Atrial Fibrillation In Population Research Articles

Renal Function Protection as an Important Component of a Comprehensive Approach to the Management of Patients with Atrial Fibrillation

The increase in the life expectancy of the population is accompanied by an increase in the prevalence of diseases for which old and senile age are risk factors. Atrial fibrillation (AF) and chronic kidney disease (CKD) are two diseases that can coexist in a patient. The risk of ac thromboembolic and hemorrhagic events in this case increases due to the mutual aggravating influence of these diseases. In addition, these patients have a high incidence of coronary events, and cardiovascular complications are the main cause of death in patients with AF and CKD. Consequently, such patients require an integrated approach to treatment, and their management is a complex clinical task. The direct oral anticoagulant rivaroxaban has been most studied in a population of comorbid AF and CKD patients and has proven a high efficacy and safety profile in these patients in randomized controlled trials. In addition, rivaroxaban has shown a significant reduction in the risk of myocardial infarction in various patients, as well as the possibility of preserving renal function to a greater extent compared with warfarin therapy, and a possible positive effect on reducing the risk of cognitive impairment. A single dosing regimen can improve adherence to treatment, which is one of the key conditions for achieving the above effects. Thus, these factors make it possible to achieve comprehensive protection of comorbid patients with AF and CKD.

Collagen Remodeling and Fatty Acid Regulation Biomarkers in Understanding the Molecular Pathogenesis of Atrial Fibrillation.

Atrial Fibrillation (AF) is the most common cardiac arrythmia in the world. Structural remodeling and fatty acid metabolism dysregulation are believed to play a role in the development of AF. This study explored different biomarkers in the blood of AF patients and a control population to determine if there was a significant difference between the two groups. Plasma samples were collected from 73 patients with confirmed diagnosis of AF from Loyola University Clinic. Control group represented commercially available plasma (n = 50). Sandwich ELISA kits were used to quantify the collagen remodeling proteins and liver type fatty acid binding protein (L-FABP) in the AF population and the control population. Non-esterified fatty acids (NEFAs) were measured using an enzymatic colorimetric kit from Wako Diagnostics. Statistical analyses were performed using GraphPad Prism. All the collagen remodeling biomarkers were significantly higher in AF patients compared to the control group. The fatty acid dysregulation biomarkers were elevated in the AF patients. Spearman correlation analyses yielded significant correlations between L-FABP and TIMP-1 (r = 0.47, P < 0.001), NEFA and TIMP-2 (r = 0.41, P = 0.002), NEFA and ICTP (r = 0.41, P =0 .002), and NEFA and PIIINP (r = 0.61, P < 0.0001). The elevation of collagen remodeling biomarkers suggests an upregulation of these biomarkers and their potential role in AF, which may contribute to atrial fibrosis. L-FABP and NEFAs were elevated in AF patients. The correlations between the collagen remodeling and fatty acid dysregulation biomarkers may be due to their involvement in structural remodeling of the atria.

POSB152 The Health and Budget Impact of Safer Lower Dose Direct Oral Anticoagulant Formulations in Non-Valvular Atrial Fibrillation Patients

To assess the comparative health and budget impact of low-dose dabigatran indicated for non-valvular atrial fibrillation (AF) population versus reduced doses of apixaban and rivaroxaban in the Netherlands.

Standalone epicardial left atrial appendage exclusion for thromboembolism prevention in atrial fibrillation

OBJECTIVESMost strokes associated with atrial fibrillation (AF) result from left atrial appendage thrombi. Oral anticoagulation can reduce stroke risk but is limited by complication risk and non-compliance. Left atrial appendage exclusion (LAAE) is a new surgical option to reduce stroke risk in AF. The study objective was to evaluate the safety and feasibility of standalone thoracoscopic LAAE in high stroke risk AF patients.METHODSThis was a retrospective, multicentre study of high stroke risk AF patients who had oral anticoagulation contraindications and were not candidates for ablation nor other cardiac surgery. Standalone thoracoscopic LAAE was performed using 3 unilateral ports access and epicardial clip. Periprocedural adverse events, long-term observational clinical outcomes and stroke rate were evaluated.RESULTSProcedural success was 99.4% (174/175 patients). Pleural effusion occurred in 4 (2.3%) patients; other periprocedural complications were <1% each. One perioperative haemorrhagic stroke occurred (0.6%). No phrenic nerve palsy or cardiac tamponade occurred. Predicted annual ischaemic stroke rate of 4.8/100 patient-years (based on median CHA2DS2-VASc score of 4.0) was significantly higher than stroke risk observed in follow-up after LAAE. No ischaemic strokes occurred (median follow-up: 12.5 months), resulting in observed rate of 0 (95% CI 0–2.0)/100 patient-years (P < 0.001 versus predicted). Six all-cause (non-device-related) deaths occurred during follow-up.CONCLUSIONSStudy proved that a new surgical option, standalone thoracoscopic LAAE, is feasible and safe. With this method, long-term stroke rate may be reduced compared to predicted for high-risk AF population.

