Direct-acting Oral Anticoagulant Therapy 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

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.

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.

Development and validation of the DOAC Score: a novel bleeding risk prediction tool for patients with atrial fibrillation

Abstract Background Clinicians and patients must balance the ischemic benefits and bleeding risks when deciding to anticoagulate patients with atrial fibrillation (AF). Current clinical decision tools for assessing bleeding risk have limited performance and were developed for individuals anticoagulated with warfarin. Purpose This study develops and validates a clinical risk score to personalize estimates of bleeding risk for individuals with AF taking direct-acting oral anticoagulants (DOACs). Methods Among individuals taking dabigatran 150mg twice per day from 44 countries and 951 centers in this secondary analysis of the RE-LY trial, a risk score was developed to determine the probability for bleeding, based on covariates derived in a Cox proportional hazards model. The risk prediction model was internally validated with bootstrapping. We then refined the model in the GARFIELD-AF registry, with individuals taking dabigatran, edoxaban, rivaroxaban, and apixaban. To determine generalizability in external cohorts and among individuals on different DOACS, the risk prediction model was validated in the COMBINE-AF pooled clinical trial cohort and the RAMQ administrative database. The primary outcome was major bleeding. The risk score, termed the DOAC Score, was compared to the HAS-BLED score. Results Of the 5684 patients in RE-LY, 386 experienced a major bleeding event, within a median follow-up of 1.74-years. The prediction model was well-calibrated (goodness-of-fit P = 0.57) and had an optimism-corrected C statistic of 0.73 after internal validation with bootstrapping. The DOAC Score assigned points for age, creatinine clearance/glomerular filtration rate, underweight status, stroke/transient ischemic attack/embolism history, diabetes, hypertension, antiplatelet use, non-steroidal anti-inflammatory use, liver disease, and bleeding history, with each additional point scored associated with a 48.7% (95% CI: 38.9%-59.3%, P&amp;lt;0.001) increase in major bleeding in RE-LY. The score had superior performance to the HAS-BLED score in RE-LY (C Statistic: 0.73 vs 0.60, P for difference &amp;lt;0.001) and among 12,296 individuals in GARFIELD-AF (C statistic: 0.71 vs 0.66, P for Difference = 0.025). The DOAC Score had stronger predictive performance than the HAS-BLED score in both validation cohorts, including 25,586 individuals in COMBINE-AF (C statistic: 0.67 vs 0.63, P for Difference &amp;lt;0.001) and 11,945 individuals in RAMQ (C statistic: 0.65 vs 0.58, P for Difference &amp;lt;0.001). Conclusion In individuals with AF on DOAC therapy, the DOAC Score can help stratify patients based on expected bleeding risk.

Development and Validation of the DOAC Score: A Novel Bleeding Risk Prediction Tool for Patients With Atrial Fibrillation on Direct-Acting Oral Anticoagulants.

Current clinical decision tools for assessing bleeding risk in individuals with atrial fibrillation (AF) have limited performance and were developed for individuals treated with warfarin. This study develops and validates a clinical risk score to personalize estimates of bleeding risk for individuals with atrial fibrillation taking direct-acting oral anticoagulants (DOACs). Among individuals taking dabigatran 150 mg twice per day from 44 countries and 951 centers in this secondary analysis of the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy), a risk score was developed to determine the comparative risk for bleeding on the basis of covariates derived in a Cox proportional hazards model. The risk prediction model was internally validated with bootstrapping. The model was then further developed in the GARFIELD-AF registry (Global Anticoagulant Registry in the Field-Atrial Fibrillation), with individuals taking dabigatran, edoxaban, rivaroxaban, and apixaban. To determine generalizability in external cohorts and among individuals on different DOACs, the risk prediction model was validated in the COMBINE-AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) pooled clinical trial cohort and the Quebec Régie de l'Assurance Maladie du Québec and Med-Echo Administrative Databases (RAMQ) administrative database. The primary outcome was major bleeding. The risk score, termed the DOAC Score, was compared with the HAS-BLED score. Of the 5684 patients in RE-LY, 386 (6.8%) experienced a major bleeding event, within a median follow-up of 1.74 years. The prediction model had an optimism-corrected C statistic of 0.73 after internal validation with bootstrapping and was well-calibrated based on visual inspection of calibration plots (goodness-of-fit P=0.57). The DOAC Score assigned points for age, creatinine clearance/glomerular filtration rate, underweight status, stroke/transient ischemic attack/embolism history, diabetes, hypertension, antiplatelet use, nonsteroidal anti-inflammatory use, liver disease, and bleeding history, with each additional point scored associated with a 48.7% (95% CI, 38.9%-59.3%; P<0.001) increase in major bleeding in RE-LY. The score had superior performance to the HAS-BLED score in RE-LY (C statistic, 0.73 versus 0.60; P for difference <0.001) and among 12 296 individuals in GARFIELD-AF (C statistic, 0.71 versus 0.66; P for difference = 0.025). The DOAC Score had stronger predictive performance than the HAS-BLED score in both validation cohorts, including 25 586 individuals in COMBINE-AF (C statistic, 0.67 versus 0.63; P for difference <0.001) and 11 945 individuals in RAMQ (C statistic, 0.65 versus 0.58; P for difference <0.001). In individuals with atrial fibrillation potentially eligible for DOAC therapy, the DOAC Score can help stratify patients on the basis of expected bleeding risk.

