Lower Risk Of Stroke Research Articles

Optimal direct oral anticoagulant for upper gastrointestinal endoscopic submucosal dissection.

The patients taking direct oral anticoagulants (DOACs) are at high risk for developing ischemic stroke and delayed bleeding in upper gastrointestinal endoscopic submucosal dissection (ESD). We aimed to identify the optimal DOAC based on both adverse events in upper gastrointestinal ESD. A retrospective population-based cohort study was conducted using the Diagnosis Procedure Combination database in Japan. We included patients on a DOAC undergoing upper gastrointestinal ESD between 2012 and 2021. The primary outcomes were ischemic stroke occurring after upper gastrointestinal ESD and delayed bleeding in gastroduodenal and esophageal ESD. Inverse probability weightings were applied to balance the four DOAC groups (dabigatran, rivaroxaban, apixaban, and edoxaban), and logistic regression analyses were performed to compare the outcomes. We analyzed 9729 patients on a DOAC undergoing upper gastrointestinal ESD. Ischemic stroke developed after upper gastrointestinal ESD in 1.4%, 0.7%, 0.6%, and 0.8% of patients taking dabigatran, rivaroxaban, apixaban, and edoxaban, respectively, after weighting. Rivaroxaban and apixaban showed significantly lower risk of ischemic stroke compared with dabigatran (odds ratio, 0.15 and 0.12, respectively) in standard doses. The delayed bleeding developed after gastroduodenal ESD in 7.6%, 14.6%, 19.2%, and 17.3% of patients taking each DOAC, respectively, with the lowest risk in dabigatran, followed by rivaroxaban. A similar pattern was observed in delayed bleeding in esophageal ESD (3.2%, 5.4%, 7.5%, and 5.5% in each DOAC), but with no significant results. Rivaroxaban might be an optimal DOAC for upper gastrointestinal ESD showing a lower risk for both ischemic stroke and delayed bleeding.

Trajectories of physical activity after ischaemic stroke: Exploring prediction of change.

Physical activity (PA) is associated with lower risk of stroke and better functional outcome. However, low levels of PA after stroke are prevalent. The aim was to identify predictors of PA change after first-time ischaemic stroke and to develop prediction models to predict change in PA. Pre-stroke and 6 months post-stroke PA were quantified with the Physical Activity Scale for the Elderly (PASE). Considered predictors were clinical data and demographics including data on socioeconomic status (SES). PASE change was analysed using mixed models of repeated measures. Elastic net regression models were used to predict decrease from higher PASE quartile to the lowest and increase from lowest to higher. A total of 523 first-time ischaemic stroke patients were included. Median (interquartile range, IQR) age was 69 years (IQR 59, 77), 181 (35%) were female and median National Institutes of Health Stroke Scale score was 3 (IQR 2, 5). Overall PASE score did not change, but 20% of patients decreased to the lowest PASE quartile whereas 48% from the lowest quartile increased to a higher. Prediction performance measured by area under the receiver operating curve was 0.679 for PA decrease and 0.619 for increase. SES factors were the most consistent predictors. Half of the least active patients increased PA level after stroke whereas a fifth decreased with SES being the most consistent predictor. Despite comprehensive data, the prediction models only performed modestly. Efforts to optimize PA should include all stroke survivors to increase PA for least active patients and to prevent PA decrease.

Reassessing the Association of Sedentary Behavior and Physical Activity with Ischemic Stroke: A Mendelian Randomization Study

ABSTRACT Purpose Findings from previous Mendelian randomization (MR) studies disagreed with the current scientific consensus regarding the role of physical activity (PA) and sedentary behavior in ischemic stroke (IS). We reassessed these associations with a focus on etiological subtypes of IS and the potential mediating roles of cardiometabolic traits and brain imaging-derived phenotypes (IDPs). Methods We performed MR analyses using summary statistics from genome-wide association studies of sedentary behavior and PA (n = 88,411~608,595), cardiometabolic traits (n = 393,193~694,649), brain IDPs (n = 33,224) and the latest IS data (62,100 cases and 1,234,808 controls). Inverse-variance weighted regression was used as the primary method, complemented by several sensitivity analyses. A two-step MR approach was employed to assess the mediating effects of cardiometabolic traits and brain IDPs. Results Genetic liability to leisure-time moderate-to-vigorous PA (LTMVPA) and higher overall PA (OPA) were associated with reduced risks of IS and small vessel stroke (Benjamini–Hochberg adjusted P < 0.05). Suggestive associations were observed between longer leisure-screen time and higher IS risk and between higher OPA and lower cardioembolic stroke risk (P < 0.05). The isotropic volume fraction in the anterior limb of the left internal capsule (ALIC), as well as some cardiometabolic metrics, partially mediated these associations. There was no evidence for causal effects of overall MVPA, overall light-intensity PA or overall sedentary duration on IS. Conclusions Longer LST, less OPA and not engaging in moderate-to-vigorous PA during leisure time were associated with higher risk of ischemic stroke. The associations between PA and ischemic stroke depended on different subtypes and were mediated by changes in ALIC and cardiometabolic biomarkers.

