Anticoagulation and Antiplatelet Regimen in Cardiac Transplant. Clinical Characteristics, Outcomes, and Blood Product Transfusion.

BACKGROUND: We aimed to evaluate the characteristics, clinical outcomes, and blood product transfusion (BPT) rates of patients undergoing cardiac transplant (CT) while receiving uninterrupted anticoagulation and antiplatelet therapy. METHODS: A retrospective, single-center, and observational study of adult patients who underwent CT was performed. Patients were classified into four groups: (1) patients without anticoagulation or antiplatelet therapy (control), (2) patients on antiplatelet therapy (AP), (3) patients on vitamin K antagonists (AVKs), and (4) patients on dabigatran (dabigatran). The primary endpoints were reoperation due to bleeding and perioperative BPT rates (packed red blood cells (PRBC), fresh frozen plasma, platelets). Secondary outcomes assessed included morbidity and mortality-related events. RESULTS: Of the 55 patients included, 6 (11%) received no therapy (control), 8 (15%) received antiplatelet therapy, 15 (27%) were on AVKs, and 26 (47%) were on dabigatran. There were no significant differences in the need for reoperation or other secondary morbidity-associated events. During surgery patients on dabigatran showed lower transfusion rates of PRBC (control 100%, AP 100%, AVKs 73%, dabigatran 50%, p = 0.011) and platelets (control 100%, AP 100%, AVKs 100%, dabigatran 69%, p = 0.019). The total intraoperative number of BPT was also the lowest in the dabigatran group (control 5.5 units, AP 5 units, AVKs 6 units, dabigatran 3 units; p = 0.038); receiving significantly less PRBC (control 2.5 units, AP 3 units, AVKs 2 units, dabigatran 0.5 units; p = 0.011). A Poisson multivariate analysis showed that only treatment on dabigatran reduces PRBC requirements during surgery, with an expected reduction of 64.5% (95% CI: 32.4%-81.4%). CONCLUSIONS: In patients listed for CT requiring anticoagulation due to nonvalvular atrial fibrillation, the use of dabigatran and its reversal with idarucizumab significantly reduces intraoperative BPT demand.

Comparison of warfarin, rivaroxaban, and dabigatran for effectiveness and safety in atrial fibrillation patients with different CHA2DS2-VASc scores: a retrospective cohort study.

BACKGROUND: This retrospective cohort study aims to compare the effectiveness and safety of warfarin, rivaroxaban, and dabigatran in atrial fibrillation (AF) patients with different CHA2DS2-VASc scores in northern China. METHODS: A retrospective cohort study was performed to evaluate anticoagulation in AF patients at the second affiliated hospital of Harbin Medical University from September 2018 to August 2019. Patients included in this study (n = 806) received warfarin (n = 300), or rivaroxaban (n = 203), or dabigatran (n = 303). Baseline characteristics and follow-up data including adherence, bleeding events and ischemic stroke (IS) events were collected. RESULTS: Patients receiving rivaroxaban (73.9%) or dabigatran (73.6%) showed better adherence than those receiving warfarin (56.7%). Compared with warfarin-treated patients, dabigatran-treated patients had lower incidence of bleeding events (10.9% vs 19.3%, χ2 = 8.385, P = 0.004) and rivaroxaban-treated patients had lower incidence of major adverse cardiovascular events (7.4% vs 13.7%, χ2 = 4.822, P = 0.028). We classified patients into three groups based on CHA2DS2-VASc score (0-1, 2-3, ≥ 4). In dabigatran intervention, incidence of bleeding events was higher in patients with score 0-1 (20.0%) than those with score 2-3 (7.9%, χ2 = 5.772, P = 0.016) or score ≥ 4 (8.6%, χ2 = 4.682, P = 0.030). Patients with score 0-1 in warfarin or rivaroxaban therapy had a similar but not significant increase of bleeding compared with patients with score 2-3 or score ≥ 4, respectively. During the follow-up, 33 of 806 patients experienced IS and more than half (19, 57.6%) were patients with score ≥ 4. Comparing patients with score 0-1 and 2-3, the latter had an significant reduction of IS in patients prescribed warfarin and non-significant reduction in rivaroxaban and dabigatran therapy. CONCLUSION: Compared with warfarin therapy, patients with different CHA2DS2-VASc scores receiving either rivaroxaban or dabigatran were associated with higher persistence. AF patients with score ≥ 4 were more likely to experience IS events while hemorrhagic tendency preferred patients with low score 0-1.

Direct factor Xa inhibitors and the risk of cancer and cancer mortality: A Danish population-based cohort study.

