Oral Anticoagulant Prescription Research Articles

Clinical characteristics and atrial fibrillation management in hospitalized patients with heart failure with reduced versus preserved ejection fraction

Abstract Funding Acknowledgements None. Background Non-valvular atrial fibrillation (NVAF) and heart failure (HF) frequently coexist. AF management in HF is currently changing with increasing role of rhythm control. Data about clinical characteristics and AF management in hospitalized patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) are lacking. The purpose of the study was to assess the clinical characteristics and AF management in hospitalized patients with NVAF and HFrEF and compare them to those of NVAF and HFpEF. Methods Consecutive NVAF patients hospitalized with HF decompensation between January 2020 and May 2022 were retrospectively evaluated. Patients were divided into two groups: HFrEF and HFpEF (defined as left ventricular ejection fraction > 40%). Clinical characteristics and AF treatment strategy in both groups were studied and compared. Numerical data are expressed as median (interquartile range). P<0.05 was considered significant. Results In a total of 388 AF-HF patients (age 73.5 years [66-82], 59.3% males), 147 (37.9%) had reduced ejection fraction. Patients with HFrEF compared to those with HFpEF were younger (69.3 vs 74.7 years; P < 0.001), more often male and with a higher rate of NYHA classes III-IV (73.9% vs 63.5%; P < 0.05), N-terminal pro-B-type natriuretic peptide level (2658.5 pg/ml vs 1799.1 pg/ml; p<0.001), sum of B-lines by lung ultrasound (35.2 vs 28.9; P<0.05) and prevalence of non-paroxysmal forms of AF (70.4% vs 50.4%; p < 0.05). Patients with HFrEF had a higher burden of coronary artery disease, chronic kidney disease and prior stroke (31.7% vs 19.2%, 83.9% vs 69.0, 18.5% vs 9.7%, respectively; p< 0.05 for all) than HFpEF patients. Patients with HFpEF were more likely than those with HFrEF to have diabetes mellitus (25.9% vs 37.1%; p< 0.05) The subgroup of patients with HFrEF compared to those with HFpEF had higher bleeding risk (HAS-BLED ≥3 in 32.1% vs 20.4%, P<0.05) due to more frequent abnormal renal/liver function, concomitant antithrombotic treatment/alcohol, prior stroke (24.7% vs 10.6%, 28.4% vs 16.8%, 18.5% vs 9.7%, respectively; P<0.05 for all) but lower thromboembolic risk according to CHA 2 DS 2 -VASc (4.0 vs 4.4; p < 0.05). Oral anticoagulants (OAC) were administered in 88% of patients on discharge. Patterns of anticoagulation administration didn’t differ between the two groups. Patients with HFrEF were less likely to receive first-line rhythm control for AF compared to HFpEF patients (36.1% vs 68.1%; p<0.05). Conclusion Hospitalized patients with NVAF and HFrEF compared to those with HFpEF were younger, with greater severity of HF, higher burden of comorbidities and bleeding risk and slightly lower thromboembolic risk. Despite different clinical characteristics, OAC administration patterns were similar and OAC prescription rate was not optimal in both groups. There is a need for improvement of guideline adherence to first-line rhythm control strategy in AF and HFrEF.

Ischemic stroke subtypes: risk factors, treatments, and 1-month prognosis – The Lille, France Stroke Registry

ObjectivesFirst, this registry-based study aimed to comprehensively analyze patients' medical histories and treatments based on ischemic strokes’ etiology. We focused on the management of atrial fibrillation among patients diagnosed with cardioembolic stroke. Then, our objective was to identify prognostic factors associated with 28-day mortality. Materials and methodsAll ischemic strokes occurring in adults between 2014 and 2021 in Lille, France, were categorized using the TOAST classification. Comparative analyses of patients' medical characteristics were conducted across subtypes. Survival rates within 28 days post-stroke were assessed, and factors influencing mortality were identified using a multivariate Cox model. Results1912 ischemic strokes were recorded, due to cardioembolism (36%), large-artery atherosclerosis (9%), small-artery occlusion (9%), other determined causes (6%), or undetermined causes (39%). The median NIHSS score after cardioembolic stroke (6, IQR: 3-13) was twice that after small-artery occlusion (3, IQR: 2-5). Among patients with cardioembolic stroke, 26% were diagnosed post-admission with atrial fibrillation. For the 42% diagnosed pre-admission, only 54% had prior prescriptions for oral anticoagulants. Reperfusion therapies were administered in 21% of cases, with significant variations across subtypes. Mortality rates were higher after cardioembolic strokes (17%) than after small-artery occlusions (3%). Prognostic factors included etiology, high NIHSS score, atrial fibrillation, and previous heparin prescription. ConclusionsWhile atrial fibrillation was underdiagnosed and undertreated, patients with cardioembolic stroke exhibited high severity and elevated mortality rates. Etiology emerged as an independent predictor of early mortality, regardless of NIHSS score upon admission. These findings underscore the importance of targeted prevention to improve patient outcomes after ischemic stroke.

