Direct-acting Oral Anticoagulants Research Articles

Gender and racial differences in outcomes among patients with NVAF treated with oral anticoagulants: a real-world evaluation of Medicare beneficiaries

Abstract Introduction Anticoagulation therapies are essential component of disease management for patients with atrial fibrillation (AF). Direct-acting oral anticoagulants (DOACs), such as apixaban, rivaroxaban, and dabigatran have shown greater benefit in reducing stroke/systemic embolism (SE) and bleeding risk compared to warfarin. However, few studies have assessed whether the beneficial effects of DOACs are consistent across gender and race. Purpose To assess the association between apixaban use and the risk of stroke/SE and major bleeding (MB) compared to warfarin, rivaroxaban, and dabigatran; and to determine whether the associations differ by gender and race. Methods Adult patients with AF diagnosis who initiated warfarin or a DOAC between January 1, 2013 and December 31, 2019 were identified using Medicare claims databases. Patients were classified into warfarin, apixaban, dabigatran, or rivaroxaban cohorts based on index prescription. Inverse Probability Treatment Weighting Cox proportional hazard models were used to assess the association between DOAC therapy initiation and risk of stroke/SE and MB, overall and among gender and race. Results Among a total of 1,079,540 included patients, 486,257 (45.04%) were in the apixaban cohort, 46,920 (4.35%) in the dabigatran cohort, 267,991 (24.82%) in the rivaroxaban cohort, and 278,372 (25.79%) in the warfarin cohort. Overall, the risks of stroke/SE and MB were lower for apixaban when compared with warfarin (stroke/SE: HR: 0.69 [95% confidence interval (CI): 0.65-0.74], MB: 0.59 [95% CI: 0.57-0.60]), rivaroxaban (stroke/SE: 0.88 [95% CI: 0.84-0.92], MB: 0.60 [95% CI: 0.58-0.61]) and dabigatran(stroke/SE: 0.88 [95% CI: 0.80-0.95], MB: 0.76 [95% CI: 0.72-0.80]). Among 140,587 females, the risk was lower for apixaban as compared with warfarin (stroke/SE: 0.72 [95% CI: 0.67-0.78], MB: 0.60 [95% CI: 0.58-0.62]) and rivaroxaban (stroke/SE: 0.88 [95% CI: 0.83-0.93], MB: 0.59 [95% CI: 0.57-0.61]), but similar risk of stroke/SE was noted for apixaban compared to dabigatran (stroke/SE: 0.98 [95% CI: 0.86-1.11]). Among 137,785 males, the risk of stroke/SE and MB were lower for apixaban compared with warfarin, rivaroxaban, and dabigatran. Among 16,288 Black patients, the risk was lower for apixaban as compared with warfarin (stroke/SE: 0.72 [95% CI: 0.63-0.83] MB: 0.59 [95% CI: 0.54-0.65]), also lower risk of MB was noted for apixaban as compared with rivaroxaban (MB: 0.56 [95% CI: 0.5-0.62]), but a similar risk of stroke/SE was noted compared to rivaroxaban and dabigatran, and similar risk of MB was noted compared to dabigatran. Among 247,642 White patients, the risk of stroke/SE and MB were lower for apixaban compared with warfarin, rivaroxaban, and dabigatran. All the results along with comparisons are displayed in the accompanying figures. Conclusion Apixaban demonstrated lower risk of stroke/SE and major bleeding when compared to warfarin, rivaroxaban, and dabigatran across most race and gender subgroups.Figure 1_Risk of stroke/SEFigure 2_Risk of Major Bleeding

The triglyceride-glucose index is a marker of thromboembolic events in atrial fibrillation patient under oral anticoagulation therapy