Hemoglobin-to-red blood cell distribution width ratio is negatively associated with stroke: a cross-sectional study from NHANES

Numerous studies have suggested that the hemoglobin-to-red blood cell distribution width ratio (HRR) is associated with the onset, progression, and prognosis of various diseases. However, to the best of our knowledge, no research has conducted statistical analyses to determine the association between HRR and stroke. This cross-sectional study was conducted among adults with complete data on hemoglobin-red cell distribution width ratio (HRR) and stroke from the 2005–2018 National Health and Nutrition Examination Survey (NHANES). HRR was calculated by dividing hemoglobin (HGB) in grams per deciliter (g/dL) by the red blood cell distribution width (RDW). Weighted multivariable logistic regression and generalized additive models were employed to investigate the independent and nonlinear relationships between HRR and stroke. Threshold effects were assessed using two-piece linear regression models. Additionally, subgroup analyses and interaction tests were performed. A total of 36,215 participants were included, with 2.92% classified as stroke patients. The prevalence of stroke decreased across increasing tertiles of HRR (Q1: 5.07%; Q2: 2.63%; Q3: 1.69%; P < 0.0001). A negative association between HRR and stroke was observed in both unadjusted and adjusted models. In Model III, each one-unit increase in HRR was associated with a 58% reduction in the likelihood of stroke (Model III: OR = 0.42, 95% CI: 0.29–0.63). Subgroup analyses and interaction tests revealed that the association between HRR and stroke was BMI-dependent (P < 0.05), with the negative association only observed in participants with BMI < = 25 and BMI 25–30, but not in those with BMI > 30. Using a two-piece linear regression model, a threshold effect was identified at a BMI of 30 (K = 1.16). To the left of this breakpoint, there was a negative association between HRR and stroke (OR = 0.55, 95% CI: 0.27–0.97), whereas no such association was detected to the right of the breakpoint (OR = 6.49, 95% CI: 0.75–56.11). HRR is negatively associated with the likelihood of stroke, with a lower risk of stroke in individuals with higher HRR levels.

Changes in the prognosis of CADASIL over time: a 23-year study in 555 individuals

BackgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is associated with early-onset stroke and dementia. Whether its clinical phenotype...

Biologics and Oral Small Molecules Are Not Associated With Increased Major Adverse Cardiovascular Events or Venous Thromboembolism in Inflammatory Bowel Disease.

Biologics and oral small molecules (OSM) effectively treat inflammatory bowel disease (IBD), but some are linked to higher risks of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE). This study evaluates the MACE and VTE risks in IBD patients treated with biologics or OSM. Using the TrinNetX multi-institutional database, we examined MACE and VTE in adult IBD patients on biologics and compared them to IBD patients not on biologics. We also compared IBD patients on OSM to those not on OSM. We performed 1:1 propensity score matching. MACE (myocardial infarction [MI], stroke, and all-cause mortality) and VTE were assessed from 30 days to 3 years after drug prescription. After matching, IBD patients on biologics had reduced risk of MI, stroke, and all-cause mortality at 1 year, compared to those not on biologics (P < .05). No significant difference in VTE was observed (P = .5). At 3 years, biologic-treated patients had lower risks of MI, stroke, all-cause mortality, and VTE (P < .05). Inflammatory bowel disease patients on OSM showed no significant differences in MI, stroke, or VTE at 1 and 3 years, but had lower all-cause mortality (P < .05). In older IBD patients with at least 1 cardiovascular risk factor, OSM usage showed no significant difference in MI, stroke, or VTE risk compared to nonusers; however, all-cause mortality was decreased at 3 years (P < .05). Inflammatory bowel disease patients treated with biologics or OSM were not at increased risk of MACE or VTE. Although further studies and longer follow-up periods are needed to confirm these findings, our results provide reassurance regarding the safety of these medications in IBD.

Abstract 4126158: Persistence to once weekly GLP-1 RAs is associated with lower risk of MI, stroke, and 2-point MACE among patients with T2D and ASCVD in the real world.

Introduction: Studies have shown the reduction of CV events in patients with T2D treated with GLP-1 RAs. However, little is known about how persistent use of GLP-1 RA therapy affects CV outcomes in patients with T2D and ASCVD. The objective of this study was to estimate the association between persistent use of once weekly (OW) GLP-1 RAs and 2-point MACE and its components (MI, stroke) in patients with T2D and ASCVD in a real-world setting. Methods: Adult patients with T2D and ASCVD with ≥1 pharmacy claim for OW GLP-1 RAs during Jan 2018-Nov 2022 were identified in the Optum Research Database. The date of the first OW GLP-1 RA claim was defined as the index date. Patients were followed until a CV event occurred or censored. Discontinuation was defined as a ≥60-day gap in supply of OW GLP-1 RAs. All patients were required to be persistent for ≥3 months of follow-up to allow titration of the therapy. CV events of interest include 2-point MACE, MI and stroke. Kaplan-Meier analyses were used to examine risk of CV events by persistent status within 6, 12, or 18 months of follow-up. Cox proportional hazards models with time-varying exposures were used to assess associations between persistent status and MACE, with persistent status of patients updated for each day of follow-up, adjusting for demographic and baseline clinical characteristics. Results: Among a total of 29516 patients, the median follow up duration was 412 days, median persistence was 254 days, and 63.9% of patients (n=18849) were persistent throughout their variable follow up period. Kaplan-Meier analyses indicated risk of 2-point MACE, MI, and stroke was significantly lower in patients who were persistent within 6, 12 or 18 months of follow-up compared to patients who discontinued within 6, 12 or 18 months of follow-up (all p&lt;0.05); longer persistence led to a qualitatively greater risk reduction. Adjusted hazard ratio (95% confidence interval) from Cox regression with time-varying persistence status during the full variable follow up in all patients for risk of 2-point MACE, MI, and stroke associated with persistent use of OW GLP-1 RAs was 0.70 (0.63-0.77), 0.71 (0.62-0.81), and 0.67 (0.57-0.78), respectively. Conclusions: Patients with T2D and ASCVD who were persistent with OW GLP-1 RAs had a lower risk of 2-point MACE, MI, and stroke than those who discontinued the therapy in real-world clinical practice. Longer persistence of OW GLP-1 RAs appeared to provide greater CV benefits.