Direct-Acting Oral Anticoagulant Therapy in Cancer Patients-A Review.

Venous thromboembolism (VTE) is an important aspect in cancer patients. There are various pharmacological methods used for thrombotic event treatment. DOACs (direct-acting oral anticoagulants) are gaining popularity among both physicians and researchers and are slowly starting to replace VKAs (vitamin K antagonists), thus becoming a substitute or alternative option for LMWHs (low-molecular-weight heparins). In this article, we present DOACs' main therapeutic advantages and disadvantages in patients with cancer. The only major concern with using DOACs is the higher risk of bleeding; however, there are discrepancies in this matter. There are still some types of cancer for which DOACs are not recommended. Specific cancer types may influence the efficacy of DOAC therapy. Additionally, race and ethnicity may affect therapy in cancer patients with DOACs. A sizeable number of clinical trials are focused on comparing DOACs with other anticoagulants. The current guidelines of different scientific associations are not unanimous in their DOAC assessments. There is still a need for more evidence of DOACs' potential advantages over other methods of anticoagulation in cancer patients to facilitate their position in this recommendation. This literature review presents the current state of knowledge about the use of DOACs in patients with neoplastic growth.

Clinical outcomes and predictors of a gap in direct-acting oral anticoagulant therapy in the elderly: A time-varying analysis of a nationwide cohort study

IntroductionAs direct-acting oral anticoagulants (DOACs) have short half-lives of around 12 h, even a short gap in DOAC therapy may diminish anticoagulation effects, increasing risks of adverse clinical outcomes. We aimed to evaluate clinical consequences of a gap in DOAC therapy with atrial fibrillation (AF) and to identify its potential predictors. Materials and methodsIn this retrospective cohort study, we included DOAC users aged over 65 years with AF from the 2018 Korean nationwide claims database. We defined a gap in DOAC therapy as no claim for a DOAC one or more days after the due date of a refill prescription. We used a time-varying-analysis method. The primary outcome was a composite of death and thrombotic events including ischemic stroke/transient ischemic attack or systemic embolism. Potential predictors of a gap included sociodemographic and clinical factors. Results and conclusionsAmong 11,042 DOAC users, 4857 (44.0 %) patients had at least one gap. Standard national health insurance, non-metropolitan locations of medical institutions, history of liver disease, chronic obstructive pulmonary disease, cancer, or dementia, and use of diuretics or non-oral agents were associated with increased risks of a gap. In contrast, history of hypertension, ischemic heart disease, or dyslipidemia were associated with a decreased risk of a gap. A short gap in DOAC therapy was significantly associated with a higher risk of the primary outcome compared to no gap (hazard ratio 4.04, 95 % confidence interval 2.95–5.52). The predictors could be utilized to identify at-risk patients to provide additional support to prevent a gap.

Trajectories of Oral Anticoagulation Adherence and Associated Clinical Outcomes During Long-Term Anticoagulation Among Medicare Beneficiaries With Venous Thromboembolism.

