Reduction In Stroke Research Articles

Clinical outcomes of atrial fibrillation screening: a meta-analysis of randomized controlled trials

Background Several randomized controlled trials (RCTs) have investigated the benefits of atrial fibrillation (AF) screening. However, since none have shown a significant reduction in stroke rates, the impact of screening on clinical outcomes remains uncertain. Materials and methods We conducted a systematic review and meta-analysis of RCTs reporting clinical outcomes of systematic AF screening in participants without known AF. Pooled risk ratios (RRs) were computed for all-cause stroke or systemic embolism, major bleeding, and all-cause mortality, comparing screening with no screening. Results Seven RCTs encompassing 76 458 participants were identified. One trial utilized implantable loop recorders for rhythm monitoring, while the others employed non-invasive screening methods. Pooled results indicated that AF screening was associated with a significant reduction in all-cause stroke or systemic embolism (RR 0.932, 95% CI 0.873–0.996, I2 = 0%, p = 0.037), but had no effect on major bleeding (RR 0.996, 95% CI 0.935–1.060, I2 = 0%, p = 0.876) or all-cause mortality (RR 0.987, 95% CI 0.945–1.031, I2 = 0%, p = 0.550). We estimated a number needed to screen of 148 to prevent one stroke or systemic embolism over a 10-year period in a population of 75-year-olds. When only non-invasive screening methods were considered, the reduction in strokes was not statistically significant (RR 0.942, 95% CI 0.880–1.008, I2 = 0%, p = 0.083). Conclusions Systematic AF screening is associated with a modest yet statistically significant 7% relative reduction in stroke and systemic embolism, with no observed impact on major bleeding or all-cause mortality.

Integrated care management for patients following acute stroke: a systematic review.

Contemporary stroke care is moving towards more holistic and patient-centred integrated approaches, however, there is need to develop high quality evidence for interventions that benefit patients as part of this approach. This study aims to identify the types of integrated care management strategies that exist for people with stroke, to determine whether stroke management pathways impact patient outcomes, and to identify elements of integrated stroke care that were effective at improving outcomes. Systematic review with meta-analysis. The review was conducted using Medline, CINAHL, Web of Science and the Cochrane Database of randomised controlled trials from January 2012 to January 2024. Studies that evaluated interventions as part of integrated care against a control or standard treatment group were included. Primary outcomes included mortality, recurrent stroke and major bleeding. Secondary outcomes included quality of life, unplanned readmission, anxiety and depression, lifestyle and cardiovascular risk factors, and adherence to intervention. In total, 99 studies were included and 63 were meta-analysed. Patients receiving integrated stroke care had significant reductions in recurrent stroke (RR 0.79, 95% CI: 0.63-1.00, P = 0.05, I 2 = 39%), significant improvements in quality of life (SMD = 0.41, 95% CI: 0.26-0.56, P < 0.00001, I 2 = 91%) and reduced incidence of depression (RR 0.95, 95% CI: 0.92-0.99, P = 0.007, I 2 = 22%). There were no significant differences in mortality or major bleeding. The findings of this study showed that integrated care post-stroke is associated with better quality of life and reduced depression and recurrent stroke.

Emulation of ARISTOTLE and ROCKET AF trials in real-world atrial fibrillation patients results in similar efficacy and safety as original landmark trials: insights from the GARFIELD-AF registry

AimsThis study aimed to determine the robustness, reproducibility and representativeness of the landmark Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (AF) (ARISTOTLE) and Rivaroxaban Once...

Combination Antithrombotic Therapy for Reduction of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease.