Abstract 4131630: Comparative Outcomes of Left Atrial Appendage Occlusion Device Implantation in Atrial Fibrillation Patients with a Lower Stroke Risk

Introduction: Current guidelines recommend oral anticoagulation in atrial fibrillation (AF) patients with a CHA 2 DS 2 -VASc score ≥ 2 for stroke prevention. Left atrial appendage occlusion (LAAO) devices serve as alternatives to reduce stroke risk in select AF patients that are unable to tolerate long-term oral anticoagulation. However, Centers for Medicare&amp;Medicaid Services reimburses left atrial appendage occlusion (LAAO) for patients with CHA 2 DS 2 -VASc score ≥ 3. Objective: To evaluate differences in outcomes and complications of LAAO therapy in AF patients with a CHA 2 DS 2 -VASc score of ≥ 3 versus &lt; 3. Methods: National Inpatient Sample and International Classification of Diseases, 10th Revision codes were used to identify AF patients who underwent LAAO device implantation in the U.S. from 2016−2020. The study population was stratified by stroke risk into two groups, CHA 2 DS 2 -VASc ≥ 3 and &lt; 3. Study endpoints assessed included procedural complications, inpatient outcomes and resource utilization. A multivariable logistic regression model was used to assess the independent association of CHA 2 DS 2 -VASc score with study outcomes. Results: A total of 73,795 and 15,500 LAAO devices were implanted in patients with CHA 2 DS 2 -VASc ≥ 3 and &lt; 3, respectively. Compared to patients with CHA 2 DS 2 -VASc score of ≥ 3, patients with CHA 2 DS 2 -VASc &lt; 3 had lower overall (6.9% vs 9.9%, P&lt; 0.01) and major (4.5% vs 6.2%, P&lt; 0.01) complications in the crude analysis. After multivariable adjustment for potential confounders, CHA 2 DS 2 -VASc &lt; 3 was associated with lower overall complications (aOR 0.84, 95% CI 0.78 – 0.91), major complications (aOR 0.90, 95% CI 0.81-0.99) and cost of hospitalization (aOR 0.95, 95% CI 0.91-0.99). Conclusions: Patients with CHA 2 DS 2 -VASc &lt; 3 had lower complications and hospitalization costs after LAAO device implantation than patients with CHA 2 DS 2 -VASc ≥ 3 . These data, if redemonstrated in a large randomized trial can have important clinical implications for stroke prevention in AF patients.

Anticoagulation vs Antiplatelets Across Subgroups of Embolic Stroke of Undetermined Source: A Meta-Analysis of Randomized Controlled Trials.

The term "embolic stroke of undetermined source" (ESUS) encompasses a substantial but heterogeneous population of patients with ischemic stroke, underscoring the importance of identifying personalized treatment strategies. In subgroups of patients randomized in ESUS trials, we evaluated the effectiveness of anticoagulation compared with antiplatelet therapy in secondary ischemic stroke prevention. A study-level meta-analysis was conducted on randomized controlled trials of patients with ESUS, comparing anticoagulation with antiplatelet therapy. The primary efficacy outcome was recurrent ischemic stroke, and safety outcomes were major bleeding and death. Subgroups assessed were age, sex, presence of patent foramen ovale (PFO), left atrial enlargement (LAE), and atrial cardiopathy. Pooled risk ratios (RRs) were meta-analyzed. Cochrane Risk of Bias Tool 2.0 was used for risk-of-bias assessment. A total of 7 randomized controlled trials involving 14,804 patients were analyzed, with 7,406 patients treated with anticoagulation and 7,398 treated with antiplatelet therapy. Compared with antiplatelet therapy, anticoagulation was associated with a similar rate of recurrent ischemic stroke (RR 0.91, 95% CI 0.80-1.05; I2 = 0%). In ESUS with PFO, anticoagulation was associated with significantly lower risk of ischemic stroke (RR 0.59, 95% CI 0.35-0.98; I2 = 0%). Heterogeneity was present in those with LAE: antiplatelet therapy was superior in trials allowing cardiac monitoring after randomization (RR 6.65, 95% CI 1.26-35.08; I2 = 0%), but anticoagulation was superior in trials prohibiting cardiac monitoring after randomization (RR 0.25 95% CI 0.07-0.89). Subgroups based on age, sex, or presence of atrial cardiopathy did not benefit from anticoagulation over antiplatelet therapy. In this meta-analysis, an empiric anticoagulation approach is not beneficial for patients with ESUS. This finding highlights the importance of an individualized treatment strategy. Such a strategy should include prolonged cardiac monitoring for atrial fibrillation, particularly in patients with moderate-to-severe LAE. Anticoagulation treatment showed promise in patients with medically treated PFO. Other subgroups did not benefit from anticoagulation therapy. Large prospective studies within ESUS subgroups are needed to validate our findings.

