Oral Anticoagulants Research Articles

How much does elective cardioversion increase the risk of ischaemic stroke compared to the baseline risk in atrial fibrillation? A nationwide study

Abstract Background Patients with atrial fibrillation (AF) undergoing cardioversion (CV) are exposed to an increased risk for stroke during the post-cardioversion period, but the exact magnitude of this risk after elective CV with preceding appropriate oral anticoagulant (OAC) therapy is unknown. Purpose We explored the rate of ischaemic stroke (IS) after elective CV and compared the IS rate during the post-cardioversion period with the long-term stroke rate in patients with AF using guideline-recommended OAC therapy. Methods This is a nationwide register-based study, including all AF patients undergoing their first-ever elective CV between 2012-18 in Finland. Data were collected from the Finnish health care registers covering uniquely all levels of care. Visual assessment of the survival curve identified a cut-off point in IS rate at 1 week after CV. Therefore, the follow-up time was split into two intervals, the 1-week post-cardioversion period and the subsequent period up to 360 days. Stroke rates were calculated separately for these periods. Unadjusted and adjusted incidence rate ratios were estimated with Poisson regression. Moreover, interaction between the two follow-up periods and conventional IS risk factors as well as OAC treatment was assessed. Results A total of 9625 AF patients undergoing their first elective CV were identified (mean age 67.7±9.9 years, 61.2% men, mean CHA2DS2-VASc score 2.6±1.6). Warfarin was used in 6 245 (64.9%) and non-vitamin K oral anticoagulants in 3 380 (35.1%) patients. Overall, 92 (1.0%) patients suffered an IS during the year after CV. The survival plot displayed a higher incidence of IS within the first week after CV, stabilizing thereafter to a consistent level (Figure). In the adjusted regression analyses, IS rate within the first week after elective CV was 13.6-fold (95% confidence interval [CI]: 8.6-21.5) compared the subsequent rate of IS (Table). We observed no significant interaction between any of the conventional IS risk factors or OAC treatment and the two follow-up time periods, indicating that their association with IS rate did not differ during the post-cardioversion period compared to the subsequent time period. Conclusions In this nationwide study, the rate of IS was roughly 14 times higher during the first week after elective CV compared to the subsequent follow-up time.Cumulative risk of IS after elective CVIncidence rates of IS after elective CV

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<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<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<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.

Risks of incident genitourinary malignancies in anticoagulated atrial fibrillation patients experiencing hematuria

Abstract Background When managing oral anticoagulant (OAC)-related bleeding in patients with atrial fibrillation (AF), the possibility of occult malignancies should be kept in mind, as suggested by guidelines. In this study, we aimed to investigate the incidence of genitourinary (GU) trat cancer in anticoagulated AF patients experiencing hematuria. Also, we aimed to report the prevalence of other causes of hematuria beside malignancy. Methods We conducted a nationwide, retrospective cohort study in Taiwan. A total of 19,974 AF patients aged ≥ 20 years on OAC treatment (warfarin 9232, non-vitamin K antagonist OACs [NOACs] 10,742) experiencing hematuria were enrolled. Risk of newly diagnosed GU malignancy within one year after hematuria was reported and compared between patients receiving warfarin and NOACs. Results A total of 738 patients (3.99%) were diagnosed to have GU tract cancers within 1 year after OAC-related hematuria, with prostate cancer (52.30%) being as the commonest subtype, followed by bladder cancer (31.71%) and kidney/ureter/urethra in origin (15.99%)(Figure 1). The risk of GU tract cancer was higher for warfarin compared to NOAC users (4.10% versus 3.89%; odds ratio 1.169, p = 0.041)(Figure 1). For patients without diagnosed GU tract cancers, urinary tract infection (42.3%) was the leading cause of hematuria followed by benign prostate hyperplasia (37.6%), GU tract stone (16.7) and cystitis (9.2%)(Figure 2). Overall, 27.5% of patients whose causes of hematuria could not be identified (Figure 2). Conclusions Incident GU cancers were diagnosed in 1 of 25 AF patients at 1 year after OAC-related hematuria. Detailed examinations for occult GU cancers and other etiologies are necessary.

Predictors of discordance in estimating the presence of chronic kidney disease among patients with atrial fibrillation and impact on prescription of anticoagulants and cardiovascular outcomes

Abstract Background In patients with atrial fibrillation (AF), the prevalence, predictors and clinical implications of a potential discordance in estimating the presence/absence of chronic kidney disease (CKD) according to Cockroft-Gault (CG) and CKD-EPI formulas remain unclear. Objective To examine patients characterized by discordance in evaluation of renal function, specifically with regard to the threshold for defining the presence of CKD according to an estimated glomerular filtration rate (eGFR) < 60 ml/min, in a large cohort of European AF patients, and to assess the association with prescriptions of oral anticoagulants (OAC) and the risks of adverse outcomes. Methods Data related to AF patients enrolled in a large European observational prospective registry with an average follow up of 645.2 days were analysed. We evaluated renal function for assessing the presence of CKD according to CG and CKD-EPI formulas and we categorized the population in four groups: eGFR ≥ 60 ml/min according both to CG and CKD-EPI (Concordant ≥ 60); < 60 ml/min according to both formulas (Concordant <60); CG <60 ml/min and CKD-EPI ≥60 ml/min (Discordant-CKD-EPI), CG ≥ 60 ml/min and CKD-EPI <60 ml/min (Discordant-CG). Logistic regression analyses were used to assess factors associated with a Discordant assessment of CKD and its association with OAC therapy. Cox regression analysis was used to determine association between categories and the risk of adverse outcome. The primary endpoint was a composite of all-cause death and major adverse cardiovascular events (MACEs). Results 8.786 patients with AF (mean age 68.70, SD 11.58 years; 40.9% female) were included in the analysis. 1360 (15.5%) of them had Discordant CKD assessment: 577 (6.6%) with Discordant-CKD-EPI and 783 (8.9%) with Discordant-CG. Increasing age, female sex and coronary artery disease (CAD) were associated with Discordant-CKD-EPI, while BMI and heart failure (HF) showed an inverse association (Figure 1). Conversely, BMI and HF were factors significantly associated with Discordant-CG. Discordant-CKD-EPI patients showed lower odds of being prescribed with OAC therapy (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.54-0.95) with no significant differences regarding the type of OAC therapy (warfarin or direct oral anticoagulants). At Cox regression analysis, patients with Discordant-CKD-EPI showed a higher risk of composite endpoint events (Figure 2) and both Discordant-CKD-EPI and Discordant-CG patients were associated with a higher risk of all-cause death. Conclusions Age, BMI, female sex and comorbidities associated with AF (CAD and HF) significantly influenced the probability of having a discordant assessment of the presence of CKD, according to estimation of renal function impairment using CG or CKD-EPI formulas, respectively. A discordant assessment of CKD influenced the probability of being prescribed with OAC and was associated with a higher risk of adverse outcomes.Figure 1Figure2