High Incidence of Bleeding Found with Direct Oral Anticoagulant Use in Myeloproliferative Neoplasm Patients

▪ BACKGROUNDPatients with myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are at increased risk of arterial (ATE) and venous thromboembolism (VTE). There are no clear guidelines regarding selection of anticoagulation (AC) in MPN patients. Direct oral anticoagulants (DOACs) are increasingly used in the general population to treat a variety of conditions including VTE, ATE, and atrial fibrillation (AF). Data on the safety and efficacy of DOACs in MPNs limited. We conducted a multi-center, retrospective analysis of DOAC use in MPN patients to characterize real-world practice patterns and evaluate thrombosis and bleeding risks. METHODSWe retrospectively analyzed 133 MPN patients prescribed DOACs across the Massachusetts General Brigham / Dana Farber Harvard Cancer Center system from 1995 to 2020. Patients were identified using ICD-9 and 10 codes in the electronic medical record. Patient and treatment characteristics were described with summary statistics. We calculated cumulative incidence functions of VTE and ATE, and major and clinically relevant non-major bleeding (CRNMB) by ISTH criteria, using death on DOAC as a competing risk. A Gray's test was used to compare cumulative incidence between groups. Analysis of risk factors associated with bleeding/thrombosis was carried out by univariate and multivariable Fine-Gray models. RESULTSBaseline characteristics are displayed in Table 1. Seventy-five (56.4%) MPN patients were prescribed DOAC for VTE, 46 (34.6%) for AF, 7 (5.3%) for stroke, and 5 for other ATE (3.8%). The median age at DOAC initiation was 71; the AF population was significantly older than patients with VTE (75 vs 59, p<0.001). Fifty-seven percent of patients (N = 76) had a diagnosis of PV, with 89% (N = 118) of patients carrying a JAK2 driver mutation. Apixaban was the most commonly prescribed DOAC (N = 83, 62.4%). Nearly half (N = 59, 45%) of patients had a prior VTE/ATE at DOAC initiation, and 23% (N = 31) of patients were switched from warfarin. Among the VTE-treated patients, 43% of events were deep vein thrombosis (N = 39), 31% (N = 28) were pulmonary embolism, 21% (N = 19) were splanchnic vein thrombosis (SVT), and 4.4% (N=4) were other VTE.Table 2 displays practice patterns of DOAC use in MPN patients. The median duration of AC was 37.0 months for all patients, with no difference (p=0.01) between patients treated for AF (42.3 months) and VTE (37.0 months). Twenty-one percent of VTE-treated patients completed a finite course of AC of 6 months median duration. Fifteen percent (N = 11) of VTE-treated and 4.3% (N = 2) of AF patients had reduction to prophylactic dosing. Fifty percent (N = 66) of patients took aspirin and AC concurrently; 83% (N = 110) of patients took cytoreduction with AC.After a median follow-up of 37 months, we found 12 thrombotic (7 arterial, 3 venous, 2 TIPS occlusions) and 28 bleeding (6 major with 4 contributing to patient death, 2 CRNMB) events on DOAC. The estimated 1-year cumulative incidence of thrombosis and bleeding on DOAC was 5.5% (1.5%-9.5%) and 12.3% (6.4%-18.2%), respectively (Figure 1). Thrombosis and bleeding rates were not significantly different between patients treated for VTE versus AF.Prior history of thrombosis and use of dabigatran or edoxaban were significantly associated with increased thrombosis on both univariate and multivariable analysis (p<0.05). Age ≤ 65 also emerged as a risk factor for recurrent thrombosis in multivariate analysis (p=0.04). Use of dabigatran or edoxaban trended toward increased bleeding, but otherwise we found no significant risk factors for bleeding at α=0.05 level, including concomitant aspirin use. DISCUSSIONDOACs are increasingly prescribed in MPN patients for a wide range of indications, with heterogeneity in practice patterns. In our cohort, 1-year thrombosis and bleeding incidence rates on DOAC were 5.5% and 12.3%, respectively. While our 5.5% thrombosis rate is similar to recurrent thrombosis rates reported in MPN patients on DOACs and VKA, our 12.3% bleeding rate appears much higher. This may be related to the complexity of patients seen at our tertiary referral center. The higher-than-expected bleeding rate found in our study indicates the continued need for rigorous evaluation of DOACs in this population, with the gold standard being randomized controlled trials comparing DOAC with warfarin. [Display omitted] DisclosuresNeuberg: Madrigal Pharmaceuticals: Other: Stock ownership; Pharmacyclics: Research Funding. Rosovsky: Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Inari: Consultancy, Membership on an entity's Board of Directors or advisory committees; Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hobbs: Bayer: Research Funding; Merck: Research Funding; AbbVie.: Consultancy; Celgene/Bristol Myers Squibb: Consultancy; Novartis: Consultancy; Incyte Corporation: Research Funding; Constellation Pharmaceuticals: Consultancy, Research Funding. Connors: Abbott: Consultancy; Bristol-Myers Squibb: Honoraria; takeda: Honoraria; Alnylam: Consultancy; Pfizer: Honoraria; CSL Behring: Research Funding.