Stroke secondary to intracranial atherosclerotic disease (ICAD) is associated with high recurrence risk despite currently available secondary prevention strategies. In patients with systemic atherosclerosis, a significant reduction of stroke risk with no increase in intracranial or fatal hemorrhage was seen when rivaroxaban 2.5 mg twice daily was added to aspirin. However, there are no trials in ICAD using this combination. To facilitate the design of future ICAD trials, the CATIS-ICAD study (Combination Antithrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease) assessed (1) the feasibility of recruitment, (2) the safety of low-dose rivaroxaban plus aspirin compared with standard-of-care antiplatelet therapy, and (3) trends toward efficacy. This was a prospective, randomized, open-label, blinded end point pilot trial conducted in 10 Canadian centers. Eligible participants aged ≥40 years, with acute ischemic stroke or high-risk transient ischemic attack, were randomly assigned in a 1:1 ratio to receive low-dose rivaroxaban plus aspirin or aspirin alone within 7 to 100 days of their index event. The primary safety outcome was hemorrhagic stroke. The main efficacy end point was the composite of ischemic stroke or covert brain infarct on magnetic resonance imaging at the end of the study. A total of 101 participants were randomized. Average enrollment was 10 participants/site per year. Average follow-up was 20 months. Median time from index stroke to randomization was 67 days. The median age of participants was 67 years (±10.94), and 29% of participants were women. There was no hemorrhagic stroke in either arm. The composite efficacy outcome was less frequent in the combination arm (15.7%) compared with the aspirin arm (24.0%), with a hazard ratio of 0.78 ([95% CI, 0.32-1.93]; P=0.59) favoring the intervention. A multicenter randomized trial comparing the combination of low-dose rivaroxaban and aspirin in patients with recent ischemic stroke or transient ischemic attack due to ICAD is feasible and appears safe without an increased risk of hemorrhagic stroke. A numerical trend toward efficacy for the composite primary end point of symptomatic ischemic stroke and covert infarcts was observed. These findings will inform the design of a phase III trial. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04142125.

ASSESSING THE IMPACT OF LOW-DOSE ASPIRIN ON CARDIOVASCULAR DISEASE PREVENTION IN DIABETIC PATIENTS

Background: Diabetes significantly increases the risk of cardiovascular disease (CVD), prompting interest in preventive treatments such as low-dose aspirin. Despite its potential, the efficacy of aspirin in this context remains debated. Objective: This study aimed to evaluate the effectiveness of low-dose aspirin in preventing CVD among individuals with type 2 diabetes. Methods: In this double-blind, placebo-controlled, randomized trial, 100 type 2 diabetic patients without previous CVD were enrolled. Participants were randomly assigned to receive either 81 mg/day of aspirin or a placebo for one year. The primary endpoint was the incidence of major adverse cardiovascular events (MACE). Results: Each group comprised 50 participants with comparable baseline characteristics. The incidence of MACE was 10% in the aspirin group compared to 28% in the placebo group, achieving statistical significance (p=0.03). While the aspirin group also showed reductions in myocardial infarction and stroke, these differences were not statistically significant. Conclusion: Low-dose aspirin significantly reduces the incidence of MACE in type 2 diabetic patients, supporting its use as a preventive intervention in this high-risk group.

Atherothrombotic Outcomes After Sodium-Glucose Cotransporter 2 Inhibitors Versus Dipeptidyl Peptidase-4 Inhibitors in Patients With Type 2 Diabetes: A Territory-Wide Retrospective Cohort Study.

This study compared the risks of atherothrombotic major adverse cardiovascular events in patients with type 2 diabetes taking SGLT2 (sodium-glucose cotransporter 2) inhibitors to those taking DPP-4 (dipeptidyl peptidase-4) inhibitors. All adult patients (≥18 years of age) with type 2 diabetes and newly prescribed with SGLT2 inhibitors or DPP-4 inhibitors across all public hospitals in Hong Kong between January 2015 and December 2019 were included. Patients were propensity matched in a 1:1 ratio using a caliper distance of 0.2 without replacement. The primary outcome was atherothrombotic major adverse cardiovascular events as a composite outcome of cardiovascular mortality, nonfatal stroke, and nonfatal myocardial infarction. Time-to-first event analysis was conducted using a univariable Cox proportional hazards model. Primary and secondary analyses were repeated using stabilized inverse probability weighting and propensity score adjustment in the complete case cohort. A total of 20 642 patients (10 321 SGLT2 inhibitors versus 10 321 DPP-4 inhibitors) were included in the final analysis. The mean age was 59±11 years, and 13 142 (63.7%) were men. The median follow-up period was 2.9 years. The use of SGLT2 inhibitors was associated with a significant reduction in atherothrombotic major adverse cardiovascular events (453 [4.4%] versus 719 [7.0%]; hazard ratio, 0.64 [95% CI, 0.57-0.72]; P<0.001) compared with DPP-4 inhibitors. SGLT2 inhibitors were independently associated with reduced all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, and incident dialysis (all P values <0.001). SGLT2 inhibitors in patients with diabetes were independently associated with reduction in atherothrombotic major adverse cardiovascular events, all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, and incident dialysis, compared with DPP-4 inhibitors.

