Risk Of Recurrent Stroke Research Articles

Abstract 4120716: Aspirin plus clopidogrel versus aspirin alone in patients with mild-to-moderate stroke: A systematic review and meta-analysis

Background: Studies have shown that dual antiplatelet therapy (DAPT) is superior to aspirin monotherapy in patients with minor stroke or transient ischemic attacks. However, there is limited evidence regarding the efficacy and safety of DAPT in mild-to-moderate stroke. Aims: We conducted a systematic review and meta-analysis to evaluate whether DAPT is superior to single antiplatelet among patients with mild to moderate ischemic stroke. Methods: PubMed/MEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from inception till March 2024 for published randomized controlled trials (RCTs) and observational studies that compared aspirin plus clopidogrel versus aspirin monotherapy in patients with mild-to-moderate stroke. R version 4.3.2 was used to calculate risk ratios (RRs) with 95% confidence intervals (95% CIs). Results: A total of 4 studies reporting data for 15,173 patients were included. DAPT was associated with a reduced risk of early neurological deterioration (END) (RR: 0.55, 95% CI: 0.28 to 1.05, p = 0.07 Figure 1A) and recurrent ischemic stroke (RR: 0.65, 95% CI: 0.41 to 1.04, p = 0.07 Figure 1B) without reaching statistical significance. The risk of recurrent hemorrhagic stroke (RR: 0.94, 95% CI: 0.47 to 1.86, p = 0.86 Figure 2A), all-cause death (RR: 0.75, 95% CI: 0.52 to 1.08 Figure 2B), or myocardial infarction (RR: 0.83, 95% CI: 0.45 to 1.54 Figure 2C) was comparable across the two groups. DAPT was not associated with an increased risk of any bleeding event (RR: 0.70, 95% CI: 0.36 to 1.36 Figure 2D). Conclusion: DAPT possibly reduces the risk of END and recurrent ischemic stroke as compared to aspirin monotherapy in mild or moderate stroke without increasing the risk of bleeding events.

Abstract 4137665: Getting to the Heart of Stroke TM : A Novel American Heart Association Initiative Which Increases Identification of Stroke Etiology and Evidence-Based Post-Stroke Evaluation by Strengthening Cardiology and Neurology Collaboration

Background: Nearly one million individuals in the U.S. experience ischemic stroke annually and one-year recurrent stroke risk may exceed 10%. American Heart Association (AHA) Get-With-The-Guidelines-Stroke® Registry (GWTG-S) data suggests that up to 40% of stroke patients are discharged with an undocumented or cryptogenic etiology which may lead to suboptimal secondary prevention. Consequently, improved cardiology and neurology collaboration and evidence-based post-stroke evaluation may help identify stroke etiology, reduce recurrent stroke risk and improve outcomes. Methods: In 2022, the AHA, in collaboration with HCA Healthcare and HCA Healthcare Foundation, designed and launched Getting to the Heart Of Stroke TM (GTTHOS) in 10 HCA Healthcare comprehensive stroke centers to improve: 1) cardiology and neurology stroke care collaboration, 2) evidence-based post-stroke diagnostic evaluation and 3) assessment of social determinants of health and barriers to care. Components included a learning collaborative model, virtual performance improvement consultations, Plan-Do-Study-Acts, multidisciplinary teams, custom and existing GWTG-S metrics and performance improvement feedback. Results: Using existing and custom GWTG-S data, GTTHOS centers increased rates of documented stroke etiology (58.06% vs. 48.63%), while decreasing cryptogenic stroke rates (31.01% vs. 34.89%) and lack of a documented stroke etiology (10.93% vs. 16.48%) (all comparisons on discharge, follow-up vs. baseline, p<0.0001). In addition, the use of evidence-based post-stroke diagnostic evaluation increased in GTTHOS centers, including intracranial vascular and carotid imaging, echocardiography, short-term and extended (surface, implantable) cardiac monitoring (Table). Conclusion: In this novel AHA GTTHOS initiative in patients with stroke, which includes improved cardiology and neurology collaboration, rates of identified stroke etiology increased, while cryptogenic stroke and lack of a documented stroke etiology decreased. Furthermore, evidence-based post-stroke diagnostic evaluation, including imaging, echocardiography and short- and long-term surface and implantable cardiac monitoring, increased. These findings may contribute to improved outcomes.

Abstract 4123899: Stroke Risk in Patients with an Isolated Interventricular Membranous Septal Aneurysm

