On Oral Anticoagulation Research Articles

Abstract 4119189: Imaging practices prior to cardioversion in patients presenting post percutaneous left atrial appendage occlusion.

Background: Direct current cardioversion (DCCV) carries a risk for stroke in AF patients, for that reason there are guidelines for mitigating this risk in AF patients on oral anticoagulation (OAC). Meanwhile, no consensus on the best approach for cardioverting patients with an appendage occlusion device in situ. This led to a very wide variation in pre and post DCCV practices in these patients. Aims: We aim to explore different factors that might be associated with the variation seen in pre-DCCV imaging practices in patients presenting post- percutaneous LAAO. Methods: This was a multi-center retrospective cohort study of patients who received DCCV for AF or AFL during follow up after LAAO procedure within a single healthcare system from 2016-2024. Results: A total of 119 patients were included, there were more females 70 (59%), with more than half (64 (54%)) receiving a first-generation WATCHMAN™ 2.5, while the rest had WATCHMAN FLX™. Median age at presentation was 77 years (72,82), BMI of 31 kg/m 2 (26,37), average CHADSVASC score of 4.5 and HASBLED score of 3. A median duration of 10 months (3,21) between LAAO to presentation for DCCV . Forty-four (37%) patients had pre-DCCV imaging (imaging cohort). Number of males was significantly higher in the imaging cohort (24 (54.5%) vs 25 (33.3%), p=0.038), compared to those without imaging. There was a significant difference (p<0.001) between the two cohorts in the location (center) where DCCV was done. The site with the highest number of pre-DCCV imaging cases had an equal gender ratio of patients presenting for DCCV. Patients who received imaging presented earlier (11.2 months vs 15.8 months, p=0.068) compared to those without imaging, though the difference was not significant. Between the two groups, there was no significant difference in OAC (VKA-antagonist/DOAC) usage prior to presentation (8 (18.6%) vs 12 (16.4%), P=0.9). There was no significant difference in baseline CHADSVASC score, HASBLED score, age, LVEF. Higher percentage of patients were discharged on OAC post DCCV in the imaging arm (13 (30.2%) vs 14 (19.4%), p=0.27), but the difference was non-significant. No Device related thrombus nor significant PDL was detected on imaging. Conclusion: There was male preference in providing pre-DCCV imaging for ruling out DRT. Location of care was also associated with the variation in pre-DCCV protocols. Additional research is needed to understand other factors associated with variation seen in pre-DCCV practices.

Peripheral artery disease, antithrombotic treatment and outcomes in European and Asian patients with atrial aibrillation: a report from 2 prospective observational registries

Abstract Background In patients with atrial fibrillation (AF), the impact of peripheral artery disease (PAD) on oral anticoagulant (OAC) therapy use and the risk of outcomes remains unclear. Objective To analyse the epidemiology of PAD in a large cohort of European and Asian AF patients, and the impact on treatment patterns and risks of adverse outcomes. Methods We analysed AF patients from two large prospective observational registries. We identified patients with PAD as reported by the investigators. Logistic regression analysis was used to assess factor associated with the presence of PAD at baseline. OAC prescription and risk of outcomes were analyzed according to the presence of PAD, using adjusted Logistic and Cox regression analyses. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). Interaction analyses were also performed according to different subgroups. Results 15,497 patients with AF (mean age 68.9, SD 11.6 years; 38.6% female, 30% from Asia) were included in the analysis. PAD was found in 941 patients (6.1%), with higher prevalence among European individuals compared to Asian (8.1% vs 1.2%, p<0.001). Patients with PAD were older, more likely with permanent AF, more symptomatic and with higher thromboembolic and bleeding risk. On logistic regression analysis, European patients had 6-fold higher odds of presenting with PAD compared with Asians (Figure 1, Panel A). Other comorbidities and increasing age were associated with higher odds of prevalent PAD (Figure 1 Panel A). Conversely, female sex was associated with lower odds of having PAD at baseline. With age modelled as a continuous variable, and odds of PAD at baseline, there was a non-linear relationship, with the odds of PAD increasing almost linearly until 70 years, plateauing afterwards (Figure 1 Panel B). After adjustments, PAD was associated with lower use of OAC (OR 0.69, 95% CI 0.57-0.85). On Cox regression analysis, PAD was associated with a higher risk of the primary composite outcome (HR 1.28, 95%CI: 1.08-1.52) and all-cause death (HR 1.40, 95%CI: 1.16-1.69). A significant interaction was observed between PAD and age, with greater risks of PAD found in younger patients (<65 years) for the primary outcome (pint=0.014, Figure 2, panel A). Consistent results were observed when we analysed the interaction between PAD and age, modelled as a restricted cubic spline, where the risk of the primary outcome followed a J-curve across age, while patients without PAD showed an approximately linear relationship (pint<0.001, Figure 2, Panel B). Conclusions In patients with AF, PAD is associated with lower use of OAC and higher risk of adverse outcomes, with a greater risk seen in younger patients.Figure 1Figure 2

