Anticoagulated Atrial Fibrillation Patients Research Articles

Risk of Incident Genitourinary Cancer Following Hematuria in Patients with Atrial Fibrillation Receiving Oral Anticoagulants

BackgroundHematuria is common in patients with atrial fibrillation (AF) on oral anticoagulants (OAC). However, risks of incident genitourinary (GU) malignancy and detailed etiologies of hematuria have not been well studied. ObjectiveWe aimed to investigate the risk of hematuria and underlying GU malignancy in AF patients receiving OACs. MethodsA total of 192,728 AF patients receiving OACs were identified from Taiwan National Health Insurance Research Database. The risk of hematuria was compared between patients receiving warfarin (n = 75,541) and non-vitamin K antagonist OACs ([NOACs], n = 117,187). Among them, 18,509 patients experiencing hematuria without prior history of GU malignancy were defined as the study population. One-year risks of GU cancers were studied and compared between warfarin and NOAC users. ResultsCompared to warfarin, NOACs were associated with a higher risk of mild (2.29%/year vs 1.71%/year, adjusted hazard ratio [aHR] 1.107, p<0.0001) or moderate hematuria (0.84%/year vs 0.62%/year, aHR 1.075, p=0.0189), but a lower risk of severe hematuria (0.15%/year vs 0.17%/year, aHR 0.630, p<0.0001). Within one year after hematuria, 738 (3.99%) patients were diagnosed to have incident GU cancers and the risk was higher among warfarin compared to NOAC users (4.10% vs 3.89%, odds ratio [OR] 1.1169, p=0.041). Age ≥75 years (OR 1.486, p<0.0001), male gender (OR 2.342, p<0.0001) and abnormal renal function (OR 1.319, p=0.0015) were important clinical factors associated with the diagnosis of GU cancer. ConclusionGU malignancy occurs in around 4% of anticoagulated AF patients experiencing hematuria. Comprehensive evaluations of underlying etiologies of hematuria are necessary.

Long-term risks and benefits of oral anticoagulation in atrial fibrillation patients with cancer: A report from the GLORIA-AF registry.

Anticoagulation therapy in patients with atrial fibrillation (AF) and concomitant cancer can be challenging due to the significantly increased risk of both embolism and bleeding. Moreover, the benefits and risks of vitamin K antagonists (VKA, eg. warfarin) versus non-vitamin K antagonist oral anticoagulants (NOACs) in such patients are less well understood. From the prospective, global, multi-centered Global Registry on Long-Term Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), we characterized these patients according to their history of prior cancer when enrolled. All patients received anticoagulant therapy. The primary outcome was the composite of all-cause mortality, stroke, transient ischemic attack, systemic embolism. The secondary endpoints were all-cause mortality, cardiovascular death, stroke, major bleeding and thromboembolism during the 3 years follow-up period. Cox regression analyses were used to calculate the hazard ratio (HR) and confidence interval (CI) following propensity score matching (PSM). Overall, among 16,700 patients enrolled in Phase III in GLORIA-AF, 1725 (10%) patients had concomitant cancer(s) at enrolment. After PSM, the primary outcome occurred in 250 (14.8%) of patients with cancer(s) and 160 (9.3%) without cancer(s) (HR, 1.62 [95% CI, 1.33-1.97], p < .001) during the 3 years follow-up period. The risk of all-cause mortality was significantly higher in patients with cancer(s) versus non- cancer(s) (HR, 1.71 [95% CI, 1.37-2.12], p < .001). In patients with cancer(s), after PSM, the use of NOACs was associated with reduced risk of the primary outcome compared with that of VKA (HR, .69 [95% CI, .49-.99], p = .043), as well as a lower risk of thromboembolism (HR, .49 [95% CI, .24-1.00], p = .051), but the risk of major bleeding was not significantly different (HR, .87 [95% CI, .48-1.56], p = .635). Subgroup analysis in patients with cancers showed a reduced risk of major bleeding with NOACs compared with VKA (HR, .18 [95% CI, .04-.8], p = .024) in patients with coronary artery disease (CAD). For the main cancer subtypes (genitourinary, breast, gastrointestinal, haematological and skin), the trends for the risk of primary outcome were consistently favouring NOACs compared with VKA without any significant interaction among these five cancers. Cancer is a common comorbidity in patients with AF and is associated with increased risk of composite of all-cause mortality and thromboembolism. Compared with VKA, NOACs was associated with a lower risk of composite events and showed an advantage in lower risk of thromboembolism, as well as a reduced risk of major bleeding when CAD was also present.

