Use Of DOACs Research Articles

Acute ischemic stroke on anti-Xa inhibitors: Pharmacokinetics and outcomes

Background and PurposeDirect oral anticoagulant (DOAC) ingestion within 48 h is an exclusion for thrombolysis in acute ischemic stroke (AIS) patients. We aim to shed light on pharmacokinetic correlates and outcomes in patients with AIS excluded from thrombolysis due to DOAC use. MethodsThis is a single center retrospective study of consecutive patients with AIS within 4.5 h from last known normal and excluded from thrombolytic therapy due to confirmed Xa inhibitor DOAC (DOACXa) intake within the prior 48 h. We used linear regression to test the correlation between time from last DOACXa ingestion and anti-Xa level. ResultsOver a period of 2.5 years, we identified 44 patients who did not receive thrombolysis because of presumed DOAC intake within 48 h. In adjusted linear regression, there was an association between time from last DOAC ingestion and Xa level (beta = −0.69, p < 0.001). Among the 37 patients with known atrial fibrillation not receiving alteplase due to DOAC use, the 90-day mortality was 35.1% (13/37) and 77% (10/13) of deaths were stroke related. ConclusionsPatients with AIS on DOAC therapy face a heightened risk of mortality. Studies are needed to investigate the safety and efficacy of thrombolysis in such patients based on time of last DOAC ingestion and/or anti-Xa/drug level.

P1695: CEREBRAL VENOUS THROMBOSIS AND ANTITHROMBOTIC THERAPY: A SYSTEMATIC REVIEW

Background: Cerebral venous thrombosis (CVT) is a cause of stroke especially in the young. The anticoagulant treatment remains controversial as it prevents neurological deterioration, new venous infarcts and death but there is a risk of bleeding complications Aims: The aim of the study was to systematically review the available studies on the efficacy and safety of anticoagulant therapy in CVT Methods: A literature search was performed (PubMed) by a combination of the terms: 1. cerebral vein thrombosis 2. cerebral venous thrombosis 3. antithrombotic therapy 4. anticoagulant therapy 5. heparin 6. warfarin 7. VKA 8. DOAC. The references of the studies were checked to obtain additional studies. The search included studies: a) related to humans b) in English and c) period:1991-2021. The following data were extracted: study characteristics (year of publication, country, study-type, sample size), demographic characteristics, type/dose of anticoagulant therapy, median follow-up, major bleeding complications, other complications during follow-up. The inclusion criteria were: 1) CVT confirmed by imaging (angiography,CT,MRI,MRV) 2) any type of anticoagulation 3) sample size>5 & 4) age>16 years Results: 25 studies were included with a total number of 2320 patients. The percentage of female patients was 70%. The age ranged 16-86 years. A total of 6 RCT, 9 prospective observational studies, 9 retrospective observational studies and 1 ambidirectional observational study were detected. Based on the limited data the anticoagulant therapy appears safe and effective, as in the acute phase it improves the clinical outcome. It is recommended that patients with acute CVT are treated with heparin. It is not contraindicated even in hemorrhagic infarcts but should be used with caution in extensive hemorrhagic infarcts, in-depth localization of the infarct and coma. LMWH appears to be associated with better outcome and fewer new intracranial hemorrhages than UFH. There is no study evaluating the role of antiplatelets. There are also insufficient data on the optimal duration of anticoagulation therapy. The use of DOAC is not recommended for the treatment of CVT, especially in the acute phase, due to the poor available evidence. Nevertheless, the limited data on the use of DOAC in the treatment of CVT imply adequate safety and efficacy. There is no study comparing different DOAC for CVT treatment. There are also insufficient data to support the use of thrombolysis in patients with CVT, as only case-reports and patient-series have been published. There is only 1 RCT in which “high-risk” patients were randomized to intravascular thrombolysis or heparin-controlled treatment. According to the European Guideline for the diagnosis and management of CVT it is not possible to provide recommendation for thrombolysis. It is suggested though not to use thrombolysis in patients with acute CVT with a low risk of poor outcome. The present systematic review highlights the lack of adequate data on optimal anticoagulation therapy in CVT Summary/Conclusion: Anticoagulant therapy for CVT appears to be safe and effective. It is recommended that patients with acute CVT are treated with heparin even cases with bleeding elements at diagnosis. LMWH appears to be associated with better outcomes and fewer new intracranial hemorrhages. The position of DOACs is an object of future research. Thrombolysis in CVT should be reserved for high-risk patients. Given the low incidence of the disease the cooperation of centers at international level is necessary. The subject of anticoagulant therapy in the treatment of CVT remains open for further research

European Stroke Organisation (ESO) guideline on pharmacological interventions for long-term secondary prevention after ischaemic stroke or transient ischaemic attack.

