Anticoagulated Atrial Fibrillation Patients Research Articles

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 <10% in 37% of patients to >30% in 18% of patients, with low-dose NOACs ranged from <10% in 47% of patients to >30% in 12% of patients compared without OACs. Three-year absolute risk reductions (ARRs) for SSTE with standard-dose NOACs ranged from <7% in 48% of patients to >15% in 22% of patients, with low-dose NOACs ranged from <7% in 57% of patients to >15% in 17% of patients compared without OACs. The ARI cutoff for MB and ARR cutoff for SSTE with OAC were shown as >2.4%/year and >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.
 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.
 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.
 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.

Estimating the impact of implementing an integrated care management approach with Atrial fibrillation Better Care (ABC) pathway for patients with atrial fibrillation in England from 2020 to 2040.

Stroke prevention is central to the management of atrial fibrillation (AF), but there remains a residual risk of adverse outcomes in anticoagulated AF patients. Hence, current guidelines have proposed a more holistic or integrated approach to AF management, based on the Atrial fibrillation Better Care (ABC) pathway, as follows: (A) avoid stroke with anticoagulation; (B) better symptom control with patient-centred symptom directed decisions on rate or rhythm control; and (C) cardiovascular and comorbidity management, including lifestyle factors. There has been no formal healthcare cost analysis from the UK National Health Service (NHS) perspective of ABC pathway implementation to optimize the management of AF. Our aim was to estimate the number of patients with AF in the UK each year up to 2040, their morbidity and mortality, and the associated healthcare costs, and secondly, to estimate improvements in morbidity and mortality of implementing an ABC pathway, and the impact on costs. In 2020, there were an estimated 1 463 538 AF patients, resulting in £286million of stroke care and £191million of care related to bleeds annually. By 2030, it is expected that there will be 2 115 332 AF patients, resulting in £666million of stroke healthcare and £444million of healthcare related to bleeds. By 2040, this is expected to rise to 2 856 489 AF patients, with £1096million of stroke healthcare and £731million of healthcare related to bleeds for that year. If in 2040 patients are managed on an ABC pathway, this could prevent between 3724 and 18 622 strokes and between 5378 and 26 890 bleeds, and save between 16 131 and 80 653 lives depending on the proportion of patients managed on the pathway. This would equate to cost reductions of between £143.9million and £719.6million for the year. We estimate that there will be a substantial healthcare burden in the UK NHS associated with AF, from strokes, bleeds, and mortality over the next decades. If patients are managed with a holistic or integrated care approach based on the ABC pathway, this could prevent strokes and bleeds that equate to substantial NHS healthcare cost reductions, and save lives.

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.

Management of anticoagulation in atrial fibrillation patients in Italy: insight from the <i>Atrial Fibrillation-Survey on Anticoagulated Patients Register</i> (AF-START)

The survey on anticoagulated patients register (START-Register) is an independent, prospective, inception-cohort observational study aimed at providing information on patients on vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) in Italy. In this study, we describe the cohort of atrial fibrillation (AF) patients in the START-Register and report outcomes and changes in anticoagulant prescription from 2011 to 2021. The study included 11,078 AF patients, enrolled in 47 Italian centers distributed all over the Country; the median age was 77 years (range 18-99 years); 6029 (54.3%) were men; 5135 (46.4%) were on VKAs, and 5943 (53.6%) were on DOACs. Warfarin was the most prescribed VKA (98.4%), and apixaban was the most prescribed DOAC (31.6%). Among DOAC users, 4022 (67.7%) patients were naive to anticoagulation, and 2562 (43.1%) patients were treated with a reduced dose. DOAC patients were significantly older than VKA patients (median age 79 years vs 76 years respectively, P<0.001), but no gender difference was detected. The mean CHA2DS2VASc score was higher in DOAC users than in VKA users (3.7 vs 3.6; P=0.03). The mean HAS-BLED score was not different between the two groups. During follow-up, 542 bleeding events were recorded [2.44 per 100 patient-years (pt-yrs)]; 240 were major (1.08 per 100 pt-yrs), and 301 were clinically relevant non-major bleedings (1.34 per 100 pt-yrs). 146 thrombotic events were recorded during follow-up (0.66 per 100 pt-yrs). The total mortality rate was 3.5 per 100 pt-yrs; the mortality rate was 4.54 per 100 pt-yrs among patients on VKAs and 2.31 per 100 pt-yrs among patients on DOACs. During the last 10 years, in Italy, AF patient management has changed with the large spread of DOACs all over the Country. DOAC patients are frequently treated with reduced doses and show a lower mortality rate in comparison to patients on VKAs.