Clinical outcomes of edoxaban treatment in atrial fibrillation patients with high bleeding risk: insights from the ETNA-AF-China 1-year follow-up

Abstract Background In China and many other countries, anticoagulated atrial fibrillation (AF) patients with high bleeding risk often raises clinical concern; the optimal dose of direct oral anticoagulants (DOACs) preventing stroke/systemic embolic events (SEE) in those population remains unclear. Purpose To assess the effectiveness and safety of edoxaban treatment in Chinese AF patients with high bleeding risk, and to compare 60 mg vs 30 mg dose in this real-world registry. Methods ETNA-AF-China is a prospective, observational study conducted in 89 centres across Chinese Mainland enrolling AF patients receiving edoxaban. This subgroup analysis was based on 1-year follow-up data. Patients were categorized to high bleeding risk group who had a DOAC score ≥6 (age, creatinine clearance, underweight, history of stroke/TIA/SEE, diabetes, hypertension, antiplatelet use, NSAIDs use, history of major/critical bleeding, liver disease) at baseline, or moderate-to-low bleeding risk group meeting criteria of DOAC score &amp;lt;6. The safety, effectiveness, and composite outcomes were reported by comparison between patient subgroups using Cox proportional hazards models. Results Of 4883 patients with 1-year follow-up, 1534 (31.4%, 60 mg: n=518, 30 mg: n=1016) were identified as high bleeding risk and 3349 (68.6%) as moderate-to-low bleeding risk. As expected, patients with high bleeding risk were more often elderly (48.2% ≥80 years), had lower body weight, worse renal function, higher CHA2DS2-VASc score than those with moderate-to-low risk (Figure 1). In both high risk and moderate-to-low risk subgroups, patients receiving 60 mg edoxaban were younger, with better renal function, lower CHA2DS2-VASc score compared with 30 mg. Annualised event rates of major bleeding (HR 2.95, 95%CI 1.62–5.36), all cause death (3.42, 2.29–5.09), CV death (3.27, 1.52–7.04), major adverse cardiac events (MACE, 2.61, 1.69–4.02) and all NCOs were significant higher in patients with high bleeding risk compared with moderate-to-low risk (Figure 2). After multivariable adjustment, edoxaban dose of 60 mg other than 30 mg were associated with significantly lower rates of all cause death (adjusted HR 0.41, 0.18–0.90) and lower trend of NCO3 (0.51, 0.28–0.92) and NCO4 (0.51, 0.30–0.88) by composite of stroke/SEE, major bleeding and death events in high risk subgroup; no significant difference between edoxaban doses and stroke or bleeding outcomes with cumulative low event rates were observed. Conclusion In routine clinical care, AF patients at high bleeding risk faces worse outcomes of death events, MACE, as well as the composite outcomes over moderate-to-low risk patients. Among patients with high bleeding risk, edoxaban use showed effectiveness and safety with overall low incidence, and potential better survival, composite endpoint benefit could be associated with 60mg. Further investigation is ongoing.

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 &amp;lt; 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 &amp;gt; 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 &amp;lt; 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 &amp;gt;= 95 and &amp;lt; 30, NOAC therapy, was associated with lower risks of adverse outcomes.Figure 1Figure 2

Altered fibrin clot properties and elevated von Willebrand Factors level are associated with progression to permanent atrial fibrillation during follow-up: a cohort study

Abstract Introduction Little is known about association of prothrombotic markers and atrial fibrillation (AF) progression to permanent arrythmia (PerAF). Formation of denser and poorly lysable fibrin clots have been observed in AF including patients with sinus rhythm in association with stroke and bleeding risk. We investigated whether altered fibrin clot properties and other prothrombotic state markers may contribute to AF transition to PerAF. Methods In the cohort study, in 226 anticoagulated AF patients (median age 69 years, median CHA2DS2-VASc of 3)with paroxysmal (n=83, 36.7%) or persistent (n=143, 63.3%) arrythmia we assessed at baseline plasma clot permeability (Ks), lysis time (CLT), and fibrinolysis involved proteins, including plasminogen activator inhibitor type 1 (PAI-1) along with von Willebrand factor (vWF) antigen. We recorded patients with PerAF during a median follow-up of 58 months. Results PerAF was documented in 62 (27.4%, 5.7%/year) subjects. These patients were older, with larger prevalence of heart failure (HF), higher body mass index by 9.6%, more often presented persistent AF and had longer history of arrythmia by 60%. We observed by 25.7% longer CLT and similar Ks, compared with the remainders, along with higher levels of vWF by 29% and PAI-1 by 21.3%. By multivariable analysis CLT, vWF and HF were independently associated with PerAF (R2=0.697, P&amp;lt;0.001). A cut-off CLT value of ≥105 min had a sensitivity of 88.7% and specificity of 78.7% in prediction of PerAF (area under curve 0.892, 95% confidence interval 0.848-0.935, P&amp;lt;0.001). Conclusion Impaired global fibrinolysis and elevated vWF levels are independently associated with faster progression to PerAF despite anticoagulation.Figure1