Can SGLT-2 inhibitors improve cardiovascular outcomes and ensure safety for patients with type 2 diabetes and heart failure in Thailand? A real-world multicentre retrospective cohort study

ObjectivesTo assess the real-world effectiveness and safety of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on cardiovascular outcomes in patients with type 2 diabetes mellitus (T2D) and heart failure (HF) and to evaluate...

Long-Term Cardiovascular Disease Outcomes Following Bariatric Surgery

IntroductionThe long-term cardiovascular benefits of bariatric surgery remain unclear. We aimed to analyze the association between bariatric surgery and cardiovascular disease outcomes. MethodsThe Maryland Health Services Cost Review Commission database (2015-2022) was queried for patients aged 15 to 84 y with obesity. Bariatric surgery patients were matched with nonsurgical patients using propensity score matching. Primary outcomes included all-cause mortality, new-onset heart failure (HF), myocardial infarction (MI), and ischemic stroke. A subgroup analysis of outcomes based on age, sex, diabetes, and smoking status was performed. ResultsA total of 222,700 patients met the inclusion criteria. 104,855 (47.09%) bariatric and 117,845 (52.90%) nonsurgical patients were analyzed. Bariatric surgery was associated with reduced risk of all-cause mortality 12.1 versus 15.7 per 1000 person-years (hazard ratio [HR] = 0.77, 95% confidence interval [CI] = 0.73-0.79, P < 0.001), HF (HR = 0.63, 95% CI = 0.69-0.67, P < 0.001), MI (HR = 0.69, 95% CI = 0.63-0.74, P < 0.001), and stroke (HR = 0.75, 95% CI = 0.69-0.80, P < 0.001). The association between bariatric surgery in the obese population and the improvement in cardiovascular outcomes was significantly pronounced in the pre-existing diabetes mellitus (DM) group compared to the non-DM group in terms of all-cause mortality, HF, and MI (adjusted HR = 0.59, 0.62, 0.59 respectively, P < 0.05). Bariatric surgery was also associated with a statistically significant reduction in all-cause mortality, MI, and stroke in smokers compared to nonsmokers (adjusted HR = 0.61, 0.59, 0.59 respectively, P < 0.05). ConclusionsOur study demonstrates a statistically significant association between bariatric surgery and improvement in long-term cardiovascular outcomes and reduction in all-cause mortality in the obese population following bariatric surgery.

SGLT2 inhibitors in the prevention of diabetic cardiomyopathy: Targeting the silent threat.

Heart failure (HF) is a major global health challenge, particularly among individuals with type 2 diabetes mellitus (T2DM), who are at significantly higher risk of developing HF. Diabetic cardiomyopathy, a unique form of heart disease, often progresses silently until advanced stages. Recent research has focused on sodium-dependent glucose transporter 2 inhibitors (SGLT2i), originally developed for hyperglycemia, which have shown potential in reducing cardiovascular risks, including HF hospitalizations, irrespective of diabetic status. In this editorial we comment on the article by Grubić Rotkvić et al published in the recent issue of the World Journal of Cardiology. The investigators examined the effects of SGLT2i on myocardial function in T2DM patients with asymptomatic HF, finding significant improvements in stroke volume index and reductions in systemic vascular resistance, suggesting enhanced cardiac output. Additionally, SGLT2i demonstrated anti-inflammatory and antioxidant effects, as well as blood pressure reduction, though the study's limitations-such as small sample size and observational design-necessitate larger randomized trials to confirm these findings. The study underscores the potential of early intervention with SGLT2i in preventing HF progression in T2DM patients.

Clinical and economic outcomes with rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and obstructive sleep apnea: retrospective analysis of US healthcare claims.

Atrial fibrillation (AF) and obstructive sleep apnea (OSA) are often comorbid and associated with increased risk of cardiovascular events such as stroke. We evaluated the effectiveness, safety, healthcare resource utilization, and costs of rivaroxaban versus warfarin in patients with nonvalvular AF (NVAF) and comorbid OSA. We used the IQVIA PharMetrics® Plus adjudicated claims database to evaluate patients with NVAF, OSA, and moderate-to-severe stroke risk who initiated rivaroxaban or warfarin between November 2011 and December 2022. We adjusted for potential confounders with propensity score overlap weighting. Primary endpoints were evaluated based on intent-to-treat (ITT) and on-treatment follow-up to compare stroke or systemic embolism risk, major bleeding risk, all-cause healthcare resource utilization (inpatient hospitalizations, emergency department visits, outpatient visits, and pharmacy fills), and costs (per patient per year [PPPY]) by treatment cohort. In total, 14,765 patients were included (9133 received rivaroxaban; 5632 received warfarin). Rivaroxaban significantly reduced stroke or systemic embolism versus warfarin by 26% (ITT-hazard ratio, 0.74 [95% CI 0.60-0.91]; P = 0.004) and 30% (on-treatment-hazard ratio, 0.70 [95% CI 0.55-0.89]; P = 0.004). Major bleeding was not significantly different between rivaroxaban and warfarin in either analysis. All-cause healthcare resource utilization was significantly reduced with rivaroxaban versus warfarin, leading to significantly reduced PPPY costs. Among patients with NVAF and OSA, rivaroxaban was associated with a significant reduction in stroke or systemic embolism risk versus warfarin with no difference in major bleeding. Rivaroxaban significantly reduced healthcare resource utilization and costs compared with warfarin, providing support for the use of rivaroxaban in this population.

