is to respond to doubts that may arise in the management of OACs in patients with non-valvular AF in this geographical area. A consensus project was performed on the basis of a systematic review of the literature, a recommended ADOLOPMENT-like approach, and the application of a two-round Delphi survey. In the first round, 31 recommendations were evaluated and 30 reached consensus, of which, 10 unanimously agreed. The study assessed expert opinions in a wide variety of contextualized recommendations for the optimal management of DOACs in patients with non-valvular atrial fibrillation (NVAF). There is a broad consensus on the clinical practice guideline (CPG) statements used related to anticoagulation indication, patient follow-up, anticoagulation therapy complications, COVID-19 management and prevention, and cardiac interventions.

An isolated pontine infarct extending to the basal pontine surface has a higher abnormal ankle-brachial index

Patients with ischemic stroke and branch atheromatous disease (BAD) have worse neurological deficits and prognoses than those with small vessel occlusion (SVO). However, both disorders are forms of deep brain infarctions. This study aimed to investigate an MRI-based etiological classification for isolated pontine infarctions and assess differences in vascular risk factors and peripheral arterial disease among etiological subtypes. Consecutive data of patients admitted for acute ischemic stroke or transient ischemic attack between August 2016 and July 2019 were reviewed. Acute isolated pontine infarcts were classified into 3 groups: BAD, SVO, and large-artery atherosclerosis (LAA), according to basilar or vertebral artery steno-occlusion and the extent of the infarct lesion on the basal pontine surface as displayed on magnetic resonance imaging and angiography. Vascular risk factors, ankle-brachial index (ABI), and brachial-ankle pulse wave velocity were analyzed in the 3 groups. Among 64 enrolled patients, BAD was the most common cause of isolated pontine infarct. The BAD group had a higher frequency of abnormal ABI and hypertension than the SVO group. The BAD group had abnormal ABI and hyperlipidemia more frequently than the LAA group. No significant difference was found in diabetes or brachial-ankle pulse wave velocity incidence between the BAD and SVO groups. ABI and vascular risk factors in the BAD group were more similar to those in the LAA group than to those in the SVD group. This finding suggests that pontine lesions extending to the basal pontine surface have an atherosclerotic mechanism in BAD, requiring potent antiplatelet therapy for the secondary prevention of ischemic stroke.