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.

Safety and Effectiveness of Oral Anticoagulants in Atrial Fibrillation: Real-World Insights Using Natural Language Processing and Machine Learning.

Background/Objectives: We assessed the effectiveness and safety of vitamin K antagonists (VKAs) versus direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) using artificial intelligence techniques. Methods: This is a retrospective study in 15 Spanish hospitals (2014-2020), including adult AF patients with no history of anticoagulation, thrombosis events, rheumatic mitral valvular heart disease, mitral valve stenosis, or pregnancy. We employed EHRead® technology based on natural language processing (NLP) and machine learning (ML), along with SNOMED-CT terminology, to extract clinical data from electronic health records (EHRs). Using propensity score matching (PSM), the effectiveness, safety, and hospital mortality of VKAs versus DOACs were analyzed through Kaplan-Meier curves and Cox regression. Results: Out of 138,773,332 EHRs from 4.6 million individuals evaluated, 44,292 patients were included, 79.6% on VKAs and 20.4% on DOACs. Most patients were elderly [VKA 78 (70, 84) and DOAC 75 (66, 83) years], with numerous comorbidities (75.5% and 70.2% hypertension, 47.2% and 39.9% diabetes, and 40.3% and 34.8% heart failure, respectively). Additionally, 60.4% of VKA and 48.7% of DOAC users had a CHA2DS2-VASc Score ≥4. After PSM, 8929 patients per subgroup were selected. DOAC users showed a lower risk of thrombotic events [HR 0.81 (95% CI 0.70-0.94)], minor bleeding [HR 0.89 (95% CI 0.83-0.96)], and mortality [HR 0.80 (95% CI 0.69-0.92)]. Conclusions: Applying NLP and ML, we generated valuable real-world evidence on anticoagulated AF patients in Spain. Even in complex populations, DOACs have demonstrated a better safety and effectiveness profile than VKAs.

USO DE ANTICOAGULANTES EM PACIENTES COM FIBRILAÇÃO ATRIAL: UMA REVISÃO SISTEMÁTICA

Atrial fibrillation (AF) is one of the most prevalent cardiac arrhythmias, associated with a high risk of thromboembolic complications such as stroke. The use of anticoagulants is essential to prevent these events, with warfarin being widely used for many years. However, new oral anticoagulants (NOACs), such as apixaban and rivaroxaban, have emerged as saferand more effective alternatives, especially in vulnerable subgroups like patients with chronickidney disease and the elderly. This study reviews recent literature on the use of anticoagulants in AF patients, comparing NOACs with warfarin in terms of efficacy, safety,and adherence. Nine studies were selected from PubMed and ScienceDirect databases. Theresults indicate that NOACs have a better safety profile concerning hemorrhagic events and are easier to use due to the lack of frequent monitoring requirements. However, warfarin is still widely used, especially in lower-income countries, due to its more accessible cost. It is concluded that while NOACs represent a significant advancement in AF management, their widespread implementation depends on financial accessibility and the individual suitability ofeach patient.

Timing of oral anticoagulation in atrial fibrillation patients after acute ischaemic stroke and outcome after 3 months: results of the multicentre Berlin Atrial Fibrillation Registry

BackgroundOral anticoagulation (OAC) is key in stroke prevention in patients with atrial fibrillation (AF) but there is uncertainty regarding the optimal timing of OAC (re)initiation after stroke, as recent large...

Impact of bridging thrombolysis versus endovascular thrombectomy alone on outcomes in anticoagulated patients with atrial fibrillation and acute ischaemic stroke.

