Anticoagulated Atrial Fibrillation Patients Research Articles

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.

Temporary omission of oral anticoagulation in atrial fibrillation patients undergoing percutaneous coronary intervention: rationale and design of the WOEST-3 randomised trial.

The optimal antithrombotic management of atrial fibrillation (AF) patients who require oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) remains unclear. Current guidelines recommend dual antithrombotic therapy (DAT; OAC plus P2Y12 inhibitor - preferably clopidogrel) after a short course of triple antithrombotic therapy (TAT; DAT plus aspirin). Although DAT reduces bleeding risk compared to TAT, this is counterbalanced by an increase in ischaemic events. Aspirin provides early ischaemic benefit, but TAT is associated with an increased haemorrhagic burden; therefore, we propose a 30-day dual antiplatelet therapy (DAPT; aspirin plus P2Y12 inhibitor) strategy post-PCI, temporarily omitting OAC. The study aims to compare bleeding and ischaemic risk between a 30-day DAPT strategy following PCI and a guideline-directed therapy in AF patients requiring OAC. WOEST-3 (ClinicalTrials.gov: NCT04436978) is an investigator-initiated, international, open-label, randomised controlled trial (RCT). AF patients requiring OAC who have undergone successful PCI will be randomised within 72 hours after PCI to guideline-directed therapy (edoxaban plus P2Y12 inhibitor plus limited duration of aspirin) or a 30-day DAPT strategy (P2Y12 inhibitor plus aspirin, immediately discontinuing OAC) followed by DAT (edoxaban plus P2Y12 inhibitor). With a sample size of 2,000 patients, this trial is powered to assess both superiority for major or clinically relevant non-major bleeding and non-inferiority for a composite of all-cause death, myocardial infarction, stroke, systemic embolism or stent thrombosis. In summary, the WOEST-3 trial is the first RCT temporarily omitting OAC in AF patients, comparing a 30-day DAPT strategy with guideline-directed therapy post-PCI to reduce bleeding events without hampering efficacy.

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.

Temporary omission of oral anticoagulation in atrial fibrillation patients undergoing percutaneous coronary intervention: rationale and design of the WOEST-3 randomised trial

Temporary omission of oral anticoagulation in atrial fibrillation patients undergoing percutaneous coronary intervention: rationale and design of the WOEST-3 randomised trial

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

Individual risk prediction of anticoagulation in atrial fibrillation patients with cirrhosis

Abstract Background We aimed to assess absolute risk and benefit from OAC therapies in individual AF patients with liver cirrhosis (LC), and to develop the optimal dose selecting risk calculator for each patient. Methods We derived and validated a prediction model for major bleeding (MB) and stroke/systemic thromboembolism (SSTE) in AF patients with LC from two-center observational cohort (n=420 in derivation cohort, n=180 in validation cohort) with 4 treatment options (standard-, low-dose NOACs, warfarin, and no OACs). Readily available clinical variables were included in machine learning-based ensembled risk calculation models. Results Model calibration and discrimination was adequate with c-statistics of 0.77[0.66-0.87] for MB and 0.74[0.74-0.84] for SSTE. Three-year absolute risk increases (ARIs) for MB with standard-dose NOACs ranged from &amp;lt;10% in 37% of patients to &amp;gt;30% in 18% of patients, with low-dose NOACs ranged from &amp;lt;10% in 47% of patients to &amp;gt;30% in 12% of patients compared without OACs. Three-year absolute risk reductions (ARRs) for SSTE with standard-dose NOACs ranged from &amp;lt;7% in 48% of patients to &amp;gt;15% in 22% of patients, with low-dose NOACs ranged from &amp;lt;7% in 57% of patients to &amp;gt;15% in 17% of patients compared without OACs. The ARI cutoff for MB and ARR cutoff for SSTE with OAC were shown as &amp;gt;2.4%/year and &amp;gt;1.2%/year (c-statistics 0.81[0.78-0.83], 0.75[0.72-0.79]). Conclusions Artificial intelligence combining clinical variables was found to predict individual patient’s bleeding and stroke/systemic embolism risks well and it can also guide each patient’s appropriate OAC dose in AF patients with LC (web-calculator can be accessed as: https://riskcalc.shinyapps.io/AFLC/).