Abstract 4125493: Is There an Obesity Paradox for Cardiovascular Outcomes in Patients Undergoing Transcatheter Edge-to-Edge Repair? A Pilot Meta-Analysis

Background: The impact of body mass index (BMI) on Transcatheter Edge-to-Edge Repair (TEER) outcomes remains uncertain, with studies showing conflicting results. Some suggest an 'obesity paradox' exists, favoring better outcomes for obese patients and worse outcomes for underweight patients, while others report no significant impact of BMI. Methodology: We conducted a systematic literature search using major databases to identify studies investigating the association between baseline BMI status and post-procedural outcomes in patients undergoing TEER. Patients were categorized into four BMI groups: underweight (BMI &lt; 18.5 kg/m 2 ), normal weight (BMI 18.5-24.9 kg/m 2 ), overweight (BMI 25-29.9 kg/m 2 ), and obese (BMI ≥ 30 kg/m 2 ). The endpoints included were the risk of in-hospital mortality, myocardial infarction, and stroke. Data were pooled using Review Manager with a random-effects model. Risk ratios (RRs) with their 95% confidence intervals (CIs) were used as the effect measure. Statistical significance was set at p&lt;0.05. Results: Our study included a total of six observational studies, encompassing 7,627 obese and 74,820 non-obese patients. The outcome of in-hospital mortality revealed no significant difference between the two groups (RR: 0.85; 95% CI: 0.57, 1.27; p=0.43). Subgroup analysis showed a trend towards higher in-hospital mortality risk for underweight patients compared to overweight (RR: 1.48; 95% CI: 1.11, 1.95; p=0.007) and obese patients (RR: 1.40; 95% CI: 1.02, 1.92; p=0.04). The comparison between underweight and normal-weight patients did not reach statistical significance (RR: 1.18; 95% CI: 0.91, 1.55; p=0.22). Additionally, the risk of myocardial infarction (RR: 1.10; 95% CI: 0.77, 1.58; p=0.59) and stroke (RR: 0.43; 95% CI: 0.13, 1.42; p=0.17) did not differ significantly between obese and non-obese patients. Conclusions: Our study found no significant difference in in-hospital mortality between obese and non-obese patients. However, underweight patients had a higher mortality risk compared to both overweight and obese patients. While myocardial infarction rates were similar across all groups, there was a non-significant trend suggesting a potentially lower risk of stroke in obese patients. These findings warrant further prospective studies to provide robust evidence.

Comparison of Direct Oral Anticoagulants and Vitamin K Antagonists for Left Ventricular Thrombus: A Global Retrospective Study

IntroductionGuidelines for managing left ventricular thrombus remain limited, particularly when incorporating oral anticoagulants into dual antiplatelet therapy for acute myocardial infarction. This study aims to assess the safety and efficacy of direct oral anticoagulants (DOAC) versus vitamin K antagonist (VKA) in managing left ventricular thrombus among patients with and without recent myocardial infarction. MethodsThis retrospective observational study used data from the TriNetX research network. Patients with left ventricular thrombus treated with either DOACs or VKAs between December 1, 2013, to December 1, 2023, were included. Subgroup analyses were conducted for patients with or without recent acute coronary syndrome (<1 month). Risk and Kaplan-Meier survival analysis were conducted at 90 days since the indexed event. ResultsA total of 39,770 patients were included. DOACs treatment had lower rates of stroke (11.8% vs. 13.7%, RR=0.859, 95% CI 0.816-0.905, p<0.001), major bleeding (4.8% vs. 5.3%, RR=0.902, 95% CI 0.829-0.982, p=0.018), and systemic embolism (3.5% vs. 4.2%, RR=0.841, 95% CI 0.762-0.928, p=0.001) compared to VKAs in overall cohort. Within acute coronary syndrome group (N=14,302), DOACs had lower stroke (12.3% vs. 14.4%, RR=0.860, 95% CI 0.791-0.935, p<0.0001) and systemic embolism (3.1% vs. 4%, RR=0.774, 95% CI 0.651-0.919, p=0.003) risks. For non-acute coronary syndrome group (N=24,162), DOACs had lower stroke (11.4% vs. 13.1%, RR=0.868, 95% CI 0.811-0.929, p<0.001) and major bleeding (4.8% vs. 5.5%, RR=0.877, 95% CI 0.787-0.977, p=0.017) risks. No significant differences in all-cause mortality were observed across groups. ConclusionDOACs demonstrated better safety and efficacy outcomes when compared to VKAs in left ventricular thrombus treatment, with or without recent acute coronary syndrome.