Outcomes and management of Haemoptysis in the Fontan population

Abstract Background Patients with a Fontan circulation for palliation of a univentricular congenital heart defect commonly possess pulmonary vascular abnormalities including arteriovenous malformations (AVM), aortopulmonary and venous-venous collaterals (1). These vessels are prone to haemorrhage which may result in life-threatening haemoptysis (2). This risk is increased with oral anticoagulant medication, given to reduce the risk of thromboembolism in Fontan patients (3). Management of these patients is difficult, and strategies vary across institutions. Purpose We aim to describe our experience with managing adult Fontan patients presenting with haemoptysis in a tertiary centre with a large Fontan cohort. Methods We retrospectively reviewed the records of 410 adult Fontan patients. Individuals admitted to our institution with an episode of haemoptysis were included. Details relating to anticoagulation regimens, interventions and mortality of patients were captured. Results From a cohort of 410 Fontan patients, 35 haemorrhagic events were observed in 11 patients (2.68%). The median age at initial haemoptysis was 24.5 years (range 19 to 43 years). 6 of the 11 patients were female (54.5%). Haemoptysis recurred in 8 of the 11 patients (72.7%). 2 out of 11 had a prior history of haemoptysis in childhood. All patients were administered with oral vitamin K antagonists at presentation. 24 of the 35 events were managed conservatively with IV fluids, anticoagulation reversal and tranexamic acid (66.7%). 11 events required catheter-based interventions, with coil and/or plug embolization of bleeding vessels. Prior to intervention, CT successfully identified potential bleeding sites in 10 of the 11 events (90.9%) but could not visualise all vessels that were subsequently embolized. The most common culprits for haemoptysis were aortopulmonary collaterals, followed by AVMs and venous-venous collaterals. In severe cases, more extensive management was required including transfusions, bronchoscopy, intubation, surgical exploration (1 patient) and pneumonectomy (1 patient). 3 patients died following recurrent severe haemoptysis (27.3%), and 2 patients died of subsequent Fontan failure and sudden cardiac death respectively. Total mortality of the cohort is 5 out of 11 (45.5%) with a median follow up of 10.75 years (range 3 days to 27 years). Conclusions Haemoptysis is a rare but potentially fatal complication in patients who have undergone a Fontan procedure. The variability in presentation of this condition mandates an individualised approach to management with involvement of a multidisciplinary team. There is a high rate of recurrence following haemoptysis and a comprehensive assessment of all potential bleeding sites is necessary. CT is a useful tool to help facilitate this and guide further management. Our policy is to close all potential sources of bleeding as CT and invasive angiography rarely identifies an active point of bleeding.

PPGAF-score: a photoplethysmographic risk prediction tool for developing atrial fibrillation

Abstract Background Digital screening for AF was recently shown to significantly increased the detection rate of treatment-relevant AF when compared to usual care. In this post-hoc analysis of the eBRAVE-AF trial, we hypothesized that information derived from sequential PPG-measurements in sinus rhythm might be predictive for future AF-development and we aimed to develop a dynamic AF-risk score (PPGAF-score). Methods In eBRAVE-AF, individuals who were free of AF were randomized to digital screening or usual care. For digital screening, participants screened for irregularities by means of PPG and abnormal findings were confirmed by a 14-day Holter-ECG. The primary endpoint was newly diagnosed AF treated with oral anticoagulation (OAC) within 6 months. After 6 months, participants were invited to a second, cross-over study phase. In this sub-study we identified participants who performed PPG-measurements both on day (8 am-6 pm) and at night (10 pm-6 am). PPGAF-score was calculated using the coefficients derived from Cox regression analysis. The multivariable model included age ≥ 65 years, sex and three PPG-derived parameters: (i) mean heart rate (HR) of each single PPG-measurement and (ii) the standard deviation (SD) of the HR between subsequent PPG-measurements, which were both dichotomized at the median value and (iii) the failure to demonstrate nocturnal HR reduction (day HR/night HR < 1). PPGAF-score was dichotomized at the median value. Results Of the 2,436 participants included in this analysis, 1,208 (50%) were ≥ 65 years old and 776 (32%) participants were females. Cumulatively 186,551 PPG measurements were performed, corresponding to a median of 28 (IQR 23) daytime and 3 (IQR 5) nighttime measurements per participant. The median HR per measurement was 69 (IQR 11) bpm, the median SD of the HR was 6 (IQR 2) bpm, and 759 (31%) participants failed to show a nocturnal HR reduction. During a follow-up time of 12 months, 53 subjects reached the primary endpoint. Cox regression analysis showed that age ≥ 65 years (HR 3.6; 95% CI 1.9–7.0; p < 0.001), male sex (2.7; 95% CI 1.2–5.9;p = 0.017), HR < 69bpm (HR 1.9; 95% CI 1.1–3.5;p=0.028), SD of HR ≥ 6bpm (HR 2.2; 95% CI 1.2–4.0;p=0.011) and the failure to show nocturnal HR reduction (HR 3.2; 95% CI 1.9–5.5; p < 0.001) were all independent predictors of the primary endpoint. PPGAF-score was calculated from the multivariable model. The median value was 0.22. PPGAF-score > 0.22 compared to a risk score ≤ 0.22 was associated with a significantly higher risk for developing AF requiring OAC (HR 6.9, 95% CI 3.1–15.4;p < 0.001; Figure 1). Conclusion Combining demographic and PPG-derived parameters, we developed a dynamic prediction tool for assessing the one-year risk of developing AF requiring OAC. A risk score of > 0.22 was associated with a 7-fold increased risk for developing treatment-relevant AF. PPG recordings might provide a valuable tool not only for diagnosing AF, but also for selecting high-risk individuals.