External Validation of HASBLED and ORBIT bleeding risk scores in Wales-AF population

Abstract Background Anticoagulant therapy (AC) is recommended for Atrial Fibrillation (AF) patients when formal assessment of thromboembolic and bleeding risk suggests a net benefit of AC treatment. Recent UK National Institute of Health and Care Excellence guidelines consider that the ORBIT bleeding risk score(1) provides a more accurate assessment of bleeding risk with AC than the HASBLED score(2) and is recommended for routine clinical use in the UK. Purpose To compare the performance of HASBLED and ORBIT scores to predict hospitalisations for bleeding (HB) in a large population of UK patients with AF receiving AC. Methods We conducted a retrospective longitudinal analysis using linked primary and secondary care health records in the All-Wales SAIL databank. Patients with a diagnosis of AF treated with AC were identified between 2012 and 2018. Both HASBLED and ORBIT scores were calculated for each patient annually based on identified comorbidities, demographics and prescription data. All HB were evaluated. Logistic regression models were used to compare sensitivity and specificity of each score for HB prediction. The Area Under Curve for the Receiver operating Characteristic plot (AUC) was generated for each score to illustrate the risk discrimination ability of each prediction schemes. Results A total of 107,137 (45% female, mean age=74) AF patients were evaluated over the study period. The number of anticoagulated AF patients increased from 27,959 in 2012 (49.3% of cohort) to 48,595 in 2018 (66.8%), providing a total of 265,410 patient years of AC therapy for analysis. There were 710 HB (2.5% of AC patients) in 2012 increasing to 1,146 (2.4%) in 2018. The predictive power of HASBLED and ORBIT increased slightly over the period of study: with observed HASBLED AUC of 60.8 and ORBIT AUC of 64.8 in 2018 (Figure 1). Over the period of study, the observed HB rates for AC AF patients with HAS BLED scores of 0-3 and ORBIT scores of 0-5 were similar to those observed in the original studies, but observed HB for patients with higher HASBLED and ORBIT scores were less consistent (Fig. 2) Conclusion Our findings demonstrated that HASBLED and ORBIT were relatively limited in their predictive performance for HB in a large, real-world AC AF population, with ORBIT providing more accurate prediction across the overall risk range. This highlights the need to develop and validate new bleeding risk scores from the wide range of clinical and demographic factors in AF patients to improve effectiveness of risk communication and AC prescribing in AF.Figure 1Figure 2

The Role of Extracellular Matrix and Inflammation in the Stratification of Bleeding and Thrombotic Risk of Atrial Fibrillation on Oral Anticoagulant Therapy: Insights from Strat-Af Study.

In anticoagulated atrial fibrillation (AF) patients, the validity of models recommended for the stratification of the risk ratio between benefits and hemorrhage risk is limited. We hypothesize that both circulating and neuroimaging-based markers might improve the prediction of bleeding and thrombotic risk in anticoagulated AF patients. The Strat-AF study is an observational, prospective, single-center study enrolling 170 patients with AF; recruited patients are evaluated by means of a comprehensive protocol, with clinical, cerebral magnetic resonance imaging and circulating biomarkers assessment. The main outcome is the evaluation of cerebral microangiopathy related to the levels of circulating biomarkers of inflammation and extracellular matrix (ECM) remodeling. At multivariate logistic regression analysis adjusted for age, sex, CHA2DS2-VASc, HAS-BLED and type of anticoagulant, matrix metalloproteinases (MMP)-2 levels were significantly and positively associated with the presence of cerebral microbleeds (CMBs). A significant association between MMP-2, tissue inhibitor of metalloproteinases (TIMP)-1,-2,-4 levels and white matter hyperintensity was also found. Concerning the small vessel disease (SVD) score, MMP-2 and TIMP-1,-2 levels were associated with the presence of two and three or more signs of SVD, whereas TIMP-4 levels were associated with the presence of three signs of SVD with respect to patients with no instrumental signs of SVD. As regarding the presence of enlarged perivascular spaces (EPVS), a significant association was found for high levels of interleukin (IL)-8 and TIMP 1-2-3. These results demonstrate that patients with AF have evidence of impaired ECM degradation, which is an independent risk factor for thrombotic complications of AF patients on oral anticoagulant therapy. The incorporation of these markers in the prognostic schemes might improve their clinical capability in predicting stroke risk and thrombotic complications.