Aim: This study investigates the prevalence of isolated interventricular membranous septal (IVMS) aneurysms detected via echocardiography and assesses the associated stroke risk without other classical risk factors. Methods: We searched the echocardiography database at Mount Sinai Morningside from January 2017 to September 2023. Identified echocardiograms were reviewed to confirm IVMS aneurysms and exclude sinus of Valsalva aneurysms. Patients with concurrent structural heart anomalies were excluded. Medical records were examined for baseline characteristics, risk factors, and cortical brain infarcts. Results: From 51,732 subjects, 18 were identified with IVMS aneurysms, yielding a prevalence of 0.04%. Four patients with significant structural heart disease were excluded, resulting in a final sample size of 14. Of these, 9 (64%) were female with a mean age of 59.6, and 5 (36%) were male with a mean age of 55.4. The mean BMI was 27.9 kg/m 2 , with 4 classified as obese. All patients were nonsmokers; 2 had a family history of stroke. One patient had diabetes, 8 had hyperlipidemia, and 9 had hypertension. Only one patient had paroxysmal atrial fibrillation, with a CHA2DS2-VASc score of 0. Echocardiography revealed structurally normal hearts with a mean left ventricular ejection fraction of 61% and a mean left atrial volume index of 24.8 mL/m 2 . The mean neck diameter of the aneurysm was 8.7 mm, and the mean diameter was 11.9 mm. Two patients had inter-atrial septal aneurysms, and one had a patent foramen ovale. Out of the 14 patients, 5 had a history of ischemic stroke (4) or transient ischemic attacks (1), all of whom were 64 years or younger with a mean RoPE Score of 6 and a mean CHA2DS2-VASc score of 1.6 at the time of their first neurologic event. All patients were treated with aspirin and statin therapy. Two patients had recurrent strokes, one of whom had four recurrent strokes, all cortical infarcts. These patients were switched to clopidogrel after 3 months of dual antiplatelet therapy. No anticoagulation was used. Conclusion: This retrospective study highlights a notable association between isolated IVMS aneurysms and an increased risk of ischemic stroke (36%) and recurrent ischemic stroke (14%). Despite their rarity, these anomalies should be considered in unexplained strokes. Optimal management strategies remain ambiguous, but anticoagulation may be favored based on presumed stroke mechanisms. Large-scale multicenter studies are needed for validation.

ECG-based machine learning model for AF identification in patients with first ischemic stroke.

The recurrence rate of strokes associated with atrial fibrillation (AF) can be substantially reduced through the administration of oral anticoagulants. However, previous studies have not demonstrated a clear benefit from the universal application of oral anticoagulants in patients with embolic stroke of undetermined source. Timely detection of AF remains a challenge in patients with stroke. This study aims to develop a convolutional neural network (CNN) model to accurately identify patients with AF using a 12-lead sinus-rhythm electrocardiogram (ECG) recorded around the time of the first ischemic stroke. Additionally, this study also evaluates the model's ability to predict future occurrence of AF. A CNN model was trained with ECG data from patients at Taipei Veterans General Hospital. External validation was performed on ischemic stroke patients from National Taiwan University Hospital. The model's performance was assessed for detecting AF at the stroke event and predicting future AF occurrences. The model demonstrated an area under curve (AUC) of 0.91 for internal validation and 0.69 for external validation in identifying AF at the stroke event, with sensitivity and negative predictive value both achieving 97%. Kaplan-Meier survival analysis of patients without a prior diagnosis of AF revealed a significant increase in future AF incidence among the high-risk group identified by the model (adjusted hazard ratio: 4.06; 95% confidence interval: 2.74-6.00). The CNN model effectively identifies AF in stroke patients using 12-lead ECGs and predicts future AF events, facilitating early anticoagulation therapy and potentially reducing recurrent stroke risk. Further prospective studies are warranted to confirm these findings.

Direct Oral Anticoagulants Versus Aspirin for Stroke Prevention After Embolic Stroke of Undetermined Source: An Updated Meta-Analysis of Randomized Controlled Trials

Background: Four randomized controlled trials (RCTs) did not show a benefit of direct oral anticoagulant (DOAC) treatment compared with antiplatelet therapy for the prevention of recurrent strokes in patients with embolic stroke of undetermined source (ESUS). However, the balance between efficacy and safety in subgroups needs to be better defined. We aimed to assess the relative benefits of DOACs in key subgroups of adult patients with ESUS. Methods: We searched major databases (PubMed, Embase, CENTRAL, and Web of Science) for RCTs published from inception to 16 June 2024. The primary outcome was recurrent stroke, and the main safety outcomes were major bleeding and clinically relevant non-major bleeding (CRNB). We assessed the risk of bias using the Cochrane Risk of Bias tool 2. Results: We identified four RCTs, involving a total of 13,970 patients with ESUS. Compared to antiplatelet therapy, treatment with DOAC did not reduce the risk of recurrent stroke (RR 0.95, 95% CI 0.83–1.08, p = 0.45) or ischemic stroke (RR 0.92, 95% CI 0.80–1.05, p = 0.22) or increase major bleeding (RR 1.57, 95% CI 0.87–2.83; p = 0.14). DOAC treatment was associated with a significantly higher risk of CRNMB compared to aspirin (RR 1.52, 95% CI: 1.22–1.90; p = 0.0002). The subgroup analysis demonstrated that use of DOACs was associated with a significant protective effect in patients aged 75 or older (RR 0.76, 95% CI 0.60–0.97, p = 0.03) and when the time from index stroke to randomization was ≥8 days (RR 0.80, 95% CI 0.66–0.97, p = 0.02) in preventing recurrency of any type of stroke. Conclusions: Our meta-analysis showed lack of overall benefit of anticoagulation with DOAC compared to antiplatelet therapy for recurrent stroke prevention in adult patients with ESUS. However, the subgroup analyses suggest the possibility of interactions between age and timing of randomization since stroke and treatment with an DOAC in terms of recurrent stroke prevention. Further research toward tailoring the antithrombotic strategy according to patient characteristics is needed.