Anticoagulant in atrial fibrillation patients with prior intracranial haemorrhage: a meta-analysis

BackgroundThe benefit of resuming anticoagulation in atrial fibrillation (AF) patients with prior intracranial haemorrhage (ICH) and which anticoagulant to choose are controversial.Summary of reviewPubMed, Embase, Web of Science and the...

Outcomes associated with sodium glucose co-transporter 2 inhibitors in anticoagulated atrial fibrillation patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Sodium glucose co-transporter 2 inhibitors (SGLT2i) have been associated with favourable outcomes in patients with heart failure. Studies also indicate a reduced risk of atrial fibrillation (AF). Purpose We performed an exploratory analysis to evaluate the impact of SGLT2 inhibitors in anticoagulated patients with AF. Method All anticoagulated patients with AF and type 2 diabetes between January 2014 and December 2018 were identified from a federated electronic medical record database (TriNetX), and followed up for 3 years. A 1:1 propensity score matched (PSM) analysis was performed to balance the SGLT-2i and non-SGLT-2i cohorts. The primary outcome was ischaemic stroke/ transient ischaemic attack (TIA), bleeding events, hospitalisation for AF and composite of cardioversion and ablations. Secondary outcomes included all-cause mortality, haemorrhagic stroke, ventricular arrhythmias, cardiac arrest, incident heart failure and composite of arterial and venous thrombotic events. Results A total of 236,493 and 20,841 were identified from the non-SGLT2 and SGLT2 inhibitor groups respectively. After PSM, each group had 17,968 patients. In anticoagulated AF patients, SGLT2 inhibitor use was associated with a significantly lower risk of ischaemic stroke/ TIA, hazard ratio (HR) 0.759 (95% CI 0.719-0.802), bleeding HR 0.657 (95% CI 0.619-0.697), hospitalisation for AF HR 0.875 (95% CI 0.855-0.897), and composite of cardioversion/ablations HR 0.705 (95% CI 0.655-0.759). A lower risk of all-cause mortality HR 0.481 (95% CI 0.453-0.510), haemorrhagic stroke HR 0.54 (95% CI 0.454-0.642), ventricular arrhythmias HR 0.766 (95% CI 0.719-0.816), cardiac arrests HR 0.539 (95% CI 0.476-0.611), incident heart failure HR 0.709 (95% CI 0.661-0.760) and composite of arterial and venous thrombotic events HR 0.737 (95% CI 0.712-0.763) were also observed with SGLT2 inhibitor use. Conclusion Our findings suggest that SGLT2i use is associated with a lower risk of AF-related complications such as ischaemic stroke/ TIA, bleeding, ventricular arrhythmias and reduced need for procedures such as cardioversion and ablations. Further studies are required to confirm this association.

Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients without previous oral anticoagulants or stable under warfarin: a nationwide cohort study