Direct oral anticoagulants or warfarin in patients with left ventricular thrombus: a meta-analysis of randomized clinical trials

Abstract Background/Introduction There are limited randomized controlled trials (RCTs) data on the use of direct oral anticoagulants (DOAC) versus warfarin in patients with left ventricular (LV) thrombus. Current AHA and ESC guidelines recommend oral anti-coagulants (either DOAC or warfarin) for 3 to 6 months without any preference. Purpose We aimed to compare outcomes with DOACs versus warfarin in patients with LV thrombus. Methods A comprehensive literature search was performed from inception to 02/01/2024 of the PubMed database. RCTs of adult patients comparing DOAC to warfarin were evaluated for mortality, major bleeding, stroke, and LV thrombus resolution. Meta-analytic Odds ratio (OR) with 95% confidence intervals (CI) were calculated using DerSimonian-Laird method. Results From 100 studies, four RCTs with 188 subjects (95 DOAC and 93 warfarin) were included with mean age of 53.4 years, 69.5% males, and mean follow up 5.03 months. There was no difference in mortality (OR= 0.67 [95% CI 0.15-3.06]; p=0.60; I2=0%; 3 trials), stroke (OR= 0.46 [95% CI 0.09-2.44]; p=0.37; I2=0%; 4 trials), major bleeding (OR= 0.43 [95% CI 0.12-1.55]; p=0.20; I2=0%; 4 trials), and LV thrombus resolution (OR= 1.33 [95% CI 0.45-3.95]; p=0.61; I2=0%; 2 trials) with use of DOAC compared to warfarin (Figure Panel A to D). Overall, there was no evidence of publication bias using either funnel plot or eggers test (p > 0.05). Conclusions In this meta-analysis of 4 RCTs, there was similar efficacy and safety of DOAC and warfarin in patients with LV thrombus. However, the evidence is limited by small sample size with lesser precision in the estimates. Future large-scale trials are needed to confirm these findings.

Complex versus non-complex, should we adjust the antiplatelet strategy to the type of percutaneous coronary intervention? Results from a real world PCI population

Abstract Background/introduction Personalized dual antiplatelet treatment (DAPT) using risk stratification is key to minimize bleeding- and ischemic events after percutaneous coronary intervention (PCI). Known ischemic risk factors include complex procedures which are integrated in the recommendation for extended DAPT in patients with additional ischemic risk factors. Purpose We aimed to provide insight whether a complex PCI (CPCI) should be regarded as an individual risk factor, regardless of other risk factors, to adjust the antiplatelet strategy. Also, we determined the effect of DAPT duration and choice of P2Y12 inhibitor on outcomes. Methods We included patients from the South East (Zuid Oost) Netherlands Heart Registry (ZON-HR) and excluded patients using oral anticoagulants. This PCI registry prospectively collects baseline-, procedural- and follow-up data including medication use and the intended DAPT duration. Patients were stratified to non-CPCI or CPCI comprising of bifurcation lesions with two stents, venagraft PCI, chronic total occlusion (CTO) or ≥ 60mm stent. Analyses were conducted using Cox regression analysis. Multivariate analysis was performed to adjust for risk factors and baseline differences. Results We included 3691 patients (842 CPCI). Table 1 demonstrates the baseline characteristics and DAPT strategy. CPCI was more often required in patients with a high ischemic risk profile based on the extensiveness of atherosclerosis and comorbidities. Non-CPCI patients more often underwent PCI for acute coronary syndrome. Outcomes are presented in table 2. Compared to non-CPCI, CPCI increased the risk of major adverse cardiac and cerebral events (MACCE) in the second half of the year as opposed to bleeding events, which more often occurred in the first months after CPCI, driven by access site bleedings (73% in CPCI versus 56% in non-CPCI, p=0.01). All-cause mortality was higher during the overall follow-up period after a CPCI compared to non-CPCI. These findings remain significant when corrected for additional risk factors in both groups. In patients with CPCI, treatment with ticagrelor or prasugrel strongly reduced MACCE between 6-12 months when compared to clopidogrel (multivariate HR: 0.28, 95% CI: 0.08-0.98), but did not influence bleeding events or all-cause mortality. No effect of extended DAPT was observed. Conclusions A CPCI is an important ischemic risk factor that could be used for risk stratification to guide antiplatelet strategy. Treatment with ticagrelor or prasugrel strongly diminished the risk of MACCE without increasing the bleeding risk in patients with a CPCI. As the risk of MACCE increases between 6-12 months after PCI while the risk of bleeding events diminishes in this period, extended DAPT from 6 to 12 months could also be considered to provide extended protection.Table 1.Table 2

Prevention of thromboembolic events in atrial fibrillation patients with persistent leaks following the watchman implantation