Clinical characteristic and long-term prognosis in vertebrobasilar stroke

Vertebrobasilar stroke (VBS) is 20-25% of the ischemic stroke structure, however, the clinical features and long-term outcome of the disease studied poorly in the domestic population.The aim of the study was to analyze the clinical features of the acute period of VBS and calculate the 5-year risk of cardiovascular events and death.Material and methods. We analyzed the data of 1569 patients with ischemic stroke. There were analyses of patient complaints, neurological status, brain imaging, NIHSS and POST-NIHSS. The logistic regression model was built for an integral assessment of predictors of five-year mortality.Results. 386 (25%) patients with VBS were diagnosed and 147 (9,4%) cases of VBS were diagnosed with CT-scan. The top complaints were dizziness, unsteadiness and blurred speech. 72 (48,9%) patients were low neurological deficit, the most common neurological syndromes were ataxia, prosoparesis, hemiparesis, dysarthria and nystagmus. More than 60% of patients had an unspecified stroke subtype, despite the diagnostic search performed. The 19,4% patients were recurrent ischemic stroke and 37,2% patients died. Predictors of mortality were age and the presence of cardiovascular disease. Conclusion. Patients with VBS are characterized by a predominantly nonspecific clinical picture of the disease, in half of the cases a minor neurological deficit, insufficient information content of the initial computed tomography of the brain, a low frequency of intravenous thrombolysis, difficulties in determining the cause of stroke and a high risk of recurrent stroke and death within 5 years.

Diagnosis and management of adult Moyamoya angiopathy: An overview of guideline recommendations and identification of future research directions.

Despite the progress made in understanding the management and outcomes of Moyamoya angiopathy (MMA), several aspects of the disease remain largely unknown. In particular, evidence on the disease history and management of MMA is lacking, mainly due to methodological and selection biases in the available studies and the lack of large, randomized prospective studies. Therefore, the care of MMA patients remains limited to a few expert centers worldwide, and management is often based on local expertise and available resources. Over the years, recommendations or expert opinions have been written to provide guidance to physicians in the treatment of this condition with the goal of reducing the risk of stroke recurrence and long-term disability. However, there is no complete agreement between the available guidelines and recommendations due to differences in the articles addressed, methodologies, expertise, and validated approaches to literature review. This lack of consensus on the management of MMA may confuse clinicians and highlight some important issues and points. The aim of this comprehensive review article is to critically examine three recent guidelines and recommendations on MMA, discussing their differences and similarities and highlighting gaps in MMA care that need to be covered.

Tmax >4 s volume predicts stroke recurrence in symptomatic intracranial atherosclerotic stenosis with optimal medical treatment

BackgroundThe time to maximum (Tmax) profile based on computed tomography perfusion (CTP) provides a quantitative assessment of cerebral hemodynamic compromise. We aimed to delineate the Tmax profile in stroke patients...

Are People Living With Dementia Receiving High Intensity Statin Therapy After Stroke? A Population-Based Cohort Study.

This Australian population-based study investigated statin intensity after hospitalization for ischemic stroke in a matched cohort of people living with and without dementia. We identified all patients aged ≥ 30 years hospitalized in the state of Victoria, Australia, for ischemic stroke from July 1, 2013 to April 30, 2018 from the Victorian Admitted Episodes Data set. People with dementia were matched 1:4 for sex, 5-year age group and index date ± 90 days with people without dementia. Records of statin dispensing within 60 days postdischarge were extracted from prescription claims data. The intensity of the first postdischarge statin dispensing was determined. Odds ratios for high versus low-moderate intensity and no statin dispensing were estimated using multinomial logistic regression adjusted for factors including age, sex, and comorbidity. The cohorts comprised 11,105 people (dementia: N = 2221; without dementia: N = 8884 and 52% were female. Compared to people without dementia, people with dementia had 35% (95% confidence interval [CI]: 24%-44%) lower odds of receiving a high intensity versus a low-moderate intensity statin and 54% (95% CI: 48%-59%) lower odds of receiving a high intensity versus no statin. Compared to men, women with and without dementia had 16% (95% CI: 5%-25%) lower odds of receiving a high- versus low-moderate intensity statin and 28% (95% CI: 19%-35%) lower odds of receiving a high intensity versus no statin. People living with dementia are less likely to receive high-intensity statins post-discharge compared to people without dementia. There is a gender gap in receipt of guideline-recommended high-intensity statin therapy for secondary prevention after ischemic stroke. Guidelines recommend all people with reasonable life expectancy receive a high-intensity statin after stroke to reduce the risk of recurrent stroke and other adverse cardiovascular events. More research is needed to understand why people living with dementia might not receive guideline recommended care, and how statin use and statin intensity impact the health outcomes of people living with dementia and stroke.