Investigations on non-VKA oral anticoagulants (NOACs) for atrial fibrillation (AF) patients without taking any oral anticoagulants (OACs) or staying well on warfarin were limited. We aimed to investigate the associations between stroke prevention strategies and clinical outcomes among AF patients who were previously well without taking any OACs or stayed well on warfarin for years. The retrospective analysis included a total of 54 803 AF patients who did not experience an ischaemic stroke or intra-cranial haemorrhage (ICH) for years after AF was diagnosed. Among these patients, 32 917 patients who did not receive OACs were defined as the 'original non-OAC cohort' (group 1), and 8007 patients who continuously received warfarin were defined as the 'original warfarin cohort' (group 2). In group 1, compared to non-OAC, warfarin showed no significant difference in ischaemic stroke (aHR 0.979, 95%CI 0.863-1.110, P = 0.137) while those initiated NOACs were associated with lower risk (aHR 0.867, 95%CI 0.786-0.956, P = 0.043). When compared to warfarin, the composite of 'ischaemic stroke or ICH' and 'ischaemic stroke or major bleeding' was significantly lower in the NOAC initiator with an aHR of 0.927 (95%CI 0.865-0.994; P = 0.042) and 0.912 (95%CI 0.837-0.994; P < 0.001), respectively. In group 2, when compared to warfarin, those shifted to NOACs were associated with a lower risk of ischaemic stroke (aHR 0.886, 95%CI 0.790-0.993, P = 0.002) and major bleeding (aHR 0.849, 95%CI 0.756-0.953, P < 0.001). The NOACs should be considered for AF patients who were previously well without taking OACs and those who were free of ischaemic stroke and ICH under warfarin for years.

Cardiovascular outcomes in patients with atrial fibrillation concomitantly treated with antiarrhythmic drugs and non-vitamin k antagonist oral anticoagulants.

Limited data compared antiarrhythmic drugs (AADs) with concomitant non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients, hence the aim of the study. National health insurance database were retrieved during 2012-17 for study. We excluded patients not taking AADs, bradycardia, heart block, heart failure admission, mitral stenosis, prosthetic valve, incomplete demographic data, and follow-up <3 months. Outcomes were compared in Protocol 1, dronedarone vs. non-dronedarone; Protocol 2, dronedarone vs. amiodarone; and Protocol 3, dronedarone vs. propafenone. Outcomes were acute myocardial infarction (AMI), ischaemic stroke/systemic embolism, intracranial haemorrhage (ICH), major bleeding, cardiovascular death, all-cause mortality, and major adverse cardiovascular event (MACE) (including AMI, ischaemic stroke, and cardiovascular death). In Protocol 1, 2298 dronedarone users and 6984 non-dronedarone users (amiodarone = 4844; propafenone = 1914; flecainide = 75; sotalol = 61) were analysed. Dronedarone was associated with lower ICH (HR = 0.61, 95% CI = 0.38-0.99, P = 0.0436), cardiovascular death (HR = 0.24, 95% CI = 0.16-0.37, P < 0.0001), all-cause mortality (HR = 0.33, 95% CI = 0.27-0.42, P < 0.0001), and MACE (HR = 0.56, 95% CI = 0.45-0.70, P < 0.0001). In Protocol 2, 2231 dronedarone users and 6693 amiodarone users were analysed. Dronedarone was associated with significantly lower ICH (HR = 0.53, 95%=CI 0.33-0.84, P = 0.0078), cardiovascular death (HR = 0.20, 95% CI = 0.13-0.31, P < 0.0001), all-cause mortality (HR 0.27, 95% CI 0.22-0.34, P < 0.0001), and MACE (HR = 0.53, 95% CI = 0.43-0.66, P < 0.0001), compared with amiodarone. In Protocol 3, 812 dronedarone users and 2436 propafenone users were analysed. There were no differences between two drugs for primary and secondary outcomes. The use of dronedarone with NOACs was associated with cardiovascular benefits in an Asian population, compared with non-dronedarone AADs and amiodarone.

Impact of frailty on the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation: a nationwide cohort study.