BACKGROUND: Preclinical animal studies have suggested that myeloid cell-synthesized coagulation factor X dampens antitumor immunity and that rivaroxaban, a direct factor Xa inhibitor, can be used to promote tumor immunity. This study was aimed at assessing whether patients with atrial fibrillation taking direct factor Xa inhibitors have lower risk of cancer and cancer-related mortality than patients taking the direct thrombin inhibitor dabigatran. METHODS AND FINDINGS: This nationwide population-based cohort study in Denmark included adult patients with atrial fibrillation and without a history of cancer, who started taking a factor Xa inhibitor or dabigatran between 2011 and 2015. Data on medical history, outcomes, and drug use were acquired through Danish healthcare registries. The primary outcome was any cancer. Secondary outcomes were cancer-related mortality and all-cause mortality. Outcome events were assessed during 5 years of follow-up in an intention-to-treat analysis. The propensity score-based inverse probability of treatment weighting was used to compute cumulative incidence and subdistribution hazard ratios (SHRs) and corresponding 95% confidence intervals (CIs), with death as a competing event. Propensity scores were estimated using logistic regression and including in the model sex, age group at index date, comorbidities, and use of comedications. A total of 11,742 patients with atrial fibrillation starting a factor Xa inhibitor and 11,970 patients starting dabigatran were included. Mean age was 75.2 years (standard deviation [SD] 11.2) in the factor Xa cohort and 71.7 years (SD 11.1) in the dabigatran cohort. On the basis of the propensity score-weighted models, after 5 years of follow-up, no substantial difference in the cumulative incidence of cancer was observed between the factor Xa inhibitor (2,157/23,711; 9.11%, 95% CI [8.61%,9.63%]) and dabigatran (2,294/23,715; 9.68%, 95% CI [9.14%,10.25%]) groups (SHR 0.94, 95% CI [0.89,1.00], P value 0.0357). We observed no difference in cancer-related mortality (factor Xa inhibitors cohort 1,028/23,711; 4.33%, 95% CI [4.02%,4.68%]. Dabigatran cohort 1,001/23,715; 4.22%, 95% CI [3.83%,4.66%]; SHR 1.03, 95% CI [0.94,1.12]), but all-cause mortality was higher in the factor Xa inhibitor cohort (factor Xa inhibitors cohort 7,416/23,711; 31.31%, 95% CI [30.37%,32.29%]. Dabigatran cohort 6,531/23,715; 27.56%, 95% CI [26.69%,28.45%]; HR 1.17, 95% CI [1.13,1.21]). The main limitations of the study were the possibility of residual confounding and the short follow-up period. CONCLUSIONS: In this population based cohort study, factor Xa inhibitor use was not associated with an overall lower incidence of cancer or cancer-related mortality when compared to dabigatran. We did observe an increase in all-cause mortality in the factor Xa inhibitor cohort.

Efficacy and safety of antithrombotic therapy for preventing and treating pediatric thromboembolic disease: a systematic review.

This review used traditional and network meta-analyses (NMA) to conduct a comprehensive study of antithrombotic therapies in children with thromboembolic disease. We searched the PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov databases from their inception to 26 February, 2023. And we finally included 16 randomized controlled trials. In the prevention of thromboembolic events (TEs), the use of anticoagulants had a low risk of TEs (relative risk (RR) 0.73, 95% CI 0.56 to 0.94) and a high risk of minor bleeding (RR 1.43, 95% CI 1.09 to 1.86) compared with no anticoagulants. In the treatment of TEs, direct oral anticoagulants (DOACs) were not inferior to standard anticoagulation in terms of efficacy and safety outcomes. In NMA, rivaroxaban and apixaban showed the lowest risk for TEs and major or clinically relevant nonmajor bleeding. According to the overall assessment of efficacy and safety, dabigatran may be the best choice for children with thromboembolic disease. The results of our study will provide references and suggestions for clinical drug selection.

Population Dementia Incidence and Direct Oral Anticoagulant Use in a Representative Population With Atrial Fibrillation.