Efficacy of Dual Antiplatelet therapy after Ischemic Stroke According to hsCRP Levels and CYP2C19 Genotype

BackgroundBoth high-sensitive C-reactive protein (hsCRP) and CYP2C19 genotypes are independent predictors of clinical outcomes after ischemic stroke. We aim to evaluate the association of CYP2C19 loss-of-function alleles (LoFA) carrying status with the effects of dual/single antiplatelet therapy at different hsCRP levels using the CHANCE trial. MethodsSubjects with both of CYP2C19 major alleles information (*2, *3, and *17) and hsCRP measurements were enrolled from the prespecified subgroup. CYP2C19 LoFA carriers were defined as patients with either*2 or *3 allele. Cox proportional hazards models were used to assess the interaction of CYP2C19 LoFA carrying status with the effects of dual/single antiplatelet therapy at different hsCRP levels. The primary outcome was recurrent stroke within 90 days. ResultsAmong 2801 patients, 1646 (58.8%) were LoFA carriers, and 922 (32.9%) had elevated hsCRP. In patients with non-elevated hsCRP, there was a significant interaction effect between CYP2C19 LoFA carrying status and dual/single antiplatelet regimens for prevention of recurrent stroke and combined vascular events (p =0.048, 0.048, respectively), but, not in patients with elevated hsCRP (p =0.502, 0.472, respectively). Only among patients with non-elevated hsCRP and non-carrier of CYP2C19 LoFA, dual antiplatelets significantly reduced the risk of recurrent stroke compared with aspirin alone (hazard ratio= 0.44 [0.26-0.74], p=0.003). No significant differences in bleeding were found. ConclusionsNon-elevated hsCRP and non-carrier of CYP2C19 LoFA may predict a better response to dual antiplatelet therapy in reducing stroke recurrence and composite vascular events for patients with minor stroke and high-risk TIA. TRIAL REGISTRATIONclinicaltrials.gov Identifier: NCT00979589

Clinical Features, Management, and Recurrence of Acute Ischemic Stroke Occurring in Patients on Oral Anticoagulant Treatment for Nonvalvular Atrial Fibrillation: A Real-World Retrospective Study.

The optimal management of acute ischemic stroke (AIS) in patients with oral anticoagulation (OA) is challenging. Our study aimed to analyze the clinical characteristics and outcome of AIS in patients with OA for nonvalvular atrial fibrillation (NVAF). We retrospectively analyzed data on NVAF patients with AIS on direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA) admitted to our Stroke Unit from 2017 to 2022. Ninety-day modified Rankin Scale (mRS), 90-day, and 12-month stroke recurrences were recorded. A total of 169 patients (53.2% female, mean age 82.8±6.7 y), 117 (69.2%) on DOAC, and 52 on VKA (30.8%), were enrolled. Mean age, in-hospital mortality, and 90-day mRS ≥4 were significantly higher in VKA patients. 63.4% of VKA patients had subtherapeutic INR, whereas 47.1% of DOAC patients were on low-dose (14.2% off-label). Large vessel occlusion and embolic etiology were more frequent in VKA patients (34.6% vs. 26.4%, P =0.358; 92.3% vs. 74.3%, P =0.007, respectively), whereas lacunar strokes were more frequent in DOAC patients (19.8% vs. 12.2%, P =0.366). Among patients on VKA before AIS 86.4% were switched to DOAC, whereas a DOAC-to-VKA and a DOAC-to-DOAC switch were done in 25.4% and 11.7%, respectively. Stroke recurrence occurred in 6.4% of patients at 90 days and 10.7% at 12 months. Anticoagulant switching was not associated with stroke recurrences. In our study, nonembolic etiology was more frequent in DOAC patients and anticoagulant switching did not reduce the risk of stroke recurrence. Prospective multicentric studies are warranted.

Breaking boundaries: exploring recent advances in anticoagulation and thrombosis management: a comprehensive review.

Thromboembolic disorders globally contribute to morbidity and mortality, emphasizing adequate anticoagulation and thrombosis management. Therapeutic advances are essential in preventing complications like pulmonary embolism, stroke, and myocardial infarction. This review summarizes recent anticoagulation advances, current challenges, future directions, and novel anticoagulants and drug delivery systems on clinical outcomes. This paper assesses the effectiveness and safety of new anticoagulants through a systematic review of recent clinical trials, meta-analyses, and guideline publications. Key studies, including PACIFIC-AF, RIVER, ENAVLE, ENVISAGE-TAVI AF, and ARCADIA, were analyzed to provide a perspective on therapeutic advancements. The review highlights key findings from vital clinical trials. Asundexian, in the PACIFIC-AF trial, demonstrated a 34% reduction in bleeding events compared to Apixaban. In the RIVER trial, Rivaroxaban reduced significant bleeding events by 20% compared to warfarin in patients with bioprosthetic mitral valves. In the ENAVLE trial, Edoxaban achieved a 3.7% decrease in thromboembolic events compared to warfarin without increasing significant bleeding rates. In the ENVISAGE-TAVI AF trial, edoxaban was noninferior to VKAs in preventing thromboembolic events but showed a slight increase in major bleeding events by 1.5%. Lastly, the ARCADIA trial highlighted that apixaban did not significantly reduce recurrent stroke risk compared to aspirin, with both treatments having an annualized stroke rate of 4.4%. Advances in anticoagulant therapies and drug delivery systems aim to enhance patients' clinical outcomes for thromboembolic disorders. While recent trials show promising data, ongoing patient-specific responses and monitoring challenges require further research. Continuous innovation and investigation are essential to refine anticoagulation practices and tailor treatments.