Prescribing patterns of new oral anticoagulants in patients with atrial fibrillation and chronic kidney disease: A narrative review

This study aimed to investigate the prescribing patterns of new oral anticoagulants in atrial fibrillation patients based on creatinine clearance. A thorough analysis of articles published between 2017 and 2021 in databases such as PubMed, Scopus, and Google Scholar was conducted.&#x0D; The review revealed distinctive features in the use of new oral anticoagulants concerning glomerular filtration rate. Apixaban was identified as a judicious choice for individuals with kidney disorders, with approximately 25% of its dose excreted in urine. American guidelines specifically recommend apixaban for those with a creatinine clearance of less than 15 mL/min, while European recommendations contraindicate all new oral anticoagulants for such rates.&#x0D; In instances where the glomerular filtration rate ranges from 15 to 29 mL/min, apixaban or edoxaban may be preferred due to the substantial renal elimination of edoxaban. Reduced dose regimens of rivaroxaban, edoxaban, and apixaban are advised for individuals with chronic kidney disease and a creatinine clearance between 15 and 30 mL/min.&#x0D; Dabigatran, characterized by an 80% renal elimination rate, is recommended for individuals with a creatinine clearance exceeding 30 ml/min according to European guidelines and those with a clearance of at least 15 ml/min according to American guidelines.

Outcomes of Oral Anticoagulation in Atrial Fibrillation Patients With or Without Comorbid Vascular Disease: Insights From the GARFIELD-AF Registry

BackgroundMany patients with atrial fibrillation suffer from comorbid vascular disease. The comparative efficacy and safety of different types of oral anticoagulation (OAC) in this patient group have not been widely studied. MethodsAdults with newly diagnosed atrial fibrillation were recruited into the prospective observational registry, GARFIELD-AF, and followed for 24 months. Associations of vascular disease with clinical outcomes were analyzed using adjusted hazard ratios (HR) obtained via Cox proportional-hazard modeling. Outcomes of OAC vs no OAC, and of non-vitamin K antagonist OAC (NOAC) vs vitamin K antagonist (VKA) treatment, were compared by overlap propensity-weighted Cox proportional-hazard models. ResultsOf 51,574 atrial fibrillation patients, 25.9% had vascular disease. Among eligible atrial fibrillation patients, those with vascular disease received OAC less frequently than those without (63% vs 73%). Over 2-year follow-up, patients with vascular disease showed a higher risk of all-cause mortality (HR 1.30; 95% confidence interval [CI], 1.16-1.47) and cardiovascular mortality (HR 1.59; 95% CI, 1.28-1.97). OAC was associated with a significant decrease in all-cause mortality and non-hemorrhagic stroke, and increased risk of major bleeding in non-vascular disease. In vascular disease, similar but non-significant trends existed for stroke and major bleeding. A significantly lower risk of all-cause mortality (HR 0.74; 95% CI, 0.61-0.90) and major bleeding (HR 0.45; 95% CI, 0.29-0.70) was observed in vascular disease patients treated with NOACs, compared with VKAs. ConclusionsAtrial fibrillation patients with a history of vascular disease have worse long-term outcomes than those without. The association of NOACs vs VKA with clinical outcomes was more evident in atrial fibrillation patients with vascular disease.

Clinical benefits of oral anticoagulants in atrial fibrillation patients with dementia: a systematic review and meta-analysis.