The role of maintaining lower LDL-C level during statin treatment for advanced CKD patients

Background and aimsDifferent from other high cardiovascular (CV) risks populations, the evidence supporting the CV protective effect of LDL-C reduction with statins in chronic kidney disease (CKD) patients is comparatively scarce. This study is aimed to investigate the role of maintaining lower LDL-C level in advanced CKD patients. MethodsBy using Chang Gung Research Database, on the basis of Taiwan's largest healthcare group, a total of 5367 adult patients newly-diagnosed with stage 4 CKD and receiving statin were extracted and further categorized into three groups based on their LDL-C levels: <70 mg/dL, 70–100 mg/dL, and ≥100 mg/dL. The main outcome is major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiovascular death, myocardial infarction, and stroke. The inverse probability of treatment weighting was performed to achieve balance of baseline characteristics. ResultsAt 5-year follow-up, the LDL-C < 70 mg/dL group exhibited significantly lower risks of MACCEs (14.3 % vs. 18.7 %, hazard ratio [HR]: 0.77, 95 % CI: 0.69–0.86), cardiovascular death (7.1 % vs. 9.7 %, subdistribution HR [SHR]: 0.75, 95 % CI: 0.65–0.88), ischemic stroke (4.1 % vs. 5.4 %, [SHR]: 0.65, 95 % CI: 0.54–0.79), and new-onset end-stage renal disease requiring chronic dialysis (25.6 % vs. 29.4 %, SHR: 0.87, 95 % CI: 0.80–0.91) compared to LDL-C > 100 mg/dL group. In contrast, the group with LDL-C levels between 70 and 100 did not significantly differ from the group with LDL-C > 100 mg/dL in study outcomes. ConclusionsMaintaining LDL-C lower than 70 mg/dL may be beneficial for cardiovascular protection in advanced CKD patients and a lower LDL-C treatment target may be required as CKD progression.

Education level and the incidence of heart failure, acute myocardial infarction, and stroke in patients with atrial fibrillation

Abstract Background Education level is an important socioeconomic factor affecting the incidence, symptoms, and treatment of atrial fibrillation (AF). Despite this, data on the association between education level and the incidence of major AF consequences – heart failure (HF), acute myocardial infarction (AMI), and stroke – are limited. Aim To investigate the association between education level and the risk of HF, AMI, and stroke in patients hospitalized with AF. Methods This retrospective cohort study is based on data generated by crosslinking of several Swedish national registries. All patients hospitalized between 1998 and 2003 with a diagnosis of AF were included. The relative risk for incident HF, AMI, and stroke were assessed according to education level categories during a 5–year follow–up. Education levels were categorised as primary, secondary, and academic. Kaplan-Meier curves and Cox regression models adjusted for age, sex, time of AF diagnosis, and the variables of Charlson´s Comorbidity Index were used to estimate the relative risk of the examined outcomes. Hazard ratios (HR) with 95% confidence intervals (CI) were used as estimate of associations and statistical significance level was 5%. Results The study included 263,172 patients (56.2% male; mean age 72.5±10.4 years). There was a statistically significant dose-dependent association between education level and the risk of AMI and HF in both sexes. Compared to primary education, the HR for AMI was 0.89 (95% CI: 0.85-0.93) for secondary education and 0.71 (95% CI: 0.65-0.78) for academic education in women; and 0.91 (95% CI: 0.87-0.94) for secondary education and 0.75 (95% CI: 0.71-0.80) for academic education in men. The relative risk for HF was similar, with HRs of 0.96 (95% CI: 0.93-1.00) for secondary and 0.82 (95% CI: 0.77-0.87) for academic education in women, and HRs of 0.93 (95% CI: 0.90-0.96) for secondary and 0.76 (95% CI: 0.72-0.80) for academic education in men. Patients with academic education had a significantly lower risk for stroke compared to those with primary education (HR 0.77 (95% CI: 0.71-0.84) in women; HR 0.84 (95% CI: 0.79-0.90) in men), while patients with secondary education did not have a significantly different relative risk for stroke compared to those with primary education. Conclusion Secondary and academic education levels were associated with a significantly lower risk of HF and AMI in both women and men with AF compared to primary education. Furthermore, academic education was associated with a lower risk of stroke. In conclusion, , higher education levels were associated with a lower 5-year risk of HF, AMI, and stroke compared to primary education

Combination of moderate-intensity statins and ezetimibe versus high-intensity statins alone for primary prevention of cardiovascular events

Abstract Background Combination of a moderate-intensity statin with ezetimibe can lead to similar reductions in cardiovascular events as monotherapy with a high-intensity statin in patients with established atherosclerotic cardiovascular disease (ASCVD). The comparative effectiveness of these two cholesterol-lowering strategies in the primary prevention setting is unknown. Purpose To compare incident ASCVD events associated with a combination of moderate-intensity statin and ezetimibe versus monotherapy with a high-intensity statin in adults without prior history of cardiovascular disease. Methods We conducted a new-user active comparator retrospective population-based cohort study in Canada. We included all adults aged ≥ 67 years (eligible for drug coverage) with a first prescription of either a combination of moderate-intensity statin with ezetimibe ("combination therapy") or high-intensity statin alone between January 2010 and December 2022. Patients were excluded if they had not received any prior lipid lowering therapies or had a history of myocardial infarction (MI), stroke, heart failure, peripheral vascular disease or prior coronary revascularisation at any time before or within 3 months of treatment initiation. The primary outcome was a composite of all-cause death, hospitalization for MI or stroke, or coronary revascularization. An inverse probability of treatment weighting propensity score was used to account for confounding (demographics, comorbidities, laboratory tests, other medications). Results Among 67,884 patients (mean age: 74.0±5.5y; 53% females), 8,798 (13%) initiated combination therapy and 59,086 (87%) initiated a high-intensity statin. At 1 year, after weighting, the mean achieved LDL-C was ~1.9 mmol/L in both groups. The median follow-up was 6.5 years. The cumulative incidence of the primary outcome at 10 years in the weighted cohort was 32.7% in the combination therapy group and 36.1% in the high-intensity statin group (HR: 0.87; 95% CI: 0.82 to 0.92; p&amp;lt;0.001; absolute risk reduction: 3.5%; 95% CI: 0.8 to 6.1; Figure 1). This result was primarily driven by a lower risk of all-cause death (HR: 0.85; 95% CI: 0.80 to 0.91; p&amp;lt;0.001; Figure 2) and stroke (cause-specific [cs] HR: 0.86; 95% CI 0.74 to 0.99; p=0.04), whereas no differences were observed in the risk of MI (csHR: 0.97; 95% CI: 0.82 to 1.15) or coronary revascularization (csHR: 0.97; 95% CI 0.85 to 1.11). Conclusion The combination of moderate-intensity statins with ezetimibe was associated with a lower risk of incident ASCVD compared with high-intensity statins alone among primary prevention patients in a real-world setting. These results were driven by a lower risk of all-cause death and stroke, but not coronary events. The influence of statin intolerance on the allocated strategy and adherence to therapy cannot be addressed in this analysis, which, along with verifying these estimates, may be best determined in a prospective randomized trial.