Stratification of residual thromboembolic risk among anticoagulated atrial fibrillation patients: a hierarchical cluster analysis from a global, real-world population

Abstract Background Assessment of residual thromboembolic risk among atrial fibrillation (AF) patients despite being on oral anticoagulants (OACs) poses a significant challenge. This study utilises a hierarchical cluster analysis approach to identify risk phenotypic profiles in a global prospective AF registry. Methods Data were drawn from recently diagnosed non-valvular AF patients receiving OACs, as recorded in phases II and III of the GLORIA-AF (Global Registry on Long-Term Oral Anti-thrombotic Treatment in Patients With Atrial Fibrillation) registry. A hierarchical cluster analysis based on patient demographics was performed to identify distinct phenotypes. The incidence and risks of thromboembolic events (ischaemic stroke, transient ischaemic attack, or systemic embolism) and relevant events (major bleeding and all-cause death) were compared across clusters. Results The study included 22,410 patients (mean age 70±8 years; 56% male), from which 5 phenotypes were delineated: Cluster 1 ("uncontrolled hypertension"), Cluster 2 ("young with a history of coronary artery disease"), Cluster 3 ("young and obese"), Cluster 4 ("frailty"), and Cluster 5 ("non-paroxysmal AF with tachycardia"). Cluster 4 was associated with the highest rates of thromboembolic events (1.66/100 person-years), major bleeding (1.92/100 person-years), and all-cause mortality (6.02/100 person-years). Conversely, Cluster 3 showed the lowest risk profiles across all outcomes (thromboembolic events: 0.64 events/100 person-years, major bleeding: 0.83 events/100 person-years, and all-cause death: 1.44 events/100 person-years). Cluster 1 displayed a moderate thromboembolic event rate (1.04/100 person-years), although lower rates were observed in Clusters 2 and 5 (Figure 1). Conclusions Hierarchical cluster analysis effectively identified distinct phenotypes within a global AF population, offering valuable insights for stratifying the risks of residual thromboembolic events and other significant outcomes in anticoagulated AF patients (Figure 2).Figure 1Figure 2

Management of Patients Treated With Oral Anticoagulant Therapy Undergoing Percutaneous Coronary Intervention With Stent Implantation: The PERSEO Registry.

In patients on oral anticoagulant (OAC) therapy undergoing percutaneous coronary intervention (PCI) with stent, international guidelines endorse the use of direct oral anticoagulants (DOAC) rather than vitamin K antagonists (VKA) and dual antithrombotic therapy (DAT) rather than triple antithrombotic therapy (TAT). The aim of this study was to evaluate contemporary real-world data on antithrombotic regimens and outcome in patients on OAC undergoing PCI with stent. Consecutive patients on OAC undergoing PCI were enrolled in the multicenter, prospective, observational PERSEO registry (NCT03392948). Primary end point was net adverse clinical events (NACE) with VKA versus DOAC, whereas a secondary prespecified end point was NACE with DAT versus TAT both at 1-year follow-up. From February 2018 to February 2022; in total, 1234 consecutive patients were included. The main indication for OAC was atrial fibrillation (86%), and the mean CHA 2 DS 2 VASc and HAS-BLED scores were 4 ± 2 and 3.6 ± 1, respectively. Of the 1228 patients discharged alive, 222 (18%) were on VKA and 1006 (82%) on DOAC ( P < 0.01). DAT was employed in 197 patients whereas TAT in 1028. At follow-up, NACE rate was significantly higher than VKA compared with DOAC (23% vs. 16%, P = 0.013) and confirmed after propensity score adjustment. TAT and DAT did not differ as regards NACE rate (17% vs. 19%, P = 0.864) although, compared with TAT, DAT was associated with less major bleedings (2% vs. 5%, P = 0.014), confirmed after propensity score adjustment. In conclusion, in patients on OAC undergoing PCI, DOAC, compared with VKA, was associated with a significantly lower occurrence of NACE and DAT reduced bleedings compared with TAT.

Adherence to oral anticoagulants in patients with non-valvular atrial fibrillation: the role of patients’ characteristics and out-of-pocket payments

ABSTRACT Background Recent practice guidelines favor direct oral anticoagulants (DOACs) over warfarin for primary stroke prevention in patients with non-valvular atrial fibrillation (NVAF). However, challenges persist in Iraq’s private pharmaceutical sector. DOACs have been sold at high and inconsistent retail prices and lack insurance coverage, leading to significant out-of-pocket (OOP) costs. The objective of this study is to investigate the impact of OOP costs on oral anticoagulants (OAC) adherence among NVAF patients. Research design and methods This multicenter cross-sectional study interviewed 359 eligible patients attending three private cardiology clinics within Iraq’s southern region from December 2022 to February 2023. The 8-item Morisky Adherence Scale evaluated patient adherence. Statistical analyses, including descriptive analysis, ANOVA, and chi-square. p < 0.05 was considered statistically significant. Results The most frequently prescribed OAC were DOACs (62.8%). Patient adherence level to OAC was chiefly medium (54.6%) with no significant difference in adherence based on OAC type. Patient adherence was significantly associated with monthly income (p = 0.001), number of daily pills (p = 0.006), and OACs’ average monthly cost (p = 0.011). Conclusion Addressing the issue of cost-related non-adherence to OACs requires multiple actions. These include ensuring comprehensive health insurance coverage for OACs, increasing the use of affordable generic alternatives, and establishing effective cost-related discussions between healthcare providers and patients.