Abstract Introduction Peri-device leak is not uncommon after percutaneous occlusion of left atrial appendage using the Watchman device. Prior studies have reported the clinical relevance of small leaks (<5mm) as they were associated with a significant increase in ischemic events. Purpose We evaluated the prevalence of stroke in patients with post-watchman leaks on half-dose non-vitamin K oral anticoagulants (HD-NOAC) vs antiplatelet therapy (APT). Methods This consecutive series included post-watchman cases that had a residual leak of ≤5 mm at the 45-day echocardiogram and were unwilling to undergo any leak-closure procedure. Based on their subsequent antithrombotic therapy, they were classified into group 1: HD-NOAC and group 2: dual-APT for 6 months followed by Aspirin only. Patients were closely monitored for thromboembolic (TE) events via telemedicine. Stroke/transient ischemic attacks that occurred while the patients were in full compliance with the anti-thrombotic therapy, were counted as the reportable TE events. Results A total of 141 (age: 66.89± 8.76 years, male: 88 (62.4%), CHA2DS2-VASc score: 3.41 ± 1.56, HAS-BLED: 3.72 ± 1.01) and 154 (age: 72.45 ±7.05 years, male: 99 (64.3%), CHA2DS2-VASc score: 3.75 ± 1.61, HAS-BLED: 3.89 ± 1.05) patients were included in group 1 and 2 respectively. All leaks were between 3-5 mm. TE events were reported in 2 (2/141, 2.12%) patients in group 1 and 9 (9/154, 5.8%) in group 2 while being on antithrombotic therapy (p=04). No residual neurological deficits were detected in the 2 patients from group 1 contrary to the 9 subjects in group 2 that had neurological deficits persistent at follow-up. Of note, 8 (5.6%) patients in group 1 experienced stroke after discontinuing the drug for other medical procedures or due to poor compliance. Conclusion Under full compliance, HD-NOAC is associated with significantly lower TE rate compared to the APT therapy in post-watchman cases with persistent leaks of ≤5 mm. However, discontinuation of the HD-NOAC increases the stroke-risk to a comparable level.

Rivaroxaban or warfarin in atrial fibrillation and coronary stent implantation in real-world patients involving chronic kidney disease (REWRAPS): 5-year follow-up study

Abstract Background Recent guidelines recommended either non vitamin K antagonist oral anticoagulants (NOAC) or vitamin K oral anticoagulant (VKA) one year after coronary stenting in patients with atrial-fibrillation (AF). However, whether NOAC is still superior to VKA at 5-years in patients involving chronic kidney disease (CKD) with AF and coronary stenting >1-year remains unclear. Methods In a multicenter, prospective, non-randomized registry, 493 patients were treated with either rivaroxaban or warfarin, while the majority (66.3%) of them had CKD. The primary efficacy endpoint was major adverse cardiac and cerebral events (MACCE). The primary safety endpoint was major bleeding (Bleeding Academic Research Consortium [BARC] 3 and 5). Net adverse clinical events (NACE) were defined as the composite of all-cause mortality and major bleeding. Both crude and propensity score matched (PSM) analyses were performed. P <0.05 was considered as statistically significant. Results At a median follow-up of 4.8 years MACCE rates did not differ between rivaroxaban and warfarin in 486 patients with crude-analysis (23.0% versus 29.0%, hazard-ratio [HR], 0.79; 95% confidence interval [CI], 0.55 to 1.11; P=0.17), while in 316 patients with PSM-analysis rivaroxaban met non-inferiority criteria to warfarin (HR, 0.86; 95% CI, 0.56 to 1.33; p=0.020 for non-inferiority). Rivaroxaban was associated with lower major bleeding risk compared with warfarin (6.5% versus 12.6%; HR, 0.50; 95% CI, 0.27 to 0.91; P=0.025) at crude analyses, which was no longer significant at PSM analyses (5.7% versus 10.8%; HR, 0.53; 95% CI, 0.24 to 1.19; P=0.12). However, NACE rates were significantly lower in rivaroxaban compared to warfarin at both crude (19.0% versus 35.7%; HR, 0.50; 95% CI, 0.35 to 0.72; P=0.0002) and PSM-analyses (19.6% versus 31.0%; HR, 0.63; 95% CI, 0.40 to 0.98; P=0.043), respectively. Conclusions Rivaroxaban did not differ from warfarin for efficacy endpoints of MACCE but was associated with lower NACE rates (i.e. all-cause mortality and major bleeding) in AF and coronary stent in real-world patients having CKD at 5-year follow-up (NCT02024230).

Comparative analysis of vitamin K antagonists and direct oral anticoagulants for left ventricular thrombus management: a retrospective study utilising TriNetX

Abstract Introduction Despite progress in cardiovascular medicine, guidelines for addressing left ventricular thrombus (LVT) remain limited. Furthermore, incorporating oral anticoagulants into dual antiplatelet therapy for acute myocardial infarction (MI) adds complexity to treatment decisions. While conventional guidance favors vitamin K antagonists (VKAs), emerging evidence suggests favorable outcomes with direct oral anticoagulants (DOACs). Purpose This study aims to assess the safety and efficacy of DOACs versus VKAs in managing LVT among patients with and without recent acute coronary syndrome (ACS). Methods This was a retrospective observational study conducted within TriNetX, a global federated health research network with access to electronic medical records (EMRs) from participating health care organizations including academic medical centres and community hospitals covering approximately 70 million individuals, mainly in the United States. The search was conducted on 26th Februrary 2024 with a study cohort comprising patients with LV thrombus treated with either DOAC or VKA between 1st December 2013 to 1st December 2023. Subgroup analyses were conducted for patients with ACS within one month and those without ACS within a month of treatment. Cohort data were subject to propensity matching (PSM) for age, gender, ethnicities, medical and drug history. Risk analysis and Kaplan-Meier survival analysis were computed for each subgroup at 90 days since the indexed event. Results Following PSM, a total of 39,770 patients were included and 14,302 were in the ACS group and 24,162 in the non-ACS group. DOAC treatment exhibited favourable outcomes for stroke, bleeding, and systemic embolism (p<0.05) compared to VKA in the overall cohort (Table 1). In the ACS group, DOAC was linked to a reduced risk of stroke and systemic embolism (p<0.05) but not bleeding (p=0.066). In the non-ACS group, DOAC was associated with a decreased risk of stroke and bleeding (p<0.05) but not systemic embolism (p=0.113). Across all groups, there were no disparities in overall all causes of mortalities. Conclusion DOACs demonstrated better safety and efficacy outcomes when compared to VKAs in LVT treatment. Interestingly, DOACs utilisation within the ACS context resulted in a diminished risk of embolic complications without the benefit of reduced bleeding risk seen in patients without ACS, suggesting potential implications of triple therapy within first month of ACS treatment, removing the bleeding risk reduction of DOACs. This shows a fundamental difference in LVT between the 2 groups of patients so future studies should aim to differentiate between the 2.