Data on non-vitamin K antagonist oral anticoagulants (NOACs) use in patients with atrial fibrillation (AF) and frailty are scarce. Therefore, the impact of frailty on AF-related outcomes and benefit-risk profiles of NOACs in patients with frailty were investigated. AF patients initiating anticoagulation between 2013 and 2019 were included using Belgian nationwide data. Frailty was assessed with the Claims-based Frailty Indicator. Among 254478 anticoagulated AF patients, 71638 (28.2%) had frailty. Frailty was associated with higher all-cause mortality risks [adjusted hazard ratio (aHR) 1.48, 95% confidence interval (CI) (1.43-1.54)], but not with thromboembolism or bleeding. Among subjects with frailty (78080 person-years of follow-up), NOACs were associated with lower risks of stroke or systemic embolism (stroke/SE) [aHR 0.77, 95%CI (0.70-0.86)], all-cause mortality [aHR 0.88, 95%CI (0.84-0.92)], and intracranial bleeding [aHR 0.78, 95%CI (0.66-0.91)], a similar major bleeding risk [aHR 1.01, 95%CI (0.93-1.09)], and higher gastrointestinal bleeding risk [aHR 1.19, 95%CI (1.06-1.33)] compared with VKAs. Major bleeding risks were lower with apixaban [aHR 0.84, 95%CI (0.76-0.93)], similar with edoxaban [aHR 0.91, 95%CI (0.73-1.14)], and higher with dabigatran [aHR 1.16, 95%CI (1.03-1.30)] and rivaroxaban [aHR 1.11, 95%CI (1.02-1.21)] compared with VKAs. Apixaban was associated with lower major bleeding risks compared with dabigatran [aHR 0.72, 95%CI (0.65-0.80)], rivaroxaban [aHR 0.78, 95%CI (0.72-0.84)] and edoxaban [aHR 0.74, 95%CI (0.65-0.84)], but mortality risk was higher compared with dabigatran and edoxaban. Frailty was an independent risk factor of death. Non-vitamin K antagonist oral anticoagulants had better benefit-risk profiles than VKAs in patients with frailty, especially apixaban, followed by edoxaban.

Efficacy and safety of anticoagulation in atrial fibrillation patients with intracranial hemorrhage: A systematic review and meta-analysis.

Background: The benefits and risks of starting anticoagulation therapy, such as direct oral anticoagulations (DOACs) or warfarin, in atrial fibrillation (AF) patients with a history of intracranial hemorrhage (ICH) remain controversial. We performed a systematic review and meta-analysis to compare the safety and efficacy of starting oral anticoagulation (OAC) and non-oral anticoagulation in these patients. Methods: PubMed, Cochrane Library, and Embase were searched from inception to 01 May 2022 for randomized controlled trials and cohort studies, reporting effectiveness and safety outcomes for anticoagulation therapy in atrial fibrillation patients with intracranial hemorrhage. The Newcastle-Ottawa Scale (NOS) and the Cochrane Collaboration tool were used to evaluate bias risks for all randomized controlled trials (RCTs) and cohort studies. An effects model was applied to calculate adjusted hazard ratios (aHRs) for randomized controlled trials and cohort studies. Results: We analyzed data from two randomized controlled trials (304 patients) and seven Cohort studies (17,477 patients). Compared to non-oral anticoagulation, starting oral anticoagulation therapy reduced the risk of Ischemic Stroke/Systemic Embolism (SE) (aHR: 0.64, 95% CI: 0.55-0.57) and all-cause death (aHR: 0.53, 95% CI: 0.35-0.80) in atrial fibrillation patients and a prior history intracranial hemorrhage. Starting oral anticoagulation therapy did not increase the risk of recurrent intracranial hemorrhage (aHR: 1.07, 95% CI: 0.66-1.74), but increased the risk of major bleeding (aHR: 1.38, 95% CI: 1.00-1.91) than no oral anticoagulation therapy. The DOACs had a lower risk of Ischemic Stroke/SE (aHR: 0.84, 95% CI: 0.70-1.00), recurrent intracranial hemorrhage (aHR: 0.63, 95% CI: 0.49-0.82), and all-cause death (aHR: 0.65, 95% CI: 0.48-0.88) compared to warfarin. According to subgroup analyses, starting oral anticoagulation therapy have a higher risk of recurrent intracranial hemorrhage than non-oral anticoagulation therapy (aHR: 1.57, 95% CI: 1.36-1.81) for Asians. Conclusion: After intracranial hemorrhage in atrial fibrillation patients, restarting or initiating oral anticoagulation therapy decreased the risk of Ischemic Stroke/SE and all-cause death but did not increase the risk for recurrent intracranial hemorrhage. Direct oral anticoagulations have better efficacy and safety than warfarin if oral anticoagulation therapy is started. However, starting oral anticoagulation increases the risk for recurrent intracranial hemorrhage in the Asian region.