Risk factors for major bleeding in patients with atrial fibrillation and CKD G3-G5D on oral anticoagulants.

Patients with chronic kidney disease (CKD) and atrial fibrillation (AF) on oral anticoagulants (OACs) are at high risk of bleeding. Determinants of major bleeding risk in OAC users with AF and CKD are not well established and available bleeding score systems do not perform well in CKD. This study aims to present risk factors associated with major bleeding in a Swedish cohort of OAC-treated patients with CKD G3-5D. We conducted a Swedish register-based cohort study including patients with AF and CKD G3-5D on warfarin or direct OACs (DOACs) between 2009 and 2018. Data were collected from high-quality registers including the Swedish Renal Registry and Auricula, a register for AF and OACs. Risk factors for major bleeding were investigated with Cox regression analysis. Of 2453 included patients, 59% were on warfarin (time in therapeutic range 67%) and 41% on DOACs. Major bleeding rates were 8.9/100 patient-years. Factors associated with increased bleeding risk were glomerular filtration rate category, G5/5D versus G3 {hazard ratio [HR] 1.92 [95% confidence interval (CI) 1.43-2.56]}, previous gastrointestinal bleeding [HR 1.77 (95% CI 1.39-2.25)], previous other bleeding [HR 1.33 (95% CI 1.09-1.62)], congestive heart failure [HR 1.36 (95% CI 1.11-1.68)], male sex [HR 1.28 (95% CI 1.03-1.60)] and vascular disease [HR 1.35 (95% CI 1.01-1.79)]. Patients with AF and G3-5D on OACs are at a high risk of bleeding. Previous major bleeding and kidney failure are strongly associated with major bleeding. The present study also shows an association between OAC-associated bleeding and male sex, congestive heart failure and vascular disease. Knowledge about determinants of bleeding in advanced CKD is essential when deciding on when to anticoagulate or not.

Statin Usage in Peripheral Arterial Disease Patients.

Atherosclerotic cardiovascular disease (ASCVD) events have been shown to occur at higher frequency in patients with peripheral arterial disease (PAD). In this study, our aim is to evaluate whether statin is being used appropriately in patients with PAD and also evaluate its usage with the number of vascular beds involved. This retrospective cross-sectional study reviewed data of patients with a confirmed diagnosis of PAD based on invasive or noninvasive imaging. Demographic, clinical, laboratory, and treatment data collected were described using descriptive statistics. Multiple logistic regression analysis was conducted to determine the predictors for the prescription of statins (HIS). High-intensity statin therapy was defined as atorvastatin ≥40 mg per day, rosuvastatin ≥20 mg per day, or simvastatin ≥80 mg per day, according to American College of Cardiology (ACC)/American Heart Association (AHA) guidelines. We analyzed data from 166 patients who met the inclusion criteria. The mean age was 63.34 years. The most common comorbidity was diabetes mellitus (DM) (68.86%). Statins were used in 82% of patients, among whom only 39% were on high-intensity statins. Multiple logistic regression analysis revealed that patients with cerebrovascular disease (CVD) [odds ratio (OR) = 0.19, 95% confidence interval (CI) = 0.06-0.61, p = 0.005], on oral anticoagulants (OAC) (OR = 0.16, 95% CI = 0.04-0.62, p = 0.008) and on dual antiplatelet therapy (DAPT) (OR = 0.20, 95% CI = 0.08-0.47, p < 0.000) had lower odds of receiving lower extremity revascularization (LIS) therapy. Despite having a high risk of future adverse cardiac events, patients with PAD are less likely to receive appropriate statin therapy. Involvement of more vascular beds was associated with higher chances of initiating high-intensity statin.

Left atrial appendage closure for patients with atrial fibrillation at high intracranial haemorrhagic risk

Background and objectivesAlthough left atrial appendage closure (LAAC) is performed in patients with non-valvular atrial fibrillation (NVAF) at increased risk of intracranial haemorrhage (ICH), outcome data are scarce. We assessed...