The management of atrial fibrillation (AF) with oral anticoagulants (OAC) is generally recommended to reduce the risk of stroke. However, the decision to prescribe these medications for patients with AF and dementia remains controversial. A systematic review and meta-analysis of retrospective cohort studies were conducted. The search encompassed PubMed, Cochrane Library, Web of Science, and Embase databases from inception until May 1st, 2023, with language limited to English. Eligible studies included comparisons between exposure to OAC vs. non-OAC in the AF population with dementia or cognitive impairment. Studies that compared the effects of direct oral anticoagulants (DOAC) and vitamin-K antagonists were also included. The primary outcome was all-cause mortality, and the secondary outcomes were ischemic stroke and major bleeding. This study was registered with PROSPERO (No. CRD42023420678). A total of five studies (N = 21,962 patients) met the eligibility criteria and were included in this review. The follow-up duration ranged from 1 to 4 years. Meta-analysis demonstrated that OAC treatment was associated with a lower risk of all-cause mortality in AF patients with dementia with a hazard ratio (HR) of 0.79 and a 95% confidence interval (CI) ranging from 0.68 to 0.92, compared to non-OAC treatment. No statistical differences were observed in the risk of major bleeding (HR = 1.12, 95% CI: 0.88-1.42) or ischemic stroke (HR = 0.77, 95% CI: 0.58-1.00). Three studies reported comparisons between DOAC and warfarin; however, pooled analysis was not performed due to heterogeneity. The use of OACs in individuals diagnosed with both AF and dementia holds the potential to reduce all-cause mortality rates, thereby improving the overall clinical prognosis within this specific population. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023420678, PROSPERO identifier, CRD42023420678.

Predictors of intracranial hemorrhage in patients with atrial fibrillation treated with oral anticoagulants: Insights from the GARFIELD-AF and ORBIT-AF registries.

An unmet need exists to reliably predict the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs). An externally validated model improves ICH risk stratification. Independent factors associated with ICH were identified by Cox proportional hazard modeling, using pooled data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) and ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registries. A predictive model was developed and validated by bootstrap sampling and by independent data from the Danish National Patient Register. In the combined training data set, 284 of 53 878 anticoagulated patients had ICH over a 2-year period (0.31 per 100 person-years; 95% confidence interval [CI]: 0.28-0.35). Independent predictors of ICH included: older age, prior stroke or transient ischemic attack, concomitant antiplatelet (AP) use, and moderate-to-severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) were associated with a significantly higher risk of ICH compared with non-VKA oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25-2.08; p = .0002). The ability of the model to discriminate individuals in the training set with and without ICH was fair (optimism-corrected C-statistic: 0.68; 95% CI: 0.65-0.71) and outperformed three previously published methods. Calibration between predicted and observed ICH probabilities was good in both training and validation data sets. Age, prior ischemic events, concomitant AP therapy, and CKD were important risk factors for ICH in anticoagulated AF patients. Moreover, ICH was more frequent in patients receiving VKA compared to NOAC. The new validated model is a step toward mitigating this potentially lethal complication.

Effect of Oral Anticoagulants in Atrial Fibrillation Patients with Polypharmacy: A Meta-analysis.

The aim of the present meta-analysis was to evaluate the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with polypharmacy. Randomized controlled trials or observational studies reporting the data of NOACs versus VKAs among AF patients with polypharmacy were included. The search was performed in the PubMed and Embase databases up to November 2022. A total of 12 studies involving 767,544 AF patients were included. For the primary outcomes, the use of NOACs compared with VKAs was significantly associated with a reduced risk of stroke or systemic embolism in AF patients with moderate polypharmacy (hazard ratio [HR]: 0.77 [95% confidence interval [CI]: 0.69-0.86]) and severe polypharmacy (HR: 0.76 [95% CI: 0.69-0.82]), but there was no significant difference in major bleeding (moderate polypharmacy: HR: 0.87 [95% CI: 0.74-1.01]; severe polypharmacy: HR: 0.91 [95% CI: 0.79-1.06]) between the two groups. In secondary outcomes, there were no differences in the rates of ischemic stroke, all-cause death, and gastrointestinal bleeding between the NOAC- and VKA- users, but NOAC users had a reduced risk of any bleeding compared with VKA- users. Compared with VKAs, the risk of intracranial hemorrhage was reduced in NOAC- users with moderate polypharmacy but not severe polypharmacy. In patients with AF and polypharmacy, NOACs showed advantages over VKAs in stroke or systemic embolism and any bleeding, and were comparable to VKAs for major bleeding, ischemic stroke, all-cause death, intracranial hemorrhage, and gastrointestinal bleeding.