BACKGROUND AND OBJECTIVES: Incidence and prevalence of atrial fibrillation (AF), a risk factor of dementia, have been increasing over time. Oral anticoagulation reduces risk of stroke and other negative outcomes of AF and may reduce dementia health inequities. The objective of this study was to estimate dementia incidence in patients with newly-diagnosed AF and taking an anticoagulant as use of direct oral anticoagulants (DOACs) increased. METHODS: We used a retrospective cohort design with annual incident AF cohorts of community-dwelling Medicare Fee-for-Service beneficiaries, enrolled in Parts A, B, and D from 2007 to 2017. The sample was limited to beneficiaries aged 67 years and older with incident AF; no prior dementia; and use of anticoagulants warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban in year t. RESULTS: A total of 1,083,338 beneficiaries were included in the study, 58.5% female, with mean (SD) age 77.2 (6.75) years. Among anticoagulated, incident AF cohorts, use of DOACs increased from 10.6% in their first year of availability (2011) to 41.4% in 2017. Among incident AF cohorts taking any oral anticoagulant, 3-year dementia incidence did not change significantly over the cohorts after adjusting for confounders. For example, incidence was 9.1% (95% CI 8.9-9.4) among White persons diagnosed with AF in 2007 and 2008 and 8.9% (95% CI 8.7-9.1) in 2017. Across cohorts, dementia incidence was consistently highest for Black persons, followed by American Indian/Alaska Native and White persons, and lowest for Asian persons. In 2017, 10.9% (95% CI 10.4-11.3) of Black persons in the cohort developed dementia within 3 years, 9.4% (95% CI 8.0-10.9) of American Indian/Alaska Native, 8.9% (95% CI 8.7-9.1) of White, 8.7% (95% CI 8.2-9.1) of Hispanic, and 6.9% (95% CI 6.4-7.4) of Asian persons. Across race/ethnicity, 3-year stroke risk decreased consistently over time; however, the increasing availability of DOACs did not alter the trend. DISCUSSION: Increased use of DOACs among incident AF cohorts from 2007 to 2017 was not associated with significant declines in dementia or stroke risk. Consideration of similar stroke and dementia risk, as well as differences in cost, is warranted when weighing the risks and benefits of available oral anticoagulants.

Selection criteria for anticoagulants: survey of Japanese cardiologists based on their daily clinical practice: the Selection DOAC study.

BACKGROUND: In patients with atrial fibrillation (AF), direct oral anticoagulants (DOACs) have been utilized as an alternative to warfarin, which is known to have several limitations. This study aimed to clarify the selection criteria for anticoagulants, considering both individual patient factors and the differences between various drugs. METHODS: This study conducted a web-based questionnaire from September 20, 2023 to October 3, 2023, among physicians who were members of a cardiology-specific website. RESULTS: In total, 172 respondents were enrolled in this study. Edoxaban was the most frequently selected anticoagulant (39.1%), followed by apixaban (32.7%) and rivaroxaban (16.8%). Logistic regression analysis revealed that increased concern for adherence enhanced the frequency of selecting edoxaban (odds ratio [OR] = 2.42; p = 0.047), with the opposite trend observed for dabigatran (OR = 0.404; p = 0.029). The selection of apixaban is related to whether the patient is able to maintain a regular lifestyle, including adherence to medication schedules (OR = 1.874; p = 0.031). Furthermore, detailing activities from a medical representative, especially regarding a new indication, were found to influence drug selection for rivaroxaban (OR = 2.422; p = 0.047). CONCLUSION: This study revealed that edoxaban is the most frequently selected anticoagulant. Although prescribing cardiologists select drugs based on background factors, adherence to medication and information from medical representatives were also crucial factors in the selection process.

Predictors of adherence to direct oral anticoagulants after cardiovascular or bleeding events in Medicare Advantage Plan enrollees with atrial fibrillation.

BACKGROUND: Direct oral anticoagulants (DOACs) are recommended for patients with atrial fibrillation (AF) given their improved safety profile. Suboptimal adherence to DOACs remains a significant concern among individuals with AF. However, the extent of adherence to DOACs following a cardiovascular or bleeding event has not been fully evaluated. OBJECTIVE: To evaluate the pattern of adherence trajectories of DOACs after a cardiovascular or bleeding event and to investigate the sociodemographic and clinical predictors associated with each adherence trajectory by using claims-based data. METHODS: This retrospective study was conducted among patients with AF prescribed with DOACs (dabigatran/apixaban/rivaroxaban) between July 2016 and December 2017 and who were continuously enrolled in the Texas-based Medicare Advantage Plan. Patients who experienced a cardiovascular or bleeding event while using the DOACs were further included in the analysis. The sample was limited to patients who experienced a clinical event such as a cardiovascular or bleeding event while using the DOACs. The clinical events considered in this study were cardiovascular (stroke, congestive heart failure, myocardial infarction, systemic embolism) and bleeding events. To assess adherence patterns, each patient with a DOAC prescription was followed up for a year after experiencing a clinical event. The monthly adherence to DOACs after these events was evaluated using the proportion of days covered (PDC). A group-based trajectory model incorporated the monthly PDC to classify groups of patients based on their distinct patterns of adherence. Predictors associated with each trajectory were assessed using a multinomial logistic regression model, with the adherent trajectory serving as the reference group in the outcome variable. RESULTS: Among the 694 patients with AF who experienced clinical events after the initiation of DOACs, 3 distinct adherence trajectories were identified: intermediate nonadherent (30.50%), adherent (37.7%), and low adherent (31.8%); the mean PDC was 0.47 for the intermediate nonadherent trajectory, 0.93 for the adherent trajectory, and 0.01 for low adherent trajectory. The low-income subsidy was significantly associated with lower adherence trajectories (odds ratio [OR] = 4.81; 95% CI = 3.07-7.51) and with intermediate nonadherent trajectories (OR = 1.57; 95% CI = 1.06-2.34). Also, nonsteroidal anti-inflammatory drug use was significantly associated with lower adherence trajectories (OR = 5.10; 95% CI = 1.95-13.36) and intermediate nonadherent trajectories (OR = 3.17; 95% CI = 1.26-7.93). Other predictors significantly associated with both nonadherent trajectories are type of DOACs (OR = 0.53; 95% CI = 0.35-0.79), presence of coronary artery disease (OR = 1.89; 95% CI = 1.01-3.55), and having 2 or more clinical events (OR = 1.65; 95% CI = 1.09-2.50). CONCLUSIONS: Predictors identified provide valuable insights into the suboptimal adherence of DOACs among Medicare Advantage Plan enrollees with AF, which can guide the development of targeted interventions to enhance adherence in this high-risk patient population.