Risk of death and thromboembolic events in patients with supraventricular arrhythmias admitted to the emergency department

Abstract Background Few data are available on the risk of death and thromboembolism in patients with supraventricular tachycardia (SVT). Purpose To assess the risk of adverse events in SVT patients admitted to the emergency department (ED). Methods Retrospective study utilizing a global federated health research network (TriNetX). Based on the ICD codes recorded at the ED admission, patients were categorized in: SVT (I41.1), atrial fibrillation (AF, I48.0,1,2,91), atrial flutter (I48.3,4,92), and a control group with palpitations (R00.2) without arrhythmias (CTRL). Primary outcome was the 1-year risk of a composite of all-cause death and thromboembolism (ischemic stroke, transient ischemic attack, and peripheral arterial embolism). Secondary outcomes were the 1-year risk of each component of the composite outcome. Cox-regression analysis was used to produce hazard ratios (HRs) and 95% confidence intervals (CI) after 1:1 propensity score matching (PSM). The exploratory analysis was performed to assess the risk of first episode of thromboembolism. Other sensitivity analyses were performed to validate the results of the main analysis in patients ≥65 years, with multimorbidity, and not on oral anticoagulation (OAC). Results We identified 37,793 SVT patients (58.5±19.2 years, 55.8% females), 239,490 AF patients (70±19.2 years, 47.3% females), 20,674 atrial flutter patients (68.6±15.1, 15.1% females), and 89,152 CTRL (43.5±17.8 years, 60.1% females). Before PSM, in SVT patients the mean age and the prevalence of cardiovascular risk factors was lower than AF and atrial flutter patients but higher than CTRL. After PSM, no difference was found among the three groups. After PSM, the risk of composite outcome in SVT patients was higher compared to CTRL (HR 2.80, 95%CI 2.61-3.00), similar to atrial flutter patients (HR 0.98, 95%CI 0.94-1.03), and a lower compared to AF patients (HR 0.85, 95%CI 0.82-0.88) (Figure 1). These results were consistent also for the secondary outcomes, for the risk of the first thromboembolic event (Figure 2), and in all the sensitivity analyses. Conclusion SVT patients have a risk of death and thromboembolism comparable to those with atrial flutter, but lower than AF. Further studies are needed to evaluate the possible beneficial effect of OAC in this clinical context.Figure 1Figure 2

Efficacy and safety of oral anticoagulants according to kidney function among patients with atrial fibrillation.

Patients with severely reduced kidney function have been excluded from randomized controlled trials and data on the safety and efficacy of direct oral anticoagulants (DOACs) according to kidney function remain sparse. The aim was to evaluate the safety and efficacy of the DOACs across subgroups of kidney function. Using multiple Danish nationwide registers and laboratory databases, we included patients initiated on oral anticoagulants (OACs) with atrial fibrillation and available creatinine level and followed patients for 2 years to evaluate occurrence of stroke/thromboembolism (TE) and major bleeding. Among 26 686 included patients, 3667 (13.7%) had an estimated glomerular filtration rate (eGFR) of 30-49mL/min/1.73m2 and 596 (2.2%) had an eGFR below 30 mL/min/1.73m2. We found no evidence of differences regarding the risk of stroke/TE between the OACs (P-value interaction >0.05 for all). Apixaban was associated with a lower 2-year risk of major bleeding compared to vitamin K antagonists (VKA) [hazard ratio 0.79, 95% confidence interval (CI) 0.67-0.93], and the risk difference was significantly larger among patients with reduced kidney function (P-value interaction 0.018). Rivaroxaban was associated with a higher risk of bleeding compared to apixaban (hazard ratio 1.78, 95%CI 1.32-2.39) among patients with eGFR 30-49mL/min/1.73m2. Overall, we found no differences regarding the risk of stroke/TE, but apixaban was associated with a 21% lower relative risk of major bleeding compared to VKA. This risk reduction was even greater when comparing apixaban to VKA among patients with eGFR 15-30mL/min/1.73m2, and when comparing apixaban to dabigatran and rivaroxaban among patients with eGFR 30-49mL/min/1.73m2.

Description of self-care behaviours in patients with non-valvular atrial fibrillation on oral anticoagulant therapy: a scoping review.

The primary aim of this scoping review was to explore and categorize the medication-related self-care behaviours exhibited by patients with non-valvular atrial fibrillation (NVAF) who are on oral anticoagulant (OAC) therapy. A scoping review was performed, and the systematic search of the literature yielded an initial 887 records. After deduplication and screening, 61 studies were included in the analysis, ranging from 2003 to 2023. The studies represented a wide geographical distribution and diverse methodologies. The results identified 16 self-care behaviours: a higher focus of the included literature on self-care monitoring (60.65% of studies), followed by self-care management and self-care maintenance (each 16.39%). These behaviours ranged from regular blood testing to consulting healthcare providers and lifestyle changes. The results also highlighted the relationship between treatment satisfaction, self-efficacy, and adherence. Several studies emphasized the critical role of healthcare providers in influencing medication adherence. Furthermore, patient knowledge, quality of life, and psychological factors were identified as key elements affecting self-care behaviours. The review provides a comprehensive landscape of medication-related self-care behaviours among NVAF patients on OAC therapy. It underscores the predominance of self-care monitoring behaviours and the critical roles of healthcare providers, psychological factors, and patient knowledge in influencing these behaviours. The findings also highlight the necessity for an integrated, patient-centred approach to improving self-care and self-management in OAC treatment. Future research should focus on addressing the identified gaps, including the relative lack of studies on lifestyle modification, emotional well-being, and technology-assisted interventions. This review is part of a broader project and is documented at ClinicalTrials.gov: NCT05820854.