Advances in Neurocardiology: Focus on Atrial Fibrillation.

Advances in Neurocardiology: Focus on Atrial Fibrillation.

Reasons for non-adherence to thromboprophylaxis prescribing guidelines in atrial fibrillation in Western Australia: A qualitative descriptive study of general practitioners' views

BackgroundA significant proportion of the atrial fibrillation (AF) population attending Australian primary care is not receiving guideline-adherent oral anticoagulant (OAC) treatment. This study aimed to explore reasons for non-adherence to thromboprophylaxis guidelines in AF from the perspectives of general practitioners (GPs) and to map these reasons to the Capability, Opportunity, Motivation-Behaviour (COM-B) model to identify potential opportunities to support practice change. MethodsAn exploratory qualitative descriptive study among GPs practising in Western Australia was conducted using semi-structured interviews, from November 2020 to February 2021. The Framework Method was employed to facilitate thematic analysis, using NVivo software. Interview responses were also mapped to the COM-B model. ResultsNine of the 10 GPs initially consented participated in the semi-structured interview (Male = 56%, median age = 52 years, data saturation reached with 6 participants). Two themes emerged from analysis of the interview transcripts: (1) GPs' decision-making process and (2) Patient refusal to take OACs. The COM-B model mapping identified behavioural factors that could impact adherence: capability (GPs' knowledge and understanding of AF guideline recommendations), opportunity (access to a cardiologist, and patients' refusal to take OACs), and motivation (using formal bleeding risk assessment tools). ConclusionGPs identified various reasons contributing to non-adherence to thromboprophylaxis guidelines in patients with AF. Multifaceted interventions should consider behavioural opportunities to improve adherence, including education and training, electronic decision support, clinical audits by allied health professionals, partnership between general practices and local hospitals, and cardiologist-led interventions to support GPs. Further studies are needed to capture patients' reasons for refusing OACs.

New evidence of direct oral anticoagulation therapy on cardiac valve calcifications, renal preservation and inflammatory modulation

BackgroundRivaroxaban is a direct inhibitor of activated Factor X (FXa), an anti-inflammatory protein exerting a protective effect on the cardiac valve and vascular endothelium. We compare the effect of Warfarin and Rivaroxaban on inflammation biomarkers and their contribution to heart valve calcification progression and renal preservation in a population of atrial fibrillation (AF) patients with chronic kidney disease (CKD) stage 3b – 4. MethodsThis was an observational, multicenter, prospective study enrolling 347 consecutive CKD stage 3b – 4 patients newly diagnosed with AF: 247 were treated with Rivaroxaban and 100 with Warfarin. Every 12 months, we measured creatinine levels and cardiac valve calcification via standard trans-thoracic echocardiogram, while plasma levels of inflammatory mediators were quantified by ELISA at baseline and after 24 months. ResultsOver a follow-up of 24 months, long-term treatment with Rivaroxaban was associated with a significative reduction of cytokines. Patients treated with Rivaroxaban experienced a more frequent stabilization/regression of valve calcifications comparing with patients treated with Warfarin. Rivaroxaban use was related with an improvement in kidney function in 87.4% of patients, while in those treated with Warfarin was reported a worsening of renal clearance in 98% of cases. Patients taking Rivaroxaban experienced lower adverse events (3.2% vs 49%, p-value <0.001). ConclusionsOur findings suggest that Rivaroxaban compared to Warfarin is associated with lower levels of serum markers of inflammation. The inhibition of FXa may exert an anti-inflammatory effect contributing to reduce the risk of cardiac valve calcification progression and worsening of renal function.