S-10-5: OPTIMAL BLOOD PRESSURE AND CARDIOVASCULAR RISK MANAGEMENT IN PATIENTS WITH ATRIAL FIBRILLATION

Hypertension is one of the most common cardiovascular disorders. On a population basis, and high blood pressure (BP) is a major independent risk factor for incident atrial fibrillation (AF) and AF-related complications. Given the high prevalence and both disorders being commonly asymptomatic, opportunistic arrhythmia screening in hypertensive patients is needed. In terms of management, AF could be regarded as a manifestation of hypertensive target organ damage, and optimal BP control is recommended, ideally aiming for a target systolic BP of 120–129mmHg, and diastolic BP of &lt; 80mmHg. There is a close link between hypertension and the risk of stroke in AF, as well as the risk of serious bleeds in anticoagulated AF patients. Also, hypertension burden can be related to other AF-related complications, such as dementia and end renal disease. BP control should also be complementary to lifestyle factors, such as weight reduction, smoking cessation, alcohol reduction and regular exercise, given the close association with incident AF and AF-related complications such as stroke, major adverse cardiac events (MACE) and heart failure. Contemporary management of AF has moved towards a more holistic or integrated care approach to AF management, summed up as the ABC (Atrial fibrillation Better Care) pathway: A/Avoid stroke with Anticoagulation; B/ Better symptom control with patient-centred symptom-directed decisions on rate or rhythm control; and C/Cardiovascular risk and comorbidity management, including lifestyle changes. Adherence to the ABC pathway is associated with a profound reduction in death, hospitalisation, stroke and bleeding in AF patents [Fgure]. In summary, increased awareness, diagnosis and proactive management of detected hypertension is crucial in patients with AF. Optimised blood pressure control is an essential component of such a holistic approach to AF care.

Exploring clinician perspectives on patients with atrial fibrillation who are not prescribed anticoagulation therapy.

To explore themes underlying why anticoagulants are under-prescribed for stroke prevention in atrial fibrillation (AF) patients from the clinician's perspective and characteristics of those patients. Clinicians at the University of Utah Health system were recruited for semi-structured 15-minute interviews. An interview guide focused on anticoagulant prescribing practices for patients with AF. Interviews were transcribed verbatim. Two reviewers independently coded passages corresponding with key themes. Eleven practitioners were interviewed from cardiology, internal medicine, and family practice. Five themes were found: the role of compliance in anticoagulation decision making, the role of pharmacists in supporting clinicians, the use of shared decision making and risk communication, risk of bleeding as the main barrier to taking anticoagulants, and the variety of reasons patients have for not starting or discontinuing anticoagulants. Fear of bleeding was the foremost reason underlying anticoagulant underutilization in patients with AF followed by compliance, and patient worries. Communication between patients and clinicians as well as interdisciplinary teamwork are key to understanding and improving anticoagulant prescribing in AF. Our study was the first to assess the role pharmacists play in prescribing clinician's decisions surrounding anticoagulant use in AF. Pharmacists could play an important collaborative role in SDM.

Abstract 9757: Real World Experience With Anticoagulation in Atrial Fibrillation Patients After Pulmonary Vein Isolation: Associations With Cha 2 Ds 2 -vasc Score, Sex and Maintenance of Sinus Rhythm