Subclinical atrial fibrillation in embolic stroke of undetermined source: Management and stroke recurrence

Subclinical atrial fibrillation (SAF) represents the most prevalent underlying etiology detected after an embolic stroke of undetermined source (ESUS). Investigating SAF is strongly recommended during the diagnostic work-up. The efficacy of oral anticoagulant (OAC) therapy in reducing the risk of stroke recurrence post-SAF detection remains a conundrum. Thus, our study aimed to analyze the management of secondary antithrombotic prophylaxis and the rate of 12-month stroke recurrence in real-life ESUS patients. We retrospectively analyzed clinical, radiographic, and echocardiographic findings of patients with ESUS who underwent non-implantable 2-week electrocardiogram (ECG) monitoring after discharge. Episodes of SAF of any duration were considered diagnostic. Antithrombotic treatment at hospital discharge and after ECG monitoring, as well as 12-month recurrence, were registered. We compared the rate of stroke recurrence between patients with and without detection of SAF. One hundred and fifty-nine patients (75 females) with a median age of 73.5 (interquartile range [IQR] = 66.75 – 79) years represented the study population. At hospital discharge, 96.9% of patients received antiplatelet therapy as secondary antithrombotic prophylaxis. SAF was detected in 82 patients (51.5%), and OAC was prescribed in 98.6% of them. The median time from stroke onset to OAC prescription was 143 (IQR = 94 – 178) days. Overall, 12-month stroke recurrence occurred in eight patients (5%). The stroke recurrence rate was lower in patients prescribed OAC compared with those not prescribed it, although the difference was not significant (3.7% vs. 6.25%; P = 0.7202). In our study, OACs prescribed post-SAF detection in patients with ESUS reduced, but not significantly, the risk of stroke recurrence. Future research and prospective multicenter studies are warranted.

Evaluating the effect of inequalities in oral anti-coagulant prescribing on outcomes in people with atrial fibrillation

Abstract Aims Whilst anti-coagulation is typically recommended for thromboprophylaxis in atrial fibrillation (AF), it is often never prescribed or prematurely discontinued. The aim of this study was to evaluate the effect of inequalities in anti-coagulant prescribing by assessing stroke/systemic embolism (SSE) and bleeding risk in people with AF who continue anti-coagulation compared with those who stop transiently, permanently, or never start. Methods and results This retrospective cohort study utilized linked Scottish healthcare data to identify adults diagnosed with AF between January 2010 and April 2016, with a CHA2DS2-VASC score of ≥2. They were sub-categorized based on anti-coagulant exposure: never started, continuous, discontinuous, and cessation. Inverse probability of treatment weighting-adjusted Cox regression and competing risk regression was utilized to compare SSE and bleeding risks between cohorts during 5-year follow-up. Of an overall cohort of 47 427 people, 26 277 (55.41%) were never anti-coagulated, 7934 (16.72%) received continuous anti-coagulation, 9107 (19.2%) temporarily discontinued, and 4109 (8.66%) permanently discontinued. Lower socio-economic status, elevated frailty score, and age ≥ 75 were associated with a reduced likelihood of initiation and continuation of anti-coagulation. Stroke/systemic embolism risk was significantly greater in those with discontinuous anti-coagulation, compared with continuous [subhazard ratio (SHR): 2.65; 2.39–2.94]. In the context of a major bleeding event, there was no significant difference in bleeding risk between the cessation and continuous cohorts (SHR 0.94; 0.42–2.14). Conclusion Our data suggest significant inequalities in anti-coagulation prescribing, with substantial opportunity to improve initiation and continuation. Decision-making should be patient-centred and must recognize that discontinuation or cessation is associated with considerable thromboembolic risk not offset by mitigated bleeding risk.

Appropriateness of direct oral anticoagulant prescribing in older subjects with atrial fibrillation discharged from acute medical wards.

Knowledge on the prescriptive practice of direct oral anticoagulants (DOACs) in older subjects with atrial fibrillation (AF) hospitalized in acute medical wards is limited. This study aimed to evaluate the prevalence and appropriateness of DOAC prescriptions in hospitalized older subjects with AF, discharged from acute medical wards. We analysed a cohort of 609 subjects with AF, aged ≥65 years (mean age 85 years) enrolled from 39 geriatric and nephrology wards in Italy. DOAC prescriptive appropriateness was evaluated according to the summary of product characteristics (smPC), 2019 Beers and STOPP criteria, and drug-drug interactions (DDIs). At hospital discharge, 33% of patients with AF were prescribed with DOAC, 26% with vitamin-K antagonist, while 41% did not receive any anticoagulant. Among subjects on DOAC therapy, 31% presented a violation of the smPC criteria (mainly underdosage-17%), while 48% and 18% presented a Beers/STOPP inappropriate prescription, or a DDI, respectively. Older age, lower body mass index (BMI), cancer and higher estimated glomerular filtration rate (eGFR) were independently associated with DOAC underdosage or missed prescription (age: adjusted odds ratio [aOR] 1.06, 95% confidence interval [95% CI] 1.00-1.12 for underdosage; eGFR: aOR 1.04, 95% CI 1.02-1.07 for underdosage; BMI: aOR 0.95, 95% CI 0.91-0.99 for missed prescription; cancer: aOR 1.93, 95% CI 1.19-3.13 for missed prescription). This study showed a suboptimal DOAC prescriptive practice in older in-patients, with frequent missed prescription and DOAC underdosage. Contrary to current recommendations, physicians appear overly concerned by bleeding risk in real-life older and frailer subjects. Strategies should be developed to promote appropriate DOAC prescription in the hospital setting.