The impact of bridging thrombolysis prior to endovascular thrombectomy (EVT) compared to EVT alone on intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH), and death in anticoagulated atrial fibrillation (AF) patients with acute ischaemic stroke (AIS) is not well defined. A retrospective study was conducted using data from a federated research network (TriNetX) including 114 health care organisations in the United States. Anticoagulated AF patients with AIS who received either bridging thrombolysis (BT) or EVT alone from September 2018 to November 2023 were included. Following propensity score matching, Cox regression analyses examined the risk of ICH, SAH, and death within 30 and 90 days, comparing anticoagulated AF patients receiving BT versus EVT only. A total of 3156 patients with AIS were treated with BT or EVT alone. Following 1:1 propensity score matching, the cohort included 766 patients in each group. ICH occurred within 30 and 90 days in 6.9% and 8.0% in the BT group compared with 7.4% and 7.7% in the EVT-only group (hazard ratios [HR] = 0.92, 95% confidence interval [CI] = 0.63-1.33 and HR = 1.01, 95% CI = 0.71-1.45, respectively). SAH occurred within 30 and 90 days in 4.2% and 4.4% of patients in the BT compared to 3.0% and 3.4% in the EVT-only group (HR = 1.38, 95% CI = 0.81-2.38 and HR = 1.29, 95% CI = 0.77-2.14, respectively). Death occurred within 30 and 90 days in 17.8% and 19.8% of patients in the BT compared to 22.2% and 27.3% in the EVT-only group (HR = 0.77, 95% CI = 0.62-0.97 and HR = 0.65, 95% CI = 0.56-0.86, respectively). In anticoagulated AF patients with AIS, BT was associated with a significantly lower risk of death, with no difference in ICH or SAH risk within 30 and 90 days compared to EVT only.

Comparison of warfarin, rivaroxaban, and dabigatran for effectiveness and safety in atrial fibrillation patients with different CHA2DS2-VASc scores: a retrospective cohort study

BackgroundThis retrospective cohort study aims to compare the effectiveness and safety of warfarin, rivaroxaban, and dabigatran in atrial fibrillation (AF) patients with different CHA2DS2-VASc scores in northern China.MethodsA retrospective cohort study was performed to evaluate anticoagulation in AF patients at the second affiliated hospital of Harbin Medical University from September 2018 to August 2019. Patients included in this study (n = 806) received warfarin (n = 300), or rivaroxaban (n = 203), or dabigatran (n = 303). Baseline characteristics and follow-up data including adherence, bleeding events and ischemic stroke (IS) events were collected.ResultsPatients receiving rivaroxaban (73.9%) or dabigatran (73.6%) showed better adherence than those receiving warfarin (56.7%). Compared with warfarin-treated patients, dabigatran-treated patients had lower incidence of bleeding events (10.9% vs 19.3%, χ2 = 8.385, P = 0.004) and rivaroxaban-treated patients had lower incidence of major adverse cardiovascular events (7.4% vs 13.7%, χ2 = 4.822, P = 0.028). We classified patients into three groups based on CHA2DS2-VASc score (0–1, 2–3, ≥ 4). In dabigatran intervention, incidence of bleeding events was higher in patients with score 0–1 (20.0%) than those with score 2–3 (7.9%, χ2 = 5.772, P = 0.016) or score ≥ 4 (8.6%, χ2 = 4.682, P = 0.030). Patients with score 0–1 in warfarin or rivaroxaban therapy had a similar but not significant increase of bleeding compared with patients with score 2–3 or score ≥ 4, respectively. During the follow-up, 33 of 806 patients experienced IS and more than half (19, 57.6%) were patients with score ≥ 4. Comparing patients with score 0–1 and 2–3, the latter had an significant reduction of IS in patients prescribed warfarin and non-significant reduction in rivaroxaban and dabigatran therapy.ConclusionCompared with warfarin therapy, patients with different CHA2DS2-VASc scores receiving either rivaroxaban or dabigatran were associated with higher persistence. AF patients with score ≥ 4 were more likely to experience IS events while hemorrhagic tendency preferred patients with low score 0–1.

Elevated plasma protein carbonylation increases the risk of ischemic cerebrovascular events in patients with atrial fibrillation: association with a prothrombotic state.