Natural language processing tool for automatic diseases and drugs recognition from electronic health records in polish- pilot study

Abstract Background An estimate of 80% of data gathered in electronic health records is unstructured, textual information that cannot be utilized for research purposes until it is manually coded into a database. Manual coding is a both cost and time- consuming process. Natural language processing (NLP) techniques may be utilized for extraction of structured data from text. However, little is known about the accuracy of data obtained through these methods. Purpose To evaluate the possibility of employing NLP techniques in order to obtain data regarding risk factors needed for CHA2DS2VASc scale calculation and detection of antithrombotic medication prescribed in the population of atrial fibrillation (AF) patients of a cardiology ward. Methods An automatic tool for diseases and drugs recognition based on regular expressions rules was designed through cooperation of physicians and IT specialists. Records of 194 AF patients discharged from a cardiology ward were manually reviewed by a physician- annotator as a comparator for the automatic approach. Results Median CHA2DS2VASc score calculated by the automatic was 3 (IQR 2–4) versus 3 points (IQR 2–4) for the manual method (p=0.66). High agreement between CHA2DS2VASc scores calculated by both methods was present (Kendall's W=0.979; p&amp;lt;0.001). In terms of anticoagulant recognition, the automatic tool misqualified the drug prescribed in 4 cases. Conclusion NLP-based techniques are a promising tools for obtaining structured data for research purposes from electronic health records in polish. Tight cooperation of physicians and IT specialists is crucial for establishing accurate recognition patterns. Funding Acknowledgement Type of funding sources: None.

Oral Anticoagulant Use in Patients with Morbid Obesity: A Systematic Review and Meta-Analysis

Obesity is associated with increased risks of atrial fibrillation (AF) and venous thromboembolism (VTE) for which anticoagulation is commonly used. However, data on the efficacy and safety of oral anticoagulants in patients with morbid obesity are limited. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) for AF or VTE in patients with morbid obesity. We included three randomized controlled trials (5 studies) and 18 observational studies in adult patients with a body weight ≥120 kg, body mass index ≥40 kg/m2, or classified as morbid obesity who received DOACs or VKAs for AF or VTE (N = 77,687). The primary efficacy outcome was stroke/systemic embolism or recurrent VTE, and the primary safety outcome was major bleeding. DOACs were associated with a pooled incidence rate of stroke/systemic embolism of 1.16 per 100 person-years, compared to 1.18 with VKAs. The incidence of recurrent VTE on DOACs was 3.83 per 100 person-years, compared to 6.81 on VKAs. In both VTE and AF populations, DOACs were associated with lower risks of major bleeding compared to VKAs. However, all observational studies had moderate to serious risks of bias. Patients with morbid obesity on DOACs had similar risks of stroke/systemic embolism, lower rates of recurrent VTE, and major bleeding events compared to those on VKAs. However, the certainty of evidence was low given that studies were mostly observational with high risk of confounding.

Safety and efficacy of apixaban and rivaroxaban versus warfarin in real-world atrial fibrillation patients are similar to their randomized trials: insights from GARFIELD-AF registry

Abstract Introduction Generalisability of patient selection in the landmark trials for the approval of apixaban (ARISTOTLE) and rivaroxaban (ROCKET AF) for use in non-valvular atrial fibrillation (AF) is limited. Although observational data have confirmed the safety and efficacy of these non-vitamin K oral anticoagulants (NOACs) in unselected AF populations, robust replication of randomized trials in observational studies is warranted. Purpose To investigate the proportion of real-world AF patients who would have been eligible for the landmark trials for ARISTOTLE and ROCKET AF, and to assess reproducibility of these landmark trials in the largest, worldwide, prospective registry of newly diagnosed AF patients. Methods We analysed data from the Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) registry. We assessed the eligibility of AF patients treated with apixaban or vitamin K antagonist (VKA) for ARISTOTLE, and those treated with rivaroxaban or VKA for ROCKET AF, using the selection criteria of the original trials. We replicated the inclusion and exclusion criteria of ARISTOTLE and ROCKET AF by deriving the set of patients eligible for each trial and calculating the adjusted hazard ratios (HRs) for stroke or systemic embolism, major bleeding, and all-cause mortality within 2 years of enrolment, using a propensity score overlap weighted Cox model. We compared the results from observational data with those reported in the original ARISTOTLE and ROCKET AF publications. Results Among all patients enrolled in GARFIELD-AF, 67% were eligible for recruitment in ARISTOTLE and 37% in ROCKET AF. The corresponding proportions among anticoagulated patients were 70% and 39%, respectively. Among patients on apixaban and VKA, 2570/3615 (71%) and 8005/11718 (68%), respectively, were eligible for ARISTOTLE. Of patients using rivaroxaban and VKA, 2005/4914 (41%) and 4368/11721 (37%), respectively, were eligible for ROCKET AF. Annual eligibility rates among real-world NOAC users were stable over time (Figure 1). Registry participants on rivaroxaban or VKA eligible for ROCKET AF had a higher burden of cardiovascular co-morbidity than those on apixaban or VKA eligible for ARISTOTLE. The adjusted HRs in observational data were compatible with results of the original trials in all selected outcomes (Figure 2). Conclusion Representativeness of ARISTOTLE and ROCKET AF for real-world AF populations was limited, with ROCKET AF's criteria being more restrictive. Despite inclusion of only incident AF cases in GARFIELD-AF versus mostly prevalent AF cases in the original trials, the results were similar. Our work indicates that the results from ARISTOTLE and ROCKET AF appear robust and reproducible in real-world patients with newly diagnosed AF. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by an unrestricted research grant from Bayer AG, Berlin, Germany, to TRI, London, UK, which sponsors the GARFIELD-AF registry. This work is supported by KANTOR CHARITABLE FOUNDATION for the Kantor-Kakkar Global Centre for Thrombosis Science.