Abstract Background Atrial fibrillation (AF) increases the risk of stroke and thromboembolism; and appropriate risk stratification is central for better targeted patient management. The triglyceride-glucose (TyG) index indirectly assesses insulin resistance, and has been associated with cardiovascular risk. Purpose To investigate whether the TyG index could be a biomarker for assessing the risk of thromboembolic events in patients with AF. Methods We performed an observational prospective cohort study including outpatients diagnosed with AF starting vitamin K antagonist (VKA) or direct-acting oral anticoagulants (DOAC) therapy from January, 2016 to November, 2021. The primary endpoint was a combination of thromboembolic events, considered as the composite of myocardial infarction, and/or venous thromboembolism, and/or ischemic stroke/transient ischemic attack, over 2 years of follow-up. The TyG index was calculated as the natural logarithm (Ln) of the product of baseline plasma glucose and triglyceride using the following formula: Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. Patients were stratified into tertiles according to their TyG index (ie. first tertile: TyG index <4.59; second tertile: TyG index 4.59-4.83; third tertile: TyG index >4.83). Results We included 2907 patients (median age 77 [70-83] years; 52.5% female). The median TyG index was 4.71 (4.53-4.91), and 34% (989) where in the third tertile of TyG index. During a follow-up of 2 years, 209 (7.2%) patients suffered a thromboembolic event. Compared to patients in the first or second tertiles of TyG index, patients in the third tertile had an increased annual event rate of thromboembolic events (3.40 per 100 patient-years vs. 4.76 per 100 patient-years, p=0.043; and 3.41 per 100 patient-years vs. 4.76 per 100 patient-years, p=0.044), and higher incidence rate ratio (1.41 [95% CI 1.01-1.98], p=0.044 vs. first tertile; 1.40 [95% CI 1.01-1.97], p=0.044 vs. second tertile). Cox regression analyses adjusted for several risk factors demonstrated that the TyG index was an independent predictor for thromboembolic events (aHR 1.82; 95% CI 1.15-2.89; p=0.011). Patients in the third tertile of TyG index presented a 64% higher risk of thromboembolic events (aHR 1.64; 95% CI 1.17-2.29; p=0.004) (Table), with significantly lower event free survival (log-rank test p-value = 0.016) (Figure). Conclusions In this real-world cohort of AF patients under oral anticoagulation therapy, elevated TyG index was an independent risk factor for thromboembolic events. The TyG index is a simple, low-cost indicator, that could be used as a screening tool in everyday clinical practice.

The level is in the details: Why differences between direct-acting oral anticoagulants should be considered in the treatment of patients with epilepsy.

The level is in the details: Why differences between direct-acting oral anticoagulants should be considered in the treatment of patients with epilepsy.

Delphi consensus on oral anticoagulation management in special clinical situations in the cardiology setting.

Background: Management of oral anticoagulation (OAC) can be challenging, such as in complex cases of nonvalvular atrial fibrillation (NVAF).Materials & methods: A Delphi study comprising two rounds was used for gathering expert opinion through an online questionnaire (83 items grouped in 8 dimensions) on OAC management in specific clinical settings.Results: Consensus was reached for 79 items (95%) in round 1. Experts recommended direct-acting oral anticoagulants (DOACs) for pericardioversion, uninterrupted OAC for catheter ablation, and dual therapy with a DOAC and clopidogrel after percutaneous coronary intervention. They also recommended restarting OAC with a DOAC after an intracranial haemorrhage.Conclusion: The expert-based recommendations obtained may contribute to standardizing and guiding the management of OAC in complex clinical situations in cardiology.

Direct-Acting Oral Anticoagulants and Potential Inconsistencies with FDA-Approved Dosing for Non-Valvular Atrial Fibrillation: A Retrospective Real-World Analysis Across Nine US Healthcare Systems.