Plasma protein carbonylation that reflects oxidative stress has been demonstrated to be associated with the prothrombotic fibrin clot phenotype. However, the role of protein carbonyls (PC) in predicting ischemic stroke in atrial fibrillation (AF) is largely unknown. This study aimed to investigate whether PC increase the risk of stroke in anticoagulated AF patients during follow-up. In 243 AF patients on anticoagulation (median age 69years; median CHA2DS2-VASc of 4), we measured plasma PC using the assay by Becatti, along with plasma clot permeability (Ks), clot lysis time (CLT), thrombin generation, and fibrinolytic proteins, including plasminogen activator inhibitor type 1 (PAI-1) and thrombin activatable fibrinolysis inhibitor (TAFI). Ischemic stroke, major bleeding, and mortality were recorded during a median follow-up of 53months. Plasma PC levels (median, 3.16 [2.54-3.99] nM/mg protein) at baseline showed positive associations with age (P < 0.001), CHA2DS2-VASc (P = 0.003), and N-terminal B-type natriuretic peptide (P = 0.001), but not with type of AF or comorbidities except for heart failure (P = 0.007). PC levels were correlated with CLT (r = 0.342, P < 0.001), endogenous thrombin potential (r = 0.217, P = 0.001) and weakly with Ks (r = -0.145, P = 0.024), but not with fibrinogen, PAI-1, or TAFI levels. Stroke was recorded in 20 patients (1.9%/year), who had at baseline 36% higher PC levels (P < 0.001). Elevated PC (P = 0.003) at baseline were independently associated with stroke risk. Our findings suggest that in patients with AF enhanced protein carbonylation is associated with increased "residual" risk of stroke despite anticoagulation, which is at least in part due to unfavorably altered fibrin clot phenotype.

Clinical impact of renal function changes in patients with atrial fibrillation receiving anticoagulation with marginal renal function

Abstract Background Renal function changes were frequently observed in patients with marginal renal function. Renal function is one of crucial components to determine the doses and types of oral anticoagulants in atrial fibrillation (AF) patients and also closely associated with the risk of stroke and bleeding. However, the incidence of renal function changes and its impact on the clinical outcomes were not well-elucidated in anticoagulated AF patients. Purpose To evaluate renal function changes during follow-up in anticoagulated AF patients with marginal renal function defined as estimated glomerular filtration rate (eGFR) 45 to &amp;lt;60 ml/min/1.73m2. We also analysed the association between renal function changes and clinical outcomes. Methods Using a Korean nationwide claims database, we included anticoagulated AF patients who underwent a national health examination from January 2014 to December 2018 and also had follow-up examination within 2-year. Patients with eGFR 45 to &amp;lt;60 ml/min/1.73m2 at baseline examination were included. Based on the follow-up eGFR values, patients were categorised into three groups according to the change in renal function: maintained group (maintaining follow-up eGFR ranges from eGFR 45 to &amp;lt;60 ml/min/1.73m2), improved group (eGFR &amp;gt;60 ml/min/1.73m2), and aggravated group (eGFR &amp;lt;45 ml/min/1.73m2). After follow-up examination, ischemic stroke, major bleeding, end-stage renal disease (ESRD), all-cause death, and the composite of all clinical outcomes were evaluated. Results A total of 5126 patients were included: 42.3 % of patients (n=2170) maintained their renal function at follow-up examination, renal function of 44.4 % of patients (n=2276) were improved, whereas 13.3% of patients (n=680) were aggravated at follow-up examination. The mean eGFR values at baseline of maintained, improved, and aggravated groups were 54.2±4.1, 55.5±3.7, and 52.2±4.3 ml/min/1.73m2, respectively (p&amp;lt;0.001). The aggravated group was older, had higher CHA2DS2-VASc scores, and had more prevalent comorbidities, including hypertension, diabetes, prior myocardial infarction, and heart failure, than other groups. After multivariable adjustment, the aggravated group was associated with significantly higher risks of major bleeding, ESRD, all-cause death, and the composite outcome (HR [95% confidence interval], 1.46 [1.03-2.07], p=0.035; 1.49 [1.24-1.80], p&amp;lt;0.001; 9.29 [4.92-17.6], p&amp;lt;0.001; 1.57 [1.36-1.83], p&amp;lt;0.001, respectively). Conclusion In the anticoagulated AF patients with marginal renal function, a substantial proportion of patients (13%) experienced renal function decline below eGFR 45 ml/min/1.73m2 within 2-year. Renal function decline was associated with higher risks of major bleeding, ESRD, all-cause death and the composite outcome than those maintained their baseline renal function. Performing regular check-ups of renal function and protecting renal function should be emphasised in anticoagulated patients with AF and marginal renal function.