Dual antithrombotic therapy on early clinical outcomes in patients with atrial fibrillation after percutaneous coronary intervention: a nationwide study in the era of NOAC

Abstract Background/Introduction Recent evidence has confirmed low bleeding risk with double antithrombotic therapy, combining oral anticoagulant (OAC) and single platelet inhibitor, in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). Among the Asian AF population, most of the patients received dual antiplatelet therapy (DAPT) without OACs, even after the introduction of non-vitamin K oral anticoagulants (NOACs). Purpose The current nationwide study assessed 3-month ischemic and bleeding risks of DAPT in comparison to triple antithrombotic therapy among the Korean AF population undergoing PCI. Methods We analyzed the claims records of 11,039 patients (mean age 70 years, 66.3% male, and mean CHA2DS2-VASc score 3.2) between 2013 to 2018. Patients were categorized into triple therapy group with vitamin K antagonists (VKAs-TT), or NOACs (NOACs-TT), and DAPT group according to the antithrombotic therapy after PCI. 3-month risks of ischemic stroke, non-fatal myocardial infarction, any in-hospital death, and major bleeding were compared between groups after baseline adjustment using inverse probability weighting. Results A total of 1,786, 1,997, and 7,256 patients were allocated to the VKAs-TT, NOACs-TT, and DAPT groups. The DAPT group had a higher prevalence of prior MI and coronary revascularization, but had lower thromboembolic and bleeding risks than the triple antithrombotic therapy groups (mean CHA2DS2-VASc score 3.8, 4.1, and 3.5; and mean HAS-BLED score 3.3, 3.4, and 3.1 for VKAs-TT, NOACs-TT, and DAPT groups, respectively). The NOACs-TT group was associated with a lower risk of ischemic stroke (hazard ratio [HR] 0.38, 95% confidence interval [CI] 0.20–0.70) and any in-hospital death (HR 0.70, 95% CI 0.49–0.98) compared with the VKAs-TT group. The DAPT group showed a lower risk of ischemic stroke (HR 0.41, 95% CI 0.27–0.63) and major bleeding (HR 0.55, 95% CI 0.37–0.84) than the VKAs-TT group, especially in patients without prior OAC treatment. The DAPT group showed a comparable ischemic risk against the NOACs-TT group, although the risk of major bleeding was lower in the DAPT group, especially among old age (HR 0.47, 95% CI 0.29–0.78) or OACs-naive patients (HR 0.50, 95% CI 0.29–0.86). Conclusion Among the Asian AF population, using short-term DAPT for 3-month after PCI was associated with a lower risk of bleeding without increasing ischemic risk compared to triple antithrombotic therapy with OAC. This may be a therapeutic option in very high bleeding risk patients who have had complex PCI necessitating focus on DAPT in the initial 3 month period. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This study was supported by grant no 3020200200 from the Seoul National University Hospital Research Fund, by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health &amp; Welfare, Republic of Korea, the Ministry of Food and Drug Safety) (Project Number: 202013B14), and by the Korea National Research Foundation funded by the Ministry of Education, Science and Technology (grant 2020R1F1A106740). Figure 1Figure 2

DOAC versus warfarin in patients with atrial fibrillation and stage IV-V chronic kideny disease including patients on dialysis