Racial and Ethnic Disparities in Initiation of Direct Oral Anticoagulants Among Medicare Beneficiaries.

Importance: The influence of race and ethnicity on initiation of direct oral anticoagulants (DOACs) is relatively understudied in Medicare data. Objective: To investigate disparities in the initiation of DOACs compared with warfarin by race, ethnicity, and social vulnerability. Design, Setting, and Participants: This retrospective cohort study used a 50% sample of Medicare fee-for-service data from January 1, 2010, to December 31, 2019 (mean patient enrollment duration, 7.7 years). Analysis took place between January 2023 and February 2024. A cohort of older adults (aged ≥65 years) with atrial fibrillation who newly initiated warfarin or DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) was identified. Exposure: Patients were classified as non-Hispanic White, non-Hispanic Black, and Hispanic. Main Outcomes and Measures: The likelihood of starting use of DOACs compared with warfarin was modeled, adjusting for race, ethnicity, age, sex, county-level social vulnerability, and other clinical factors. Results: Among 950 698 anticoagulation initiations, consisting of 680 974 DOAC users and 269 724 warfarin users (mean [SD] age, 78.5 [7.6] years; 52.6% female), 5.2% were Black, 4.3% were Hispanic, and 86.7% were White. During the 10-year study period, DOAC use increased for all demographic groups. After adjustment, compared with White patients, Black patients were 23% less likely (adjusted odds ratio [AOR, 0.77; 95% CI, 0.75-0.79) and Hispanic patients were 13% less likely (AOR, 0.87; 95% CI, 0.85-0.89) to initiate DOAC use. Disparities in DOAC initiation were greatest among Black patients in the earlier years but attenuated during the study period. For instance, in 2010, the OR of Black patients initiating DOACs was 0.54 (95% CI, 0.50-0.57), attenuating linearly over time to 0.69 by 2013 (95% CI, 0.65-0.74) and 0.83 (95% CI, 0.78-0.89) by 2017. By 2019, these differences became nonsignificant (OR, 1.08; 95% CI, 0.99-1.18). Conclusions and Relevance: In this cohort study of Medicare patients with atrial fibrillation, Black and Hispanic patients were less likely to initiate DOACs for atrial fibrillation, although these differences diminished over time. Identifying the factors behind these early disparities is crucial for ensuring equitable access to novel therapies as they emerge for Black and Hispanic populations.

Efficacy and safety of dabigatran and rivaroxaban in atrial fibrillation patients with impaired liver function: a multicenter retrospective cohort study.

BACKGROUND: The efficacy and safety of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with impaired liver function (ILF) have not been sufficiently studied. The aim of this study was to evaluate the efficacy and safety of DOACs for stroke prevention in patients with AF and ILF. METHOD: This study was based on data from 15 centers in China, including 4,982 AF patients. The patients were divided into 2 subgroups based on their liver function status: patients with normal liver function (NLF)(n = 4213) and patients with ILF (n = 769). Logistic regression analysis was used to investigate the risk of total bleeding, major bleeding, thromboembolism, and all-cause deaths in AF patients with NLF and ILF after taking dabigatran or rivaroxaban, respectively. RESULTS: Among AF patients treated with dabigatran or rivaroxaban, patients with ILF were associated with significantly higher major bleeding, compared with NLF patients (aOR: 4.797; 95% CI: 2.224-10.256; P < 0.001). In patients with NLF, dabigatran (n = 2011) had considerably lower risk of total bleeding than rivaroxaban (n = 2202) (aOR: 1.23; 95% CI: 1.002-1.513; P = 0.049). In patients with ILF, dabigatran (n = 321) significantly favored lower risks of major bleeding compared with rivaroxaban(n = 448) (aOR: 5.484; 95% CI: 1.508-35.269; P = 0.026). CONCLUSION: After using dabigatran or rivaroxaban, patients with ILF had remarkably increased risk of major bleeding compared with patients with NLF. In AF patients with NLF, dabigatran had the distinct strength of significantly reduced risk of total bleeding compared with rivaroxaban. In patients with AF and ILF, dabigatran use was associated with lower risk for major bleeding compared with rivaroxaban.