Direct-acting oral anticoagulants (DOACs) are recommended to reduce risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). However, DOAC dosing inconsistent with FDA-approved product labels is common and associated with poor clinical outcomes. Identify DOAC dosing inconsistent with FDA-approved product labels in ambulatory care patients with NVAF; identify variables associated with dosing lower and higher than label. Retrospective analysis using electronic health records from nine US healthcare systems. Adults with NVAF receiving DOAC therapy in 2022. Rates of label-inconsistent dosing; multivariable regression analysis to identify demographic and clinical variables associated with dosing lower and higher than label. Among 51,128 NVAF patients (56.1% male, 94.3% White, mean [SD] age 73.5 [10.5] years), 5008 (9.8%) were prescribed label-inconsistent doses of DOACs (6.8% lower and 3.0% higher than label). Age ≥ 75years, renal impairment, and hypertension were significantly associated with inconsistent dosing both higher and lower than label. Female sex and higher weight were significantly associated with dosing lower than label, as were heart failure, vascular or liver disease, and bleeding history. Dosing higher than label was significantly associated with male sex, race (African American/Black), weight < 60kg, and use of drugs with potential drug-drug interactions. When prescribed by primary care physicians, DOAC doses were 37% (95% CI, 27-49%) more likely to be lower than label and 30% (95% CI, 16-46%) more likely to be higher than label than when prescribed by cardiologists or electrophysiologists. Label-inconsistent dosing varied (6.7 to 15.8%) across participating systems. DOAC dosing inconsistent with label varied by demographics, clinical characteristics, prescriber specialty, and healthcare system, suggesting a need to monitor and assess dosing decisions in NVAF. Identification of variables associated with dosing inconsistencies may enable targeted interventions to ensure label-consistent dosing in vulnerable populations.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants vs Warfarin among Nursing Home Residents with Atrial Fibrillation: A Retrospective Cohort Study

ObjectiveResidents of nursing homes are usually excluded from clinical trials, including trials to assess treatments for common conditions such as nonvalvular atrial fibrillation (NVAF). We aimed to quantify the real-world comparative safety and effectiveness of direct-acting oral anticoagulants (DOACs) vs warfarin among nursing home residents with NVAF. DesignRetrospective cohort study using 100% national Minimum Data Set and linked Medicare claims from January 2011 through December 2018. Setting and ParticipantsLong-term care nursing home residents aged ≥66 years enrolled in fee-for-service Medicare. We included individuals diagnosed with NVAF newly initiating oral anticoagulants. MethodsWe identified exposure to DOACs (apixaban, dabigatran, rivaroxaban, and edoxaban) vs warfarin. Outcomes were hospitalization for ischemic stroke/systemic embolism, major bleeding, pneumonia (negative control outcome), and all-cause death. We used inverse probability of treatment weighting competing risk regression models for clinical outcomes and Cox proportional hazards regression for all-cause death. ResultsOf 38,983 individuals newly initiating anticoagulants, 19,366 (49.7%) initiated DOACs and 19,617 (50.3%) initiated warfarin. In the inverse probability of treatment weighting analysis, compared with warfarin, there was no statistically significant association between DOAC use and ischemic stroke/systemic embolism [4.5 vs 4.7 events per 100 person-years; adjusted hazard ratio (aHR), 0.94; 95% CI, 0.84–1.05] or major bleeding (12.6 vs 12.4 events per 100 person-years; aHR, 1.03; 95% CI, 0.96–1.10). DOACs use was associated with a modest but statistically significant lower risk of all-cause death (48.1 vs 49.0 events per 100 person-years; IPTW analysis aHR, 0.95; 95% CI, 0.91–0.98). Conclusions and ImplicationsAmong nursing home residents with NVAF, DOACs and warfarin were associated with a similar risk of ischemic stroke/systemic embolism and major bleeding. However, the use of DOACs was associated with a slightly reduced risk of all-cause mortality.

Non-Medical Switching or Discontinuation Patterns among Patients with Non-Valvular Atrial Fibrillation Treated with Direct Oral Anticoagulants in the United States: A Claims-Based Analysis.