Abstract Introduction Patients with atrial fibrillation (AF) and severe chronic kidney disease (CKD) were excluded from most phase III randomized controlled trials (RCTs) of direct oral anticoagulants (DOACs). Evidence of warfarin versus DOAC in the AF population with stage IV-V CKD is therefore limited. Aim To evaluate the effectiveness and safety of DOAC compared with warfarin on this population including dialysis patients. Methods A systematic review and meta-analysis of RCTs and observational studies involving AF patients with stage IV-V CKD treated with warfarin versus DOACs were conducted to evaluate the following outcomes: stroke (ischemic and hemorrhagic) or systemic embolism (SE), all-cause mortality, major bleeding, gastrointestinal (GI) bleeding, and intracranial bleeding. If the heterogeneity between studies was moderate to high calculated as the I2 ≥50%, a meta regression was undertaken between baseline characteristics and the study outcomes. We conducted a literature search using key words related to AF, severe CKD, DOAC and warfarin in PubMed, Embase and Cochrane Library. Results Nine studies were included in the meta-analysis. Compared to warfarin, DOAC was significantly associated with a reduced risk of stroke or systemic embolism (SE) (risk ratio [RR] = 0.69; 95% confidence interval [CI] 0.50–0.95) (Figure 1), intracranial bleeding (RR=0.54; 95% CI 0.35–0.84) and hemorrhagic stroke (RR=0.39; 95% CI 0.16–0.95). There was no significant difference between DOACs and warfarin in the risk of all-cause mortality (RR=0.80; 95% CI 0.57–1.13), major bleeding (RR = 0.70; 95% CI 0.44–1.11) (Figure 2) and GI bleeding (RR=0.76; 95% CI 0.56–1.02). For the outcome stroke or SE, dabigatran (compared with apixaban) significantly eliminated the net effect of DOAC as compared with warfarin (coefficient, 0.8; P=0.003). Regarding major bleeding, rivaroxaban and dabigatran both eliminated the DOAC effect from the meta-analysis as compared to apixaban (P=0.01 &amp; P&amp;lt;0.0001). Dabigatran significantly increased the risk of GI bleeding in comparison to apixaban (coefficient, 0.48; P=0.002) in comparison with the overall similar effect of warfarin in the meta-analysis. Conclusion Among patients with AF and stage IV or V CKD including dialysis patients, DOAC appears to have similar or better effectiveness and safety compared to warfarin. Funding Acknowledgement Type of funding sources: None. Stroke or systemic embolism

Cerebral microbleeds and risk of adverse outcomes in patients with atrial fibrillation: a systematic review and meta-analysis

Abstract Background Long-term anticoagulation in patients with atrial fibrillation (AF) imposes a careful balance between the thromboembolic and hemorrhagic risks. An association between cerebral microbleeds (CMBs) and an increased risk of intracranial hemorrhage (ICH) has already been described; however, conflicting evidence exist on the association with ischemic stroke (IS). Although CMBs are often observed in AF patients, the actual prevalence and the magnitude of the risk of adverse events in patients with CMBs is unclear. Purpose We aimed to estimate the pooled prevalence of CMBs in patients with AF through a systematic review and meta-analysis of the literature. Additionally, we evaluated the risk of ICH and IS according to the presence and burden of CMBs. Methods We perform a systematic search on PubMed and EMBASE from inception to 6th March 2021. We included all studies reporting the prevalence of CMBs, the incidence of ICH and/or IS in AF by presence of CMBs. Pooled prevalence and odds ratios (OR), along with their 95% Confidence Intervals (CI), were computed using random-effect models; we also calculated 95% Prediction Intervals (PI) for each outcome investigated. Additionally, we performed subgroup analyses according to the number and localization of CMBs. Results We retrieved 562 records from the literature search, and 17 studies were finally included. Pooled prevalence of CMBs in AF population was 28.3% (95% CI: 23.8%-33.4%; 95% PI: 12.2%-52.9%, Figure 1). Individuals with CMBs showed a higher risk of both ICH (OR: 3.04, 95% CI: 1.83–5.06) and IS (OR: 1.78, 95% CI: 1.26–2.49). Moreover, patients with more than 5 CMBs, as well as patients with both lobar and mixed CMBs, showed a higher risk of ICH. Conclusions CMBs were found in 28.3% of AF patients, with 95% PIs indicating a potentially higher prevalence. Moreover, CMBs were associated with an increased risk of both ICH and IS, with the effect potentially modulated by their number and localization. CMBs may represent an important and often overlooked risk factor for adverse outcomes in patients with AF. Funding Acknowledgement Type of funding sources: None. Prevalence of CMBs in patients with AF

Use of oral anticoagulation for people with atrial fibrillation post-stroke and associations with recurrent stroke and mortality: a systematic review