Recurrent stroke affects 9% to 15% of people within 1 year. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations on pharmacological management of blood pressure (BP), diabetes mellitus, lipid levels and antiplatelet therapy for the prevention of recurrent stroke and other important outcomes in people with ischaemic stroke or transient ischaemic attack (TIA). It does not cover interventions for specific causes of stroke, including anticoagulation for cardioembolic stroke, which are addressed in other guidelines. This guideline was developed through ESO standard operating procedures and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The working group identified clinical questions, selected outcomes, performed systematic reviews, with meta-analyses where appropriate, and made evidence-based recommendations, with expert consensus statements where evidence was insufficient to support a recommendation. To reduce the long-term risk of recurrent stroke or other important outcomes after ischaemic stroke or TIA, we recommend: BP lowering treatment to a target of <130/80 mmHg, except in subgroups at increased risk of harm; HMGCoA-reductase inhibitors (statins) and targeting a low density lipoprotein level of <1.8 mmol/l (70 mg/dl); avoidance of dual antiplatelet therapy with aspirin and clopidogrel after the first 90 days; to not give direct oral anticoagulant drugs (DOACs) for embolic stroke of undetermined source and to consider pioglitazone in people with diabetes or insulin resistance, after careful consideration of potential risks. In addition to the evidence-based recommendations, all or the majority of working group members supported: out-of-office BP monitoring; use of combination treatment for BP control; consideration of ezetimibe or PCSK9 inhibitors when lipid targets are not achieved; consideration of use of low-dose DOACs in addition to an antiplatelet in selected groups of people with coronary or peripheral artery disease and aiming for an HbA1c level of <53 mmol/mol (7%) in people with diabetes mellitus. These guidelines aim to standardise long-term pharmacological treatment to reduce the burden of recurrent stroke in Europe.

ANMCO position paper 'Appropriateness of prescribing direct oral anticoagulants in stroke and systemic thromboembolism prevention in adult patients with non-valvular atrial fibrillation'.

The appropriateness of prescribing direct oral anticoagulants [dabigatran, rivaroxaban, apixaban, and edoxaban (DOACs)] is regulated on the criteria established in Phase III trials. These criteria are reported in the summary of the product characteristics of the four DOACs. In clinical practice, prescriptions are not always in compliance with established indications. In particular, the use of lower doses than those recommended in drug data sheets is not uncommon. Literature data show that the inappropriate prescription of reduced doses causes drug underexposure and up to a three-fold increase in the risk of stroke/ischaemic transient attack, systemic thromboembolism, and hospitalization. Possible causes of the deviation between the dose that should be prescribed and that prescribed in the real world include erroneous prescription, an overstated haemorrhagic risk perception, and the presence of frail and complex patients in clinical practice who were not included in pivotal trials, which makes it difficult to apply study results to the real world. For these reasons, we summarize DOAC indications and contraindications. We also suggest the appropriate use of DOACs in common clinical scenarios, in accordance with what international guidelines and national and international health regulatory bodies recommend.

C67A BLITZ-AF CANCER REGISTRY: BASELINE CHARACTERISTICS OF PATIENTS WITH ATRIAL FIBRILLATION AND CANCER

Abstract Background Evidences on atrial fibrillation (AF) in patients with cancer are limited, specifically with respect to antithrombotic therapy. Methods BLITZ-AF Cancer is a prospective, non-interventional study of the epidemiology and management of AF in patients with cancer. Patients were included from 112 cardiology units in Italy, Belgium, Netherlands, Spain, Portugal, and Ireland, based on the following criteria: age ≥18 years; documented cancer other than basal-cell or squamous-cell carcinoma of the skin diagnosed within 3 years; electrocardiographically confirmed AF within 1 year; no concomitant interventional study. Follow-up is ongoing. Results From June 26th, 2019 to Sep. 30th, 2021, 1,514 subjects were enrolled. The most frequent cancer locations were lung (14.9%), colorectal (14.1%), breast (13.9%), prostate (8.8%), and non-Hodgkin lymphoma (8.1%); 463 (30.6%) of participants had metastases. AF was first-detected in 323 (21.3%), paroxysmal in 460 (30.4%), persistent in 192 (12.7%), long-standing persistent in 33 (2.2%), and permanent in 506 (33.4%); 590 (39.0%) patients had symptoms attributable to AF. Baseline characteristics are presented in the Table. Males were more than women and almost half of the subjects was &amp;gt;75 years-old. Cardiovascular risk factors were common and approximately 31% had heart failure or coronary artery disease. Previous thromboembolic and haemorrhagic events had occurred in 14% and 10% of subjects, respectively. The median CHA2DS2VASc score was 3. As shown in the Figure, the prescription of oral anticoagulants, especially direct-acting ones (DOACs), rose after the cardiology assessment, while the percentage of participants without any antithrombotic therapy declined. Among 1,427 patients with non-valvular AF (i.e., no mitral stenosis or prosthetic mechanical valve), 997 (69.9%) were prescribed on DOACs at discharge/after consultation. At multivariable logistic regression analysis, variables associated with DOAC use were female sex (OR 1.58, 95% CI 1.22-2.05), age (OR 2.00, 95% CI 1.39-2.88 and OR 2.63, 95%CI 1.84-3.76, respectively, for 65-74 years and ≥75 years vs &amp;lt;65 years), hypertension (OR 1.43, 95%CI 1.10-1.87), long-standing persistent or permanent AF (OR 1.36, 95%CI 1.05-1.78). Haemoglobin &amp;lt;12 g/dL (OR 0.57, 95%CI 0.45-0.73), and planned cancer treatment (OR 0.72, 95%CI 0.57-0.92) were independently associated with a lower prescription of DOACs. Conclusions BLITZ-AF Cancer provides extensive information on a large, contemporary cohort of individuals with AF and cancer. This baseline snapshot indicates that cardiologists pursue the implementation of DOACs in these patients, although residual use of other antithrombotic therapies or lack of any thrombo-prophylaxis remains substantial.