Little is known about anticoagulation medication nonadherence patterns impacting effectiveness and safety outcomes in clinical practice. We identified adherence trajectories of extended therapy with direct-acting oral anticoagulants (DOACs) and warfarin after 6 months initial anticoagulant therapy among Medicare beneficiaries with venous thromboembolism (VTE). We further assessed the associated recurrent VTE and major bleeding risks. Using group-based trajectory models, this retrospective cohort study identified distinct beneficiary subgroups with similar adherence patterns of extended-phase anticoagulant treatment (DOACs or warfarin) for patients with VTE who completed 6 months of initial anticoagulant treatment. We examined associations between adherence trajectories and risks of recurrent VTE and major bleeding using inverse probability treatment weighted Cox proportional hazards models. Compared with no extended treatment, consistently high DOAC adherence was associated with decreased recurrent VTE risk (hazard ratio [HR] = 0.33, 95% confidence interval [CI] = 0.21-0.51) without increased major bleeding risk, and consistently high warfarin adherence was associated with decreased recurrent VTE risk (HR = 0.62, 95% CI = 0.40-0.95) and increased major bleeding risk (HR = 1.64, 95% CI = 1.12-2.41). Gradually declining adherence to DOACs (HR = 1.80, 95% CI = 1.07-3.03) or warfarin (HR = 2.34, 95% CI = 1.57-3.47) was associated with increased bleeding risk with no change in recurrent VTE risk. This real-world evidence suggests persistently adhering to extended DOAC therapy is associated with lower recurrent VTE risk without increasing major bleeding among Medicare beneficiaries with VTE. Persistently adhering to extended warfarin therapy was associated with lower recurrent VTE risk but higher major bleeding risk.

Outcomes with direct-acting oral anticoagulants in patients with a history of bariatric surgery: a retrospective cohort study

<h2>Abstract</h2><h3>Background</h3> Patients who undergo bariatric surgery have major physiologic changes in their gastrointestinal tract, which can theoretically alter drug absorption and pharmacokinetics. This is especially concerning for drugs with a narrow therapeutic index, as small changes in absorption can have significant effects on safety and efficacy. One class of interest is direct-acting oral anticoagulants (DOACs), for which there is a paucity of data in this population. <h3>Objective</h3> To characterize the use of DOACs (apixaban, dabigatran, rivaroxaban) in patients with a history of bariatric surgery and incidence of clotting and bleeding events. <h3>Setting</h3> Public healthcare system/university hospital, United States. <h3>Methods</h3> This retrospective cohort study included adult patients who were prescribed a DOAC for the prophylaxis or treatment of venous thromboembolism or for stroke and systemic embolism prevention in atrial fibrillation between January 2011 and December 2018. <h3>Results</h3> A total of 191 patients with a history of bariatric surgery were included. Clotting events occurred in 11 of 191 patients (5.8%) receiving DOAC therapy, with a calculated clotting rate of 3.9 clots per 100 person-years. Bleeding events occurred in 42 of 191 patients (22%) receiving a DOAC, with a calculated bleeding rate of 17.1 bleeds per 100 person-years. The use of rivaroxaban versus apixaban was associated with a statistically significant increased risk of bleeding in patients with a history of bariatric surgery. <h3>Conclusion</h3> In this retrospective cohort of bariatric surgery patients receiving DOACs, we found clotting rates consistent with expected rates and bleeding rates above expected rates based on historical data. We also found an increased risk of bleeding in rivaroxaban users compared with apixaban users. Careful evaluation of bleeding risks in bariatric surgery patients is encouraged.