This study assessed direct-acting oral anticoagulant (DOAC) switching/discontinuation patterns in patients with non-valvular atrial fibrillation (NVAF) in 2019, by quarter (Q1-Q4), and associated socioeconomic risk factors. Adults with NVAF initiating stable DOAC treatment (July 2018-December 2018) were selected from Symphony Health Solutions' Patient Transactional Datasets (April 2017-January 2021). Switching/discontinuation rates were reported in 2019 Q1-Q4, separately. Non-medical switching/discontinuation (NMSD) was defined as the difference between switching/discontinuation rates in Q1 and mean rates across Q2-Q4. The associations of socioeconomic factors with switching/discontinuation were assessed. Of 46,793 patients (78.7% ≥ 65 years; 52.6% male; 7.7% Black), 18.0% switched/discontinued their initial DOAC in Q1 vs. 8.8% on average in Q2-Q4, corresponding to an NMSD of 9.2%. During the quarter following the switch/discontinuation, more patients who switched/discontinued in Q1 remained untreated (Q1: 77.0%; Q2: 74.3%; Q3: 71.2%) and fewer reinitiated initial DOAC (Q1: 17.6%; Q2: 20.8%; Q3: 24.0%). Factors associated with the risk of switching/discontinuation in Q1 were race, age, gender, insurance type, and household income (all p < 0.05). More patients with NVAF switched/discontinued DOACs in Q1 vs. Q2-Q4, and more of them tended to remain untreated relative to those who switched/discontinued later in the year, suggesting a potential long-term impact of NMSD. Findings on factors associated with switching/discontinuation highlight potential socioeconomic discrepancies in treatment continuity.

Assays for Monitoring Apixaban and Rivaroxaban in Emergency Settings, State-of-the-Art Routine Analysis, and Volumetric Absorptive Microsamples Deliver Discordant Results.

Our aim was to compare the performance of complementary clinical laboratory approaches to monitoring exposure to apixaban and rivaroxaban, the most prescribed direct-acting oral anticoagulants (DOAC's): an automated commercial anti-Xa chromogenic assay suitable for emergency and pre-surgery testing and a laboratory-developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) method employed for non-emergency analysis in plasma and in dried blood volumetric absorptive microsamples (VAMS) collectible by the patients in their homes. The full validation of the LC-MS/MS method was performed. Cross-validation of the methodologies was accomplished by processing 60 specimens collected for whole blood count and DOAC monitoring in a central clinical laboratory. For VAMS samples, dried plasma and whole blood calibrators were found to be suitable, and a cycle run for seven days could be implemented for rational and economic sample processing. The anti-Xa chromogrenic assay and the LC-MS/MS method delivered discordant plasma analyte concentrations. Moreover, the lack of agreement between plasma and VAMS concentrations was observed. Clinical laboratories must be aware of the differences between the performance of apixaban and rivaroxaban LC-MS/MS and anti-Xa assays. Hematocrit must always be measured along with VAMS samples to obtain accurate results.

Chronic Anticoagulation in Patients Who Have Atrial Fibrillation Undergoing Outpatient Total Knee Arthroplasty: A Retrospective Matched Cohort Study

BackgroundPatients who have atrial fibrillation frequently require long-term anticoagulation with warfarin or a direct-acting oral anticoagulant (DOAC), such as apixaban or rivaroxaban, to avoid vascular complications. However, the impact of anticoagulant use on postoperative complications following total knee arthroplasty (TKA) in an outpatient setting has not been thoroughly elucidated. The purpose of this study was to examine the impact of anticoagulant use on early postoperative complications among atrial fibrillation patients undergoing outpatient TKA. MethodsAn insurance claims database was queried to identify all patients who underwent outpatient TKA between January 2010 and April 2022. There were two cohorts of patients, with associated 1:1 matched controls, who had atrial fibrillation and filled a prescription of either warfarin (N = 4,396) or DOAC (N = 5,383) for at least 30 days. The mean age was 70 years (range, 51 to 84), and 47.9% were women in the warfarin cohort, while the mean age was 70 years and 49.2% were women in the DOAC cohort. Postoperative 30-day medical and 90-day surgical complications were subsequently compared. ResultsPatients on warfarin had a higher incidence of pulmonary embolism (1.1 versus 0.2%, P < 0.001) and a lower incidence of TKA revision (0.1 versus 0.4%, P = 0.003) than matched controls. Similarly, patients on DOACs exhibited a higher incidence of pneumonia (1.4 versus 0.6%, P < 0.001) and myocardial infarction (3.2 versus 1.5%, P < 0.001) and a lower incidence of wound dehiscence (0.1 versus 0.5%, P < 0.001), joint infection (0.4 versus 0.9%, P = 0.002), and TKA revision (0.1 versus 0.4%, P = 0.002) than matched controls. ConclusionsAtrial fibrillation patients on long-term anticoagulants undergoing outpatient TKA experience higher rates of medical complications and lower rates of surgical complications than matched controls. Thus, patients on long-term anticoagulants may be considered for outpatient TKA but should be counseled appropriately on associated medical risks.