Edoxaban dose, frailty, and outcomes in patients with atrial fibrillation: the ETNA-AF-Europe 4-year follow-up

Abstract Background Frailty is a common reason to choose non-recommended (non-rec) doses of non-vitamin-K-antagonist oral anticoagulants in patients with atrial fibrillation (AF); however, it is not known how this practice affects stroke and bleeding outcomes. Purpose To assess clinical outcomes in frail patients with AF receiving non-rec vs recommended (rec) doses of edoxaban using 4-yr follow-up data from ETNA-AF-Europe. Methods The prospective, observational ETNA-AF-Europe study followed patients with AF receiving edoxaban for up to 4 yrs. In ETNA-AF-Europe, perceived frailty was based on investigators’ own clinical binary judgement in each patient. Objective frailty was determined using a simplified adaptation of the Rockwood’s Frailty Index. For objective frailty, patients with missing index were categorised as non-frail. Patients with perceived or objective frailty were combined for this analysis. Baseline characteristics and hazard ratios (HRs) with 95% confidence intervals (CIs) assessing risk of outcomes in frail patients prescribed non-rec vs rec edoxaban doses (i.e., non-rec 60mg vs rec 30mg and non-rec 30mg vs rec 60mg) are presented. Data were adjusted for age, sex, and derived versions of the CHA2DS2-VASc and HAS-BLED scores. Net clinical benefit was defined as any stroke/systemic embolic event (SEE), transient ischaemic attack, venous thromboembolic event, major bleeding, or cardiovascular death, whichever came first. Results Of 13164 patients, 1786 were frail (13.6%; perceived frailty [n=1410], age [IQR]: 82.0 [78.0-86.0] yrs, women: 57.9%; objective frailty [n=540], age [IQR]: 77.0 [71.0-82.0] yrs, women: 31.9%; both, n=164). Baseline characteristics are reported in Table 1. Risk of all-cause death was higher in frail patients treated with non-rec 30mg vs rec 60mg (HR [95% CI]: 1.44 [1.06,1.96]). The annualised rate [CI] of any stroke/SEE was non-significantly higher (HR [95% CI]:1.60 [0.80,3.20]) with non-rec 30mg (n=169; 2.25 [1.25,4.06]) vs rec 60mg (n=622; 1.54 [1.08,2.20]). There was, however, no association between treatment received and risk (HR [95% CI]) of major bleeding (1.19 [0.58,2.43]) or net clinical benefit (1.26 [0.84,1.87]) (Figure 1). In frail patients who received non-rec 60mg (n=183) vs rec 30mg (n=695), risk of any stroke/SEE (HR [95% CI]) was higher (2.15 [1.03,4.49]), but there were no significant differences in the risk (HR [95% CI]) of major bleeding (1.03 [0.52,2.01]), net clinical benefit (1.15 [0.78,1.71]), or all-cause death (0.79 [0.59,1.05]) (Figure 1). Conclusions In this large European AF registry, the presence of frailty should not drive dosing recommendations for edoxaban. In particular, when compared with the rec 60mg dose, the non-rec 30mg (reduced) dose, was associated with more all-cause death and no benefits on major bleeding.Baseline Characteristics

Gender and racial differences in outcomes among patients with NVAF treated with oral anticoagulants: a real-world evaluation of Medicare beneficiaries

Abstract Introduction Anticoagulation therapies are essential component of disease management for patients with atrial fibrillation (AF). Direct-acting oral anticoagulants (DOACs), such as apixaban, rivaroxaban, and dabigatran have shown greater benefit in reducing stroke/systemic embolism (SE) and bleeding risk compared to warfarin. However, few studies have assessed whether the beneficial effects of DOACs are consistent across gender and race. Purpose To assess the association between apixaban use and the risk of stroke/SE and major bleeding (MB) compared to warfarin, rivaroxaban, and dabigatran; and to determine whether the associations differ by gender and race. Methods Adult patients with AF diagnosis who initiated warfarin or a DOAC between January 1, 2013 and December 31, 2019 were identified using Medicare claims databases. Patients were classified into warfarin, apixaban, dabigatran, or rivaroxaban cohorts based on index prescription. Inverse Probability Treatment Weighting Cox proportional hazard models were used to assess the association between DOAC therapy initiation and risk of stroke/SE and MB, overall and among gender and race. Results Among a total of 1,079,540 included patients, 486,257 (45.04%) were in the apixaban cohort, 46,920 (4.35%) in the dabigatran cohort, 267,991 (24.82%) in the rivaroxaban cohort, and 278,372 (25.79%) in the warfarin cohort. Overall, the risks of stroke/SE and MB were lower for apixaban when compared with warfarin (stroke/SE: HR: 0.69 [95% confidence interval (CI): 0.65-0.74], MB: 0.59 [95% CI: 0.57-0.60]), rivaroxaban (stroke/SE: 0.88 [95% CI: 0.84-0.92], MB: 0.60 [95% CI: 0.58-0.61]) and dabigatran(stroke/SE: 0.88 [95% CI: 0.80-0.95], MB: 0.76 [95% CI: 0.72-0.80]). Among 140,587 females, the risk was lower for apixaban as compared with warfarin (stroke/SE: 0.72 [95% CI: 0.67-0.78], MB: 0.60 [95% CI: 0.58-0.62]) and rivaroxaban (stroke/SE: 0.88 [95% CI: 0.83-0.93], MB: 0.59 [95% CI: 0.57-0.61]), but similar risk of stroke/SE was noted for apixaban compared to dabigatran (stroke/SE: 0.98 [95% CI: 0.86-1.11]). Among 137,785 males, the risk of stroke/SE and MB were lower for apixaban compared with warfarin, rivaroxaban, and dabigatran. Among 16,288 Black patients, the risk was lower for apixaban as compared with warfarin (stroke/SE: 0.72 [95% CI: 0.63-0.83] MB: 0.59 [95% CI: 0.54-0.65]), also lower risk of MB was noted for apixaban as compared with rivaroxaban (MB: 0.56 [95% CI: 0.5-0.62]), but a similar risk of stroke/SE was noted compared to rivaroxaban and dabigatran, and similar risk of MB was noted compared to dabigatran. Among 247,642 White patients, the risk of stroke/SE and MB were lower for apixaban compared with warfarin, rivaroxaban, and dabigatran. All the results along with comparisons are displayed in the accompanying figures. Conclusion Apixaban demonstrated lower risk of stroke/SE and major bleeding when compared to warfarin, rivaroxaban, and dabigatran across most race and gender subgroups.Figure 1_Risk of stroke/SEFigure 2_Risk of Major Bleeding