Ticagrelor or prasugrel vs. clopidogrel in patients with atrial fibrillation undergoing percutaneous coronary intervention for myocardial infarction.

The efficacy and safety of ticagrelor or prasugrel vs. clopidogrel in patients with atrial fibrillation (AF) on oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI) have not been established. This was a nationwide cohort study of patients on OAC for AF who underwent PCI for MI from 2011 through 2019 and were prescribed a P2Y12 inhibitor at discharge. The primary efficacy outcome was major adverse cardiovascular events (MACE), defined as a composite of death from any cause, stroke, recurrent MI, or repeat revascularization. The primary safety outcome was cerebral, gastrointestinal, or urogenital bleeding requiring hospitalization. Absolute and relative risks for outcomes at 1 year were calculated through multivariable logistic regression with average treatment effect modelling. Outcomes were standardized for the individual components of the CHA2DS2-VASc and HAS-BLED scores as well as type of OAC, aspirin, and proton pump inhibitor use. We included 2259 patients of whom 1918 (84.9%) were prescribed clopidogrel and 341 (15.1%) ticagrelor or prasugrel. The standardized risk of MACE was significantly lower in the ticagrelor or prasugrel group compared with the clopidogrel group (standardized absolute risk, 16.3% vs. 19.4%; relative risk, 0.84, 95% confidence interval, 0.70-0.98; P = 0.02), while the risk of bleeding did not differ (standardized absolute risk, 5.5% vs. 5.1%; relative risk, 1.07, 95% confidence interval, 0.73-1.41; P = 0.69). In patients with AF on OAC who underwent PCI for MI, treatment with ticagrelor or prasugrel vs. clopidogrel was associated with reduced ischaemic risk, without a concomitantly increased bleeding risk.

Impact of Access Site on Periprocedural Bleeding and Cerebral and Coronary Events in High-Bleeding-Risk Percutaneous Coronary Intervention: Findings from the RIVA-PCI Trial.

The preference for using transradial access (TRA) over transfemoral access (TFA) in patients requiring percutaneous coronary intervention (PCI) is based on evidence suggesting that TRA is associated with less bleeding and fewer vascular complications, shorter hospital stays, improved quality of life, and a potential beneficial effect on mortality. We have limited study data comparing the two access routes in a patient population with atrial fibrillation (AF) undergoing PCI, who have a particular increased risk of bleeding, while AF itself is associated with an increased risk of thromboembolism. Using data from the RIVA-PCI registry, which includes patients with AF undergoing PCI, we analyzed a high-bleeding-risk (HBR) cohort. These patients were predominantly on oral anticoagulants (OAC) for AF, and the PCI was performed via radial or femoral access. Endpoints examined were in-hospital bleeding (BARC 2-5), cerebral events (TIA, hemorrhagic or ischemic stroke) and coronary events (stent thrombosis and myocardial infarction). Out of 1636 patients, 854 (52.2%) underwent TFA, while 782 (47.8%) underwent the procedure via TRA, including nine patients with brachial artery puncture. The mean age was 75.5years. Groups were similar in terms of age, sex distribution, AF type, cardiovascular history, risk factors, and comorbidities, except for a higher incidence of previous bypass surgeries, heart failure, hyperlipidemia, and chronic kidney disease (CKD) with a glomerular filtration rate (GFR) < 60ml/min in the TFA group. No clinically relevant differences in antithrombotic therapy and combinations were present at the time of PCI. However, upon discharge, transradial PCI patients had a higher rate of triple therapy, while dual therapy was preferred after transfemoral procedures. Radial access was more frequently chosen for non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina pectoris (UAP) cases (NSTEMI 26.6% vs. 17.0%, p < 0.0001; UAP 21.5% vs. 14.5%, p < 0.001), while femoral access was more common for elective PCI (60.3% vs. 44.1%, p < 0.0001). No differences were observed for ST-segment elevation myocardial infarction (STEMI). Both groups had similar rates of cerebral events (TFA 0.2% vs. TRA 0.3%, p = 0.93), but the TFA group had a higher incidence of bleeding (BARC 2-5) (4.2% vs. 1.5%, p < 0.01), mainly driven by BARC 3 bleeding (1.5% vs. 0.4%, p < 0.05). No significant differences were found for stent thrombosis and myocardial infarction (TFA 0.2% vs. TRA 0.3%, p = 0.93; TFA 0.4% vs. TRA 0.1%, p = 0.36). In HBR patients with AF undergoing PCI for acute or chronic coronary syndrome, the use of TRA might be associated with a decrease in in-hospital bleeding, while not increasing the risk of embolic or ischemic events compared to femoral access. Further studies are required to confirm these preliminary findings.