Background: Guidelines recommend using the CHA 2 DS 2 -VASc score to determine anticoagulation decisions in atrial fibrillation (AF) patients, including those who undergo pulmonary vein isolation (PVI), however this may not consistently occur in the real-world setting because of other clinical factors. We sought to evaluate the anticoagulation prescription patterns in AF patients 1 year PVI at our institution. Methods: Consecutive AF patients undergoing PVI in our prospective registry during 2014-2018 who were alive at 1-year post-PVI were studied. Anticoagulation prescription rates at this time-point were adjudicated, and correlated to CHA 2 DS 2 -VASc score, sex and maintenance of normal sinus rhythm (NSR) at 1 year. Results: Amongst 4596 patients undergoing PVI, mean age was 64.1±10.0 years, 3308 (71.2%) were male, and based on CHA 2 DS 2 -VASc Score anticoagulation was not indicated, can be considered and indicated in 872 (19.0%), 1183 (25.7%) and 2541 (55.3%) patients respectively. At 1-year after PVI, 3504 (76.2%) patients were on anticoagulation, and 792 (17.2%) had recurrence of AF. Anticoagulation rates by sex, CHA 2 DS 2 -VASc Score category and NSR at 1-year after PVI are illustrated in the Figure. Anticoagulation was continued in over half of AF patients without classic CHA 2 DS 2 -VASc indication particularly in those with AF recurrence and women, while they were mildly under-prescribed in those with indication, especially for those without AF recurrence and men. Conclusion: In a large real world cohort of patients post PVI, anticoagulation is prescribed independent of CHA 2 DS 2 -VASc score, and is affected by both sex and NSR status. Factors determining continuous anticoagulation after successful PVI may include parameters not covered in the CHA 2 DS 2 -VASc score such as return of atrial mechanical function on echocardiography, valve disease or extra-cardiac pathologies.

Bleeding and ischaemic events after first bleed in anticoagulated atrial fibrillation patients: risk and timing.

To determine the risk of subsequent adverse clinical outcomes in anticoagulated patients with atrial fibrillation (AF) who experienced a new bleeding event. Anticoagulated AF patients were followed in two prospective cohort studies. Information on incident bleeding was systematically collected during yearly follow-up visits and events were adjudicated as major bleeding or clinically relevant non-major bleeding (CRNMB) according to the International Society on Thrombosis and Haemostasis guidelines. The primary outcome was a composite of stroke, myocardial infarction (MI), or all-cause death. Time-updated multivariable Cox proportional-hazards models were used to compare outcomes in patients with and without incident bleeding. Median follow-up was 4.08 years [interquartile range (IQR): 2.93-5.98]. Of the 3277 patients included (mean age 72 years, 28.5% women), 646 (19.7%) developed a new bleeding, 297 (9.1%) a major bleeding and 418 (12.8%) a CRNMB. The incidence of the primary outcome was 7.08 and 4.04 per 100 patient-years in patients with and without any bleeding [adjusted hazard ratio (aHR): 1.36, 95% confidence interval (CI): 1.16-1.61; P < 0.001; median time between a new bleeding and a primary outcome 306 days (IQR: 23-832)]. Recurrent bleeding occurred in 126 patients [incidence, 8.65 per 100 patient-years (95% CI: 7.26-10.30)]. In patients with and without a major bleeding, the incidence of the primary outcome was 11.00 and 4.06 per 100 patient-years [aHR: 2.04, 95% CI: 1.69-2.46; P < 0.001; median time to a primary outcome 142 days (IQR: 9-518)], and 59 had recurrent bleeding [11.61 per 100 patient-years (95% CI: 8.99-14.98)]. The incidence of the primary outcome was 5.29 and 4.55 in patients with and without CRNMB [aHR: 0.94, 95% CI: 0.76-1.15; P = 0.53; median time to a composite outcome 505 days (IQR: 153-1079)], and 87 had recurrent bleeding [8.43 per 100 patient-years (95% CI: 6.83-10.40)]. Patients who had their oral anticoagulation (OAC) discontinued after their first bleeding episode had a higher incidence of the primary composite than those who continued OAC (63/89 vs. 159/557 patients; aHR: 4.46, 95% CI: 3.16-6.31; P < 0.001). In anticoagulated AF patients, major bleeding but not CRNMB was associated with a high risk of adverse outcomes, part of which may be explained by OAC discontinuation. Most events occurred late after the bleeding episode, emphasizing the importance of long-term follow-up in these patients.