Early rhythm control of atrial fibrillation in cancer survivors: a nationwide population-based cohort study

Abstract Background Though early rhythm control (ERC) in patients with atrial fibrillation (AF) is effective in reducing stroke, the benefit of ERC has not been well-elucidated in cancer survivors. This study aimed to compare the risk of ischemic stroke between ERC and usual care in cancer survivors with AF and cancer. Methods This nationwide observational study was conducted using the Korean National Health Insurance Service database. Patients aged 20 years or older with newly diagnosed AF between 2009 and 2018 were included. Patients who received rhythm control therapy within 1-year of AF diagnosis were defined as the ERC group, while the remaining patients were defined as the usual care group. The risk of ischemic stroke in the ERC group compared to the usual care group was evaluated in long-term cancer survivors (cancer diagnosis ≥5 years) and the non-cancer group. Results A total of 591,692 patients were included in the study (18,747 patients [3.2 %] with cancer, mean age 65.7±14.6 years, 53.7% men, mean CHA2DS2-VASc score 3.3±2.0). The proportion of patients receiving ERC was slightly higher in cancer survivors compared to the non-cancer group (28.0% vs 25.3%, p&amp;lt;0.001). During a mean 4-year follow-up, incident stroke occurred in 52,500 patients (1,338 in cancer survivors, 51,182 in non-cancer). The ERC group showed a lower risk of stroke than the usual care group, regardless of the presence of cancer history(Figure); adjusted hazard ratio [95% confidence interval] 0.67 [0.58-0.76] in cancer survivors, 0.76 [0.74-0.78] in the non-cancer group (p-for-interaction=0.125). The effect of ERC on the risk of ischemic stroke in cancer group was consistent across all subgroups, including different cancer types or use of chemotherapy. Conclusion ERC was associated with a lower risk of ischemic stroke among long-term cancer survivors. An integrated approach incorporating appropriate rhythm control strategies should be considered for cancer survivors with newly diagnosed AF.

High physical activity relates to higher risk of incident carotid plaque components

Abstract Background The rupture of carotid atherosclerotic plaque, primarily driven by plaque components, is among the leading causes of ischemic stroke. Although physical activity (PA) stands as a major modifiable target for prevention of atherosclerotic diseases, recent studies suggested a potential adverse impact of high-volume PA on atherosclerotic plaque burden in athletes. Data remains scarce from the community-dwelling population regarding to the impact of PA on the longitudinal change of carotid plaque components. Objectives To assess the association between PA and the incidence of carotid plaque components and explore whether the association of PA with stroke and all-cause mortality differs by the presence of plaque components. Methods Between 2007 and 2012, in a community- dwelling cohort in Netherlands, 1327 stroke-free persons (mean ± standard deviation age 72 ± 9 years, 45% women) with carotid atherosclerosis (carotid intima-media thickness &amp;gt; 2.5 mm) were invited for magnetic resonance imaging (MRI) to assess carotid plaque components. From these, 696 persons (1267 carotid arteries) underwent a follow-up MRI between 2014 and 2017 (median between-scan interval 6 years). Carotid plaque components included calcification, intraplaque hemorrhage (IPH), and lipid-rich necrotic core (LRNC). The volume of moderate, vigorous and total PA (unit: metabolic equivalent task hour, MET-h) was assessed using LASA Physical Activity Questionnaires around the time of the first MRI scan. Participants were followed for the occurrence of stroke or all-cause mortality until December 31, 2019. Generalized estimation equation and Cox regression models were used in the analyses, with adjustments for plaque size and other cardiovascular risk factors. Results Compared to lowest quintile PA group, participants in the highest quintile total PA group had a higher risk of new onset of plaque components, odds ratio (95%CI) 2.69 (1.21; 5.94) for calcification, 1.35 (0.82; 2.24) for LRNC and 1.93 (1.12; 3.34) for IPH (Figure 1). Similar associations were observed for vigorous PA but not for moderate PA. Over a median follow-up of 9.5 years, 118 persons suffered a stroke and 298 died. As shown in table 1, baseline IPH, rather than LRNC or calcification, modulated the associations of PA with stroke and all-cause mortality (P-interaction &amp;lt;0.05): higher total PA was associated with a lower risk of stroke among IPH-free persons, with the hazard ratio (95% CI) of 0.929 (0.867; 0.996) per 10 MET-h/week increase; no associations between PA and stroke were found among those with IPH. Similar associations were found between vigorous PA and all-cause mortality. Conclusions Among the middle-aged and elderly with subclinical atherosclerosis, high level PA, especially high vigorous PA, may lead to an unstable carotid plaque. The beneficial effect of PA on stroke and all-cause mortality is only among persons with a stable carotid plaque profile, especially without IPH.