Abstract Introduction Current guidelines recommend oral anticoagulation (OAC) to reduce recurrent stroke risk for people with atrial fibrillation (AF); however, outcomes for post-stroke AF patients receiving different types of anticoagulants and optimal timing of anticoagulation in this population remains unclear. Purpose The objective of this systematic review was to summarise observational study data reporting associations between OAC use and risk of mortality, recurrent stroke, and major bleeding within post-stroke AF populations. Methods SCOPUS and OVID Medline databases were searched from inception to 02/11/2020. Studies were limited to publications in the English language post-2012. Observational studies, including case-control and cohort studies were eligible for inclusion. The outcomes examined were all-cause mortality, recurrent stroke and major bleeding. Screening and risk of bias assessment with the Newcastle-Ottawa scale were completed independently by two reviewers. Data extraction was completed by one reviewer and checked by a second. The review was registered on PROSPERO: CRD42020221105. Results Searches identified 3803 studies; 29 studies were eligible for inclusion. Variations between studies including time of OAC initiation, types of OACs used, and length of follow-up meant a meta-analysis was not possible. Four of six studies reporting effect measures of pre-admission or post-stroke OAC use found significant associations with reduced all-cause post-stroke mortality compared to no OAC use (Figure 1A). One study reported lower recurrent stroke rates in patients with no preadmission OAC use compared to preadmission OAC use (2.9% vs. 5.3%; adjusted hazard ratio (aHR) 1.50, 95% confidence interval [CI] 1.02–2.21). A separate study found post-stroke OAC use resulted in a non-significant lower stroke recurrence rate compared to no post-stroke OAC use (3.7% vs. 4.3%; p=0.9). Eight studies examined non-vitamin K antagonist OACs (NOACs) compared to warfarin; five demonstrated significant associations between post-stroke NOAC use and improved outcomes such as post-stroke mortality (Figure 1B). Two studies examined post-stroke OAC therapy timing; both suggested OAC initiation within 4 days of the index event was associated with reduced all-cause mortality (4.5% and 0.6% vs. 8.7% and 3.1%) and recurrent stroke rates (9.4% and 0.8% vs. 10.5% and 1.6%). One study reported non-significant increased major bleeding rates for earlier OAC initiation (2.7% vs. 2.2%; aHR 1.39, 95% CI 0.42–4.60). Overall, the results were consistent with previously published randomised controlled trials. Conclusions Evidence from observational studies suggest that the overall benefit of NOACs in reducing recurrent stroke and post-stroke mortality outweighs the risk of major bleeding in post-stroke AF patients. There is a need for further studies to evaluate the optimum timing of post-stroke anticoagulation initiation and management differences in patients with AF. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The project is supported by the MRes programme in the Institute of Life Course and Medical Sciences at The University of Liverpool. All-Cause Mortality Forest Plots

The impact of subjective vs objective frailty on the effectiveness and safety outcomes in patients from ETNA-AF-Europe registry

Abstract Background Since the risk of atrial fibrillation (AF) increases with ageing, frail patients tend to require long-term anticoagulation. Anticoagulated frail patients may be at increased risk of major bleeding, which becomes more frequent in the elderly. Therefore, oral anticoagulation is often withheld or discontinued in frail, older patients with AF. Purpose To compare patient characteristics and annualised stroke and bleeding event rates in subjectively and objectively frail patients in the overall population included in the ETNA-AF-Europe registry. The 1-year follow-up was based on a snapshot dated 31st October 2019. Methods ETNA-AF-Europe is a multinational, multicentre, post-authorisation, observational study conducted in patients with AF following an edoxaban treatment regimen. Subjective frailty was categorised using a yes/no option, as perceived by physicians as a personal global judgement, without any external interference. Objective frailty was assessed using an adapted Modified Frailty Index; a shortened, simplified version of the Frailty Index. Results ETNA-AF Europe compiled data from 13,092 patients treated with edoxaban once daily, 10.6% and 5.0% were classified as subjectively and objectively frail, respectively (Table 1). Patients classified as objectively frail were younger, had a higher body mass index and higher CHA2DS2-VASc and HAS-BLED scores compared with the subjectively frail patients (Table 1), showing minimal overlap between the two groups. Stroke, major bleeding, all-cause and cardiovascular deaths were higher in patients classified as frail (Figure 1). Annualised event rates were mostly comparable in subjectively and objectively frail patients, except for higher annualised rates of ischaemic stroke, observed in subjectively frail patients, and higher annualised rates of myocardial infarction in objectively frail patients (Figure 1). The adherence to drug recommendations was similar in the subjectively and objectively frail cohorts (78.0% and 79.1%, respectively), but lower than in the general AF population (82.9%) (Table 1). Conclusions The presence of frailty (either subjective or objective) predicts cardiovascular events in anticoagulated patients with AF. A comprehensive assessment of frailty could improve the routine care of patients with AF. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH

Temporal trend of clinical events in patients with atrial fibrillation on edoxaban therapy: results from the non-interventional global ETNA-AF program