Outcomes of Oral Anticoagulation with Concomitant NSAID Use: A Registry Based Cohort Study

Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs), available without a prescription, are some of the most commonly used drugs in the United States. For patients on oral anticoagulation (OAC), concomitant NSAID use can increase the risk of bleeding. Patients are often advised to avoid this drug combination, or else consider adding a proton pump inhibitor (PPI) or H2 receptor antagonists (H2RA) for gastroprotection when both NSAIDs and OAC are used. However, there are limited data on how NSAID use impacts thrombotic and hemorrhagic outcomes. Available data may be biased due to selection bias, confounding, misclassification, and variable NSAID exposure. We sought to determine the frequency of NSAID use among patients on OAC, the impact on clinical outcomes, and if gastroprotection may mitigate bleeding risk. We hypothesized that NSAIDs would increase bleeding risk without impacting thrombotic risk. We did not anticipate gastroprotection would mitigate this risk. Methods We conducted a retrospective registry-based cohort study of adults starting a direct oral anticoagulant (DOAC) or warfarin therapy for the indications of venous thromboembolism and/or non-valvular atrial fibrillation between June 2011 and June 2023. As part of the Michigan Anticoagulation Quality Improvement Initiative (MAQI 2), warfarin-treated patients were followed by six anticoagulation clinics, and four of the six clinics contributed data for patients on DOACs. Patients were excluded if they had a history of valvular AF, less than 3 months of follow-up, or on more than one antiplatelet drug. Two propensity matched cohorts (OAC alone vs. OAC+NSAID) of patients were analyzed based on NSAID use at the time of study enrollment, using a 4:1 matching ratio. Both prescribed and over the counter NSAIDs were included, potentially with the former being more frequently captured in the study registry. The primary outcome was any new bleeding event. Secondary outcomes included new episodes of arterial or venous thrombosis, bleeding event type (major, fatal, life threatening, central nervous system, and non-major bleeding), emergency room visits, hospitalizations, transfusions, and death. Random chart audits were done to confirm the accuracy of the abstracted data. Event rates were compared using Poisson regression. Results Of 12,083 patients on OAC, 449 (3.7%) were on concomitant NSAIDs. After propensity matching, we compared 1,796 patients on OAC to 449 patients on OAC+NSAIDs. Patient demographics, co-morbidities, indication for anticoagulation, history of bleeding or clotting, medications, and duration of follow-up were well-balanced after matching. Patients were followed for an average of 30 months (standard deviation 34.2 months). For patients on OAC alone vs. OAC+NSAIDs, bleeding event rates were similar: 25.1 (95% confidence interval [CI] 23.7-26.6) versus 24.3 (95% CI 21.4-27.3) bleeds per 100 patient years ( P=0.56). Rates of non-major, major, life-threatening, central nervous system, and fatal bleeding were also similar. Furthermore, rates of thrombosis, emergency room visits, hospitalizations, transfusion, and death were similar. A pre-defined subgroup analysis comparing patients on OAC+NSAIDs with gastrointestinal prophylaxis (PPIs or H2RAs, N=179) to patients on OAC+NSAIDs without gastrointestinal prophylaxis (N=270) also showed similar rates of bleeding and healthcare utilization. Conclusions Nearly 4% of patients were taking NSAIDs with OAC and outcomes were similar to patients on OAC alone. Study limitations include NSAIDs and gastroprotection were only reliably known at time of enrollment. In addition, the potential for unmeasured or unadjusted confounding inherent to observational studies. Further research is needed to determine if there is a “safe” level of NSAID use for patients on OAC and to better define the role of gastrointestinal prophylaxis.

Is there a reduced confidence towards direct oral anticoagulants compared to vitamin K antagonists in patients scheduled for an elective electrical cardioversion? The results of the BLITZ-AF study

ObjectiveTo study the confidence of cardiologists in performing an electrical cardioversion in patients on oral anticoagulation (OA) with or without transoesophageal echocardiography (TOE). MethodsData about atrial fibrillation (AF) patients admitted to cardiology wards for elective cardioversion (ECV) were extrapolated from the BLITZ-AF study. Percentage of vitamin K antagonists (VKAs), direct oral anticoagulants (DOAC) and heparin prescription were analysed in relation to the use of TOE before ECV. ResultsOverall rate of TOE was 33.7% (240/713); it was used before ECV in 124/313 (39.6%) of DOACs patients and in 96/372 (25.8%) of the patients on VKAs, showing a significant reduced resort to TOE in VKAs patients (p = 0.0001). Among non-valvular patients TOE was more frequently performed in males, at younger ages and in patients on heparin when compared to patients treated with OA. TOE was also more frequently performed in tertiary hospitals and in hospitals with cardiology wards and electrophysiology labs, when compared to hospital provided only with cardiology wards. At multivariable analysis there was a significant less recourse to TOE in patients on VKAs (OR 0.47; 95% CI: 0.33–0.67) and higher recourse in the heparin group (OR: 3.85; 95% CI:1.59–9.28) with respect to patients on DOACs; a higher recourse to TOE was observed also in tertiary hospitals (OR 4.25; 95% CI 2.69–6.69) and in hospitals with cardiology wards and electrophysiology (EP) labs (OR 1.87; 95% CI 1.23–2.82). Conclusionour study shows the reluctance in cardioverting patients on DOACs respect to VKAs without a previous TOE, despite adequate anticoagulant treatment.