PO-718-05 PRESCRIBING PATTERNS OF DIRECT ANTICOAGULANTS VERSUS VITAMIN K ANTAGONISTS IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION AND EXTREME OBESITY

Anticoagulation is an effective treatment in prevention of stroke in patients with atrial fibrillation (AF). Direct anticoagulants (DOACs) have been favored over vitamin K dependent antagonists (VKAs) given their safety and efficacy. However, there is limited real-world data on DOAC use among patients with extreme obesity. Describe the prescribing patterns of DOACs versus VKAs in patient with non-valvular AF (NVAF) and extreme obesity and the efficacy and safety of DOACs. Using a retrospective cohort study design, patients with NVAF, receiving oral anticoagulants (DOACs versus VKA), and extreme obesity (BMI ≥ 40 kg/m2 and/or weight ≥ 120 kg) during 2014 to 2020 at large healthcare system are included. Primary efficacy outcome is ischemic stroke and primary safety outcome is major bleeding. Sociodemographic and clinical characteristics were compared between DOAC and VKA groups using chi-square test for categorical variables and student’s t-test for continuous variables. Cox proportional hazards model is used to compare the primary efficacy and safety outcomes between the groups. Of the 6,930 patients, about two-third (63%) were prescribed DOACs. Patients receiving VKA were significantly older in age compared to DOAC group (66.1 (±10.2) vs 62.9 (±10.7); P=0.0321). There were no statistically significant differences in DOAC prescription by gender, race, and BMI. Even among patients with a BMI >=50, DOAC prescription rate was 61%. Across three categories of CHA2DS2VASc score (i.e., < 2, 2-4 and ≥ 5), the rate of DOAC prescription ranged from 80% to 65% and 52% respectively. Patients with higher CHA2DS2VASc score were significantly more likely to receive a VKA prescription than DOACs (P < 0.001). A third of this study patients were on concomitant antiplatelet agents with a trend towards DOACS prescribing pattern (59% vs 41%, 0.0361). In Cox regression, DOACs were associated with a significantly lower risk of ischemic stroke (hazard ratio [HR]: 0.52; 95% confidence interval [CI]: 0.42, 0.65) and major bleeding (HR: 0.55; 95% CI: 0.59, 0.90) compared to VKA. Despite lack of safety and efficacy data from clinical trials, in this extreme obese group of NVAF patients, DOACs were preferred over VKAs without an increase in stroke or major bleeding events.

Demographics and Risk Profile of Elderly Middle Eastern Patients with Atrial Fibrillation: The Jordan Atrial Fibrillation (JoFib) Study.

BackgroundAtrial fibrillation (AF) is the most common arrhythmia that is associated with high morbidity and mortality. The prevalence of AF increases with age and the elderly constitute a vulnerable cohort for higher stroke and bleeding complications.MethodsA total of 2163 adult consecutive patients with AF in 19 hospitals and 11 outpatient clinics in Jordan were enrolled in the Jordan AF study from May 2019 to January 2021. The clinical characteristics, demographics, and risk profiles of the elderly patients (≥80 years old) were compared to the younger patients (<80 years old).ResultsOf 2163 patients, 379 (17.5%) constituted the elderly group. The elderly group had higher prevalence of hypertension (79.9% vs 73.5%, p=0.01), lower prevalence of smoking (5.0% vs 15.2%, p<0.001) and lower body mass index (28.1 ± 5.5 kg/m2 vs 29.8 ± 6.2 kg/m2, p<0.001) compared with younger patients. They also had more strokes or systemic emboli (25.6% vs 14.7%, p<0.001), heart failure (30.3% vs 22.9%, p=0.002), pulmonary hypertension (30.6% vs 24.8%, p=0.02), and chronic kidney disease (13.5% vs 8.3%, p=0.002). The elderly cohort had higher mean CHA2DS2-VASc (5.0 ± 1.5 vs 3.6 ± 1.8, p<0.001) and HAS-BLED scores (2.2 ± 1.1 vs 1.5 ± 1.1, p<0.001) compared to younger group. Among 370 elderly with non-valvular AF (NVAF), oral anticoagulant agents (OACs) were prescribed for 278 (84.2%) of eligible high-risk patients. Of the 1402 younger patients with NVAF, OACs were prescribed for 1133 (84.3%) of eligible patients. Direct oral anticoagulant agents (DOACs) were more frequently used in the elderly compared to the young (72.3% vs 62.3%, p<0.001).ConclusionElderly Middle Eastern AF patients have worse baseline clinical profiles and higher risk scores compared to younger patients. The majority of the elderly were prescribed guideline directed OACs, with higher use of DOACs than the younger cohort.Clinical Studies RegistrationThe study is registered on clinicaltrials.gov (unique identifier number NCT03917992).