Cluster-specific predictors of early rhythm control in contemporary European cohort of patients with atrial fibrillation: The EHRA-PATHS Project

Abstract Background Early rhythm control (ERC) using antiarrhytmic drugs, electrical cardioversion or catheter ablation for AF within a year from first diagnosis of atrial fibrillation (AF) has been shown to reduce the risk of major adverse outcomes compared to usual care, and the effects of ERC have been suggested to be consistent across all AF subgroups with different risk profiles. We aimed to identify cluster-specific predictors of ERC in pre-defined AF clusters in contemporary European EHRA-PATHS AF cohort. Methods The EHRA-PATHS AF cohort was derived from the three prospective EurObservational Research Programme (EORP) AF registries - General Pilot, General Long-term, and AF III registry. A two-step cluster analysis was performed. A hierarchical cluster analysis with 18 variables was used to identify the optimal number of clusters, followed by a K-means cluster analysis to determine variable cluster association. Cluster-specific predictors of ERC were identified using univariate and multivariate logistic regression analyses. Results Of 18,799 patients, AF was diagnosed within 1 year in 8088 (43.0%), and 3913/8088 patients (48.4%) were treated with ERC. Among the three clusters - Cluster 1 (younger healthier AF patients) compared with Cluster 2 (Elderly with less comorbidity, mostly non-cardiovascular) and Cluster 3 (Elderly with more comorbidity, mostly cardiovascular), see Table, ERC was significantly more often used in Cluster 1 compared with Cluster 2 and Cluster 3 (both P&amp;lt;0.001), and in Cluster 2 compared with Cluster 3. Cluster-specific multivariable predictors of ERC are shown in Table. In all three clusters, asymptomatic AF (EHRA score I) and Northern Europe residence were inversely associated with ERC, while Western Europe residence was positively associated with ERC in Cluster 2 and 3. In Cluster 1, low stroke risk and hypertension were positively associated with ERC, while dilated left atrium (LA) and reduced left ventricular ejection fraction (LV EF) were negative predictors of ERC. In Cluster 2, age ≥80 years, enlarged LA, and CHA2DS2-VASc ≥2 for males and ≥3 for females were negatively associated with ERC. In Cluster 3, age ≥75 years, cardiomyopathy, liver disease, dementia and reduced LV EF were negative predictors of ERC. Conclusion Our study of a large European AF cohort showed that likelihood for ERC was greater in younger and healthier AF patients, as well as in elderly from Western Europe, while ERC was significantly less likely with increasing age and comorbidity (especially cardiovascular diseases). These findings likely reflect the lack of high-quality evidence supporting aggressive ERC in high-risk patients with AF. With increasing body of evidence favouring ERC such patients, a shift towards less selective consideration of ERC in daily practice may be expected.

Temporal trends of prescription rates, dosing of non-vitamin K antagonist oral anticoagulants and clinical outcomes in patients with atrial fibrillation

Abstract Background The launch of non-vitamin K antagonist oral anticoagulant (NOAC) has revolutionized the landscape of stroke prevention in atrial fibrillation (AF). We aimed to analyze the temporal trends of prescription rates of oral anticoagulants (OACs), NOAC dosing, clinical outcomes and in patients with AF. Methods This was a retrospective study using the Taiwan National Health Insurance Research Database. During 2011 to 2020, A total of 249,107 patients aged ≥30 years with newly diagnosed AF were identified. We analyzed the 1-year risks of ischemic stroke, intracranial hemorrhage (ICH), and all-cause mortality for overall population and specifically for NOAC users. Results The prescription rate of OAC increased from 22.1% in year 2011 to 57.7% in 2020 (P&amp;lt;0.001) with NOAC accounting for 91.0% of overall OAC prescriptions. Compared to patients with incident AF diagnosed in 2011, there were increasing trends for a greater decrease in the risks of ischemic stroke (adjusted hazard ratios [aHRs] 0.914 in 2012, 0.879 in 2013, 0.925 in 2014, 0.822 in 2015, 0.754 in 2016, 0.763 in 2017, 0.769 in 2018, 0.713 in 2019 and 0.707 in 2020; all P&amp;lt;0.05) and mortality (aHRs 0.903 in 2014, 0.899 in 2015, 0.830 in 2016, 0.808 in 2017, 0.788 in 2018, 0.810 in 2019, 0.788 in 2020; all P&amp;lt;0.05), while the risk of ICH did not change significantly (Figure 1). For NOAC users, the percentages of high-dose NOACs increased from 11.04% in year 2012 to 44.29% in year 2019 to 2020. The increasing trend in the use of high-dose NOACs was temporally associated with a lower risk of ischemic stroke observed for patients receiving NOACs in year 2015 to 2017 (aHR 0.794) and year 2018 to 2020 (aHR 0.688) compared to those in year 2012 to 2014 (Figure 2). Conclusion In this nationwide cohort study, there was an increasing trend of OAC prescription, temporally associated with a decline of the risk of ischemic stroke and mortality. Even among NOACs users, the risk of ischemic stroke declined gradually, partly explained by the increasing prescriptions of high-dose NOACs.