Guideline-discordant dosing of direct-acting oral anticoagulants in the veterans health administration

BackgroundClear guidelines exist to guide the dosing of direct-acting oral anticoagulants (DOACs). It is not known how consistently these guidelines are followed in practice.MethodsWe studied patients from the Veterans Health Administration (VA) with non-valvular atrial fibrillation who received DOACs (dabigatran, rivaroxaban, apixaban) between 2010 and 2016. We used patient characteristics (age, creatinine, body mass) to identify which patients met guideline recommendations for low-dose therapy and which for full-dose therapy. We examined how often patient dosing was concordant with these recommendations. We examined variation in guideline-concordant dosing by site of care and over time. We examined patient-level predictors of guideline-concordant dosing using multivariable logistic models.ResultsA total of 73,672 patients who were prescribed DOACS were included. Of 5837 patients who were recommended to receive low-dose therapy, 1331 (23%) received full-dose therapy instead. Of 67,935 patients recommended to receive full-dose therapy, 4079 (6%) received low-dose therapy instead. Sites varied widely on guideline discordant dosing; on inappropriate low-dose therapy, sites varied from 0 to 15%, while on inappropriate high-dose therapy, from 0 to 41%. Guideline discordant therapy decreased by about 20% in a relative sense over time, but its absolute numbers grew as DOAC therapy became more common. The most important patient-level predictors of receiving guideline-discordant therapy were older age and creatinine function being near the cutoff value.ConclusionsA substantial portion of DOAC prescriptions in the VA system are dosed contrary to clinical guidelines. This phenomenon varies widely across sites of care and has persisted over time.

Bleeding Outcomes After Dental Extraction in Patients Under Direct-Acting Oral Anticoagulants vs. Vitamin K Antagonists: A Systematic Review and Meta-Analysis.

Background: The current systematic review aimed to compare bleeding outcomes in dental extraction patients receiving uninterrupted Direct-acting oral anticoagulant (DOAC) or Vitamin K antagonists (VKAs) for various systemic diseases. Methods: PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases were searched for randomized controlled trials, controlled clinical trials, prospective and retrospective cohort studies, and case control studies, conducted on adult patients undergoing dental extraction under uninterrupted DOAC or VKAs therapy and reporting bleeding outcomes. The search was conducted up to March 31, 2021. We pooled data to calculate risk ratios (RR) with 95% confidence intervals (CI) in a random-effects model. Results: Eight studies comparing 539 patients on DOAC therapy and 574 patients on VKAs were included. Meta-analysis indicated a statistically significant lower bleeding risk in patients under DOAC therapy (RR 0.68 95% CI 0.49, 0.95 I2 = 0%). However, on sensitivity analysis, the results were statistically non-significant after exclusion of any of the included studies. On pooled analysis of limited number of studies, we found no statistically significant difference in the risk of bleeding between apixaban (RR 0.85 95% CI 0.45, 1.60 I2 = 0%), rivaroxaban (RR 0.95 95% CI 0.36, 2.48 I2 = 45%), dabigatran (RR 0.49 95% CI 0.19, 1.28 I2 = 5%), edoxaban (RR 0.41 95% CI 0.13, 1.27 I2 = 0%) and VKAs. Conclusion: The results of the first review comparing bleeding outcomes after dental extraction in patients on uninterrupted DOAC or VKA therapy indicates that patients on DOAC may have a reduced risk of hemorrhage. Current evidence is of very low-quality and should be interpreted with caution. Data on individual DOAC is scarce and at this point, the difference in the risk of bleeding between these drugs cannot be elucidated. Further studies with a large sample size shall supplement our conclusion.

Efficacy and safety of direct-acting oral anticoagulants compared to vitamin K antagonists in COVID-19 outpatients with cardiometabolic diseases

BackgroundIt remains uncertain if prior use of oral anticoagulants (OACs) in COVID-19 outpatients with multimorbidity impacts prognosis, especially if cardiometabolic diseases are present. Clinical outcomes 30-days after COVID-19 diagnosis were compared between outpatients with cardiometabolic disease receiving vitamin K antagonist (VKA) or direct-acting OAC (DOAC) therapy at time of COVID-19 diagnosis.MethodsA study was conducted using TriNetX, a global federated health research network. Adult outpatients with cardiometabolic disease (i.e. diabetes mellitus and any disease of the circulatory system) treated with VKAs or DOACs at time of COVID-19 diagnosis between 20-Jan-2020 and 15-Feb-2021 were included. Propensity score matching (PSM) was used to balance cohorts receiving VKAs and DOACs. The primary outcomes were all-cause mortality, intensive care unit (ICU) admission/mechanical ventilation (MV) necessity, intracranial haemorrhage (ICH)/gastrointestinal bleeding, and the composite of any arterial or venous thrombotic event(s) at 30-days after COVID-19 diagnosis.Results2275 patients were included. After PSM, 1270 patients remained in the study (635 on VKAs; 635 on DOACs). VKA-treated patients had similar risks and 30-day event-free survival than patients on DOACs regarding all-cause mortality, ICU admission/MV necessity, and ICH/gastrointestinal bleeding. The risk of any arterial or venous thrombotic event was 43% higher in the VKA cohort (hazard ratio 1.43, 95% confidence interval 1.03–1.98; Log-Rank test p = 0.029).ConclusionIn COVID-19 outpatients with cardiometabolic diseases, prior use of DOAC therapy compared to VKA therapy at the time of COVID-19 diagnosis demonstrated lower risk of arterial or venous thrombotic outcomes, without increasing the risk of bleeding.