Appropriateness of prescribing profiles and intake adherence to non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: analysis of a retrospective longitudinal study using real-world data from Northern Portugal (AF-React Study).

OBJECTIVES: This study aimed to assess the appropriateness of prescribing profiles and intake adherence to non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF). DESIGN: Retrospective longitudinal study. SETTING: The study was conducted in the Regional Health Administration of Northern Portugal. PARTICIPANTS: The authors selected a database of 21 854 patients with prescriptions for NOACs between January 2016 and December 2018 and were classified with AF until December 2018. OUTCOME MEASURES: The appropriate dosage of NOAC for patients with AF divided into three categories: contraindicated, inconsistent and consistent, based on the 2020 European Society of Cardiology guidelines for AF. RESULTS: Dabigatran had a lower percentage of guideline-consistent doses (n=1657, 50.1%) than other drugs such as rivaroxaban (n=4737, 81.6%), apixaban (n=3830, 78.7%) and edoxaban (n=436, 82.1%). Most patients with an inconsistent dose were prescribed a lower dose than recommended based on their glomerular filtration rate (GFR). Among patients younger than 75 years with GFR >60 mL/min, 59.8% (n=10 028) had an adequate GFR range, while 27.8% (n=7166) of GFR measurements from patients older than 75 years old and 29.4% (n=913) of GFR measurements from patients younger than 75 years with GFR <60 mL/min were within an adequate time range. Adherence to NOACs varied across different drugs, with 59.1% (n=540) adhering to edoxaban, 56.3% (n=5443) to rivaroxaban, 55.3% (n=3143) to dabigatran and 53.3% (n=4211) to apixaban. CONCLUSIONS: Dabigatran had the lowest percentage of guideline-consistent doses. Patients younger than 75 years with GFR >60 mL/min had the highest percentage with an adequate GFR range, while other groups who require closer GFR monitoring had lower percentages within an adequate GFR range. Adherence to NOACs differed among different drugs, with greater adherence to treatment with edoxaban and less adherence to apixaban.

Effect of different oral anticoagulants on cognitive function in patients with atrial fibrillation: A Bayesian network meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is 1 of the most common types of arrhythmias. At present, the treatment for patients with AF mainly includes oral anticoagulants (OACs). Studies have shown that OACs are associated with cognitive decline in patients with atrial fibrillation; however, there is a lack of relevant evidence. This study used Bayesian network meta-analysis (NMA) to investigate the effects of different oral anticoagulants on cognitive decline in patients with AF. METHODS: We systematically searched for clinical studies on oral anticoagulants in patients with AF in PubMed, Web of Science, Embase, and the Cochrane Library as of July 3, 2023. Cochrane's randomized controlled trial bias risk assessment tool and the Newcastle-Ottawa Scale were used to assess the bias risk of the included studies. The main outcome measure was decreased cognitive functioning. RESULTS: Ten studies were included, including 2 RCTs and 7 RCSs, including 882,847 patients with AF. Five oral anticoagulants and 2 anticoagulants were included: VKAs (especially warfarin), Dabigatran, Edoxaban, Rivaroxaban, Apixaban, and Aspirin, Clopidogrel. The results of the mesh meta-analysis showed that VKAs were superior to warfarin in reducing the risk of cognitive decline in patients with AF (OR = -1.19, 95% CI (-2.35, -0.06), P < .05) (Table 5). The top 3 drugs in terms of the probability of reducing the incidence of cognitive impairment in patients with AF with different oral anticoagulants were VKAs (87%), rivaroxaban (62.2%), and dabigatran (60.8%). CONCLUSION: Based on the results of this study, VKAs may be the best intervention measure for reducing the risk of cognitive decline in patients with AF. Owing to the limitations of this study, more high-quality randomized controlled trials with large sample sizes and multiple centers are required to provide more evidence.

Risk factors for thrombosis and spontaneous echocardiographic contrast with sludge in atrial fibrillation patients treated with oral anticoagulants before electrical cardioversion.