Impact of the Genotype and Phenotype of CYP3A and P-gp on the Apixaban and Rivaroxaban Exposure in a Real-World Setting.

Apixaban and rivaroxaban are the two most prescribed direct factor Xa inhibitors. With the increased use of DOACs in real-world settings, safety and efficacy concerns have emerged, particularly regarding their concomitant use with other drugs. Increasing evidence highlights drug–drug interactions with CYP3A/P-gp modulators leading to adverse events. However, current recommendations for dose adjustment do not consider CYP3A/P-gp genotype and phenotype. We aimed to determine their impact on apixaban and rivaroxaban blood exposure. Three-hundred hospitalized patients were included. CYP3A and P-gp phenotypic activities were assessed by the metabolic ratio of midazolam and AUC0–6h of fexofenadine, respectively. Relevant CYP3A and ABCB1 genetic polymorphisms were also tested. Capillary blood samples collected at four time-points after apixaban or rivaroxaban administration allowed the calculation of pharmacokinetic parameters. According to the developed multivariable linear regression models, P-gp activity (p < 0.001) and creatinine clearance (CrCl) (p = 0.01) significantly affected apixaban AUC0–6h. P-gp activity (p < 0.001) also significantly impacted rivaroxaban AUC0–6h. The phenotypic switch (from normal to poor metabolizer) of P-gp led to an increase of apixaban and rivaroxaban AUC0–6h by 16% and 25%, respectively, equivalent to a decrease of 38 mL/min in CrCl according to the apixaban model. CYP3A phenotype and tested SNPs of CYP3A/P-gp had no significant impact. In conclusion, P-gp phenotypic activity, rather than known CYP3A/P-gp polymorphisms, could be relevant for dose adjustment.

8 - Use of DOACS for cancer-associated VTE in Great Western Hospital

8 - Use of DOACS for cancer-associated VTE in Great Western Hospital

Management of Adults with Newly Diagnosed Atrial Fibrillation with and without CKD.

Atrial fibrillation (AF) is highly prevalent in CKD and is associated with worse cardiovascular and kidney outcomes. Limited data exist on use of AF pharmacotherapies and AF-related procedures by CKD status. We examined a large "real-world" contemporary population with incident AF to study the association of CKD with management of AF. We identified patients with newly diagnosed AF between 2010 and 2017 from two large, integrated health care delivery systems. eGFR (≥60, 45-59, 30-44, 15-29, <15 ml/min per 1.73 m2) was calculated from a minimum of two ambulatory serum creatinine measures separated by ≥90 days. AF medications and procedures were identified from electronic health records. We performed multivariable Fine-Gray subdistribution hazards regression to test the association of CKD severity with receipt of targeted AF therapies. Among 115,564 patients with incident AF, 34% had baseline CKD. In multivariable models, compared with those with eGFR >60 ml/min per 1.73 m2, patients with eGFR 30-44 (adjusted hazard ratio [aHR] 0.91; 95% CI, 0.99 to 0.93), 15-29 (aHR, 0.78; 95% CI, 0.75 to 0.82), and <15 ml/min per 1.73 m2 (aHR, 0.64; 95% CI, 0.58-0.70) had lower use of any AF therapy. Patients with eGFR 15-29 ml/min per 1.73 m2 had lower adjusted use of rate control agents (aHR, 0.61; 95% CI, 0.56 to 0.67), warfarin (aHR, 0.89; 95% CI, 0.84 to 0.94), and DOACs (aHR, 0.23; 95% CI, 0.19 to 0.27) compared with patients with eGFR >60 ml/min per 1.73 m2. These associations were even stronger for eGFR <15 ml/min per 1.73 m2. There was also a graded association between CKD severity and receipt of AF-related procedures (vs eGFR >60 ml/min per 1.73 m2): eGFR 30-44 ml/min per 1.73 (aHR, 0.78; 95% CI, 0.70 to 0.87), eGFR 15-29 ml/min per 1.73 m2 (aHR, 0.73; 95% CI, 0.61 to 0.88), and eGFR <15 ml/min per 1.73 m2 (aHR, 0.48; 95% CI, 0.31 to 0.74). In adults with newly diagnosed AF, CKD severity was associated with lower receipt of rate control agents, anticoagulation, and AF procedures. Additional data on efficacy and safety of AF therapies in CKD populations are needed to inform management strategies.

VENOUS THROMBOEMBOLISM IN THE EMERGENCY DEPARTMENT - SINGLE-CENTER EXPERIENCE.