Safety of direct-acting oral anticoagulant (DOAC) prescribing: OpenSAFELY-TPP analysis of 20.5 million adults' electronic health records.

During the COVID-19 pandemic many patients were switched from warfarin to DOACs which require the creatinine clearance calculated to ensure the correct dose is prescribed to avoid bleeding or reduced efficacy. To identify the study population proportion prescribed a DOAC. Of these, the proportion with recorded: weight, estimated Glomerular Filtration Rate (eGFR), creatinine, creatinine clearance (CrCl) and atrial fibrillation (AF). To analyse the proportion of patients with recorded AF and CrCl prescribed a recommended DOAC dose. A retrospective cohort study of 20.5 million adult NHS patients' electronic health records (EHRs) in England in the OpenSAFELY-TPP platform (January 2018 to February 2023). Patients on DOACs were analysed for age, sex, recorded weight, eGFR, creatinine, CrCl and AF. Prescribed DOAC doses in patients with recorded AF were compared to recommended doses for recorded CrCl and determined as either recommended, underdose or overdose. In February 2023, weight, eGFR, creatinine, CrCl, AF and, AF and CrCl were recorded in 72.8%; 92.4%; 94.3%; 73.5%; 73.9% of study population respectively. Both AF and CrCl were recorded for 56.7% of patients. Of these, 86.2% received the recommended and 13.8% non-recommended DOAC doses. CrCl is not recorded for a substantial number of patients on DOACs. We recommend that national organisations tasked with safety, collectively update guidance on the appropriate weight to use in the Cockcroft-Gault equation, clarify that CrCl is not equivalent to eGFR and work with GP clinical system suppliers to standardise the calculation of CrCl in the EHR.

Payer approval and rejection of oral anticoagulant prescriptions and prescription abandonment patterns among patients with venous thromboembolism.

Venous thromboembolism (VTE) is a major public health condition that renders patients at risk of recurrent events, which significantly increases their morbidity, mortality, and health care costs. Apart from warfarin, direct oral anticoagulants, such as apixaban, dabigatran, or rivaroxaban, are approved for VTE treatment. Cardiovascular drugs are largely impacted by formulary restrictions; however, the impact on oral anticoagulants (including warfarin and direct oral anticoagulants) in VTE has not been well studied. To describe the extent of payer-rejected claims for oral anticoagulants for VTE and the factors associated with rejected claims. Prescription abandonment of oral anticoagulants and the time to an eventual fill for oral anticoagulant after rejection or abandonment were also evaluated. A retrospective cohort study was conducted among patients with VTE newly prescribed an oral anticoagulant (first claim was the index) between October 2016 and October 2021. Descriptive statistics were used to describe the proportion of patients with paid (ie, filled), rejected, or abandoned index oral anticoagulant prescription and journey to paid prescription among those with initial rejection. Multivariable logistic regression was used to identify factors associated with initial rejection. Among the overall sample (N = 297,312), 74.3% had initial oral anticoagulant prescriptions approved, 9.1% had them rejected, and 16.7% abandoned them. Of the patients with initial rejection, 82.1% eventually filled their oral anticoagulant prescriptions; however, for 14.2% of these patients, the first fill was for an oral anticoagulant other than that initially prescribed. The mean time to a first fill for an oral anticoagulant after an initial rejection was 18.3 days. More than half of the patients with an initial rejected oral anticoagulant claim had at least 1 additional rejection during the follow-up period. Of the patients who abandoned their initial oral anticoagulant prescription, 83.9% filled an oral anticoagulant prescription during follow-up; the mean time to fill for the index oral anticoagulant was 15.6 days. Oral anticoagulant type, Medicare payer coverage, prescribing physician specialty, and VTE diagnosis setting of care were significantly associated with index oral anticoagulant claim rejection (P < 0.05). Rejection and abandonment may delay access to oral anticoagulant treatment. Factors contributing to these scenarios should be understood and addressed for proper VTE management.

Potential of Direct Oral Anticoagulant in Bleeding After Gastric Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis.