Abstract 4121516: Efficacy of Sentinel Cerebral Embolic Protection Device in Transcatheter Aortic Valve Replacement: A Meta-Analysis of Randomized Controlled Trials and Propensity Score Matched Studies

Background: Transcatheter aortic valve replacement (TAVR) is frequently associated with stroke due to debris embolization. Although the risk of stroke with the newer-generation devices is lower, stroke still represents a significant cause of mortality and morbidity after TAVR. The Sentinel cerebral embolic protection (CEP) device (Boston Scientific) is a dual embolic filter device designed to capture debris dislodged during TAVR. The current literature concerning the efficacy of Sentinel CEP in the reduction of stroke in patients undergoing TAVR is limited and inconsistent. Aim: This meta-analysis aimed to compare clinical outcomes with Sentinel CEP device in patients undergoing TAVR. Methods: A comprehensive systematic literature search was performed on PubMed, Embase, Cochrane Library and Clinicaltrial.gov from inception until 1st May 2024 to retrieve randomized controlled trials (RCTs) and propensity-matched studies comparing TAVR with and without the Sentinel CEP device. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using the DerSimonian-Laird random-effects model, with a p-value of &lt;0.05 considered statistically significant. Results: 6 studies with a total of 25,130 patients undergoing TAVR (12608: Sentinel CEP device; 12522: Without Sentinel CEP device) were included in this meta-analysis. The use of the Sentinel CEP device in TAVR was associated with a statistically significant lower risk of acute kidney injury [OR: 0.89; 95% CI: 0.81, 0.97; p=0.01]. The use of Sentinel CEP device in TAVR was associated with a statistically insignificant trend towards reduction in stroke [OR: 0.80; 95% CI: 0.58, 1.10; p=0.18], all-cause mortality [OR: 0.74; 95% CI: 0.51, 1.07; p=0.11], and major vascular complications [OR: 0.74; 95% CI: 0.46, 1.19; p=0.21]. Conclusion: The use of the Sentinel CEP device in patients undergoing TAVR does not lead to a statistically significant reduction in stroke, all-cause mortality, and major vascular complications; however, the risk of acute kidney injury is lower. Large, multicentric RCTs are warranted to corroborate the findings of this meta-analysis.

Abstract 4135723: Efficacy and Safety of Ticagrelor with Aspirin vs Ticagrelor Monotherapy in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background: Dual antiplatelet therapy (DAPT) consisting of ticagrelor, a P2Y 12 inhibitor, and aspirin, is the recommended treatment of acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI). However, recently ticagrelor monotherapy has been shown to preserve ischemic protection while reducing bleeding risk in ACS patients. We aimed to compare the clinical outcomes of DAPT and ticagrelor monotherapy in ACS patients undergoing PCI. Methods: MEDLINE, Scopus, and EMBASE were queried up to May 2024 for randomized controlled trials (RCTs) comparing ticagrelor monotherapy after 1 to 3 months of DAPT versus continued DAPT for 12 months in ACS patients. The primary outcomes were all-cause death, net adverse clinical events (NACE) and Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. Key secondary endpoints included BARC 3 or 5 bleeding, myocardial infarction (MI), hemorrhagic and ischemic stroke, and target vessel revascularization (TVR). A random-effects meta-analysis was performed to derive risk ratios (RR) and corresponding 95% confidence intervals (CI). Results: Six RCTs including 28,526 patients, with a mean age of 63.5 years, were included. DAPT was associated with a significantly higher risk of all-cause death (RR: 1.32, 95% CI: 1.05-1.64, P=0.02), NACE (RR: 1.20, 95% CI: 1.01-1.42, P=0.04), and BARC 2, 3, or 5 bleeding (RR: 1.96, 95% CI: 1.71-2.26, P&lt;0.00001) compared to monotherapy. DAPT significantly increased the risk of BARC 3 or 5 bleeding (RR: 2.06, 95% CI: 1.69-2.51, P&lt;0.00001) however, no association was seen in myocardial infarction (RR: 1.01, 95% CI: 0.84-1.20, P=0.94). Conversely, DAPT resulted in a non-significant reduction in ischemic (RR: 0.94, 95% CI: 0.63-1.41, P=0.77) and hemorrhagic stroke (RR: 0.83, 95% CI: 0.36-1.95, P=0.67). Additionally, no significant association could be ascertained in TVR (RR: 1.18, 95% CI: 0.94-1.48, P=0.15). Conclusion: Our analysis highlights the elevated risks of all-cause death, NACE, and major bleeding with DAPT compared to monotherapy in ACS patients post-PCI, favoring the latter for safety. Future investigations should refine antiplatelet therapy durations and identify specific patient subsets for optimal DAPT utilization.