Impact of anemia on major bleeding in patients taking oral anticoagulants for nonvalvular atrial fibrillation.

Anemia is encountered in patients with nonvalvular atrial fibrillation (NVAF) on oral anticoagulants (OACs) but the prognostic impact was not well scrutinized in real-world settings. We conducted a historical multicenter registry of patients with NVAF taking OACs at 71 centers in Japan. Those with mechanical heart valves or a history of pulmonary thrombosis or deep venous thrombosis were excluded. Anemic patients were divided into three groups of hemoglobin (Hb) level: moderate/severe (Hb < 11.0 g/dL), mild (men: Hb of 11.0-12.9 g/dL; women: Hb of 11.0-11.9 g/dL), and no anemia. The endpoints included major bleeding, hemorrhagic stroke, ischemic events, ischemic stroke, and all-cause mortality. Among 7558 consecutive patients (mean age, 73 years; men 67%) registered in February 2013 and followed until February 2017, 2100 (28%) patients had anemia. The anemic patients were older (moderate/severe: 79 years; mild: 77 years; no anemia: 71 years, p < .001), and HAS-BLED score was significantly higher in the anemic patients (p < .001). The cumulative incidences at 4 years of major bleeding in moderate/severe, mild, and no anemia group, were 14.9%, 10.7%, and 6.4%, respectively. The adjusted hazard ratios (HRs) (95% confidential intervals (CIs)) of major bleeding of moderate/severe and mild anemia group were 1.96 (1.49-2.58) and 1.48 (1.17-1.87) compared to no anemia group. The adjusted HRs (95% CIs) for ischemic events were 0.63 (0.39-0.99) and 1.03 (0.76-1.39). The severity of anemia in the patients with NVAF on OACs was associated with major bleeding.

PO-01-002 ASSOCIATION OF NOVEL COMBINED GENETIC POLYMORPHISMS WITH RISK OF THROMBOEMBOLISM IN PATIENTS WITH ATRIAL FIBRILLATION

AF patients remain on oral anticoagulation (OAC) or left atrial appendage (LAA) closure is performed for thromboprophylaxis. However, clots on the closure device as well as stroke/transient ischemic attack (TIA) are observed to occur in some patients despite of being on blood thinners or after being off-OAC for a very brief period. Therefore, we evaluated if genetic variants were associated with TE events in this subset of AF population. This prospective study (NCT04115436) included consecutive AF patients that were managed for AF at our center. SNP Genotyping Analysis was performed on the blood sample of the study participants using a combination of microarray and next-generation sequencing (NGS). We screened for common single nucleotide polymorphisms (SNPs) reported in the literature to be associated with stroke and thromboembolism at a genome-wide significance level. We genotyped 29 AF patients (age: 66.5±3.53 years; female: 6 (20.7%)) with thromboembolic events following AF ablation. Of these patients, device (Watchman)-associated thrombus was reported in 13 (44.8%), stroke/TIA off-OAC in 14 (48.3%) and left atrial appendage thrombus while on OAC in 2 (6.9%). One or more of the following 4 SNPs were detected in 27/29 patients (93.1%): rs11833579, rs12476527, rs505922 and rs6891174. They were homozygous for the recessive allele in all 27 patients. Of the 27, 19 (70.3%) patients including the 13 with device-clot had >2 of the 4 genetic variants reported. Location of these SNPs and their clinical significance is provided in table 1. Our findings, for the first time, document the association of four stroke-related genetic variants with prothrombotic events such as device-related clot in patients with atrial fibrillation.

PO-03-192 INTRA-DEVICE LEAKS ON POST LEFT ATRIAL APPENDAGE OCCLUDER FOLLOW UP TOMOGRAPHIC IMAGING – TRUE LEAK OR MERE INCOMPLETE ENDOTHELIALIZATION