BACKGROUND: Knowledge of thrombosis (T) risk predictors and transesophageal echocardiography (TEE) are important tools in appropriate qualification of patients for safe electrical cardioversion. AIMS: We aimed to investigate predictors of T and spontaneous echocardiographic contrast (SEC) with sludge in the left atrium (LA) and appendage (LAA) in atrial fibrillation (AF) patients on oral anticoagulation. METHODS: The study included 300 patients with AF lasting >48 hours. Two hundred and nineteen patients were treated with oral anticoagulants (OACs) (study group, rivaroxaban: 104 [47.5%], apixaban: 52 [23.7%], dabigatran: 23 [11.5%], VKAs: 40 [18.3%]). Eighty-one consecutive patients with AF lasting >48 hours and not treated with OACs constituted the control group. Before electrical cardioversion, all patients underwent transthoracic echocardiography and TEE. RESULTS: TEE revealed T in the LAA in 4.7% of cases. The number of patients with T or SEC4+ with sludge in the OAC and control groups was similar, 5.9% vs. 1.2% and 16.4% vs. 16.0%, respectively. The risk of SEC4+/T in patients treated with OACs was lowest in those taking rivaroxaban (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.21-0.87; P = 0.027) and highest in those receiving VKAs (OR, 2.49; 95% CI, 1.15-5.39; P = 0.018). Multivariable analysis showed independent prognostic factors for SEC 4+/T: female sex (OR, 3.800; 95% CI, 1.592-9.072; P = 0.003), left ventricular ejection fraction (OR, 0.932; 95% CI, 0.890-0.957; P <0.001), and minimum LAA flow velocity (LAAfly min) (OR, 0.895; 95% CI, 0.841-0.954; P <0.001). CONCLUSIONS: Female sex, transthoracic echocardiography, and TEE results should be taken into account in assessing the risk of T/SEC with sludge in LA/LAA patients with AF.

Equivalent thrombotic risk with Warfarin, Dabigatran, or Enoxaparin after failure of initial direct oral anticoagulation (DOAC) therapy.

BACKGROUND: The direct oral anticoagulants (DOACs) are now commonly regarded as first line anticoagulants in most cases of venous thromboembolism (VTE). However, the optimal choice of subsequent anticoagulant in instances of first line DOAC failure is unclear. OBJECTIVES: To describe and compare outcomes with second line anticoagulants used after DOAC failure. METHODS: Patients seen at an urban hospital system for an episode of acute VTE initially treated with either apixaban or rivaroxaban who experienced a subsequent recurrent thrombosis while on anticoagulation (1st recurrent thrombosis) were included. RESULTS: In total, 166 patients after apixaban or rivaroxaban failure were included. Following DOAC failure (1st recurrent thrombosis), the subsequent anticoagulant was warfarin in 60 patients (36%), dabigatran in 42 patients (25%), and enoxaparin in 64 patients (39%). Enoxaparin was preferentially prescribed in patients with a malignancy-associated etiology for 1st recurrent thrombosis (p < 0.01). The median follow-up time in our cohort was 16 months. There was no difference in 2nd recurrent thrombosis-free survival (p = 0.72) or risk for major bleeding event (p = 0.30) among patients treated with dabigatran, warfarin, or enoxaparin. CONCLUSIONS: In this retrospective analysis of patients failing first line DOAC therapy, rates of 2nd recurrent thrombosis and bleeding did not differ among subsequently chosen anticoagulants. Our study provides evidence that the optimal 2nd anticoagulant is not clear, and the choice of 2nd anticoagulant should continue to balance patient preference, cost, and provider experience.

Comparative effectiveness of factor Xa non-vitamin K antagonist oral anticoagulants versus phenprocoumon in patients with non-valvular atrial fibrillation.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) have largely supplanted vitamin K antagonists (VKAs) for oral anticoagulation in non-valvular atrial fibrillation (NVAF). However, data on the real-world effectiveness of NOACs vs. phenprocoumon, a VKA widely used in Germany, are limited. The RELOADED study aimed to compare effectiveness of factor Xa NOACs and phenprocoumon in NVAF in clinical practice. METHODS: Patients who started on a factor Xa NOAC or phenprocoumon for NVAF during the study period were enrolled from the Institute for Applied Healthcare Research Berlin. Patients were followed from first prescription until the end of exposure or available data. Primary outcomes were analyzed by Cox proportional hazard regression models and included ischemic stroke and systemic embolism for effectiveness, and intracranial hemorrhage (ICH) for safety. Subgroups of interest were patients with diabetes and patients with renal impairment. RESULTS: The total study population was 64,920; 36.3% of patients initiated phenprocoumon, 34.4% initiated rivaroxaban, 25.0% apixaban, and 4.4% edoxaban. Treatment with phenprocoumon is associated with a similar risk of ischemic stroke/systemic embolism as treatment with rivaroxaban or apixaban; while rivaroxaban (adjusted hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.43-0.75) and apixaban (adjusted HR 0.43, 95% CI 0.31-0.6) were associated with a lower risk of ICH compared to phenprocoumon in NVAF patients. The use of rivaroxaban and apixaban was associated with a lower risk of developing kidney failure in patients with diabetes or renal impairment in comparison to those treated with phenprocoumon. CONCLUSION: The factor Xa NOACs rivaroxaban and apixaban demonstrated similar effectiveness and lower rates of ICH compared with phenprocoumon in this study.

Comparative Safety and Effectiveness of Reduced Doses of Direct Acting Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation.