Abstract 4134384: Sotagliflozin, a Dual Inhibitor of Sodium-Glucose Transporters 1 and 2, Elicits Cardioprotective Effects Through Attenuation of Platelet Activation and Thrombosis

Sodium-glucose cotransporter (SGLT) inhibitors are used in the treatment of type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). In the SCORED trial, sotagliflozin (SOTA), a dual SGLT1/2 inhibitor, demonstrated significant reductions in both myocardial infarction (MI) and stroke in patients with T2DM and CKD. These results suggest a cardiovascular (CV) benefit of SOTA in patients with T2DM and CKD who are at increased risk of thromboembolic disease. To investigate the underlying mechanism of CV protection, we evaluated the effects of SOTA on platelet activation and thrombus formation, in both in vivo and ex vivo models, to understand its effects on MI and stroke. Washed human platelets treated with SOTA were stimulated with various agonists and platelet activation was assessed via lumi-aggregometry and flow cytometry. In whole blood, SOTA was evaluated for its potential to reduce platelet adhesion and thrombus formation in the perfusion flow chamber and Total Thrombus formation Analysis System (TTAS) assays. In vivo , mice dosed with SOTA were assessed for thrombus formation at the site of injury in real-time in the cremaster arteriole injury model. To determine the effect of SOTA on hemostasis, we assessed coagulation parameters ex vivo in human whole blood using thromboelastography. Finally, bleeding time was measured in vivo in mice dosed with SOTA using the tail bleeding assay. In washed platelets, SOTA inhibits platelet activation and aggregation in a dose-dependent manner. Similarly, a dose-dependent decrease in platelet adhesion and thrombus formation was observed in whole blood assays. In vivo , platelet accumulation and fibrin formation were decreased in mice dosed with SOTA, however no effect is observed in coagulation parameters or bleeding time. SOTA inhibits platelet activation and thrombus formation with no impact on coagulation parameters or bleeding potential. These findings highlight a potential mechanism through which SOTA reduces the risk of stroke and MI in patients with T2DM and CKD, underscoring the importance of further investigation into the role of SOTA in CV protection, particularly in patients suffering from both T2DM and CKD at high risk of thromboembolic events.