Disparities in Anticoagulant Therapy Initiation for Incident Atrial Fibrillation by Race/Ethnicity Among Patients in the Veterans Health Administration System

Atrial fibrillation is a common cardiac rhythm disturbance causing substantial morbidity and mortality that disproportionately affects racial/ethnic minority groups. Anticoagulation reduces stroke risk in atrial fibrillation, yet studies show it is underprescribed in racial/ethnic minority patients. To compare initiation of anticoagulant therapy by race/ethnicity for patients in the Veterans Health Administration (VA) system with atrial fibrillation. This retrospective cohort study included 111 666 patients within the VA system with incident atrial fibrillation between January 1, 2014, and December 31, 2018. Data were analyzed between December 1, 2019, and March 31, 2020. Any anticoagulation was defined as receipt of warfarin or direct-acting oral anticoagulants, apixaban, dabigatran, edoxaban, or rivaroxaban. Initiation of any anticoagulation (or direct-acting oral anticoagulant therapy in those who initiated any anticoagulation) was examined within 90 days of an index atrial fibrillation diagnosis. Our final cohort comprised 111 666 patients (109 386 men [98.0%] and 95 493 White patients [85.5%]; mean [SD] age, 72.9 [10.4] years). A total of 69 590 patients (62.3%) initiated any anticoagulant therapy, varying 10.5 percentage points by race/ethnicity (P < .001); initiation was lowest in Asian (52.2% [n = 676]) and Black (60.3% [n = 6177]) patients and highest in White patients (62.7% [n = 59 881]). Among anticoagulant initiators, 45 381 (65.2%) used direct-acting oral anticoagulants, varying 7.2 percentage points by race/ethnicity (P < .001); initiation was lowest in Hispanic (58.3% [n = 1470]), American Indian/Alaska Native (59.8% [n = 201]), and Black (60.9% [n = 3763]) patients and highest in White patients (66.0% [n = 39 502). Compared with White patients, the odds of initiating any anticoagulant therapy were significantly lower for Asian (adjusted odds ratio [aOR], 0.82; 95% CI, 0.72-0.94) and Black (aOR, 0.90; 95% CI 0.85-0.95) patients. Among initiators, the adjusted odds of direct-acting oral anticoagulant initiation were significantly lower for Hispanic (aOR, 0.79; 95% CI, 0.70-0.89), American Indian/Alaska Native (aOR, 0.75; 95% CI, 0.57-0.99), and Black (aOR, 0.74; 95% CI 0.69-0.80) patients. This cohort study found that in patients with incident atrial fibrillation managed in the VA system, race/ethnicity was independently associated with initiating any anticoagulant therapy and direct-acting oral anticoagulant use among anticoagulant initiators. Understanding the reasons for these treatment disparities is essential to improving equitable atrial fibrillation management and outcomes among racial/ethnic minority patients treated in the VA system.