BACKGROUND: This Nordic observational cohort study aims to assess the effectiveness and safety of reduced-dose direct-acting oral anticoagulants (DOACs) dabigatran, rivaroxaban, and apixaban compared to standard warfarin for stroke prevention in nonvalvular atrial fibrillation. METHODS: The study, utilizing nationwide administrative databases from Denmark, Sweden, Norway, and Finland, spanned from January 1, 2011 to December 31, 2018 (2017 for Sweden). The cohort included 26,883 patients initiating reduced-dose DOACs and 108,014 comparable warfarin patients. Effectiveness was measured by the composite endpoint of ischemic stroke and systemic embolism, while safety was assessed through intracranial hemorrhage. RESULTS: The meta-analysis across countries revealed similar or lower incidences of ischemic stroke and systemic embolism in patients on reduced-dose DOACs compared to standard warfarin (rivaroxaban: HR 0.93, dabigatran: HR 0.88, apixaban: HR 0.79). Incidences within warfarin groups ranged from 2.16 to 3.71 per 100 person-years, comparable to DOAC recipients. Intracranial hemorrhage rates were generally low, ranging from 0.16 to 1.85 per 100 person-years. In comparison with warfarin patients, meta-analyses yielded HRs for rivaroxaban (1.41), dabigatran (0.35), and apixaban (0.72). CONCLUSIONS: In this study, atrial fibrillation patients initiating reduced-dose rivaroxaban and dabigatran exhibited incidences of ischemic stroke and systemic embolism similar to warfarin, and for apixaban, even lower. Rates of intracranial hemorrhage were comparable to or lower for patients on DOACs compared to warfarin.

Dabigatran etexilate versus warfarin in cerebral venous thrombosis in Chinese patients (CHOICE-CVT): An open-label, randomized controlled trial.

BACKGROUND: The efficacy and safety of dabigatran etexilate for Chinese patients with cerebral venous thrombosis (CVT) has not been well established. METHODS: CHOICE-CVT was an exploratory, single-center, randomized, open-label study in the National Center for Neurological Disorders involving Chinese patients with CVT aged 18 to 80 years who were randomly assigned (1:1) to either dabigatran etexilate or warfarin. Oral anticoagulants were initiated after 10-15 days of LMWH. The primary efficacy and safety endpoints included the number of patients with recurrent CVT and/or deep venous thrombosis (DVT) and major clinical bleeding within 180 days. Secondary efficacy endpoints included venous recanalization and change in papilledema at day 180. Secondary safety outcomes comprised death, clinical nonmajor bleeding, and any bleeding. The study was registered with ClinicalTrials.gov under NCT03930940. RESULTS: Between October 2017 and February 2023, a total of 89 patients were enrolled and randomly assigned to receive either dabigatran etexilate (n = 44) or warfarin (n = 45). At day 180, the dabigatran etexilate group showed a statistically nonsignificant but likely clinically significant number of patients with recurrent CVT and/or DVT (8 (18.2%; 95% CI, 6.3-30.0) vs 3 (6.7%; 95% CI, 0.0-14.2), p = 0.099, with a power (1-ß) of 38.401%) compared with the warfarin group. The dabigatran etexilate group showed a comparable number of patients with clinical major bleeding (0 (0) vs 0 (0) p = 1.000), and clinical nonmajor bleeding (1 (2.3%; 95% CI, 0.0-6.9) vs 1 (2.2%; 95% CI, 0.0-6.7)) but demonstrated a lower risk of any bleeding (1 (2.3%; 95% CI, 0.0-6.9) vs 9 (20.0%; 95% CI, 7.8-32.2)) compared with the warfarin group. Most patients in both groups achieved venous recanalization according to the Modified Qureshi scale (27 (75%; 95% CI, 60.1-89.9) in the dabigatran etexilate group vs 34 (82.9%; 95% CI, 70.9-95.0) in the warfarin group) and exhibited improvement in papilledema as per the Frisén classification (35 (97.2%; 95% CI, 91.6-100.0) in the dabigatran etexilate group vs 37 (88.1%, 95% CI, 77.9-98.3) in the warfarin group). CONCLUSIONS: These findings regarding efficacy and safety support the consideration of dabigatran etexilate therapy as a viable treatment option for Chinese patients with CVT.

Dispensing pharmacy chains and direct anticoagulants: Potential associations with patient outcomes.