SUMMARYGiven the importance of early recognition of acute venous thromboembolism (VTE) and the nonspecificity of its symptoms and signs, it is essential to follow the guidelines for diagnostic and therapeutic decisions. Ultrasound examination of the entire lower extremity is currently the standard diagnostic method for symptomatic patients with a clinical probability of deep vein thrombosis (DVT) according to the Wells scoring system. The aim of this study is to show the demographic structure and analyze the number of patients in the emergency department with suspected venous thrombosis. In the past 10 years, 2,022 patients with DVT and 686 with pulmonary emboli have been diagnosed. Despite adherence to the diagnostic protocol, nearly two-thirds of patients require early ultrasound diagnosis. One-fifth of patients had thrombosis of the superficial venous system of the leg or arm. Thrombus was present in the veins of the lower leg in 37% of patients with DVT. The presence of thrombi above the knee, involving the deep femoropopliteal venous system, was found in as much as one-third of patients. These findings and current guidelines suggest that there is a paradigm shift toward more frequent use of DOAC in patients with DVT. However, greater educational efforts may be needed for many physicians to become comfortable with the use of DOAC in the outpatient management of patient populations at low risk for pulmonary embolism.

Safety of cold snare polypectomy with periprocedural antithrombotic agents for colorectal polyps: a systematic review and meta-analysis.

Background:We aimed to study the safety of cold snare polypectomy (CSP) for colorectal polyps in patients administered periprocedural antithrombotic agents.Methods:We searched the PubMed, Embase, and Cochrane Library databases through June 2021. The primary outcomes were the rates of delayed and immediate bleeding (requiring endoscopic hemostasis). Secondary outcomes included thromboembolic events. Meta-analysis using odds ratios (ORs) and corresponding 95% confidence intervals (CIs) was performed to compare the outcomes.Results:Seventeen studies, including five randomized trials, were included. Over 96% of polyps were ⩽1 cm. The pooled rates of delayed and immediate bleeding for patients receiving CSP and periprocedural antithrombotic agents were 1.6% and 10.5%, respectively. Both the delayed (OR = 4.02, 95% CI = 1.98–8.17) and immediate bleeding (OR = 5.85, 95% CI = 3.84–8.89) rates were significantly higher in patients using periprocedural antithrombotic agents than in non-users. Although both antiplatelet agents and anticoagulants increased the risk of delayed bleeding, the risks associated with the use of direct oral anticoagulants (DOACs; 2.5%) or multiple agents (3.9%) were particularly high. Compared to their counterparts, diminutive polyps and uncomplicated lesions not requiring hemoclipping were associated with lower risks of delayed bleeding (pooled estimates of 0.4% and 0.18%, respectively). Thromboembolic risk was similar among patients using and not using periprocedural antithrombotic agents.Conclusions:CSP with periprocedural antiplatelet agents and warfarin may be feasible, especially for diminutive polyps. However, drug discontinuation should be considered with the use of DOACs or multiple agents which entail higher bleeding risk even with hemoclipping.

679 Pharmacokinetics of direct oral anticoagulants in patient with atrial fibrillation and extreme obesity

Abstract Aims Direct oral anticoagulants (DOACs) are recommended in preference to vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation (AF) eligible for oral anticoagulation therapy; however, data and clinical experiences supporting the use of DOACs in patients with a body mass index ≥40 kg/m2 or weight &amp;gt;120 kg remain limited. The aim of this study was to evaluate the pharmacokinetic properties of DOACs in patients with AF and extreme obesity. Methods and results We enrolled all consecutive patients with AF and extreme obesity undergoing treatment with DOACs followed up at Monaldi Hospital, Naples, Italy. To determine peak plasma and trough levels of DOACs, plasma samples were collected at 2nd, 4th, 6th, and 12th hours from the last dose intake in patients receiving apixaban and dabigatran and at the 2nd, 4th, 6th, and 24th hours in those receiving edoxaban and rivaroxaban. The DOACs’ peak and trough plasma levels obtained from our study population were compared with those sourced from pharmacokinetic studies among patients without obesity, defined as a normal reference range in the literature. If at least 1 peak or trough plasma level was found below or above the normal reference ranges, the patients were classified as having out-of-range DOAC plasma levels. Study population was then divided into in-range and out-of-range groups. Baseline characteristics, including DOAC treatment, were compared between the two groups. Univariate and multivariate logistic regression analyses were performed to identify baseline variables associated with DOACs’ plasma concentration out of the expected range. A total of 58 patients [mean (SD) age, 70.93 (8.73) years; 40% female] with extreme obesity [mean (SD) body mass index, 44.43 (3.54) kg/m2] and AF while undergoing DOAC treatment was included in the present study. In nine patients (15.5%), the DOAC plasma concentrations were out of the expected ranges (out-of-range group);, indicating a greater likelihood of edoxaban 30 mg treatment (33% vs. 2%; P &amp;lt; 0.01) and inappropriate DOAC underdosing (56% vs. 4%; P &amp;lt; 0.005) compared with the in-range group. According to the multivariate logistic analysis (P = 0.0011), the inappropriate DOAC underdosing (hazard ratio = 29.37; P = 0.0002) was an independent predictor of DOAC plasma levels out of the expected ranges. Conclusions Patients with extreme obesity and AF who were receiving DOAC therapy had DOAC plasma concentrations in the expected range. The inappropriate DOAC underdosing seems to be the only independent clinical factor associated with a plasma concentration of the drug out of the expected range.