Direct-acting oral anticoagulants use prior to COVID-19 diagnosis and associations with 30-day clinical outcomes

BackgroundIt is unclear if direct-acting oral anticoagulants (DOACs) use before hospitalization due to COVID-19 diagnosis would potentially impact the severity and clinical outcomes thereafter. We compared 30-day hospitalization/re-hospitalization and clinical outcomes between patients on chronic DOAC therapy and patients not on oral anticoagulation (OAC) therapy at time of COVID-19 diagnosis. MethodsWe used data from TriNetX, a global federated health research network. Patients aged ≥18 years who were treated with DOACs at time of COVID-19 diagnosis between 20 January 2020 and 28 February 2021 were included, and matched with patients not on OAC therapy from the same period. All patients were followed-up at 30-days after COVID-19 diagnosis. The primary outcomes were all-cause mortality, hospitalization/re-hospitalization, venous thromboembolism (VTE) and intracranial hemorrhage (ICH). Results738,423 patients were included. After propensity score matching (PSM), 26,006 patients remained in the study (13,003 on DOACs; 13,003 not on OAC). DOAC-treated patients (mean age 67.1 ± 15.4 years, 52.2% male) had higher relative risks (RRs) and lower 30-days event-free survival as compared to patients not on OAC for all-cause mortality (RR 1.27, 95% CI 1.12–1.44; Log-Rank test p = 0.010), hospitalization/re-hospitalization (RR 1.72, 95% CI 1.64–1.82; Log-Rank test p < 0.001) and VTE (RR 4.51, 95% CI 3.91–5.82; Log-Rank test p < 0.001), but not for ICH (RR 0.90, 95% CI 0.54–1.51; Log-Rank test p = 0.513). ConclusionIn COVID-19 patients, previous DOAC therapy at time of diagnosis was not associated with improved clinical outcomes or lower hospitalization/re-hospitalization rate compared to patients not taking OAC therapy.

Abstract P081: Association Of Homelessness And Anticoagulation Initiation In Veterans With Atrial Fibrillation: A Nationwide Study

Introduction: Homeless individuals, overrepresented by Veterans, are more likely to have chronic medical conditions and comorbidities. They receive less medical care and have poor health outcomes, though remain understudied. Atrial fibrillation (AF), the most common cardiovascular rhythm disorder, is managed largely through anticoagulation. Direct-acting oral anticoagulants (DOACs) have been shown superior to warfarin anticoagulation in efficacy, safety, and adherence, though costlier. Hypothesis: Homeless Veterans receive a worse standard of care for AF than non-homeless Veterans in terms of initiation of any anticoagulation therapy, and in prescription of DOACs vs warfarin among those who began therapy. Methods: We studied 181,982 Veterans with incident, non-valvular AF in the Veterans Affairs Healthcare system from 2010-2018 who were not previously anticoagulated. Those who died or entered hospice were excluded. We classified Veterans who had experienced homelessness in the 2 years prior to their AF diagnosis using ICD-9/10 diagnosis codes and through VA homeless services use. We used logistic regression to examine the odds of initiation of any, DOAC, or warfarin anticoagulation. Models were adjusted for sociodemographic characteristics (year, age, race, CHA2DS2-VASc stroke risk score, HAS-BLED bleeding risk score, renal disease, BMI) and provider factors (e.g. specialty, had a patient seen a cardiologist within 90 days of their diagnosis). Facility type was modeled as a random effect. Results: Most of our cohort were male (178,400, 98%) and White (155,142, 85.6%). The homeless population of 6,472 was overrepresented by Black patients (1,574, 24.5%) and presented with AF at a younger age. The likelihood of being anticoagulated was lower in all populations before 2014. Having a BMI less than 25, liver disease, or bleeding concerns decreased the likelihood of being anticoagulated, while patients with renal disease were less likely to be prescribed DOACs. Black and Hispanic patients were less likely to be prescribed DOACs, regardless of homelessness status. We found the adjusted odds ratio (aOR) of initiating any anticoagulant therapy for homeless Veterans was 0.71 (95% CI 0.67 - 0.75). Among those who initiated anticoagulation, homeless individuals were less likely than non-homeless Veterans to initiate DOACs (aOR 0.88, 95% CI 0.80-0.96). Conclusions: In a nationwide cohort of Veterans with AF, we found that homeless Veterans were less likely to initiate any anticoagulation, especially more effective DOAC therapy. These findings persisted after adjusting for sociodemographic and clinical factors within an integrated health system with broad access to medical treatment through a uniform drug formulary. Future research must examine and address systematic biases to ensure high quality and equitable care for the most vulnerable populations, including homeless Veterans.