Cerebral Embolic Protection by Geographic Region

Transcatheter aortic valve replacement (TAVR) is an established treatment option for many patients with severe symptomatic aortic stenosis; however, debris dislodged during the procedure can cause embolic stroke. The Sentinel cerebral embolic protection (CEP) device is approved for capture and removal of embolic material during TAVR but its efficacy has been debated. To explore regional differences in the association of CEP utilization with stroke outcomes in patients undergoing TAVR. This post hoc analysis of a prospective, postmarket, randomized clinical trial evaluating TAVR performed with or without the CEP took place at 51 hospitals in the US, Europe, and Australia from February 2020 to January 2022. Patients with symptomatic aortic stenosis treated with transfemoral TAVR were included. Randomization was stratified according to center, operative risk, and intended TAVR valve type. Patients were excluded if the left common carotid or brachiocephalic artery had greater than 70% stenosis or if the anatomy precluded placement of the CEP device. Data for this post hoc study were analyzed from August to October 2024. TAVR with or without CEP. The primary end point was the rate of all stroke events at hospital discharge or 72 hours post-TAVR, whichever came first. Neurological examinations were performed at baseline and postprocedure to identify stroke, disabling stroke, and other neurological outcomes. The Stroke Protection With Sentinel During Transcatheter Aortic Valve Replacement (PROTECTED TAVR) trial enrolled and randomized 3000 patients (1803 [60.1%] male; mean [SD] age, 78.9 [7.8] years): 1833 in the US cohort (TAVR alone: 919, TAVR with CEP: 914) and 1167 patients in the outside the US (OUS) cohort (TAVR alone: 580, TAVR with CEP: 587). Patients in the US cohort were younger, more predominantly male, had a lower prevalence of atrial fibrillation, and had a higher prevalence of bicuspid aortic valve, diabetes, and peripheral vascular disease compared with the OUS cohort. In the main trial, the incidence of stroke within 72 hours after TAVR or before discharge did not differ significantly between the CEP group and the control group, and there was no interaction by geographic region. In this post hoc analysis, patients treated with CEP in the US cohort exhibited a 50% relative risk reduction for overall stroke and a 73% relative risk reduction for disabling stroke compared to TAVR alone; a treatment effect on stroke risk reduction was not observed in the OUS cohort. The PROTECTED TAVR trial could not show that the use of CEP had a significant effect on the incidence of periprocedural stroke during TAVR. Although there was no significant interaction by geographic region, this exploratory post hoc analysis suggests a trend toward greater stroke reduction in the US cohort but not in the OUS cohort. These findings are hypothesis generating, and further research is needed to determine if regional differences in patient characteristics or procedural practices affect CEP efficacy. ClinicalTrials.gov Identifier: NCT04149535.

The left atrial appendage exclusion for prophylactic stroke reduction (leaaps) trial: rationale and design

IntroductionLeft atrial appendage exclusion (LAAE) has been shown in randomized trials to reduce ischemic stroke risk in patients undergoing cardiac surgery with known atrial fibrillation (AF). Many patients undergoing cardiac surgery without pre-existing AF are at risk of stroke and may benefit from LAAE. MethodsLeft Atrial Appendage Exclusion for Prophylactic Stroke Reduction (LeAAPS) is an international, prospective, randomized, multicenter, blinded trial evaluating the effectiveness of LAAE in preventing ischemic stroke or systemic embolism in patients undergoing cardiac surgery at increased risk of AF and ischemic stroke. The trial will enroll 6500 patients at increased risk of stroke in whom a cardiac surgery is planned at 250 sites worldwide. Eligible patients are ≥18 years old, have no pre-existing AF but are at increased risk for AF and stroke (based on age, CHA2DS2-VASc score, left atrium size or brain natriuretic peptide). Patients are randomized 1:1 to receive either LAAE with AtriClip or no LAAE during cardiac surgery. Healthcare providers outside of the operating room and the patient will be blinded to allocation. The primary effectiveness endpoint is the first occurrence of ischemic stroke, systemic arterial embolism, or surgical or endovascular LAA closure. The powered secondary effectiveness endpoint is ischemic stroke or systemic arterial embolism. The primary safety endpoint is the occurrence of one of the following events (through 30 days): pericardial effusion requiring percutaneous or surgical treatment, peri-operative major bleeding, deep sternal wound infection, or myocardial infarction. Other endpoints include mortality, rehospitalizations, clinically diagnosed AF, transient ischemic attack, and cognitive and quality of life assessments. Follow-up is every 6 months for a minimum of 5 years; primary analysis occurs when 469 patients have had an ischemic stroke or systemic embolism. ConclusionThe results of the LeAAPS trial will demonstrate whether LAAE with AtriClip at the time of other routine cardiac surgery reduces stroke or systemic arterial embolism during long-term follow-up in patients at high risk of stroke without pre-existing AF. Trial RegistrationClinicalTrials.gov, Identifier: NCT05478304, https://clinicaltrials.gov/study/NCT05478304?term=%20NCT05478304&rank=1

Stroke Prevention With Prophylactic Left Atrial Appendage Occlusion in Cardiac Surgery Patients Without Atrial Fibrillation: A Meta-Analysis of Randomized and Propensity-Score Studies.