Implications of renal function on adverse clinical events in patients with atrial fibrillation: a comparative analysis of VKA and NOAC therapy - Insights from the GLORIA-AF Registry Phase III

Abstract Background Renal function, as assessed by creatinine clearance (CrCl), plays a crucial role in determining the efficacy and safety of oral anticoagulant (OAC) therapy in patients with atrial fibrillation (AF). Purpose To investigate the relationships between CrCl and the risk of clinical adverse events in patients with AF receiving OAC therapy, comparing the safety profiles of vitamin K antagonists (VKA) and non-vitamin K antagonist oral anticoagulants (NOACs). Methods Anticoagulated AF patients from the prospective Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry Phase III were studied. CrCl was calculated for renal function, according to Cockcroft-Gault equation. Restricted cubic spline (RCS) were used to explore the nonlinear association between adverse end events and CrCl, comparing VKA and NOAC therapy. Cox regression models were used to analysis the associations between adverse end events and OAC therapy in patients with different CrCl levels, adjusted by clinical features and previous disease. Patients were followed up for the composite outcome (all-cause death, thromboembolism and major bleeding), all-cause death, cardiovascular disease (CVD), major bleeding, myocardial infarction (MI) and stroke. Results In 10,594 AF patients (mean age 70.35 ± 9.92 years; 55% male; 73% on NOAC), RCS analysis revealed decreased risks of all cause death, composite outcomes and CVD with increasing CrCl in patients with CrCl < 80 mL/min. Multivariate Cox models indicated that NOAC therapy associated with lower risk of all cause death (HR 0.68, 95% CI 0.58-0.78), composite outcomes (HR 0.77, 95% CI 0.68-0.86), CVD (HR 0.7, 95% CI 0.56-0.87), major bleeding (HR 0.74, 95% CI 0.61-0.91) in AF patients. For CrCl > 95 mL/min, a lower risk of all cause death (HR 0.56, 95% CI 0.38-0.82), composite outcomes (HR 0.68, 95% CI 0.51-0.91) and major bleeding (HR 0.54, 95% CI 0.35-0.85) were associated with NOAC therapy, vs. VKA. For CrCl < 30 mL/min, a lower risk of all cause death (HR 0.47, 95% CI 0.28-0.81), composite outcomes (HR 0.56, 95% CI 0.35-0.89) and CVD (HR 0.43, 95% CI 0.20-0.90) were related to NOAC therapy. No significant difference in outcomes between VKA and NOAC were found in patients with moderate CrCl. Conclusion Increasing CrCl were associated with decreased risk of adverse clinical events, including all-cause death and CVD in anticoagulated AF patients. For patients with CrCl >= 95 and < 30, NOAC therapy, was associated with lower risks of adverse outcomes.Figure 1Figure 2

Temporal trends and regional differences of initial oral antiarrhythmic drug options in patients with new-onset atrial fibrillation: a report from the GLORIA-AF registry

Abstract Background New-onset atrial fibrillation (AF) is common and antiarrhythmic drugs (AADs) are commonly used for treating such patients. However, whether there are temporal changes and regional differences in the choice of AADs in direct acting non-vitamin K oral anticoagulants (DOACs) era is less studied. Purpose The present study aimed to analyze the temporal trends and regional differences of initial oral AAD options in patients with new-onset AF in the GLORIA-AF registry, based on a proposed modernized classification of AADs in 2018 (Circulation, 2018, PMID: 30354657). AADs involved in the present study included traditional Vaughn-Williams Class I to Class IV AAD, Class IId AAD (digoxin), and Class VII AAD, which acts on the upstream of arrhythmia including angiotensin converting enzyme inhibition, angiotensin receptor blocker, and stains. Methods Temporal changes regarding the AAD use between the two phases of GLORIA-AF and regional differences of AADs choice were investigated. Factors associated with the choice of different AADs were established by multivariate logistic regression. Results Among the 36,617 participants in the GLORIA-AF registry, 33,208 (90.7%) were prescribed with AADs: 74.0% were rate control and 10.2% were rhythm control, and among the prescribed AADs, single and dual AADs were used in 73.3% and 24.9%, respectively. Moreover, 70.5% patients received upstream target modulators (Class VII AAD). Class IIa AADs (beta-blockers) were the most commonly prescribed AAD and slightly increased from Phase II (60.58%) to Phase III (62.91%) while the use of Class IId AAD (e.g. digoxin) decreased regardless of single or combined use. AADs use varied significantly among regions but the temporal trends and regional differences were similar with that of the overall cohort. Age, gender, comorbidities, admission signs, region, and concomitant medications (e.g. anticoagulants) were associated with the choices of different AADs. Conclusions In the DOAC era, new-onset AF patients receiving AAD commonly included upstream therapy. Rate control was still the dominant strategy for patients with new-onset AF but the use of Class IId AAD significantly decreased with the increased use of Class IIa AAD. The choice of AADs demonstrated significant regional differences and concomitant anticoagulants played important roles.Temporal trends in GLORIA-AFComparisons of AADs use in GLORIA-AF