The long-term usage of statin prevents adverse events in patients with atrial fibrillation

Abstract Background The effectiveness of statins in preventing adverse cardiovascular events in individuals with atrial fibrillation (AF) has remained uncertain. This study aimed to assess whether statin use could lead to better outcomes among individuals with AF. Purpose Our study aimed to investigate the relationship between statin use and cardiovascular outcomes in patients with newly-diagnosed AF. Methods This study used the National Health Insurance Research Database (NHIRD) in Taiwan. We enrolled 397,787 patients with AF from January 1st, 2012, to December 31st, 2020. Patients with AF were divided into 2 groups (statin user and statin non-user), and the risks of composite outcomes (ischemic stroke, hemorrhagic stroke and transient ischemic attack [TIA]), all-cause death and major adverse cardiovascular events (MACEs, which encompassed cardiovascular death, non-fatal myocardial infarction and heart failure hospitalization) were analyzed. Propensity score matching with time-dependent analysis was examined. Results We analyzed 288,958 patients with newly diagnosed AF (mean age, 73 years; 44% women; mean CHA2DS2-VASc score, 3.5). Compared with patients without statin use, statin user had a lower risk of composite endpoint, which included ischemic stroke, hemorrhagic stroke and TIA. (adjusted hazard ratio, 0.92; 95% confidence interval, 0.88-0.95; p &amp;lt; 0.01) after adjusting for patients’ age, gender, CHA2DS2-VASc score, cardiovascular medications, and comorbidities. In regard to all-cause mortality, statin users exhibited a 62% risk reduction compared to statin non-users (hazard ratio, 0.38; 95% confidence interval, 0.37-0.39; p &amp;lt; 0.01). Statin use was also associated with reduced incidence of MACEs (hazard ratio, 0.70, 95% confidence interval, 0.68-0.71; p &amp;lt; 0.01). In the subgroups stratified by CHA2DS2 VASc score, statin therapy was particularly effective for patients with CHA2DS2-VASc scores 0-3 for composite endpoints but consistently reduced all-cause mortality and MACEs across all score categories. Conclusions Among patients with newly diagnosed AF, statin use was associated with a lower risk of ischemic stroke, hemorrhagic stroke, TIA, all-cause mortality and MACEs.

Adherence to the ABC pathway improves prognosis in patients with AF: preliminary findings from an updated meta-analysis of 360,000 patients

Abstract Background With the increasing complexity of patients with Atrial Fibrillation (AF), the ‘Atrial Fibrillation Better Care’ (ABC) pathway was proposed to streamline a holistic approach for the comprehensive management of patients with AF. The ABC pathway is based on three main pillars: ‘A’ Avoid stroke (through optimal anticoagulant use); ‘B’ Better symptom control; and ‘C’ Cardiovascular and Comorbidity management optimization. Such a holistic and integrated approach is currently recommended by international guidelines, including the ones from the European Society of Cardiology (ESC); a previous meta-analysis showed sub-optimal adherence to such approach in real-world cohorts, with an overall reduction in the risk of major outcomes in patients treated according to the ABC pathway. We hereby performed an updated systematic review and meta-analysis of the current evidence on the implementation of the ABC pathway in patients with AF. Methods We performed a systematic review and meta-analysis according to PRISMA Guidelines. MEDLINE and EMBASE were searched for all studies reporting data on the prevalence of ABC pathway adherent management in patients with AF, and/or the association between ABC pathway management and the incidence of major outcomes, including all-cause death, cardiovascular death, thromboembolism, and major bleeding. Data on the prevalence of ABC pathway management were pooled using a generalized linear mixed model; number of events and total number of patients were pooled using a random-effect model. Pooled estimates were reported as odds ratios (OR) and 95% Confidence Intervals (95%CI); heterogeneity was estimated using the restricted maximum-likelihood estimator, and the Inconsistency index (I2) was also reported. Results 4,059 articles were retrieved from the literature search; after duplicates removal, title and abstract screening and full-text evaluation, 16 studies were included, for a total of more than 360,000 patients. Pooled prevalence of adherence to the ABC pathway was 28.5% (95%CI: 21.1-37.3%, I2=100%; Figure 1). Adherence to the ABC pathway was associated with a significant lower risk of all-cause death (pooled OR: 0.47, 95%CI: 0.40-0.56, I2=97%), cardiovascular death (pooled OR: 0.43, 95%CI: 0.33-0.56, I2=95%) and stroke (pooled OR: 0.61, 95%CI: 0.47-0.79, I2=91%; Figure 1). Patients treated adherent to the ABC pathway also showed a lower risk of major bleeding (pooled OR: 0.77, 95%CI: 0.66-0.90, I2=85%). Conclusions In this updated systematic review and meta-analysis, adherence to the ABC pathway was found in less than one-third of patients with AF. Implementation of the ABC pathway was associated with lower risk of all major adverse events in patients with AF, including all-cause death, and thromboembolic and bleeding events. These data further reinforce the need for routine implementation of the ABC pathway for the management of AF in clinical practice.Figure 1