An increasing number of patients are undergoing gastric endoscopic submucosal dissection (ESD) with active prescriptions of direct oral anticoagulants (DOACs). Only a few reports have described the effects of DOAC intake on postoperative bleeding. We aimed to investigate the bleeding risk associated with DOACs after gastric ESD. Clinical studies published up to April 2022 showing bleeding rates after gastric ESD in patients taking DOACs were identified using electronic searches. The primary outcome was the rate of bleeding after gastric ESD in patients receiving DOACs compared to those not receiving antithrombotic therapy. In this meta-analysis, odds ratios (ORs) were calculated and pooled using a random effects model. The secondary outcome was the difference in the bleeding rate between patients treated with DOACs and those treated with warfarin and antiplatelet drugs. Seven studies were included in this meta-analysis. The pooled analysis showed that DOACs had a higher bleeding rate than non-thrombotic therapy (17.0% vs. 3.4%; OR 5.72; 95% confidence interval [CI], 4.33-7.54; I2 = 0%). The bleeding risk associated with DOAC administration was similar to that associated with warfarin (17.0% vs. 20.0%; OR 0.83; 95% CI 0.59-1.18; I2 = 0%), whereas it was higher than that associated with antiplatelet administration (16.9% vs. 11.0%; OR 1.63; 95% CI 1.14-2.34; I2 = 8%). This meta-analysis reveals that the bleeding risk of DOACs is higher than that of non-antithrombotics and antiplatelets, whereas it is comparable to that of warfarin. Gastric ESD in patients on anticoagulants requires careful postoperative management.

Assessment and predictors of inappropriate dose of direct oral anticoagulants

Direct-Acting Oral Anticoagulants (DOACs) have revolutionized the management of Atrial Fibrillation (AF) and Venous Thromboembolism (VTE). However, recent audits reveal a significant burden of inappropriate dosages in the prescribing of direct-acting oral anticoagulants. Our aim is to identify the prevalence and predictors of such inappropriate dosing in our patients. This retrospective study was conducted from June 2016 to January 2018. Patients who received dabigatran, rivaroxaban, or apixaban for treatment of venous thromboembolism or atrial fibrillation were included. Appropriateness of direct-acting oral anticoagulants dosing was assessed using US Food and Drug Administration guidelines. Data was analyzed using IBM® SPSS Version 26. 337 patients were included, with a mean age of 62.9±18.7 years. The majority were female (196, 58.3%). Of the patients, 194 (57.6%) received apixaban, 99 (29.4%) received rivaroxaban, and 44 (13.1%) received dabigatran. A total of 242 (71.8%) patients were prescribed direct-acting oral anticoagulants appropriately. Under-dosing and over-dosing were identified in 74 (22%) and 21 (6.2%) patients, respectively. Predictors of inappropriate dosing were age greater than 75 years (OR: 2.76, 95% CI: 1.67-4.56, p&lt;0.001) and creatinine clearance less than 50 ml/minute (OR: 0.38, 95% CI: 0.19-0.74, p: 0.005). Inappropriate dosing was significantly associated with mortality (p=0.010).One-third of our patients received an inappropriate dose of direct-acting oral anticoagulants, mostly from underdosing. Elderly age and low creatinine clearance are significant predictors of inappropriate dose administration.

Survey of Using Oral Anticoagulants in Patient with Non-valvular Atrial Fibrillation.

In Vietnam, there has been no survey conducted on the prescribing and monitoring practices of oral anticoagulants to ensure that patients with atrial fibrillation receive appropriate. Objective: Therefore, we conducted this research to clarify the aforementioned issue in our hospital. We carried out a cross-sectional study by reviewing outpatient electronic medical records at the University Medical Center in Ho Chi Minh City. Our study included 1087 patients aged 18 years or older diagnosed with non-valvular atrial fibrillation (NVAF), who visited the Cardiology clinic between January 1st, 2021, and June 30th, 2021. Among the 1087 patients with non-valvular atrial fibrillation (NVAF), 1036 were eligible for anticoagulant therapy. However, only 847 (81.8%) received prescriptions for either Vitamin K antagonists (VKAs) (n=129, 15.2%) or Non-Vitamin K antagonist oral anticoagulants (NOACs) (n=718, 84.8%). NOAC prescriptions were more commonly found in patients aged 75 or older (adjusted odds ratio [OR]=2), those with health insurance coverage (adjusted OR=2.9), and in individuals with a history of hypertension (adjusted OR=2). On the contrary, patients with a farming occupation were less likely to be prescribed NOACs (adjusted OR=0.4). About 75% of patients adhered to the guidelines recommending close monitoring during anticoagulant treatment. Notably, inappropriate prescriptions were identified in 27.7% of cases, especially among those with no recorded body weight (which is necessary for precise dosing based on creatinine clearance), those without health insurance, those with undocumented CHA2DS2-VASc scores, or those who were concurrently using antiplatelet agents. A discrepancy persists between clinical guidelines and the actual practice in diagnosing and managing patients with non-valvular atrial fibrillation (NVAF). It is crucial to prioritize the regular reevaluation of thromboembolic risk scores at follow-up appointments, ensure strict adherence to clinical monitoring standards, and align anticoagulant medication prescriptions with established guidelines.

Risk of stroke in patients with prior VKA or DOAC: A population-based real-world registry analysis.