Management of Heparin-Induced Thrombocytopenia: A Contemporary Review.

Heparin-induced thrombocytopenia (HIT) is a life- and limb-threatening immune-mediated emergency classically associated with heparin therapy. This review focuses on type II HIT, characterized by the development of antibodies against platelet-factor 4 (PF4) bound to heparin after exposure, causing life-threatening thrombocytopenia, arterial thrombosis, and/or venous thrombosis. The high morbidity and mortality rates emphasize the need for early recognition and urgent intervention with discontinuation of heparin and initiation of non-heparin anticoagulation. We discuss the management of HIT with an emphasis on recent developments: (i) incorporating the phases of HIT (i.e., suspected, acute, subacute A and B, and remote) into its management, categorized according to platelet count, immunoassay, and functional assay results and (ii) direct-acting oral anticoagulants (DOACs), which are increasingly used in appropriate cases of acute HIT (off-label). In comparison to parenteral options (e.g., bivalirudin and danaparoid), they are easier to administer, are more cost-effective, and obviate the need for transition to an oral anticoagulant after platelet recovery. We also identify the knowledge gaps and suggest areas for future research.

SEOM clinical guidelines on venous thromboembolism (VTE) and cancer (2023)

The Spanish Society of Medical Oncology (SEOM) last published clinical guidelines on venous thromboembolism (VTE) and cancer in 2019, with a partial update in 2020. In this new update to the guidelines, SEOM seeks to incorporate recent evidence, based on a critical review of the literature, to provide practical current recommendations for the prophylactic and therapeutic management of VTE in patients with cancer. Special clinical situations whose management and/or choice of currently recommended therapeutic options (low-molecular-weight heparins [LMWHs] or direct-acting oral anticoagulants [DOACs]) is controversial are included.

Impact of prior oral anticoagulation therapies on post-discharge outcomes after COVID-19: Results from aglobal federated health network analysis.

The impact of chronic oral anticoagulant (OACs) use on long-term post-discharge outcomes after coronavirus disease 2019 (COVID-19) hospitalisation remains unclear. Herein, we compared clinical outcomes up to 2-years after COVID-19 hospitalisation between patients on vitamin K antagonists (VKAs), direct-acting OACs (DOACs) and no OAC therapy. Data from TriNetX, a global federated health research network, were used. Adult patients on VKAs, DOACs or no OAC therapy at diagnosis of COVID-19 between 20 January 2020 and 31 December 2021, who were hospitalised for COVID-19, were included. The primary outcomes were all-cause mortality, ischaemic stroke/transient ischaemic attack (TIA)/systemic embolism (SE) and the composite of intracranial haemorrhage (ICH)/gastrointestinal bleeding, at 2 years after COVID-19 hospitalisation. We included 110,834 patients with COVID-19. Following propensity score matching (PSM), we identified a decreased mortality risk in DOAC-treated patients compared to the no OAC cohort (RR .808, 95% CI .751-.870). A higher risk of ischaemic stroke/TIA/SE was observed in VKA users compared to DOAC users (RR 1.100, 95% CI 1.020-1.220) and in VKA users compared to patients not taking OAC (RR 1.400, 95% CI 1.140-1.720). VKA use was associated with a greater risk of ICH/gastrointestinal bleeding than DOAC users (RR 1.198, 95% CI 1.066-1.347), while DOAC users had a lower risk compared to no OAC-treated patients (RR .840, 95% CI .754-.936). COVID-19 patients taking prior DOACs were associated with lower long-term mortality risk and ICH/gastrointestinal bleeding than patients not taking OAC. Compared to patients on DOACs, VKA users were associated with higher risks of mortality, ischaemic stroke/TIA/SE and ICH/gastrointestinal bleeding.

Anticoagulation strategy for patients presenting with ischemic strokes while using a direct oral anticoagulant: A systematic review and meta-analysis.