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

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

Cardiovascular risk factors in poly-vascular vs isolated lower extremity peripheral arterial disease. analysis from the SOLACI peripheral registry

Abstract Introduction Atherosclerotic disease in more than one vascular bed (Polyvascular disease), is a strong independent risk factor for ischemic events and has worse clinical outcomes than those with disease in a single territory. Aims The objective of the present interim analysis is to describe the differences in cardiovascular risk factors and clinical presentation between patients with isolated infra-aortic peripheral artery disease (lower limb: "LL-PAD") and patients with Polyvascular Disease ("PD": simultaneuous coexistence of LL-PAD and affection of at least one more vascular bed) from a cohort of patients undergoing LL endovascular procedures in Latinamerica. Methods Our cohort included patients from The SOLACI Peripheral Registry from March 2021 to February 2024 (a prospective, multi-center, observational, and hospital-based registry of patients with LL- PAD, treated with endovascular interventions across 10 Latin American countries, 42 centers). Patients were considered to have PD if besides LL-PAD, they had a documented history of previous myocardial infarction (MI), coronary revascularization, cerebrovascular, aortic, and/or carotid artery disease. Results A total of 1438 patients were included in the analysis. PD was present in 506 patients(35.1%), of which 225(44.5%) had previous MI; 296(58.5%) previous coronary revascularization;265(52.4%) had aortic and / or carotid disease; and 121(23.9%) had cerebrovascular disease. Patients with PD were older than those with LL-PAD(70.5±9.76 vs 68.6±10.7). PD was more prevalent in men(69.6% vs 62.4%), former smokers(48.2% vs 32.8%), hypertension(92.1% vs 80.5%) and patients with dyslipidemia(75.3% vs 64%). The distribution of treated lesions in the PD group was: 15.4% ilio-femoral; 34 % femoropopliteal; 23.3% infrapopliteal; and 24% had multiple peripheral territories affected and treated at the same time-point. In the LL-PAD group, the distribution of treated lesions was: 12.5% ilio-femoral; 28.6% femoropopliteal; 31.5% infrapopliteal; and 24.8% had multiple peripheral territories affected simultaneously and treated during the same procedure. In general, the lesions were shorter in the PD group: ilio-femoral(53.5±29.2 vs 66.7±48.2mm); femoropopliteal(119±73.6 vs 122±81.7mm); and infrapopliteal(129±83.1 vs 147±93.1mm). In the PD group, a higher percentage of patients were treated with statins and antithrombotic agents: statins (87.5% vs 70.8%), aspirin (91.5% vs 81.1%), clopidogrel (60.9% vs 40.1%), and oral anticoagulants (13.8% vs 6.5%). The use of rivaroxaban was similar in both groups (3.4% vs 3.9%). The PD group had higher intrahospital complication rates: intrahospital death (2.2% vs 0.8%), cardiovascular intrahospital death (1.2% vs 0.4%), MI (0.8% vs 0.1%), stroke (0.4% vs 0%) and bleeding (0.8% vs 0.9%). Conclusions Patients with PD represent a very high-risk population. Systematic screening of multiple vascular beds in patients with LL-PAD may be warranted to prevent worse outcomes.

Risk score guided dual antiplatelet therapy duration in patients with acute coronary syndrome: insights from the FORCE-ACS registry

Abstract Background The use of risk scores to guide the duration of dual antiplatelet therapy(DAPT) in patients with acute coronary syndrome(ACS) is recommended in current guidelines, however clinical data on the impact of its prospective use is lacking. Purpose To compare risk-score guided DAPT duration to standard of care in ACS patients. Methods Since 2015, patients with ACS are enrolled in the prospective FORCE-ACS registry. In 2018, we implemented a risk score-guided approach for DAPT duration. In this analysis, we compared patients in which DAPT duration was guided by bleeding and ischemic risk assessment using PRECISE-DAPT-scores and DAPT-scores to a standard treatment group in a 1:4 ratio. In risk score-guided patients, high bleeding risk patients(HBR) were advised short DAPT(≤6 months); patients without HBR or high ischemic risk(HIR) were advised 12 months DAPT; and patients without HBR but with HIR were advised prolonged DAPT(≥30 months). In the standard treatment group DAPT duration was left at the discretion of the treating physician. Exclusion criteria included no DAPT or oral anticoagulation at discharge or implanted bio-vascular stents. Primary outcome was a composite of all-cause mortality, myocardial infarction(MI), stent thrombosis(ST), stroke and Bleeding Academic Research Consortium(BARC) 3 or 5 bleeding; a secondary composite ischemic outcome consisted of cardiovascular mortality, MI, ST and ischemic stroke. Kaplan-Meier plots with log-rank testing and Cox proportional hazard regression after adjustment of potential confounders were performed for the primary outcome. Sensitivity analyses were performed for patients included after implementation of the risk score-guided approach and for censoring events within the first six months. Results Between 2015 and 2020 8,009 patients were enrolled in the FORCE-ACS registry, of which 5,518 patients were included for analysis. The risk-score guided group(n=1,200) more often presented with ST-elevation MI, percutaneous coronary intervention or optimal medical therapy, while standard treatment patients(n=4,318) were older, more often had prior MI, prior revascularization, received coronary artery bypass grafting or conservative management. In the risk-score guided group, 15.7% had HBR, 46.4% were without HBR or HIR, and 37.9% showed HIR without HBR. The primary outcome was 6.3%(n=75) in risk score-guided patients versus 14.8%(n=637) in the standard treatment group (adjusted hazard ratio(HR) 0.47 [95%CI 0.36–0.61], p<0.001). These results remained consistent after sensitivity analyses (fig 1B). Both the composite ischemic outcome(HR 0.54 [95%CI 0.41–0.72] p<0.001) and BARC 3 or 5 bleeding (HR 0.23 [95%CI 0.08-0.63], p=0.004) were significantly lower in risk score-guided patients compared to the standard treatment group. Conclusion In this prospective analysis, risk-score guided DAPT duration showed a significant reduction of both ischemic and bleeding events compared to standard treatment.