Machine learning approach for prediction of outcomes in anticoagulated patients with atrial fibrillation

Abstract Background Despite the availability of different risk scores, the accuracy of actual prediction tools for outcomes in patients with atrial fibrillation (AF) remains modest [1]. Although Machine Learning (ML) has been used to predict outcomes in the AF population, evidences about outcome prediction in a population entirely on oral anticoagulation is lacking. The aim of this study is to use ML to predict outcomes in anticoagulated patients with atrial fibrillation, processing data from the Italian AF START-2 Register. Methods and aims Different ML models were applied to predict all-cause death, cardiovascular (CV) death, major bleeding and stroke in anticoagulated patients with nonvalvular AF. Overall population, Vitamin K Antagonists (VKA) and Direct Oral Anticoagulants (DOACs) populations were considered for the analyses. Results 11078 AF patients (male n=6029, 54.3%) were enrolled with a median follow-up period of 1.5 years [IQR 1.0-2.6]. Patients on VKA were 5135 (46.4%), while 5943 (53.6%) were on DOACs. During the follow-up, 785 patients died, of which 169 (21.6%) due to CV causes; 240 major bleeding events were recorded, and 50 strokes occurred. Using Multi-Gate Mixture of Experts (MmoE), a cross-validated AUC of 0.779 ± 0.016 and 0.745 ± 0.022 were obtained, respectively, for the prediction of all-cause death and CV death in the overall population. The best ML model outperformed CHA2DSVA2SC and HAS-BLED for all-cause death prediction (p&amp;lt;0.001 for both). When compared to HAS-BLED, Gradient Boosting improved major bleeding prediction in DOACs patients compared to HAS-BLED score (0.711 vs. 0.586, p&amp;lt;0.001). Body mass index, age, glomerular filtration rate, platelet count and hemoglobin levels resulted the most important variables for ML prediction. Conclusions In patients with AF, ML models showed good discriminative ability to predict all-cause death, regardless of the type of anticoagulation strategy, and major bleeding on DOAC therapy, outperforming CHA2DS2VASC and the HAS-BLED scores for risk prediction in these populations. Anemia, platelet count, and BMI emerged as new potential risk predictors in anticoagulated AF patients. The applications of ML prediction models in clinical practice could improve the risk assessment and subsequent management of anticoagulated patients with AF.Graphical AbstractFeature importance for Bleeding in DOACs

Inappropriate Underdosing of Direct Oral Anticoagulants in Atrial Fibrillation Patients: Results from the START2-AF Registry.

Background: Direct oral anticoagulants (DOACs) are recommended for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. We aimed to describe the prevalence of inappropriate DOACs dose prescription in the START2-AF Registry, the outcomes according to the appropriateness of the dosage, and the factors associated with inappropriate dose prescription. Methods: Patients' demographics and clinical data were prospectively collected as electronic files in an anonymous form on the website of the START2-Registry; DOACs dosage was determined to be appropriate when prescribed according to the European Heart Rhythm Association Guidelines. Results: We included 5943 NVAF patients on DOACs; 2572 (46.3%) were female patients. The standard dose (SD) was prescribed to 56.9% of patients and the low dose (LD) was prescribed to 43.1% of patients; 38.9% of all NVAF patients received an inappropriate LD DOAC and 0.3% received inappropriate SD. Patients treated with LD DOAC had a significantly higher rate of all bleedings (RR 1.5; 95% CI 1.2-2.0), major bleedings (RR 1.8; 95% CI 1.3-1.7), and mortality (RR 2.8; 95% CI 1.9-4.1) with respect to patients treated with SD DOAC. No difference was found among patients treated with appropriate and inappropriate LD regarding bleeding, thrombotic, and mortality rates. Age, body weight <60 kg, and renal failure were significantly associated with inappropriate LD DOAC prescription. Conclusions: Inappropriate LD DOACs in NVAF patients is not associated with a reduction in bleeding risk, nor with an increased thrombotic risk. Instead, it is associated with higher mortality rate, suggesting that, in clinical practice, underdosing is preferred for patients at particularly high risk for adverse events.