While direct-acting oral anticoagulants (DOACs) have established efficacy in reducing the risk of ischemic stroke, they still leave a residual risk of stroke, which may be greater in practice (0.7-2.3%) than in controlled clinical trial settings. This meta-analysis examines four therapeutic approaches following a stroke in patients already on DOACs: continuing with the same DOAC, changing to a different DOAC, increasing the current DOAC dosage, or switching to a vitamin K antagonist (VKA), such as warfarin. Systematic review of literature from the MEDLINE, Embase, and Cochrane databases, was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The analysis focused on six studies with varied patient demographics, examining as outcomes as recurrent ischemic stroke, intracranial hemorrhage, other bleeding events, and mortality. Six studies comprising 12,159 patients were included, all of them were observational. Patients who remained on their initial DOAC regimen had a lower risk of experiencing ischemic strokes (risk ratio (RR) 0.55; 95% confidence interval (CI) 0.43-0.70; p < 0.001; I2 = 0%), intracranial hemorrhage (RR 0.37; 95% CI 0.25-0.55; p < 0.001; I2 = 0%), and hemorrhagic events (RR 0.44; 95% CI 0.30-0.63; p < 0.001; I2 = 6%) compared to those who were switched to warfarin, with an increase in mortality rates (hazard ratio (HR) 1.85; 95% CI 1.06-3.24; p = 0.03; I2 = 84%). In contrast, neither changing to a different DOAC nor adjusting the dose proved to be more effective than the original regimen. Post-stroke adjustments to anticoagulation therapy-whether altering the drug or its dosage-do not yield additional benefits. In addition, the results suggest that warfarin may be less effective than DOACs for preventing stroke recurrence, bleeding complications, and death in this patient population.

Navigating the bleeding risk dilemma in patients with atrial fibrillation on therapy with direct-acting oral anticoagulants: Comparing the HAS-BLED vs. DOAC Score

Navigating the bleeding risk dilemma in patients with atrial fibrillation on therapy with direct-acting oral anticoagulants: Comparing the HAS-BLED vs. DOAC Score

Patients with atrial fibrillation and common exclusion criteria from clinical trials are at high risk of clinical events: the Murcia AF Project II (MAFP-II) cohort study

BackgroundSome clinical characteristics and comorbidities in atrial fibrillation (AF) patients are exclusion criteria in randomized clinical trials (RCTs) investigating oral anticoagulants (OAC). However, these conditions are present also in everyday clinical practice patients. We compared the risk of adverse clinical outcomes between patients with and without RCT exclusion criteria.MethodsThe Murcia AF Project II was an observational cohort study including AF outpatients starting vitamin K antagonists (VKAs) from July 2016 to June 2018. For the selection of the exclusion criteria, the four pivotal RCTs of direct-acting OAC (DOACs) were used as reference. During 2 years, all ischemic strokes/transient ischemic attacks, major adverse cardiovascular events (MACEs), major bleeds, and all-cause deaths were recorded.Results1050 patients (51.5% female, median age 77 years) were included, of whom 368 (35%) met at least one exclusion criterion for RCTs. During follow-up, the incidence rate ratios for major bleeding, MACE and all-cause mortality were higher among patients with exclusion criteria (all p < 0.001). Patients fulfilling at least one exclusion criterion had increased risks of major bleeding (aHR 1.48; 95% CI 1.22–1.81; p < 0.001), MACE (aHR 1.51, 95% CI 1.10–2.09, p = 0.012), and mortality (aHR 3.22, 95% CI 2.32–4.48, p < 0.001), as well as a lower event-free survival (all log-rank p < 0.001).ConclusionsIn this AF cohort taking VKAs, more than one-third had at least one RCT exclusion criteria, which translates into higher risk of major bleeding, MACE, and death. These observations should be considered when translating RCTs results to AF patients for a proper and a more patient-centered management.