To date, risk assessment of suffering ischemic and hemorrhagic stroke in individuals under oral anticoagulation (OAC) is limited to hospital-based cohorts and patients with atrial fibrillation. Through the combination of three individual datasets, (1) the population-based Tyrolean Stroke Pathway database, prospectively documenting all (unselected) stroke patients in the entire federal state of the Tyrol and (2) nation-wide prescription data, detailing each reimbursed prescription in Austria as well as (3) the Austrian Stroke Unit Registry, a nation-wide registry comprising data on all patients admitted to any of the 38 stroke units in Austria, we assessed risk of stroke in patients with prior oral anticoagulation and compared characteristics of patients taking direct oral anticoagulants and Vitamin-K-Antagonists. In Austria, oral anticoagulant prescription reimbursements increased from 292,475 in 2015 to 389,407 in 2021. In the Tyrol, prior oral anticoagulation treatment was evident in 586 of 3861 (15.2%) patients with ischemic and 131 of 523 (25.0%) with hemorrhagic stroke, with 20% and 35% of those stroke patients respectively having prior oral anticoagulation due to other indications than non-valvular atrial fibrillation. Considering prescription rates, treatment with direct oral anticoagulants was associated with a reduced stroke risk compared to Vitamin-K-Antagonists, especially in ischemic (1.05% vs 0.62%; RR 0.59, p < 0.001) but also in hemorrhagic stroke, even if less pronounced (0.21% vs 0.14%; RR 0.68, p = 0.06). In Austria, prior intake of direct oral anticoagulants was associated with lower risk of suffering acute large vessel occlusion stroke (RR 0.79, p = 0.003). One in seven patients suffering ischemic and one in four suffering hemorrhagic stroke had prior oral anticoagulation treatment. Both ischemic and hemorrhagic strokes are less frequent in those with direct oral anticoagulant intake compared to those taking Vitamin-K-Antagonists. Establishment of clear standard operating procedures on how to best care for acute stroke patients with oral anticoagulation is essential.

Development and Validation of an Intracranial Hemorrhage Risk Score in Older Adults with Atrial Fibrillation Treated with Oral Anticoagulant.

High risk of intracranial hemorrhage (ICH) is a leading reason for withholding anticoagulation in patients with atrial fibrillation (AF). We aimed to develop a claims-based ICH risk prediction model in older adults with AF initiating oral anticoagulation (OAC). We used US Medicare claims data to identify new users of OAC aged ≥65 years with AF in 2010-2017. We used regularized Cox regression to select predictors of ICH. We compared our AF ICH risk score with the HAS-BLED bleed risk and Homer fall risk scores by area under the receiver operating characteristic curve (AUC) and assessed net reclassification improvement (NRI) when predicting 1-year risk of ICH. Our study cohort comprised 840,020 patients (mean [SD] age 77.5 [7.4] years and female 52.2%) split geographically into training (3963 ICH events [0.6%] in 629,804 patients) and validation (1397 ICH events [0.7%] in 210,216 patients) sets. Our AF ICH risk score, including 50 predictors, had superior AUCs of 0.653 and 0.650 in the training and validation sets than the HAS-BLED score of 0.580 and 0.567 (p<0.001) and the Homer score of 0.624 and 0.623 (p<0.001). In the validation set, our AF ICH risk score reclassified 57.8%, 42.5%, and 43.9% of low, intermediate, and high-risk patients, respectively, by HAS-BLED score (NRI: 15.3%, p<0.001). Similarly, it reclassified 0.0, 44.1, and 19.4% of low, intermediate, and high-risk patients, respectively, by the Homer score (NRI: 21.9%, p<0.001). Our novel claims-based ICH risk prediction model outperformed the standard HAS-BLED score and can inform OAC prescribing decisions.

Oral anticoagulant prescribing among patients with cancer and atrial fibrillation in England, 2009-2019.

Anticoagulation of patients with atrial fibrillation (AF) and cancer is challenging because of their high risk for stroke and bleeding. Little is known of the variations of oral anticoagulant (OAC) prescribing in patients with AF with and without cancer. Patients with first-time AF during 2009-2019 from the Clinical Practice Research Datalink were included. Cancer diagnosis was defined as a history of breast, prostate, colorectal, lung, or hematological cancer. Competing-risk analysis was used to assess the risk of OAC prescribing in patients with AF and cancer adjusted for clinical and sociodemographic factors. Of 177,065 patients with AF, 11.7% had cancer. Compared to patients without cancer, patients with cancer were less likely to receive OAC: prostate cancer (subhazard ratio [SHR], 0.95; 95% CI, 0.91-0.99), breast cancer (SHR, 0.93; 95% CI, 0.89-0.98), colorectal cancer (SHR, 0.93; 95% CI, 0.88-0.99), hematological cancer (SHR, 0.70; 95% CI, 0.65-0.75), and lung cancer (SHR, 0.44; 95% CI, 0.38-0.50). The cumulative incidence function (CIF) of OAC prescribing was lowest for patients with lung cancer and hematological cancer compared with patients without cancer. The difference between the CIF of OAC prescribing in patients with and without cancer becomes narrower in the most deprived areas. Elderly patients (aged ≥85years) overall had the lowest CIF of OAC prescribing regardless of cancer status. In patients with AF, underprescribing of OAC is independently associated with certain cancer types. Patients with hematological and lung cancer are the least likely to receive anticoagulation therapy compared with patients without cancer. Underprescribing of OAC in cancer is linked to old age. Further studies of patients with AF and cancer are warranted to assess the net clinical benefit of anticoagulation in certain cancer types.