The role of left atrial appendage occlusion (LAAO) in patients without previous atrial fibrillation (AF) is not established. This meta-analysis was conducted on patients with normal sinus rhythm who underwent cardiac surgery, with and without concomitant LAAO, to evaluate its effect on the incidence of cerebrovascular accidents (CVAs). A systematic review was conducted from inception until December 2023 for randomized and propensity-score studies comparing CVA in patients without AF undergoing cardiac surgery with or without LAAO. Six studies met our inclusion criteria with a total of 4130 patients: 2146 in the LAAO group and 1984 in the no-LAAO group. The risk ratio of postoperative AF was 1.05 (95% CI, 0.86-1.28); P=0.628. The CVA rates at 5 years were 6.8±1.0% in the no-LAAO group and 4.3±0.8% in the LAAO group (log-rank P=0.021). The Cox regression analysis for CVA in patients undergoing LAAO reported a hazard ratio of 0.65 (95% CI, 0.45-0.94); P=0.022. Landmark analysis at 4 years highlighted a significant difference in overall survival between no-LAAO and LAAO groups, 86±12.2% versus 89.6±11.0%; P=0.041. In this meta-analysis of patients without previous AF undergoing cardiac surgery, LAAO was associated with a decreased risk of CVA, no difference in the incidence of postoperative atrial fibrillation, and a significant overall survival benefit at a 4-year landmark analysis. Although these findings support LAAO, the randomized LeAAPS trial (Left Atrial Appendage Exclusion for Prophylactic Stroke Reduction Trial), LAA-CLOSURE trial (A Randomized Prospective Multicenter Trial for Stroke Prevention by Prophylactic Surgical Closure of the Left Atrial Appendage in Patients Undergoing Bioprosthetic Aortic Valve Surgery), and LAACS-2 trial (Left Atrial Appendage Closure by Surgery-2) will help define the effectiveness of LAAO in patients undergoing cardiac surgery who have risk factors for AF and CVA. URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42024496366.

Efficacy of Sentinel Cerebral Embolic Protection Device in Transcatheter Aortic Valve Replacement: A Meta-Analysis of Randomized Controlled Trials and Propensity Score-Matched Studies.

Transcatheter aortic valve replacement (TAVR) is frequently associated with stroke due to debris embolization. Although the risk of stroke with newer-generation devices is lower, stroke still represents a significant cause of mortality and morbidity post-TAVR. The Sentinel cerebral embolic protection device (CEPD) is a dual-embolic filter device designed to capture debris dislodged during TAVR. A systematic literature search was performed on the major bibliographic databases to retrieve studies that compared TAVR with and without Sentinel CEPD. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the DerSimonian-Laird random-effects model, with a P value of <0.05 considered statistically significant. This meta-analysis included 6 studies with 25,130 patients undergoing TAVR (12,608: Sentinel CEPD; 12,522: without Sentinel CEPD). The use of the Sentinel CEPD in TAVR was associated with a statistically significant lower risk of acute kidney injury (OR: 0.89; 95% CI: 0.81-0.97; P = 0.01]. The use of Sentinel CEPD in TAVR was associated with a statistically insignificant trend toward a reduction in stroke (OR: 0.80; 95% CI: 0.58-1.10; P = 0.18), all-cause mortality (OR: 0.74; 95% CI: 0.51-1.07; P = 0.11), and major vascular complications (OR: 0.74; 95% CI: 0.46-1.19; P = 0.21). The use of Sentinel CEPD in patients undergoing TAVR does not lead to a statistically significant reduction in stroke, all-cause mortality, or major vascular complications; however, the risk of acute kidney injury is lower. Further randomized studies are warranted to confirm these findings.

Safety and efficacy of apixaban versus warfarin in peritoneal dialysis patients with non-valvular atrial fibrillation: protocol for a prospective, randomised, open-label, blinded endpoint trial (APIDP2)

IntroductionSeveral randomised controlled trials have demonstrated that novel oral anticoagulants are safer compared with vitamin K antagonists for the management of non-valvular atrial fibrillation (NVAF) to prevent thromboembolic events in...

Risk of Stroke or Systemic Embolism According to Baseline Frequency and Duration of Subclinical Atrial Fibrillation: Insights From the ARTESiA Trial.