White matter lesions as a prognostic marker of recurrence in cryptogenic stroke with high-risk patent foramen ovale

PurposeA high-risk patent foramen ovale (PFO) could be the cause of cryptogenic stroke, and an atrial septal aneurysm (ASA) increases the risk of stroke recurrence in cryptogenic stroke patients with a patent foramen ovale (PFO). Factors related to stroke recurrence according to PFO characteristics have not been fully evaluated. MethodsData from a multicenter, observational registry of ischemic stroke patients undergoing transesophageal echocardiography were used for this study. Patients were classified into three groups: high-risk PFO, PFO with large shunt (≥20 microbubbles) or ASA; right-to-left shunt (RLS), RLS including PFO with <20 microbubbles or without ASA, or pulmonary arteriovenous fistula; and negative RLS. Cox proportional hazards regression analysis was used to explore the factors related to stroke recurrence in these three groups. ResultsIn total, 586 patients (185 females; 65.5±13.2 years) were analyzed. In cryptogenic stroke (329 patients) with median follow-up of 4.2 (interquartile range, 1.0–6.1) years, 55 patients had stroke recurrence. The negative RLS, RLS, and high-risk PFO groups included 179, 90, and 60 patients, in which stroke recurrence occurred in 5.3%, 2.5%, and 4.6% per person-year, respectively. In patients with high-risk PFO, the National Institutes of Health stroke scale score (hazard ratio [HR] 1.257 [1.034-1.530]) and periventricular hyperintensity (HR 3.369 [1.103-10.294]) were predictors of stroke recurrence on multivariable Cox hazards analysis, but no factors were related to stroke recurrence in the RLS and negative RLS groups. ConclusionPeriventricular hyperintensity was shown to predict recurrent stroke in patients with a high-risk PFO.

Efficacy and safety of P2Y12 inhibitors plus aspirin versus aspirin alone in ischemic stroke or high-risk transient ischemic attack: a meta-analysis of randomized controlled trials

Abstract Background Patients with mild ischemic stroke or transient ischemic attack (TIA) have an increased risk of recurrent stroke within 90 days after the onset of the initial thrombotic event. Antiplatelet therapy plays an essential role in reducing the risk of stroke recurrence. However, data regarding the efficacy and safety of dual antiplatelet therapy (DAPT) with P2Y12 inhibitors (clopidogrel/ticagrelor) and aspirin versus aspirin monotherapy is limited. Purpose We performed an updated systematic review and meta-analysis to evaluate the effectiveness of DAPT versus aspirin monotherapy in patients with mild ischemic stroke or TIA in the light of new published evidence. Moreover, we investigated whether antiplatelet therapy started within 72 hours is effective in reducing recurrent stroke as compared to the conventionally used 24-hour time window for initiating DAPT. Methods PubMed/MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared DAPT with aspirin plus clopidogrel to aspirin alone started within 24 hours or 72 hours in patients with acute mild ischemic stroke or high-risk TIA from inception to December 31st, 2023. A random-effects model was used to pool risk ratios (RRs) and 95% confidence intervals (CIs) for clinical endpoints. Results Five RCTs with 27,563 patients were included in this study. DAPT significantly reduced the risk of recurrent stroke by 23% (RR: 0.77; 95% CI: 0.70-0.83; p&amp;lt;0.00001), ischemic stroke by 26% (RR: 0.74; 95% CI: 0.68-0.81; p&amp;lt;0.00001), and major adverse cardiovascular events (MACE) by 23% (RR: 0.77; 95% CI: 0.71-0.84; p&amp;lt;0.00001). However, DAPT was associated with a significantly increased risk of moderate or severe bleeding (RR: 2.19; 95% CI: 1.38-3.48; p=0.0009) and hemorrhagic stroke (RR: 2.08; 95% CI: 1.13-3.82; p=0.02). No significant differences were observed for all-cause death (RR: 1.28; 95% CI: 0.95-1.71; p=0.10), cardiovascular death (RR: 1.38; 95% CI: 0.81-2.33; p=0.23), and myocardial infarction (RR: 1.63; 95% CI: 0.77-3.46; p=0.20). We performed sensitivity analysis based on the hazard ratio reported by RCTs which showed comparable results. Subgroup analysis based on treatment onset time (therapy initiation within 24 hours of thrombotic event vs therapy initiation within 72 hours of thrombotic event) showed that both strategies were effective in reducing the risk of recurrent stroke. Subgroup analysis based on the duration of DAPT (21 days vs. 90 days) showed that DAPT for 90 days was associated with an increased risk of moderate or severe bleeding as compared to therapy lasting for 21 days. Conclusion DAPT with P2Y12 inhibitors and aspirin reduces the risk of recurrent stroke and MACE but is associated with an increased risk of moderate or severe bleeding.