Abstract Background Patients with atrial fibrillation (AF) who initiated vitamin K antagonist (VKA) were at highest risk of stroke and bleeding in the first few months of therapy. Understanding of the temporal trend of clinical events in AF patients on non-VKA oral anticoagulant (NOAC) therapy should aid therapeutic decisions. Purpose To evaluate the temporal trend of clinical events in AF patients receiving edoxaban in routine clinical practice in the Global ETNA-AF program. Methods Global ETNA-AF is a multicentre, prospective, noninterventional program evaluating the safety and effectiveness of edoxaban in patients from European and Asian countries. Thromboembolic, bleeding and death events were analysed separately for the 1st and 2nd year of the follow-up period, using a time-to-first-event estimation of cumulative incidence and annual rate via Kaplan-Meier method. Results A total of 27,617 patients were included in this analysis, 48.6% from Europe and 51.4% from Japan, Korea, and Taiwan. Baseline characteristics were consistent with typical AF population in real world studies (Table 1). Approximately 83% of patients received the recommended edoxaban dose. Annualized rates of ischaemic stroke and major bleeding (ISTH) were lower in the 2nd year than in the 1st year: ischaemic stroke 0.59% (95% CI, 0.50–0.70) vs 0.86% (95% CI, 0.75–0.98), p=0.015; major bleeding 0.87% (95% CI, 0.75–1.00) vs 1.15% (95% CI, 1.02–1.29), p=0.036. The trend toward lower rates of ischaemic stroke and major bleeding in the 2nd year was consistent across regions. All-cause mortality increased slightly from the 1st year to the 2nd year, which was not statistically significant and was not driven by cardiovascular (CV) mortality (Table 2). Conclusion In routine clinical practice in the Global ETNA-AF program, major bleeding and ischaemic stroke rates in &amp;gt;27,000 patients on edoxaban therapy declined from 1st year to 2nd year. Further analyses will investigate whether such trend is influenced by selection for healthier patients over time. Longer follow-up is needed to better understand long-term trends. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Table 1. Baseline characteristicsTable 2. Annualised clinical event rates

Contemporary management of patients with atrial fibrillation in the Netherlands and Belgium: areport from the EORP-AF long-term general registry.

BackgroundContemporary data regarding the characteristics, treatment and outcomes of patients with atrial fibrillation (AF) are needed. We aimed to assess these data and guideline adherence in the EURObservational Research Programme on Atrial Fibrillation (EORP-AF) long-term general registry.MethodsWe analysed 967 patients from the EORP-AF long-term general registry included in the Netherlands and Belgium from 2013 to 2016. Baseline and 1‑year follow-up data were gathered.ResultsAt baseline, 887 patients (92%) received anticoagulant treatment. In 88 (10%) of these patients, no indication for chronic anticoagulant treatment was present. A rhythm intervention was performed or planned in 52 of these patients, meaning that the remaining 36 (41%) were anticoagulated without indication. Forty patients were not anticoagulated, even though they had an indication for chronic anticoagulation. Additionally, 63 of the 371 patients (17%) treated with a non-vitamin K antagonist oral anticoagulant (NOAC) were incorrectly dosed. In total, 50 patients (5%) were overtreated and 89 patients (9%) were undertreated. However, the occurrence of major adverse cardiac and cerebrovascular events (MACCE) was still low with 4.2% (37 patients).ConclusionsOvertreatment and undertreatment with anticoagulants are still observable in 14% of this contemporary, West-European AF population. Still, MACCE occurred in only 4% of the patients after 1 year of follow-up.Supplementary InformationThe online version of this article (10.1007/s12471-021-01634-y) contains supplementary material, which is available to authorized users.

Management of cardiovascular complications of bruton tyrosine kinase inhibitors.

Management of cardiovascular complications of bruton tyrosine kinase inhibitors.

Catheter Ablation in Persistent AF, the Evolution towards a More Pragmatic Strategy.

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and represents a heterogeneous disorder with a complex pathological basis. While significant technological advances have taken place over the last decade in the field of catheter ablation of AF, response to ablation varies and long-term success rates in those with persistent AF remain modest. Mechanistic studies have highlighted potentially different sustaining factors for AF in the persistent AF population with substrate-driven focal and re-entrant sources in the body of the atria identified on invasive and non-invasive mapping studies. Translation to clinical practice, however, remains challenging and the application of such mapping techniques to clinical ablation has yet to demonstrate a significant benefit beyond pulmonary vein isolation (PVI) alone in the persistent AF cohort. Recent advances in catheter and ablation technology have centered on improving the durability of ablation lesions at index procedure and although encouraging results have been demonstrated with early studies, large-scale trials are awaited. Further meaningful improvement in clinical outcomes in the persistent AF population requires ongoing advancement in the understanding of AF mechanisms, coupled with continuing progress in catheter technology capable of delivering durable transmural lesions.