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...

Prevalence and Time Trends of Oral Anticoagulant Utilization in Adults with Sickle Cell Disease

Background: Sickle cell disease (SCD) is an inherited red blood cell disorder, caused by a genetic mutation in the β-hemoglobin chain. SCD is associated with chronic activation of coagulation and an increased risk of venous thromboembolism (VTE). Although the American Society of Hematology guidelines recommend indefinite anticoagulation for unprovoked or recurrent provoked VTE, no guidance is given regarding choice of anticoagulant due to a paucity of data. Existing evidence on the use of anticoagulants in patients with SCD has been mostly focused on oral anticoagulants, was limited by small sample sizes, and did not clearly demonstrate the temporal utilization patterns. Real-world evidence on oral anticoagulant use in SCD from large population-based studies is largely lacking. This study examined the prevalence and time trends of oral anticoagulant utilization in patients with SCD in the United States (US). Methods: This retrospective, repeated cross-sectional study analyzed the Cerner Health Facts® database from January 1, 2011, to December 31, 2016, which captures longitudinal electronic medical records (EMR) of patient data from participating facilities in the US. To be included, patients were required to (1) have ≥ 1 inpatient or emergency department encounters with SCD, or 2 outpatient encounters that were 30 days apart in a calendar year from 2012 to 2016, (2) have ≥ 1 prescription records on the encounters with SCD, (3) aged ≥ 18 years at index, and (4) have ≥ 1 encounter with SCD in a year prior to the index. For patients with multiple encounters with SCD in the calendar year, we randomly selected one encounter with SCD and defined it as the index. In this design, a patient contributed only one observation per year but may contribute to multiple years of observations if meeting the selection criterion. The outcome was the use of anticoagulants, defined as any prescription drug encounter for an oral anticoagulant (Vitamin K antagonist [VKA]: warfarin; direct oral anticoagulants [DOACs]: apixaban, rivaroxaban, dabigatran, edoxaban) within a grace period of 7 days discharged from the index. The independent variable was each calendar year measured as dummy variables. Covariates were measured during the 12-month baseline period prior to the index, which included patient demographics, comorbidities and complications of SCD, and facility characteristics. Time trends on the proportions of eligible patients with anticoagulant use against the calendar years of the SCD diagnosis were plotted, and the significance on the crude trend was examined using Cochran-Armitage trend test. In the main analysis, a modified Poisson regression by using generalized estimating equations (GEEs) estimated the adjusted prevalence ratios (APRs) for the trends and covariates associated with any anticoagulant utilization. In subgroup analysis, we estimated the APRs of covariates for the use of DOACs versus VKA. Results: The cohort included 8,824 adult patients with SCD in 182 facilities using automated Cerner EMR system for the years 2012 to 2016. Prescription rates of all oral anticoagulants gradually increased from 2012 to 2014; the rates of VKA prescriptions substantially dropped from 11.1/1000 to 4.1/1000 persons between 2014 and 2016, whereas prescription rates of DOACs increased significantly from 12.0/1000 to 29.1/1000. Prevalence of VTE was stable at approximately 6.2/1000 to 7.5/1000 between 2012 and 2016. Prescription rates of DOACs were lower in patients with (versus without) VTE (6.1/1000 vs 7.3/1000), while a reversed prescription pattern was observed for VKA (VTE [yes vs no]: 4.4/1000 vs 1.8/1000). Controlling for covariates, our main analysis demonstrated that patients with a diagnosis of acute chest syndrome, pulmonary hypertension, and depression were 1.51, 2.30, and 1.57 times more likely to have oral anticoagulant prescription, respectively (all p &amp;lt;0.05). Subgroup analysis showed that having a diagnosis of VTE was associated with a decreased likelihood of DOACs prescription relative to VKA (APR= 0.75, 95%CI: 0.62-0.91). Conclusion: Prescription of oral anticoagulants in adults with SCD has significantly increased from 2012 to 2016 and the increase was dominated by DOACs. The treatment paradox of a lower relative rate of DOACs utilization versus VKA in adults with SCD requires more study to understand the reasons and additional clinical outcomes associated with the utilization patterns.