Abstract 16015: A Rare Cutaneous Adverse Drug Reaction With Apixaban

We report a case of apixaban-induced macular rash noticed 3 days after its initiation for atrial fibrillation. Patient denied any fever, arthralgias, myalgias or photosensitivity otherwise. On presentation, she complained of generalized pruritus with a bilateral non-blanchable macular rash on distal lower extremities and dorsum of feet. The labs showed normal cell counts, an elevated serum creatinine of 2.29mg/dl with a bland urine on microscopy. Apixaban was switched to LMWH. Serum creatinine returned to baseline with fluid therapy within 24 hours. Patient was re-challenged with apixaban that caused recurrence of generalized pruritus. It was treated successfully with diphenhydramine and prednisone. She was restarted on LMWH and rash disappeared after 3 days of stopping apixaban. She was later commenced on rivaroxaban without any complications. Several cutaneous adverse drug reactions (cADR) have been reported with direct acting oral anticoagulants (DOAC) like rivaroxaban and edoxaban but are extremely rare with apixaban. The overall reported incidence of dermatologic immune reactions with FXa inhibitors is &lt;0.1%. Previously reported skin eruptions from apixaban include palmoplantar psoriasiform rash, leucocytoclastic vasculitis and acute generalized erythematous pustulosis. Our patient’s Naranjo scale was 7 and her rash improved after cessation of apixaban. The case illustrates a hypersensitivity reaction from apixaban that did not have cross-reactivity with other FXa inhibitors. Early recognition of cADR from this widely used DOAC can avoid potential complications. Minor reactions may be managed by switching to different DOAC therapy. Whether a cross-reactivity truly exists must be explored by validated skin testing.

Utilization of direct-acting oral anticoagulation in solid organ transplant patients: A national survey of institutional practices.

The safety and efficacy of direct-acting oral anticoagulants (DOACs) and reversal strategies are not well established in the solid organ transplant population. This was a survey of pharmacists to assess DOAC and urgent reversal practices among adult transplant programs in the United States. A 27-question survey was distributed to members of transplant pharmacy organization listservs between 5/28/19 and 6/30/19. A total of 115 responses were received from kidney (43.5%), heart (20.0%), lung (18.3%), liver (13.9%), and pancreas (4.4%) transplant programs. DOAC use prior to transplant was mostly prohibited in thoracic programs (77.3%) but more permissive in kidney transplant programs (64.0%). If permitted, apixaban (57.8%) was most preferred. At transplant surgery, reversal of DOAC was performed "as needed" (20.9%) or was not routine (18.3%). DOAC use post-transplant was more permissive (94.3%). A majority of responders follow FDA recommended dosing in the setting of drug-drug interactions (51.1%). Major factors influencing DOAC prescribing decisions included renal function, drug-drug interactions, and insurance. High clinical practice variability exists regarding DOAC utilization and urgent reversal strategies in pre-, peri-, and post-transplant stages. While more research is needed to refine the clinical landscape, many institutions are using DOAC therapy under the perception that they pose a similar risk of bleeding compared to a non-transplant population.

Evaluation of the Safety and Effectiveness of Direct-Acting Oral Anticoagulants in Patients with Atrial Fibrillation and Coexisting Valvular Heart Disease.