Predictors for Adherence to Recommended Anticoagulation after Stroke Unit Discharge in Patients with Atrial Fibrillation

Introduction: Non-adherence to recommended secondary preventive anticoagulation in stroke patients with atrial fibrillation (AF) is a common phenomenon, although the introduction of direct oral anticoagulants (DOACs) has simplified anticoagulation management for physicians as well as for patients. Methods: We examined the adherence of secondary preventive anticoagulation in AF patients after re-integration in their social environment 6–12 weeks after stroke unit and rehabilitation clinic treatment and analyzed for predictors for adherence and non-adherence. We conducted a telephone survey in consecutive patients treated between January 2013 and December 2021 at our institutional stroke unit with an acute cerebrovascular ischemic event, and we analyzed discharge letters of rehabilitation clinics of those patients not anticoagulated at follow-up. All patients had known or newly diagnosed AF, and in all, we had recommended secondary preventive anticoagulation. Results: Follow-up information about anticoagulant intake could be obtained in 1,348 of 1,685 patients (80.0%) treated within the study period. Anticoagulation rate was 91.5%, with 83.6% of patients receiving DOACs and 7.9% receiving vitamin K antagonists (VKAs). Adherence to recommended anticoagulation was associated with intake of the recommended anticoagulant already at discharge (adjusted odds ratio [OR], 18.357; confidence interval [CI], 9.637–34.969), recommendation of a specific DOAC and dose (in contrast to “DOAC” as drug category) (adjusted OR, 2.971; CI, 1.173–7.255), a lower modified Rankin Scale at discharge (per point; adjusted OR, 0.813; CI, 0.663–0.996), younger age (per year; OR, 0.951; CI, 0.926–0.976), and the absence of peripheral vascular disease (adjusted OR, 0.359; CI, 0.173–0.746). In patients already anticoagulated at discharge, adherence was 98.5%, irrespective of a patient’s age, functional deficit at discharge, and peripheral vascular disease. Avoidable obstacles for non-adherence in patients not on anticoagulants at stroke unit discharge were (1) non-implementation of recommended anticoagulation by rehabilitation physicians predominantly in patients with moderate-severe or severe stroke disability (2.1%), (2) delegation of anticoagulation start from rehabilitation physicians to general practitioners/resident radiologists (1.3%), and (3) rejection of recommended anticoagulation because of patients’ severe stroke disability (0.5%). Non-avoidable obstacles were contraindications to anticoagulation (2.1%) and patients’ refusal (0.7%). Conclusions: Commencing drug administration already during stroke unit hospitalization and providing an explanation for the selection of the recommended anticoagulant in discharge letters ensures high adherence at patients’ re-integration in their social environment after acute stroke treatment. If drug administration cannot be commenced before discharge, education of rehabilitation physicians by stroke physicians and the involvement of stroke physicians into the post-stroke decision process might hinder avoidable obstacles.

Real-World Management Strategies of Anticoagulated Atrial Fibrillation Patients After a Clinically Significant Bleeding Episode

BackgroundSystemic anticoagulation for stroke prevention in patients with atrial fibrillation (AF) carries inherent bleeding risks, and determining whether and when to resume anticoagulation after significant bleeding is a common dilemma. We aimed to describe the clinical characteristics of AF patients discharged after a bleeding event, document real-life thromboembolic prevention strategy (TPS), and analyse their associated clinical outcomes. MethodsWe retrospectively reviewed the charts of anticoagulated AF patients admitted for bleeding from 2017 to 2019. ResultsA total of 140 patients were included, with a mean age of 78.6 years. Four discharge groups were defined: 75 patients (53.5%) had optimal anticoagulation (OA), 37 (26.4%) had a suboptimal antithrombotic regimen (SAR; low-dose direct oral anticoagulants without dose-reduction criteria or antiplatelet therapy), 10 (7.1%) were referred for left atrial appendage occlusion (LAAO), and 18 (12.9%) left without any TPS. All-cause mortality at 2 years was high (28.6%) but not statistically different between groups (P = 0.71). Patients discharged with a TPS (OA/SAR/LAAO referral) were more likely to be readmitted for bleeding at 2 years (34% vs 0%; P = 0.002), and those discharged without a TPS had higher rates of stroke (16.6% vs 1.4%; P = 0.003). SAR yielded readmission rates for bleeding similar to resumption of OA (27% vs 34.7%; P = 0.41) but was associated with high rates of death or readmission at 2 years. ConclusionsThis real-life cohort reveals that clinicians frequently downgrade or discontinue long-term thromboembolic protection after a bleeding event despite current guideline recommendations to the contrary, and downgrading resulted in bleeding risk similar to OA.

Discontinuation of Oral Anticoagulants in Atrial Fibrillation Patients: Impact of Treatment Strategy and on Patients' Health Status.