Multimorbidity in atrial fibrillation for clinical implications using the Charlson Comorbidity Index

BackgroundPredicting survival in atrial fibrillation (AF) patients with comorbidities is challenging. This study aimed to assess multimorbidity in AF patients using the Charlson Comorbidity Index (CCI) and its clinical implications. MethodsWe analyzed 451,368 participants from the Korea National Health Insurance Service-Health Screening cohort (2002−2013) without prior AF diagnoses. Patients were categorized into new-onset AF and non-AF groups, with a high CCI defined as ≥4 points. Antithrombotic treatment and outcomes (all-cause death, stroke, major bleeding, and heart failure [HF] hospitalization) were evaluated over 9 years. ResultsIn total, 9.5% of the enrolled patients had high CCI. During follow-up, 12,241 patients developed new-onset AF. Among AF patients, antiplatelet drug use increased significantly in those with high CCI (adjusted odds ratio [OR] 1.05, 95%confidence interval [CI] 1.02–1.08, P < .001). However, anticoagulants were significantly less prescribed in patients with high CCI (OR 0.97, 95%CI 0.95–0.99, P = .012). Incidence of adverse events (all-cause death, stroke, major bleeding, HF hospitalization) progressively increased in this order: low CCI without AF, high CCI without AF, low CCI with AF, and high CCI with AF (all P < .001). Furthermore, high CCI with AF had a significantly higher risk compared to low CCI without AF (all-cause death, adjusted hazard ratio [aHR] 2.52, 95% CI 2.37–2.68, P < .001; stroke, aHR 1.43, 95% CI 1.29–1.58, P < .001; major bleeding, aHR 1.14, 95% CI 1.04–1.26, P = .007; HF hospitalization, aHR 4.75, 95% CI 4.03–5.59, P < .001). ConclusionsHigh CCI predicted increased antiplatelet use and reduced oral anticoagulant prescription. AF was associated with higher risks of all-cause death, stroke, major bleeding, and HF hospitalization compared to high CCI.

Antithrombotic Management and Outcomes of Anterior ST-Elevation Myocardial Infarction With New-Onset Wall Motion Abnormalities in Men and Women

BackgroundIn patients with anterior ST-elevation myocardial infarction (STEMI) and new-onset antero-apical wall motion abnormalities (WMAs), whether the rate of prophylaxis against left ventricular thrombus and outcomes differ between men and women is unknown. MethodsA multicentre retrospective cohort study of patients with STEMI and new-onset antero-apical WMAs treated with primary percutaneous coronary intervention was conducted. Patients with an established indication of oral anticoagulation (OAC) were excluded. The rates of triple therapy (double antiplatelet therapy + OAC) at discharge were compared for women vs men. The rates of net adverse clinical events, a composite of mortality, myocardial infarction, stroke or transient ischemic attack, systemic thromboembolism or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at 6 months were compared across sex using a multivariate logistic regression model. ResultsA total of 1664 patients were included in the primary analysis, of whom 402 (24.2%) were women and 1262 (75.8%) were men. A total of 138 women (34.3%) and 489 men (38.7%) received a triple therapy prescription at discharge (P = 0.11). At 6 months, 33 women (8.2%) and 96 men (7.6%) experienced a net adverse clinical event (adjusted odds ratio 0.82; 95% confidence interval 0.49-1.37). No difference occurred in the risk of bleeding events and ischemic events between men and women, when these were analyzed separately. ConclusionsThe rates of OAC prescription for left ventricular thrombus prophylaxis and clinical outcomes at 6 months were similar in women and men following anterior STEMI with new-onset antero-apical WMAs.

Role of liver disease in management and outcomes of european and asian patients with atrial fibrillation: a report from two regional prospective observational AF registries

Abstract Background In patients with atrial fibrillation (AF), the impact of liver disease (LD) on prescription of oral anticoagulant (OAC) therapy and risk of outcomes remains unclear, as well as possible differences between ethnicities. Objective To examine the impact of LD in a large cohort of European and Asian AF patients on OAC prescriptions and the risks of adverse outcomes. Methods AF patients derived from from two large prospective observational AF registries, conducted in Europe and Asia, on the basis of the same electronic case report form. OAC prescription and risk of outcomes was analyzed according to LD at baseline. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). Logistic and Cox regression analyses were used to determine associations with LD, and interaction analyses were performed to examine possible differences between European and Asian patients. Results 15,681 patients (mean age 69.0, SD 11.6 years; 38.7% female) were included, with 517 (3.3%) reporting LD. AF patients with LD were more likely permanent AF, symptomatic, higher thromboembolic and bleeding risks, and had higher multimorbidity, frailty and polypharmacy than those without LD. At baseline, AF patients with LD were less prescribed OAC, as well as with NOACs, than those without [Figure 1]. After adjustments, LD was associated with lower OAC prescription (OR 0.67, 95% CI 0.53-0.84) overall. OAC was less likely prescribed in European (OR 0.54, 95% CI 0.40-0.71) than in Asian (OR 0.95, 95% CI 0.66-1.39) patients (pint=0.015). No differences were found regarding prescription of NOACs vs. VKAs [Figure 1]. Adjusted Cox regression found that LD was associated with a higher risk of composite outcome (HR 1.42, 95% CI 1.11-1.81) and MACEs (HR 1.47, 95% CI 1.07-2.02), with no ethnic differences (Pint=0.631 and Pint= 0.495 for composite outcome and MACEs respectively). LD patients not receiving OAC were at higher risk for MACEs occurrence than those prescribed (pint=0.050). No differences were found regarding major bleeding. Conclusions Presence of LD in AF is associated with a lower prescription of OAC, especially amongst European patients. LD is associated with a higher risk for adverse outcomes, especially in those not prescribed with OAC.Figure 1