Patient undergoing Left atrial appendage closure (LAAC) needs to be kept on oral anticoagulant (OAC) or dual antiplatelet therapy (DAPT) because of the time required for endothelialization of the LAAC device. Post LAAC follow-up usually is usually performed with either a transesophageal echocardiogram (TEE) or cardiac computed tomography (CCTA) at 45 days, 6 months and 12 months to ensure complete closure and endothelialization of the LAA. Contrast flow (CF) behind the LAAC device on CCTA could be indicative of either a peri-device leak (PDL) or intra-device leak due to incomplete endothelialization. Often the contrast flow into the LAA is described as a leak with implications to continued OAC. This study aims to evaluate the utility of LAA-CF on CCTA scan to predict lack of endothelialization after endocardial LAA closure and its association with peri-device leaks (PDLs). Consecutive patients who underwent LAAC at our center from June 2021 to September 2021 and had follow up CCTA at 45 days, 6 months and 12 months were included in the study. Patients who were follow up with TEE were excluded. Rate of LAA-CF was calculated. LAA-CF was defined as radiodensity > 100 HU (Hounsfield units) of the LAA separated from the device, or contrast opacification ≥ 25% of the left atrium with the presence of any LAA opacification compared with the pre-LAAC cardiac CT. Of 45 patients, 62% had Watchman FLX (n= 28) and 38% had Amplatzer Amulet (n=17) implantation. Mean age of the cohort was 74.6 + 9.3 years and 72% were males. At 45 day follow up CCTA, 40% (n=18) had LAA-CF of which 56% (n=10) had PDL whereas 44% (n=8) had no PDL. On 6 month follow up LAA-CF persisted in 44% (n=8/18) with 62.5% (n=5/8) having PDL. However, at 12 months LAA-CF persisted in only one patient who had a leak of 7 mm (Table). There were no systemic thromboembolic events. Although numbers were small Amulet had higher LAA-CF than Watchman FLX probably related to large outer disc surface area. Delayed LAA-CF is common after LAAO and is a reflection of poor endothelialization than a true PDL. It has no real long term clinical implications.

Cognitive phenotypes and factors associated with cognitive decline in a cohort of older patients with atrial fibrillation: The Strat-AF study.

The multifactorial relationship between atrial fibrillation (AF) and cognitive impairment needs to be elucidated. The aim of this study was to assess, in AF patients on oral anticoagulants (OACs), the prevalence of cognitive impairment, defined according to clinical criteria or data-driven phenotypes, the prevalence of cognitive worsening, and factors associated with cognitive outcomes. The observational prospective Strat-AF study enrolled AF patients aged ≥ 65 years who were receiving OACs. The baseline and 18-month protocol included clinical, functional, and cognitive assessment, and brain magnetic resonance imaging. Cognitive outcomes were: empirically derived cognitive phenotypes; clinical diagnosis of cognitive impairment; and longitudinal cognitive worsening. Out of 182 patients (mean age 77.7 ± 6.7 years, 63% males), 82 (45%) received a cognitive impairment diagnosis, which was associated with lower education level and functional status, and higher level of atrophy. Cluster analysis identified three cognitive profiles: dysexecutive (17%); amnestic (25%); and normal (58%). Compared to the normal group, the dysexecutive group was older, and had higher CHA2 DS2 -VASc scores, while the amnestic group had worse cognitive and functional abilities, and medial temporal lobe atrophy (MTA). Out of 128 followed-up patients, 35 (27%) had cognitive worsening that was associated with lower education level, worse cognitive efficiency, CHA2 DS2 -VASc score, timing of OAC intake, history of stroke, diabetes, non-lacunar infarcts, white matter hyperintensities and MTA. In multivariate models, belonging to the dysexecutive or amnestic group was a main predictor of cognitive worsening. In our cohort of older AF patients, CHA2 DS2 -VASc score, timing of OAC intake, and history of stroke influenced presence, type and progression of cognitive impairment. Empirically derived cognitive classification identified three groups with different clinical profiles and better predictive ability for cognitive worsening compared to conventional clinical diagnosis.

Global Cortical Atrophy Is Associated with an Unfavorable Outcome in Stroke Patients on Oral Anticoagulation

Introduction: Measures of cerebral small vessel disease (cSVD), such as white matter hyperintensities (WMH) and cerebral microbleeds (CMB), are associated with an unfavorable clinical course in stroke patients on oral anticoagulation (OAC) for atrial fibrillation (AF). Here, we investigated whether similar findings can be observed for global cortical atrophy (GCA). Methods: Registry-based prospective observational study of 320 patients treated with OAC following AF stroke. Patients underwent magnetic resonance imaging (MRI) allowing assessment of GCA. Using the simplified visual Pasquier scale, the severity of GCA was categorized as follows: 0: no atrophy, 1: mild atrophy; 2: moderate atrophy, and 3: severe atrophy. Using adjusted logistic and Cox regression analysis, we investigated the association of GCA using a composite outcome measure, comprising: (i) recurrent acute ischemic stroke (IS); (ii) intracranial hemorrhage (ICH); and (iii) death. Results: In our time to event analysis after adjusting for potential confounders (i.e., WMH, CMB, age, sex, diabetes, arterial hypertension, coronary heart disease, hyperlipidemia, and antiplatelet use), GCA was associated with an increased risk for the composite outcome in all three degrees of atrophy (grade 1: aHR 3.95, 95% CI 1.34–11.63, p = 0.013; grade 2: aHR 3.89, 95% CI 1.23–12.30, p = 0.021; grade 3: aHR 4.16, 95% CI 1.17–14.84, p = 0.028). Conclusion: GCA was associated with our composite outcome also after adjusting for other cSVD markers (i.e., CMB, WMH) and age, indicating that GCA may potentially serve as a prognostic marker for stroke patients with atrial fibrillation on oral anticoagulation.