Current guidelines recommend direct-acting oral anticoagulants (DOACs) over warfarin in patients with atrial fibrillation (AF) and valvular heart disease (VHD) without a mechanical valve or moderate to severe mitral stenosis. However, real-world data to support the safety and efficacy of DOACs in this patient population are lacking. Our objective was to assess the safety and effectiveness of DOACs in patients with AF and VHD. This retrospective chart review evaluated patients aged ≥ 18years with a diagnosis of AF and at least moderate VHD on echocardiogram. Patients were included if they received ≥ 1month of DOAC therapy from December 2016 to December 2018. Patients were excluded if they received dual antiplatelet therapy or had additional indications for anticoagulation. The primary outcomes were incidence of stroke or systemic embolism (SSE) and major bleeding. In total, 200 patients were included (disease type: aortic, n = 50; mitral, n = 50; tricuspid, n = 50; multivalve, n = 50). Most patients received apixaban (n = 133 [66.5%]) followed by rivaroxaban (n = 50 [25%]) and dabigatran (n = 17 [8.5%]). No patients received edoxaban. The mean CHA2DS2-VASc score was 4.25 and was similar among DOAC cohorts (p = 0.380). The overall SSE rate was 3.5% and was highest for dabigatran (n = 3 [17.6%]) compared with the other DOACs (apixaban, n = 1 [0.8%]; rivaroxaban, n = 3 [6%]; p = 0.001). Rates were similar among different valve types (aortic, n = 3 [6%]; mitral, n = 1 [2%]; tricuspid, n = 2 [4%]; multivalve, n = 1 [2%]; p = 0.653). The overall rate of major bleeding was 5.5% and did not differ among the DOACs (apixaban, n = 5 [3.8%]; rivaroxaban, n = 4 [8%]; dabigatran, n = 2 [11.8%]; p = 0.264) or valve type (aortic, n = 3 [6%]; mitral, n = 2 [4%]; tricuspid, n = 2 [4%]; multivalve, n = 4 [8%]; p = 0.787). In patients with AF and VHD, rates of major bleeding were similar among the DOACs and valve types; however, more patients receiving dabigatran experienced SSE. Further studies are needed to validate these findings.

200 Bleeding Outcomes With Direct-Acting Oral Anticoagulants in Patients Undergoing Cardiac Device Implantation

Over one third of patients undergoing permanent pacemaker or cardiac defibrillator implantation have an indication for therapeutic anticoagulation. Accumulating evidence supports continuation of warfarin therapy for these procedures. The evidence is less clear for direct acting oral anticoagulants (DOAC), medications now more commonly prescribed than warfarin. A best evidence topic was written according to a structured protocol addressing the question “does continuation of direct acting oral anticoagulants affect bleeding outcomes compared to discontinuation among patients undergoing cardiac pacemaker or defibrillator implantation?” Altogether, 1507 papers were found searching Medline, Embase, and Pubmed databases of which five represented the best evidence to answer the clinical question. Although modest evidence exists to answer this question, two recent randomised trials as well as two cohort studies and one case series have addressed the issue with similar findings. Interrupted and uninterrupted DOAC therapy resulted in similar rates of major bleeding (0-2.1% vs 0-4% respectively, no significant p-values reported) particularly in pocket haematoma formation, a clinically important event that substantially increases risk for infection and reoperation. Other adverse events reported were similar between the two groups. In well-selected patients at high risk for thromboembolic complications, it is reasonable to undertake cardiac device implantation without cessation of DOAC therapy as rates of bleeding complications are not significantly higher compared to interrupted therapy.

Efficacy of Direct Acting Oral Anticoagulants in Treatment of Left Ventricular Thrombus

Direct acting oral anticoagulants (DOACs) are increasingly used as off-label alternatives to vitamin K antagonists for the treatment of left ventricular (LV) thrombus. However, efficacy data is limited to small case series and one meta-analysis of case reports. We aimed to determine the efficacy and safety of DOACs in treatment of LV thrombus utilizing transthoracic echocardiography (TTE) and clinical outcomes. We identified 52 patients (mean age = 64 years, 71% men) treated with a DOAC for LV thrombus (n = 26 apixaban, n = 24 rivaroxaban, and n = 2 dabigatran). Thirty-five of the 52 patients had a follow-up TTE after DOAC initiation. The primary end point was defined as resolution of LV thrombus (in patients with a subsequent TTE), or death, major bleeding requiring transfusion, intracranial hemorrhage, ischemic stroke, or peripheral embolization. An experienced echocardiographer (M.L.M.) reviewed all TTEs for presence or absence of LV thrombus without knowledge of time point or clinical data. Twenty-nine of the 35 (83%) patients who underwent follow-up TTE had resolution of LV thrombus, with a mean duration of 264 days. Of the total study population, there was 1 cardioembolic event (transient ischemic attack) 52 days after initiating DOAC, 3 gastrointestinal bleeds requiring transfusion, and 1 patient with epistaxis requiring transfusion. All patients with a hemorrhagic complication were receiving concomitant antiplatelet therapy. DOAC therapy appears promising for the treatment of LV thrombus. A larger, prospective study is warranted to confirm these results.