Impact of resumption of Oral AntiCoagulation therapy (OAC) after GastroIntestinal Bleeding (GIB) on clinical outcomes in patients with Non-Valvular Atrial Fibrillation (NVAF)

Abstract Purpose Optimal resumption of oral anticoagulation therapy (OAC) after gastrointestinal bleeding (GIB)has not been well established. This study aimed to compare clinical outcomes between patients who resumed or discontinued OAC after index GIB. Methods We retrospectively enrolled consecutive patients with non-valvular atrial fibrillation (NVAF) and prior GIB from January 2018 to July 2022 in 16 public hospitals in Hong Kong. Resumption of OAC was substantiated by new prescription after index GIB on electronic medical records. Patients were divided into 5 groups: (i) OAC naïve (as reference group); (ii) resume direct oral anticoagulant (DOAC); (iii) resume Vitamin K antagonist (VKA); (iv) discontinue DOAC; (v) discontinue VKA. Endpoints included recurrent GIB, ischemic stroke and all-cause death. Risks of target events were estimated for all groups and compared with individuals without OAC, using adjusted sub-distribution hazard ratios (aSHR) derived from Fine and Gray regression models, accounting for death as competing risk for recurrent GIB and stroke, and COX proportional regression for all-cause mortality, adjusting for components of CHA2DS2VASC, HASBLED scores, causes of index GIB (i.e., GI ulcer, diverticular disease, angiodysplasia or undermined) and endoscopy intervention. Among patients who resumed OAC, outcomes were compared between different DOAC agents (i.e, apixaban, dabigatran, edoxaban, rivaroxaban), using VKA as reference. Results Of 2,350 patients identified (mean age 80.5±10.4, female 54.5%), 44.0% (n=1,034) were OAC naïve, 4.4% (n=103) discontinued VKA, 11.7% (n=275) discontinued DOAC, 11.2% (n=263) resumed VKA, and 28.7% (n=675) resumed DOAC. During a median follow-up duration of 1.2(IQR:0.2-2.5) years, discontinuation of DOAC (aSHR=0.5(0.29-0.9) was associated with lower risk of recurrent GIB, whereas resumption of VKA (aSHR=1.8(1.0-3.1)) was associated with the highest risk of recurrent GIB (Figure 1a). Among DOACs, apixaban (aSHR=0.5(0.3-0.9)) was associated with the lowest risk of recurrent GIB (Figure 1b). Risk of ischemic stroke across groups were similar. Patients who discontinued DOAC (aHR=1.4(1.2-1.6)) were at higher risk of all-cause mortality, whereas resumption of VKA (aHR=0.4(0.3-0.6)) and DOAC (aHR=0.4(0.4-0.5)) were both associated with decreased mortality (Figure 1c). Conclusion In this real-world dataset, resumption of VKA in NVAF patients after GIB was associated with high risk of recurrent GIB and lowest risk with apixaban. OAC resumption either VKA or DOAC was associated with reduced mortality.

Oral anticoagulants or antiplatelets for cryptogenic stroke: a systematic review and meta-analysis

Abstract Background Cryptogenic strokes comprise 20 to 30% of ischemic strokes and include a substantial proportion classified as embolic stroke of undetermined source (ESUS). However, the optimal antithrombotic strategy for cryptogenic stroke remains contentious. Purpose We conducted a systematic review and meta-analysis to compare the efficacy and safety of oral anticoagulants (OAC) versus antiplatelets in patients with cryptogenic stroke. Methods Six electronic databases of PubMed, Embase, Web of Science, the Cochrane Library, Google Scholar and ClinicalTrials.gov were searched from inception to Feb 15, 2024 to identify relevant randomized controlled trials (RCTs) comparing stroke recurrence and major bleeding rates between OAC and antiplatelets in cryptogenic stroke patients. We included trials adhering to a stringent diagnostic work-up for cryptogenic stroke, defined as cerebral infarction not attributed to definite sources of cardioembolism, large artery atherosclerosis, or small artery disease despite undergoing comprehensive investigations. The primary outcome was recurrent ischemic stroke, and the secondary outcome was major bleeding based on International Society of Thrombosis and Hemostasis criteria. Subgroup analysis was conducted for ESUS patients with an increased risk of cardiac emboli, such as patent foramen ovale (PFO) and atrial cardiopathy, defined as lead V1 terminal P-wave &amp;gt; 5000 μV × ms in electrocardiogram, serum N-terminal pro-B-type natriuretic peptide level &amp;gt; 250 pg/mL, and left atrial diameter (LAE) &amp;gt; 4 cm, or LAE index ≥ 3 cm/m2 on echocardiogram. Hazard ratio (HR) with 95% confidence (CI) was used as a measure of the effect estimates for aforementioned outcomes. Random-effects meta-analysis was performed using a restricted maximum likelihood model given between-study variance is inevitable. Results Our meta-analysis included 9 RCTs with a total of 15,139 patients (OAC = 7,343; antiplatelets = 7,796). ARCADIA, RE-SPECT ESUS, and NAVIGATE ESUS Trial investigated apixaban, dabigatran, and rivaroxaban, respectively, while warfarin was primarily used as OAC in the remaining six trials. Aspirin was predominantly utilized for antiplatelet therapy. There was no significant difference in recurrent ischemic stroke between OAC and antiplatelets (HR, 0.90; 95% CI, 0.78 to 1.04; I2 = 0%). However, OAC use was associated with a significantly higher risk of major bleeding (HR, 1.66; 95% CI, 1.07 to 2.56; I2 = 36%). Subgroup analysis in ESUS patients revealed comparable rates of recurrent ischemic stroke in those with atrial cardiopathy (HR, 0.91; 95% CI, 0.65 to 1.29; I2 = 0%) and PFO (HR, 0.72; 95% CI, 0.49 to 1.07; I2 = 0%). Conclusions Our meta-analysis suggests that OAC use does not decrease the risk of recurrent ischemic stroke compared with antiplatelet use but is associated with a significantly higher risk of major bleeding in patients with cryptogenic stroke.Primary (A) and secondary (B) outcomesSubgroup analysis for recurrent stroke