The discontinuation of oral anticoagulants (OACs) remains as a significant concern in the management of atrial fibrillation (AF). The discontinuation rate may vary depending on management strategy, and physicians may also discontinue OACs due to concerns about patient satisfaction with their care. We aimed to assess the incidence of OAC discontinuation and its relationship to patients' health in an outpatient AF registry. From a multicenter registry for newly recognized AF patients (n = 3313), we extracted 1647 (49.7%) patients with OACs and a CHA2DS2-Vasc score of ≥2. Discontinuation was defined as sustained cessation of OACs within a 1-year follow-up. We examined predictors associated with discontinuation and its relations to health status defined by the AFEQT questionnaire. Of the 1647 patients, 385 (23.6%) discontinued OACs after 1 year, with discontinuation rates varying across treatment strategies (15.3% for catheter ablation, 4.9% for rhythm control with antiarrhythmic drugs, and 3.0% for rate control). Successful rhythm control was associated with discontinuation in the catheter ablation (OR 6.61, 95% CI 3.00-14.6, p < 0.001) and antiarrhythmic drugs (OR 6.47, 95% CI 2.62-15.9, p < 0.001) groups, whereas the incidence of bleeding events within 1 year was associated with discontinuation in the rate control group. One-year AFEQT scores did not significantly differ between patients who discontinued OACs and those who did not in each treatment strategy group. OAC discontinuation was common among AF patients with significant stroke risk but varied depending on the chosen treatment strategy. This study also found no significant association between OAC discontinuation and patients' health status.

Country and health expenditure are major predictors of withholding anticoagulation in atrial fibrillation patients at high risk of stroke

BackgroundGuidelines for patients with atrial fibrillation (AF) at high thromboembolic risk recommend oral anticoagulants (OACs) for preventing stroke and systemic embolism (SE). The reasons for guideline non-adherence are still unclear.AimThe...

Medication intake reminders via a smartphone app improve real-world adherence to oral anticoagulation in atrial fibrillation patients

Abstract Introduction Treatment with oral anticoagulation (OAC) is one of the main pillars in managing atrial fibrillation (AF). Education and intake monitoring are recommended to improve therapy adherence to OAC. Over the past few years, the importance of smart devices has increased, opening up new potential for patient education and better patient follow-up. Purpose We wanted to evaluate the usage of a medication module of an in-house developed application, AF-EduApp, and its effect on patients’ therapy adherence to OAC. Methods The AF-EduApp multicenter study included 152 AF patients. The educational AF-EduApp contains, besides other modules, a medication module with the possibility to add a medication list. Patients also had the possibility to configure pill intake reminders which they could easily tick off. Adherence was calculated as the proportion of days that the medication was correctly taken, as indicated by the patient. This was compared with adherence measured by the Electronic Medication Event Monitoring System (MEMS, Aardex Group, Liège), which formed the primary outcome of this study. The MEMS cap registered the date and time of bottle opening and was used at baseline and after 12 months, each time for a monitoring period of 3 months (M1 respectively M2). Regimen adherence was defined as the proportion of days with the correct number of openings as recorded by MEMS. Results The 152 patients (Age: 68.8 ±6.7 years; Time since AF diagnosis: 5.1 ±6.6 years) used the application on 130.1 ±144.7 days during a mean follow-up of 386.8 ±108.1 days. A total of 137 patients were on OAC, of whom 87 patients set a reminder for the OAC in their medication list. If based on checking off the reminder, patients had a median therapy adherence of only 5.6% (IQR: 0.2-64.3%). This contrasts with a high regimen adherence based on MEMS: in 84 patients who completed both monitoring periods, adherence was 94.5 ±7.0% at M1 and 94.1 ±6.6% at M2 (p=0.266 between M1 and M2). At M1, there was already a trend towards a significant difference in MEMS regimen adherence between patients who did or did not set a reminder (96.3 ±4.8% vs 93.1 ±8.0%, n=84; p=0.067). At M2, patients who set a reminder took their medication significantly better than those who did not (96.2 ±5.3% vs 92.6 ±7.1%; p=0.048) (Fig 1). Conclusion The medication module was used by most of the patients, and 63.5% installed an intake reminder for at least their OAC therapy. However, checking off reminders is rarely done and cannot be used to judge adherence. On the other hand, patients who installed a reminder had a significantly higher real-world regimen adherence for OAC compared to patients who did not set a reminder. Medication intake reminders can contribute to improving adherence to OAC therapy.MEMS based real-world regimen adherence