Anticoagulation status and left atrial appendage occlusion indications in hospitalized cardiology patients with atrial fibrillation: a Hellenic Cardiorenal Morbidity Snapshot (HECMOS) sub-study

Abstract Background Proper use of oral anticoagulants is crucial in the management of non-valvular atrial fibrillation (NVAF) patients. Left atrial appendage occlusion (LAAC) may be considered for stroke prevention in patients with NVAF and contraindications for long-term anticoagulant treatment. Purpose We aimed to assess the anticoagulation status and LAAC indications in patients with NVAF from HECMOS (Hellenic Cardiorenal Morbidity Snapshot) survey. Methods HECMOS was a nationwide snapshot survey of cardiorenal morbidity in hospitalized cardiology patients. HECMOS used an electronic platform to collect demographic and clinically relevant information from all patients hospitalized on March 3, 2022, in 55 different cardiology departments. In this substudy, we included patients with known AF without mechanical prosthetic valves and moderate to severe mitral valve stenosis. Patients with poor adherence to anticoagulants, high bleeding risk, previous major bleeding, and previous stroke were considered candidates for LAAC. Results Two hundred fifty-six patients (mean age 76.6±11.7, 148 males) were included in our analysis. Most of them (n=159; 62%) suffered from persistent AF. Mean CHA 2 DS 2 - VASc score was 4.28±1.7, while mean HAS-BLED score was 1.47±0.9. Three out of 3 patients with a CHA 2 DS 2 -VASc 0 or 1 (female) received improperly anticoagulants. Sixteen out of 18 patients with a CHA 2 DS 2 -VASc 1 or 2 (female) received anticoagulants. Thirty-three out of 235 patients with a CHA 2 DS 2 -VASc > 1 or 2 (for female) did not receive improperly anticoagulants. Among 221 under anticoagulant therapy, 191 (86.4%) received non-vitamin K antagonist oral anticoagulants (NOACs) and 30 (13.6%) received vitamin K antagonists. Relative indications for LAAC were present in 77 patients with NVAF (53 had only one risk factor, while 22 had two and 2 patients had three concurrent risk factors). In detail, 15 reported poor or no adherence to the anticoagulant therapy, 17 patients had a history of major bleeding, 36 had a prior stroke and 35 had a HAS-BLED score ≥3. No LAAC treatment was recorded. Conclusion Αnticoagulation status was nearly optimal in a high thromboembolic risk population of cardiology patients, mainly treated with NOACs. Three out of ten AF patients should be screened for LAAC.Anticoagulation by thrombotic riskPotential LAAC candidates

Adherence to the Atrial Fibrillation Better Care (ABC) pathway and outcomes in patients with chronic kidney disease: A report from the APHRS-AF registry

Abstract Background The Atrial Fibrillation Better Care (ABC) pathway is based on three pillars: "A" avoid stroke with oral anticoagulation, "B" better symptoms control, and "C" optimization of cardiovascular risk factors and lifestyles. This integrated approach has been associated with improved outcomes in atrial fibrillation (AF) patients, but few data are available in patients with chronic kidney disease (CKD). Purpose To investigate the correlation between chronic kidney disease, adherence to the ABC pathway, and the occurrence of adverse events in patients with AF enrolled in the Asian-Pacific Heart Rhythm Society-AF Registry. Methods Logistic regression was used to investigate factors associated with CKD, warfarin use and rhythm control strategies. Cox regression analysis adjusted for age≥75 years, paroxysmal AF, CHA2DS2VASc≥2, chronic obstructive pulmonary disease, cancer, and ABC adherence was used to calculate Hazard Ratios (HRs) and 95% Confidence Interval (CI) for the risk of primary outcomes in patients with CKD (eGFR <60 ml/min/1.73m2). Sensitivity analyses were performed in moderate (eGFR 59-30) and severe CKD (eGFR<30). Interaction analysis investigated the effect of ABC pathway based on presence or absence of CKD. Primary outcomes were the risks of all-cause death, major cardiovascular events (MACE: Cardiovascular death, acute coronary syndromes, thromboembolic events, and acute heart failure) and major bleeding. Results We included 2 578 AF patients without CKD (age 66.5±11.3 years, 32.5% females) and 1 047 AF patients with CKD (75.3±10.3 years, 40.8% females). Lower ABC pathway full adherence was observed in CKD patients (42.1% vs 29.5%, p<0.001), primarily due to low adherence to "A" and "C" criteria. Logistic regressions confirmed the lower likelihood of anticoagulation (Odds Ratio (OR) 0.61, 95%CI 0.44-0.83), a higher use of warfarin (OR 1.50, 95%CI 1.23-1.83) and lower use of rhythm control strategies (OR 0.79, 95%CI 0.66-0.94) in CKD patients. After one-year follow up, patients with CKD had a higher incidence of all-cause death (1.6% vs 7.2%, p<0.001) and MACE (3.4% vs 8.1%, p,0.001) compared to those without CKD. On Cox multivariable analysis (Figure 1, Panel A-D), CKD and ABC adherence were independently associated with the risk of all-cause death (HR 2.54, 95%CI 1.69-3.80 and HR 0.57, 95%CI 0.35-0.93, respectively) and MACE (HR 1.58, 95%CI 1.14-2.20 and HR 0.66, 95%CI 0.46-0.95, respectively). The risk of primary outcomes was the highest in those with severe CKD. No association was found with the risk of major bleeding. The interaction analysis confirmed that the beneficial effect of ABC pathway adherence on death (p int= 658) and MACE (p int= 0.568) was irrespective of CKD. Conclusion AF patients with CKD have low ABC pathway adherence and high risk of all-cause death and MACE. Efforts to improve the ABC pathway adherence in AF patients with CKD are needed to improve their long-term clinical outcomes.Figure 1.Cox regression analyses