The clinical characteristics and prognosis of patients with acute non-ST-segment elevation myocardial infarction complicated with impaired activity daily living

Abstract Background Impaired activities of daily living (ADL) have been identified as an independent risk factor for cardiovascular diseases. This study aims to describe the clinical characteristics, treatment modalities, and prognosis of acute non-ST-segment elevation myocardial infarction (NSTEMI) patients with impaired ADL. Methods The data for this study were derived from a Health and Medical Big Data Superplatform, comprising a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals from 2010 to 2023. The inclusion criteria encompassed patients with a discharge diagnosis of NSTEMI.ADL prior to NSTEMI was evaluated using the Barthel index(BI),a widely used assessment tool for evaluating ADL.The patients' BI were obtained from patients’ resident health records, and patients were categorized into two groups: ADL normal and ADL impaired group. A comparative analysis was conducted between the two groups regarding clinical characteristics, treatment regimens, and prognosis. Results The study included 28,227 NSTEMI patients with normal ADL and 1,576 NSTEMI patients with impaired ADL. Baseline data revealed that the ADL impaired group had a higher proportion of females (49.4% vs. 43.2%, p &amp;lt; 0.001), older age (77.0 [69.0, 83.0] vs. 71.0 [66.0, 78.0], p &amp;lt; 0.001), and a higher proportion of patients with KILLIP III and above (25.86% vs. 17.44%, p &amp;lt; 0.001). Additionally, the ADL impaired group had a greater number of pre-existing comorbidities. Regarding treatment, the proportion of patients undergoing percutaneous coronary intervention (PCI) was significantly lower in the ADL impaired group (16.5% vs. 65.3%, p &amp;lt; 0.001). Moreover, the ADL impaired group showed lower utilization rates of antiplatelet agents, ACEI/ARBs, beta-blockers, ARNI, statins, and nitrates, while the utilization rates of diuretics and cardiac glycosides were higher. In terms of prognosis, the ADL impaired group exhibited a higher in-hospital mortality rate (6.03% vs. 3.35%, p &amp;lt; 0.001). During a median follow-up period of 876 days, the ADL impaired group had significantly higher rates of all-cause mortality (61.2% vs. 35.9%, p &amp;lt; 0.001) and cardiovascular mortality (41.8% vs. 24.8%, p &amp;lt; 0.001), while the rate of revascularization (6.69% vs. 9.20%, p = 0.008) was lower. There were no significant differences in the risks of recurrent non-fatal myocardial infarction (10.7% vs. 10.8%, p = 0.935), recurrent stroke (10.90% vs. 9.48%, p = 0.08), and hemorrhagic stroke (0.82% vs. 0.74%, p = 0.806). Following adjustment for age, gender, KILLIP classification, medical history, and treatment strategies in a multivariable Cox regression analysis, impaired ADL remained an independent risk factor for increased all-cause mortality (aHR 1.167, 95%CI: 1.091-1.249, p &amp;lt; 0.001). Conclusions The decline in ADL is significantly associated with adverse clinical outcomes among NSTEMI patients.Baseline characteristics of patientsMedications of patients

Atrial fibrillation detection on implantable loop recorders in embolic stroke of undetermined source