Trends in newly diagnosed atrial fibrillation and oral anticoagulant use after cardiac surgery: a population-based analysis from Ontario, Canada

Abstract Background Post-operative atrial fibrillation after cardiac surgery is associated with an increased risk of death and ischemic cardiovascular outcomes. In the non-surgical setting, oral anticoagulation (OAC) is beneficial among patients with AF in reducing their risk of thromboembolism. The use of OAC for patients with post-operative AF after cardiac surgery is not well-defined in contemporary clinical practice - at a time when direct oral anticoagulants (DOAC) are commonly prescribed in the non-surgical setting. Purpose To examine trends in OAC use among patients with post-operative atrial fibrillation after cardiac surgery at a time when DOAC is commonly prescribed in clinical practice. Methods The study cohort consisted of consecutive patients (&amp;gt;65 years) who experienced post-operative AF within 90 days after coronary artery bypass grafting (CABG), isolated left-sided non-mechanical heart valve surgery (iValve), and combined CABG + valve surgery between 2008 and 2021, identified by a mandatory provincial registry of all patients undergoing cardiac surgery in Ontario, Canada. Key exclusion criteria included: patients with pre-existing AF, end-stage renal disease requiring dialysis, mechanical heart valves, left atrial appendage ligation, and those who required anticoagulation for non-AF indications. Prescription of OAC (warfarin or DOAC) within 90 days after discharge from surgery was collected via linkage with the Ontario Drug Benefits Plan. Results The overall cohort consisted of 45,571 patients, in whom 14,572 (32.0%) developed POAF after cardiac surgery. Rates of POAF were highest among patients who underwent combined CABG + valve surgery (44.3% in 2008 to 34.2% in 2021), followed by iValve (42.6% in 2008 to 37.3% in 2021), then followed by isolated CABG (27.6% in 2008 to 24.2% in 2021). Over the study period, there was a decrease in the rates of POAF among patients who underwent all three types of cardiac surgery (P[trend] &amp;lt;0.01). In 2021, rates of oral anticoagulation were highest among patients who underwent combined CABG + valve surgery (61.1%), followed by iValve (59.2%) and isolated CABG (42.0%). Among patients who underwent isolated CABG, there was a 9% increase in the rates of OAC use during the study period (P[trend] &amp;lt;0.001). On the other hand, rates of OAC use remained largely unchanged (Figure A) among patients who underwent iValve and combined CABG + valve surgery (P[trend] 0.24 and 0.26, respectively). Since 2018, DOAC accounted for 60-70% of all OAC prescriptions (Figure B). Conclusions Despite advances in surgical techniques and post-operative care, the rates of post-operative atrial fibrillation after cardiac surgery remain substantial. Prescription rates for OAC remain modest over the past decade, but DOAC is increasingly more commonly prescribed in this patient population. Randomized trials are needed to assess the risks and benefits of OAC, specifically DOAC, in this high-risk patient population.Figure AFigure B

Oral anticoagulant use and outcomes in Asian patients with atrial fibrillation in the GLORIA-AF Registry

Abstract Background Ethnic differences in the management and outcomes of patients with atrial fibrillation (AF) have been shown in previous studies, but available data is still limited, although urgently needed. Purpose to analyse oral anticoagulant (OAC) prescription, OAC discontinuation, and long-term risk of major outcomes in Asian patients with AF, using data from a global prospective cohort study. Methods Using data from the GLORIA-AF Registry Phase II and III, we analysed patients according to their self-reported ethnicity (Asian vs. Non-Asian), and according to Asian ethnic subgroup (i.e. Chinese, Japanese, Korean and other Asian). Odds of OAC prescription were analysed through multivariable logistic regression, while the risk of OAC discontinuation and adverse outcomes were analysed through multivariable Cox-regression model. Primary outcome of this analysis was defined as the composite of all-cause death and major adverse cardiovascular events (MACE). Results 34,421 AF patients were included (70.0±10.5 years, 45.1% females, 6,900 (20.0%) Asian). Compared to Non-Asian subjects, prescription of OAC and non-vitamin K antagonist oral anticoagulant (NOAC) was lower in Asian subjects (Odds Ratio [OR] and 95% Confidence Intervals (CI): 0.23 [0.22-0.25] and 0.66 [0.61-0.71], respectively; Figure 1), but higher in the Japanese subgroup. Asian ethnicity was also associated with OAC discontinuation (Hazard Ratio [HR] and [95%CI]: 1.79 [1.67-1.92]), and lower risk of the primary composite outcome (HR [95%CI]: 0.86 [0.76-0.96]; Figure 2). Among the secondary outcomes, Asian patients had also higher risk of thromboembolism and intracranial haemorrhage, and lower risk of major bleeding events. Conclusions In this large, contemporary cohort of patients with AF, Asian subjects received suboptimal management of thromboembolic risk, and showed a peculiar long-term risk of adverse outcomes. Integrated and appropriate treatment of these patients is crucial to improve their prognosis.Figure 1Figure 2