In the ARTESiA trial (Apixaban for the Reduction of Thromboembolism in Patients With Device-Detected Subclinical Atrial Fibrillation), apixaban, compared with aspirin, reduced stroke or systemic embolism in patients with device-detected subclinical atrial fibrillation (SCAF). Clinical guidelines recommend considering SCAF episode duration when deciding whether to prescribe oral anticoagulation for this population. We performed a retrospective cohort study in ARTESiA. Using Cox regression adjusted for CHA2DS2-VASc score and treatment allocation (apixaban or aspirin), we assessed frequency of SCAF episodes and duration of the longest SCAF episode in the 6 months before randomization as predictors of stroke risk and of apixaban treatment effect. Among 3986 patients with complete baseline SCAF data, 703 (17.6%) had no SCAF episode ≥6 minutes in the 6 months before enrollment. Among 3283 patients (82.4%) with ≥1 episode of SCAF ≥6 minutes in the 6 months before enrollment, 2542 (77.4%) had up to 5 episodes, and 741 (22.6%) had ≥6 episodes. The longest episode lasted <1 hour in 1030 patients (31.4%), 1 to <6 hours in 1421 patients (43.3%), and >6 hours in 832 patients (25.3%). Higher baseline SCAF frequency was not associated with increased risk of stroke or systemic embolism: 1.1% for 1 to 5 episodes versus 1.2%/patient-year for ≥6 episodes (adjusted hazard ratio, 0.89 [95% CI, 0.59-1.34]). In an exploratory analysis, patients with previous SCAF but no episode ≥6 minutes in the 6 months before enrollment had a lower risk of stroke or systemic embolism than patients with at least one episode during that period (0.5% versus 1.1%/patient-year; adjusted hazard ratio, 0.48 [95% CI, 0.27-0.85]). The frequency of SCAF did not modify the reduction in stroke or systemic embolism with apixaban (Pinteraction=0.1). The duration of the longest SCAF episode in the 6 months before enrollment was not associated with the risk of stroke or systemic embolism during follow-up (<1 hour: 1.0%/patient-year [reference]; 1-6 hours: 1.2%/patient-year [adjusted hazard ratio, 1.27 (95% CI, 0.85-1.90)]; >6 hours: 1.0%/patient-year [adjusted hazard ratio, 1.02 (95% CI, 0.63-1.66)]). SCAF duration did not modify the reduction in stroke or systemic embolism with apixaban (Ptrend=0.1). In ARTESiA, baseline SCAF frequency and longest episode duration were not associated with risk of stroke or systemic embolism and did not modify the effect of apixaban on reduction of stroke or systemic embolism. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01938248.

Heart Failure Risk Assessment Using Biomarkers in Patients With Atrial Fibrillation: Analysis From COMBINE-AF

BackgroundHeart failure (HF) is common among patients with atrial fibrillation (AF), and accurate risk assessment is clinically important. ObjectivesThe goal of this study was to investigate the incremental prognostic performance of N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and growth differentiation factor (GDF)-15 for HF risk stratification in patients with AF. MethodsIndividual patient data from 3 large randomized trials comparing direct oral anticoagulants (DOACs) with warfarin (ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis In Myocardial Infarction 48], and RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy]) from the COMBINE-AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) cohort were pooled; all patients with available biomarkers at baseline were included. The composite endpoint was hospitalization for HF (HHF) or cardiovascular death (CVD), and secondary endpoints were HHF and HF-related death. Cox regression was used, adjusting for clinical factors, and interbiomarker correlation was addressed using weighted quantile sum regression analysis. ResultsIn 32,041 patients, higher biomarker values were associated with a graded increase in absolute risk for CVD/HHF, HHF, and HF-related death. Adjusting for clinical variables and all biomarkers, NT-proBNP (HR per 1 SD: 1.68; 95% CI: 1.59-1.77), hs-cTnT (HR: 1.39; 95% CI: 1.33-1.44), and GDF-15 (HR: 1.20; 95% CI: 1.15-1.25) were significantly associated with CVD/HHF. The discrimination of the clinical model improved significantly upon addition of the biomarkers (c-index: 0.70 [95% CI: 0.69-0.71] to 0.77 [95% CI: 0.76-0.78]; likelihood ratio test, P < 0.001). Using weighted quantile sum regression analysis, the contribution to risk assessment was similar for NT-proBNP and hs-cTnT for CVD/HHF (38% and 41%, respectively); GDF-15 provided a statistically significant but lesser contribution to risk assessment. Results were similar for HHF and HF-related death, individually, and across key subgroups of patients based on a history of HF, AF pattern, and reduced or preserved left ventricular ejection fraction. ConclusionsNT-proBNP, hs-cTnT, and GDF-15 contributed significantly and independently to the risk stratification for HF endpoints in patients with AF, with hs-cTnT being as important as NT-proBNP for HF risk stratification. Our findings support a possible future use of these biomarkers to distinguish patients with AF at low or high risk for HF.