Abstract Introduction Embolic stroke of undetermined source (ESUS) represents 17% of all ischaemic strokes, and has a 5% annual stroke recurrence risk. Recent large randomised control trials failed to demonstrate a benefit of empirical anticoagulation for all ESUS patients, with sub-analyses supporting the need for a tailored approach to those patients at greatest risk of atrial fibrillation (AF) development. Understanding how the increased incidence of ILR-detected AF in the ESUS cohort, compares with ILR-detected AF in other cohorts is an essential step in understanding the significance of this finding. Purpose To compare the incidence of ILR-detected AF following ESUS against patients undergoing ILR implantation for non-stroke indications for example syncope and palpitations. Methods We retrospectively studied all patients without known AF who were referred to our institution for ILR implantation following ESUS, syncope or palpitations from 2009 to 2019. The primary endpoint was any detection of AF or atrial flutter (AFL) by ILR. Kaplan-Meier and multivariable Cox-regression analyses were utilised to account for time-to-event. Results A total of 750 patients were included and followed up for a mean of 731 days (SD 443). An ILR was implanted following ESUS in 323 patients and for another reason in 427 patients (figure 1). The incidence of AF was significantly higher among patients with ESUS compared to the non-ESUS group; 48.6% versus 13.8% (for any duration of AF) and 32.2% versus 12.4% (for AF lasting &amp;gt; 30 seconds) both p &amp;lt;0.001. Kaplan-Meier analysis (figure 2), showed significantly higher incidence of AF for ESUS for any duration of AF. This was driven predominantly by AF duration &amp;lt;6 minutes and between 5.5 hours and 24 hours. Importantly, in a multivariable Cox regression analysis, ESUS independently conferred an almost 5-fold increase in the hazard for any duration of AF (Hazard Ratio 4.948, 95% confidence interval 3.587 – 6.825, p&amp;lt;0.001). Conclusion The incidence of AF is significantly higher amongst ESUS versus non-ESUS patients monitored constantly by an ILR. A high number of ESUS survivors have short duration AF episodes. Further work is needed to determine the optimal treatment strategy of these AF episodes in ESUS considering AF duration and overall burden.

Optimal antithrombotic therapy in ischemic stroke patients with non-valvular atrial fibrillation and atherothrombosis: study protocol for a randomized controlled trial.

The addition of antiplatelet therapy to anticoagulant therapy in patients with stroke with non-valvular atrial fibrillation (NVAF) and atherothrombotic disease may increase bleeding risk without reducing recurrent stroke risk. To evaluate the clinical benefits of anticoagulant monotherapy compared to combination therapy with anticoagulants and antiplatelet agents. This is an investigator-initiated prospective multicenter, randomized, open-label, parallel-group clinical trial. Patients with NVAF and atherothrombotic disease who have had a recent ischemic stroke or transient ischemic attack will be eligible to participate in this trial. The primary outcome is a composite of ischemic cardiovascular events, including cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, ischemic events requiring urgent revascularization, and major bleeding events within 2 years after randomization. This study will enroll 400 patients, 200 receiving anticoagulant monotherapy and 200 receiving combination therapy. This sample size will provide 90% power (one-sided p = 0.025) to detect a risk reduction in outcome events within 2 years, assuming event rates of 13 and 27% for each group, respectively, and a 10% loss to follow-up at a 2.5% significance level with one-sided log-rank tests at an interim analysis and a final analysis. This will be the first study to assess the net clinical benefit of oral anticoagulant monotherapy in ischemic stroke patients with NVAF and atherothrombosis. https://clinicaltrials.gov/study/NCT03062319, NCT03062319; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000029222, UMIN000025392; https://jrct.niph.go.jp/latest-detail/jRCTs051180202, jRCTs051180202.

Adapting a Telehealth Physical Activity and Diet Intervention to a Co-Designed Website for Self-Management After Stroke: Tutorial.

People who experience a stroke are at a higher risk of recurrent stroke when compared with people who have not had a stroke. Addressing modifiable risk factors like physical inactivity and poor diet has been shown to improve blood pressure, a leading contributor to stroke. However, survivors of stroke often experience challenges with accessing risk reduction services including long wait lists, difficulty with transportation, fatigue, impaired function, and diminished exercise capacity. Providing health interventions via a website can extend the reach when compared with programs that are only offered face to face or via real-time telehealth. Given global challenges of accessing secondary prevention programs, it is important to consider alternative ways that this information can be made available to survivors of stroke worldwide. Using the "design thinking" framework and drawing on principles of the integrated knowledge translation approach, we adapted 2 co-designed telehealth programs called i-REBOUND - Let's get moving (physical activity intervention) and i-REBOUND - Eat for health (diet Intervention) to create the i-REBOUND after stroke website. The aim of this paper is to describe the systematic process undertaken to adapt resources from the telehealth delivered i-REBOUND - Let's get moving and i-REBOUND - Eat for health programs to a website prototype with a focus on navigation requirements and accessibility for survivors of stroke. We engaged a variety of key stakeholders with diverse skills and expertise in areas of stroke recovery, research, and digital health. We established a governance structure, formed a consumer advisory group, appointed a diverse project team, and agreed on scope of the project. Our process of adaptation had the following 3 phases: (1) understand, (2) explore, (3) materialize. Our approach considered the survivor of stroke at the center of all decisions, which helped establish guiding principles related to our prototype design. Careful and iterative engagement with survivors of stroke together with the application of design thinking principles allowed us to establish the functional requirements for our website prototype. Through user testing, we were able to confirm the technical requirements needed to build an accessible and easy-to-navigate website catering to the unique needs of survivors of stroke. We describe the process of adapting existing content and co-creating new digital content in partnership with, and featuring, people who have lived experience of stroke. In this paper, we provide a road map for the steps taken to adapt resources from 2 telehealth-delivered programs to a website format that meets specific navigation and accessibility needs of survivors of stroke.