Risk Factors for Emergency Room Visits in Patients with Digestive Bleeding Associated with Direct-Acting Anticoagulants

Gastrointestinal bleeding is the main cause of admission to the emergency services of patients taking direct-acting oral anticoagulants (DOACs). Little is known about the effects of treatment modification on the risk of readmission, especially in elderly patients. This retrospective observational study included elderly patients with atrial fibrillation who were on DOACs and who were admitted to the emergency department due to gastrointestinal bleeding from 2018 to 2023. To evaluate the risk factors for readmission 90 days after discharge, a multivariate analysis was conducted, which included patient comorbidities, concomitant treatment, changes in anticoagulant treatment, and the prescription of DOACs at discharge. One hundred and thirty-nine patients were included. At discharge, anticoagulant therapy was modified in 44 (31.6%) patients, 16 (36.3%) patients were switched from one DOAC to another, 23 (52.2%) to heparins, and 5 (11.3%) to vitamin K antagonists. A total of 21 (15.1%) patients returned to the emergency department within 90 days after discharge due to new bleeding events. No significant differences were observed depending on the modification of treatment at discharge. The presence of cognitive impairment was the only factor associated with readmission at 90 days. Patients who undergo treatment with DOACs and have gastrointestinal bleeding at discharge are at risk of readmission to the emergency room due to new bleeding events. No benefit was observed in modifying anticoagulant treatment at discharge.

Incidence and predictors of major gastrointestinal bleeding in patients on aspirin, low-dose rivaroxaban, or the combination: Secondary analysis of the COMPASS randomised controlled trial.

The incidence of major gastrointestinal bleeding (GIB) in patients on low-dose direct-acting oral anticoagulants (DOACs) is relatively unknown. Estimates from randomised controlled trials (RCTs) are lacking. To assess GIB incidence and predictors from RCT data of patients on aspirin, low-dose rivaroxaban, or both. This was a secondary analysis of RCT data wherein patients received aspirin 100 mg daily and rivaroxaban 2.5 mg b.d., aspirin alone, or rivaroxaban 5 mg b.d. Patients were followed from 2013 to 2016 at 602 centres. Outcomes included overall, upper, and lower GIB. We employed multivariable logistic regression to yield odds ratios (ORs) and 95% confidence intervals for potential exposures. Among 27,395 patients, the annual incidence of GIB on rivaroxaban 2.5 mg b.d. with aspirin was 801.7 per 100,000 compared with 372.3 in 100,000 for aspirin. Age (OR 4.16, 2.53-6.82 for ≥75 vs. 55-64), peptic ulcer disease (PUD, OR 1.57, 1.01-2.44), liver disease (OR 2.09, 1.01-4.33), hypertension (OR 1.42, 1.04-1.94), and smoking (OR 1.85, 1.26-2.73) were associated with overall GIB. Kidney disease (OR 1.68, 1.12-2.51) was significantly associated with upper GIB, whereas diverticular disease (OR 3.75, 1.88-7.49) was associated with lower GIB. Addition of rivaroxaban to aspirin was associated more with lower GIB (OR 2.82, 1.64-4.84) than upper GIB (OR 1.86, 1.18-2.92). We established incidences and identified risk factors for GIB in users of low-dose DOACs. Novel risk factors included current or former smoking and diverticulosis. Future studies should aim to validate these risk factors.

Veterans Affairs Medical Center Racial and Ethnic Composition and Initiation of Anticoagulation for Atrial Fibrillation