286 Incidence of pocket haematoma with different anticoagulation strategies in patients undergoing cardiac implantable device implant or revision

Abstract Aims Direct oral anticoagulants (DOACs) are known for lower bleeding risk than vitamin K antagonist (VKA) in patients with atrial fibrillation (AF). To date, it has not been established whether in such population DOAC may offer reduction of bleeding complication in patients undergoing cardiac implantable electronic device (CIED) implant or revision (substitution, upgrade, or downgrade). We evaluated whether DOACs compared to VKAs, decrease bleeding complications at the time of CIED implant in patients with AF, requiring oral anticoagulant therapy. Methods and results We present a monocentric observational retrospective study. Patients undergoing implant, generator replacement, or upgrading/downgrading of an intracardiac device (PM, ICD, or CRT) between January 2015 and March 2021 with AF undergoing DOAC or VKA were included. The comparison of risk of clinically significant pocket hematoma at 30-days follow-up in the two-treatment group [DOAC vs. VKA and DOAC vs. VKA without low molecular weight eparin (LMWH) bridge] was performed. Cox proportional hazards regression analysis including main clinical findings was performed to test the primary endpoint. Propensity score matching analysis was performed, with inversed proportional weighted (IPW) propensity score included in the multivariate analysis. 311 patients were included, 146 (46.9%) treated with DOAC and 165 (53.1%) treated with VKA. The incidence pocket haematoma was significantly reduced in patients treated with DOAC compared with VKA (3.4% vs. 13.3%, respectively, P = 0.002), a finding confirmed on multivariate analysis (HR: 3.02, CI: 1.10–8.29, P = 0.032). The incidence of pocket haematoma in patients on DOAC vs. VKA without LMWH bridge therapy was found to be significantly higher in the latter group of patients (P = 0.033, HR: 2.93, CI: 1.01–8.49, P = 0.48). After adjusting at propensity score with IPW, DOAC use showed decreased risk of pocket haematoma (HR: 0.29, CI: 0.09–0.95, P = 0.42). Conclusions In patients with atrial fibrillation undergoing CIED implant or revision, DOAC therapy appears to be associated with lower risk of event-related pocket haematoma at 30-day follow-up, even in the absence of bridging with LWMH. Such findings are hypothesis-generating.

Risk factors for gastrointestinal bleeding in patients with gastrointestinal cancer using edoxaban

BackgroundIn the Hokusai VTE Cancer study, the risk of major bleeding was 2.9% higher in the edoxaban group compared with the dalteparin group, mainly due to more gastrointestinal bleedings in patients with gastrointestinal cancer. The identification of risk factors for gastrointestinal bleeding may help to guide the use of DOACs in these patients. ObjectivesTo evaluate risk factors for gastrointestinal bleeding in patients with gastrointestinal cancer receiving edoxaban. Patients/MethodsIn this nested case‐control study in patients with gastrointestinal cancer randomized to edoxaban in the Hokusai VTE Cancer study, cases (patients with clinically relevant gastrointestinal bleeding during treatment) were randomly matched to three controls (patients who had no gastrointestinal bleeding). Data for the 4‐week period prior to bleeding were retrospectively collected. Odds ratios (ORs) were calculated in a crude conditional logistic regression model and a multivariable model adjusted for age, sex, and cancer type. ResultsTwenty‐four cases and 64 matched controls were included. In the multivariable analysis, advanced cancer, defined as regionally advanced or metastatic cancer (OR 3.6, 95% CI 1.01–12.6) and low hemoglobin levels (OR 4.8, 95% CI 1.5–16.0) were significantly associated with bleeding. There was no significant difference in patients with resected tumors (OR 0.4, 95% CI 0.1–1.4), or in patients on chemotherapy (OR 1.3, 95% CI 0.5–3.5). ConclusionAdvanced cancer and low hemoglobin levels were associated with an increased risk of gastrointestinal bleeding in patients with gastrointestinal cancer receiving edoxaban. We were unable to identify other risk factors, mainly due to limited statistical power.

ANMCO Position paper: Prescription appropriateness of direct oral anticoagulants for stroke and systemic thromboembolis with non-valvular atrial fibrillation

The prescription appropriateness of direct oral anticoagulants (DOACs [dabigatran, rivaroxaban, apixaban, and edoxaban]) is carefully regulated, taking into account the criteria established in phase III trials and listed in the summary of the product characteristics of the four DOACs. In clinical practice, prescriptions are not always in compliance with established indications. In particular, the use of doses lower than those recommended in drug data sheets is relatively frequent. Literature data show that the inappropriate prescription of DOAC doses causes drug underexposure and an up to three-fold increase in the risk of stroke/transient ischemic attack, systemic thromboembolism, and hospitalizations. Possible causes of the deviation between the dose that should be prescribed and that actually employed may include erroneous prescriptions, an overstated bleeding risk perception, and the presence of frail patients, who were not included in pivotal trials. For these reasons, we summarize DOAC indications and contraindications and suggest the appropriate use of DOACs in common clinical scenarios, in accordance with what international guidelines and national and international health regulatory agencies recommend.

Abstract 11404: Disparities in Anticoagulation for Atrial Fibrillation: A Systematic Review of Recent Literature

Atrial fibrillation (AF) causes 1 in 7 strokes as it is the most prevalent arrhythmia in the United States. 1 Previous work has shown that even with significant recurring AF and high CHA 2 DS 2 VASc scores, there are various disparities that occur within the prescription, type, and quality of anticoagulation control. One previous systematic review published in 2018 discusses disparities within anticoagulation for AF. Given the importance of health equity for this highly efficacious intervention, we aimed to review recent data on disparities with respect to anticoagulation for AF published after 12/31/17. This systematic review used the PubMed database to identify 19 articles that discuss disparities within anticoagulation for AF. We limited our search to articles published after 12/31/17. The search string consisted of 7 phrases that combined AF, anticoagulation, and disparities involving sex, race, ethnicity, income, socioeconomic (SE) status, etc. Articles were excluded if they focused on anticoagulation for conditions other than AF, if they did not discuss anticoagulation as a treatment for AF, and/or lack of inclusion of data referring to disparity as defined above. We found 7 articles on race and anticoagulation, 6 articles on anticoagulation and sex/gender, 3 articles that discussed SE status and anticoagulation, and 5 articles that discuss other types of disparity related to anticoagulation. Results showed that black populations were much less likely to be given anticoagulation than other patients. Black patients were more likely to be given warfarin over DOACs. Women were less anticoagulated than men even when their stroke risk was higher. Some studies in this review found that there were not statistically meaningful differences in anticoagulation use in women and men. Lower income and less educated patients were less likely to receive DOAC compared to warfarin. Compared to a prior systematic review, focusing on articles after 2017 revealed much more information about DOAC use. Disparities first noted in the warfarin era have persisted with DOACs. Given that we have identified disparities in anticoagulation with respect to race, sex, and SE status, more work is needed to identify mechanisms of these disparities and identify potential solutions.

Association of Race and Ethnicity and Anticoagulation in Patients With Atrial Fibrillation Dually Enrolled in Veterans Health Administration and Medicare: Effects of Medicare Part D on Prescribing Disparities.

Racial and ethnic disparities in anticoagulation exist in atrial fibrillation management in Medicare and the Veterans Health Administration, but the influence of dual Veterans Health Administration and Medicare enrollment is unclear. We compared anticoagulant initiation by race and ethnicity in dually enrolled patients and assessed the role of Medicare part D enrollment on anticoagulation disparities. We identified patients with incident atrial fibrillation (2014-2018) dually enrolled in Veterans Health Administration and Medicare. We assessed any anticoagulant initiation (warfarin or direct-acting oral anticoagulants [DOACs]) within 90 days of atrial fibrillation diagnosis and DOAC use among anticoagulant initiators. We modeled anticoagulant initiation, adjusting for patient, provider, and facility factors, including main effects for race and ethnicity and Medicare part D enrollment and an interaction term for these variables. In 43 789 patients, 8.9% were Black, 3.6% Hispanic, and 87.5% White; 10.9% participated in Medicare part D. Overall, 29 680 (67.8%) patients initiated any anticoagulant, of whom 17 568 (59.2%) initiated DOACs. Lower proportions of Black (65.2%) than Hispanic (67.6%) or White (68.0%) patients initiated any anticoagulant (P=0.001) and, lower proportions of Black (56.3%) and Hispanic (55.9%) than White (59.6%) patients (P=0.001) initiated DOACs. Compared with White patients, Black patients had significantly lower initiation of any anticoagulant (adjusted odds ratio, 0.89 [95% CI, 0.82-0.97]). The adjusted odds ratios for DOAC initiation were significantly lower for Black (0.72 [95% CI, 0.65-0.81]) and Hispanic (0.84 [95% CI, 0.70-1.00]) than White patients. The interaction between race and ethnicity and Medicare part D enrollment was nonsignificant for any anticoagulant (P=0.99) and DOAC (P=0.27) therapies. In dually enrolled Veterans Health Administration and Medicare patients with atrial fibrillation, Black patients were less likely to initiate any anticoagulant, and Black and Hispanic patients were less likely to initiate DOACs. Medicare part D enrollment did not moderate the associations between race and ethnicity and anticoagulant therapies.