Racial and ethnic disparities exist in anticoagulation therapy for atrial fibrillation (AF). Whether medical center racial and ethnic composition is associated with these disparities is unclear. To determine whether medical center racial and ethnic composition is associated with overall anticoagulation and disparities in anticoagulation for AF. Retrospective cohort study of Black, White, and Hispanic patients with incident AF from 2018 to 2021 at 140 Veterans Health Administration medical centers (VAMCs). Data were analyzed from March to November 2023. VAMC racial and ethnic composition, defined as the proportion of patients from minoritized racial and ethnic groups treated at a VAMC, categorized into quartiles. VAMCs in quartile 1 (Q1) had the lowest percentage of patients from minoritized groups (ie, the reference group). The odds of initiating any anticoagulant, direct-acting oral anticoagulant (DOAC), or warfarin therapy within 90 days of an index AF diagnosis, adjusting for sociodemographics, medical comorbidities, and facility factors. The cohort comprised 89 791 patients with a mean (SD) age of 73.0 (10.1) years; 87 647 (97.6%) were male, 9063 (10.1%) were Black, 3355 (3.7%) were Hispanic, and 77 373 (86.2%) were White. Overall, 64 770 individuals (72.1%) initiated any anticoagulant, 60 362 (67.2%) initiated DOAC therapy, and 4408 (4.9%) initiated warfarin. Compared with White patients, Black and Hispanic patients had lower rates of any anticoagulant and DOAC therapy initiation but higher rates of warfarin initiation across all quartiles of VAMC racial and ethnic composition. Any anticoagulant therapy initiation was lower in Q4 than Q1 (69.8% vs 74.9%; adjusted odds ratio [aOR], 0.80; 95% CI, 0.69-0.92; P < .001). DOAC and warfarin initiation were also lower in Q4 than in Q1 (DOAC, 69.4% vs 65.3%; aOR, 0.85; 95% CI, 0.74-0.97; P < .001; warfarin, 5.4% vs 4.5%; aOR, 0.82; 95% CI, 0.67-1.00; P < .001). In adjusted models, patients in Q4 were significantly less likely to initiate any anticoagulant therapy than those in Q1 (aOR, 0.88; 95% CI, 0.78-0.99). Patients in Q3 (aOR, 0.75; 95% CI, 0.60-0.93) and Q4 (aOR, 0.69; 95% CI, 0.55-0.87) were significantly less likely to initiate warfarin therapy than those in Q1. There was no significant difference in the adjusted odds of initiating DOAC therapy across racial and ethnic composition quartiles. Although significant Black-White and Hispanic-White differences in initiation of any anticoagulant, DOAC, and warfarin therapy were observed, interactions between patient race and ethnicity and VAMC racial composition were not significant. In a national cohort of VA patients with AF, initiation of any anticoagulant and warfarin, but not DOAC therapy, was lower in VAMCs serving more minoritized patients.

EE36 Comparison of Healthcare Resource Utilization and Costs in Patients With Venous Thromboembolism Receiving Direct-Acting Oral Anticoagulants or Low Molecular Weight Heparins: A Real-World Data Analysis

EE36 Comparison of Healthcare Resource Utilization and Costs in Patients With Venous Thromboembolism Receiving Direct-Acting Oral Anticoagulants or Low Molecular Weight Heparins: A Real-World Data Analysis

Thinking Three-Dimensionally: A Self- and Externally-Controlled Approach to Screening for Drug-Drug-Drug Interactions Among High-Risk Populations.

The global rise in polypharmacy has increased both the necessity and complexity of drug-drug interaction (DDI) assessments, given the growing potential for interactions involving more than two drugs. Leveraging large-scale healthcare claims data, we piloted a semi-automated, high-throughput case-crossover-based approach for drug-drug-drug interaction (3DI) screening. Cases were direct-acting oral anticoagulant (DOAC) users with either a major bleeding event during ongoing dispensings for potentially interacting, enzyme-inhibiting antihypertensive drugs (AHDs) (Study 1), or a thromboembolic event during ongoing dispensings for potentially interacting, enzyme-inducing antiseizure medications (ASMs) (Study 2). 3DI detection was based on screening for additional drug exposures that served as acute outcome triggers. To mitigate direct effects and confounding by concomitant drugs, self-controlled estimates were adjusted using negative cases (external "control" DOAC users with the same outcomes but co-dispensings for non-interacting AHDs or ASMs). Signal thresholds were set based on P-values and false discovery rate q-values to address multiple comparisons. Study 1: 285 drugs were examined among 3,306 episodes. Self-controlled assessments with q-value thresholds yielded 9 3DI signals (cases) and 40 DDI signals (negative cases). External adjustment generated 10 3DI signals from the P-value threshold and no signals from the q-value threshold. Study 2: 126 drugs were examined among 604 episodes. Assessments with P-value thresholds yielded 3 3DI and 26 DDI signals following self-control, as well as 4 3DI signals following adjustment. No 3DI signals met the q-value threshold. The presented self- and externally-controlled approach aimed to advance paradigms for real-world higher order drug interaction screening among high-susceptibility populations with pre-existent DDI risk.