Bleeding Outcomes Using Novel Oral Anticoagulants (NOACs) in End-Stage Renal Disease (ESRD) Versus Coumadin

Background:Patients with end-stage renal disease (ESRD) have been excluded from pivotal clinical trials with novel oral anticoagulants (NOACs). These patients are both at increased risk of venous and arterial thromboembolism and the risk of bleeding is also elevated, thus making treating such patients a challenge. Patients with ESRD and atrial fibrillation (AF) additionally have an increased risk of stroke, compared with less severe renal impairment. The risk of venous thromboembolism (VTE) is also positively correlated with CKD, suggesting ESRD is a hypercoagulable stage.Vitamin K antagonists (VKAs) such as warfarin are the mainstay of treatment as prevention or treatment of thromboembolic disease in ESRD, although the use is highly debated. Randomized controlled trials (RCTs) evaluating DOACs in AF all demonstrated non-inferiority for stroke or side effects, however these studies excluded patients on hemodialysis (HD) and those with creatinine clearance less than 25-30. There appears to be a dearth of high-quality evidence regarding use of DOACs in patients with ESRD. This retrospective analysis aims to evaluate whether use of NOACS causes increased bleeding rates compared to warfarin in the specific population of ESRD patients.Methods:Our study was a retrospective analysis of data using chart review of patients from an urban community medical center between the years 2017-2020. Retrospective data was entered into an electronic data form. Patients required a documented diagnosis of ESRD on hemodialysis and must have received at least one dose of anticoagulation to be included in analysis. Retrospective data pertaining to bleeding events were extracted for this analysis, including GI bleeding, intracranial bleeding, or any other major bleeding. Major bleeding events were defined as those requiring hospitalization or blood transfusion, or any other specific medical intervention. Demographics and clinical variables were presented using frequency and percentages. Patients were stratified into two groups, NOAC use and warfarin use. Continuous variables were analyzed using independent T test while chi square test was used for categorical variables. A p value <0.05 was considered statistically significant.Results:A total sample of 208 patients with ESRD on dialysis who had received anticoagulation were included in this analysis. 51% of patients were male and the majority were African American (79%). The mean age was 67. 43% of patients were on NOACs while 57% were on warfarin. Several other clinical factors were also recorded, with 38% of patients being obese, 92% with hypertension, 58% with diabetes, 45% with coronary artery disease, and 67% with atrial fibrillation. Bleeding outcomes were recorded for both patients who had received a NOAC or warfarin. 24 bleeding events were noted in NOAC group versus 44 events in the warfarin group. There was a higher rate of any major bleeding in the warfarin group versus NOAC group (37% vs 27%), however this not statistically significant (p=0.138)Limitations:More data will need to be collected to gain statistical significance of primary endpoint findings, and we have estimated that a total of approximately 680 patient outcomes would need to be analyzed to gain statistical significance. This data collection is currently underway. Other limitations include the retrospective nature of this study, with heavy reliance on review of patient charts for proper documentation of clinically relevant bleeding while on anticoagulation. Ideally, a prospective study would be better able to standardize data.Conclusions:Based on current data analysis, there is a trend towards warfarin having higher rates of bleeding compared to DOACs in ESRD patients on dialysis, 37% versus 27%, although this is only approaching statistical significance. These findings may shift current lines of thought that warfarin is a more acceptable choice of anticoagulation in ESRD patients given long term experience with this drug. Further studies are needed to make more definite conclusions. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Apixaban and rivaroxaban in obese patients treated for venous thromboembolism: Drug levels and clinical outcomes

BackgroundDirect oral anticoagulants (DOAC) use remains challenging in obese patients treated for Venous-Thrombo-Embolism (VTE) due to the paucity of prospective and dedicated studies. ObjectiveTo assess rivaroxaban and apixaban concentrations at different time-points after intake, in obese patients followed at a thrombosis center and treated for VTE; to define factors associated with DOAC levels outside the on-therapy ranges; and to evaluate bleeding and thrombosis rates during follow-up. MethodsObservational prospective study in two French University hospitals.Apixaban or rivaroxaban concentrations were measured after the first visit, regardless of last intake in obese patients receiving DOAC for VTE. Concentrations were compared to published reference values for non-obese patients. Demographic, clinical, biological and therapeutic data were collected. Univariate and multivariate analyses were performed to identify factors associated to DOAC concentrations outside the on-therapy ranges. ResultsOut of the 146 patients included, 22 (15%) had DOAC concentrations outside the on-therapy ranges, mainly in the rivaroxaban group (n = 17).Age ≤ 63 years, use of rivaroxaban and time since last intake ≤8 h were associated with DOAC concentrations outside the on-therapy ranges, in multivariable analysis.During the median follow-up of 16 months, two (1%) patients receiving apixaban had recurrent VTE. No patient had major bleeding, 11 (8%) patients had minor bleeding. ConclusionIn this specific prospective bi-centric study dedicated to VTE obese patients, use of DOACs at fixed doses led to concentrations similar to those of non-obese patients in a high proportion of patients, without any effect of the BMI, and with risk-benefit profile comparable to non-obese patients.