PURPOSE: Pharmacy chains can differ with respect to the characteristics of their patient populations as well as their nonprescription products, services, and practices, and thus may serve as a surrogate for potential unmeasured confounding in observational studies of prescription drugs. This study evaluates whether a single-source drug can have different patient outcomes based on the dispensing pharmacy chain. METHODS: Separate analyses for two anticoagulant drugs, rivaroxaban and apixaban, were conducted using Medicare Fee-for-Service claims evaluating the association between dispensing pharmacy chain and outcomes of acute myocardial infarction, ischemic stroke, intracranial hemorrhage, gastrointestinal (GI) bleeding, all-cause mortality, and major GI bleeding. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates across pharmacy chain cohorts, and outcome association was assessed with a Cox Proportional Hazards model. RESULTS: We observed no differences in outcomes across pharmacy chains for apixaban recipients. Rivaroxaban recipients from pharmacy chain C, however, had lower rates of GI bleeding (adjusted HR 0.83; 95% CI 0.69-1.00) and ischemic stroke (adjusted HR 0.57; 95% CI 0.38-0.87) as compared to chain A in primary analyses with a 3-day grace period. The results moved closer to the null when 14- and 30-day grace periods were implemented. CONCLUSIONS: These results suggest that dispensing pharmacy chains may have the potential to act as a confounder of associations between drug exposure and outcome in some observational studies. Additional studies of potential confounding by pharmacy chain are needed. Further evaluation of potential pharmacy chain effects on safe use would be of value.

Retrospective study of clinical settings, indications and consequences of measurement of direct oral anticoagulant plasma levels in Northern Tasmania, Australia.

BACKGROUND: Routine monitoring of direct oral anticoagulant (DOAC) levels is not recommended but may be useful in certain clinical situations. There is a knowledge gap regarding the clinical use of DOAC levels in Australian hospitals. AIMS: To evaluate the clinical settings, indications and changes to anticoagulant management associated with DOAC levels in a tertiary hospital in Northern Tasmania, Australia. METHODS: Patients with one or more DOAC levels (dabigatran, rivaroxaban or apixaban) requested between January 2017 and December 2022 were identified. Retrospective chart review was performed to evaluate the clinical settings, indications, adequacy of request information and changes to clinical management associated with the measurement of DOAC levels. RESULTS: One hundred and twenty-nine DOAC measurements (54 rivaroxaban, 66 apixaban and nine dabigatran) were performed in 98 patients between January 2017 and December 2022. Annual requests for DOAC levels increased significantly between 2017 and 2019 and remained stable between 2020 and 2021 but declined in 2022. Overall, the most common indication for a DOAC level was renal impairment, followed by bleeding and recurrent thrombosis. Approximately 25% of requests were for acute bleeding with a reversal/haemostatic agent given in 45% of patients, while 10% were prior to urgent surgery. Measurement of DOAC levels was associated with a change in management in 50% of cases. 10% of requests did not specify anticoagulant history. CONCLUSION: Trends in requests for DOAC levels have changed over time. Clinician education regarding the importance of providing specific anticoagulant history is essential. Future prospective studies investigating the clinical utility of DOAC levels in different clinical settings are needed.

Drug-Drug Interactions in the Treatment of Cancer-Associated Venous Thromboembolism with Direct Oral Anticoagulants.

Venous thromboembolism (VTE) is a frequent complication of cancer, and management of cancer-associated thrombosis (CAT) is challenging due to increased risks of bleeding and recurrent VTE. Recent trials have shown an acceptable efficacy and safety of direct oral anticoagulants (DOACs) in the treatment of CAT compared to low-molecular weight heparin. Although DOACs provide an effective and convenient treatment option in CAT, the need to assess the risk of drug-drug interactions (DDI) with antineoplastic therapies poses a barrier to their use in clinical practice. With the aim of supporting the assessment of CAT patients for treatment with DOAC, this review provides a comprehensive overview of the compatibility of antineoplastic therapies with the individual DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban). Using several data sources, we characterized 100 widely used antineoplastic agents with regard to their effect on p-glycoprotein and cytochrome P450, both important in the transport and elimination of DOACs. This enabled us to evaluate 400 "DOAC-antineoplastic agent"-pairs regarding their likelihood to interact (unlikely, potential, or likely), ultimately leading to clinical recommendations on the appropriateness of concomitant use for each pair. A potential or likely DDI was identified for 12% of the evaluated pairs. For nearly all antineoplastic agents, at least one DOAC was considered compatible.

Association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia in patients receiving dabigatran after total knee arthroplasty.

PURPOSE: Dabigatran is usually prescribed in recommended doses without monitoring of the blood coagulation for the prevention of venous thromboembolism after joint arthroplasty. ABCB1 is a key gene in the metabolism of dabigatran etexilate. Its allele variants are likely to play a pivotal role in the occurrence of hemorrhagic complications. METHODS: The prospective study included 127 patients with primary knee osteoarthritis undergoing total knee arthroplasty. Patients with anemia and coagulation disorders, elevated transaminase and creatinine levels as well as already receiving anticoagulant and antiplatelet therapy were excluded from the study. The association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia as the outcome of dabigatran therapy was evaluated by single-nucleotide polymorphism analysis with a real-time polymerase chain reaction assay and laboratory blood tests. The beta regression model was used to predict the effect of polymorphisms on the studied laboratory markers. The probability of the type 1 error (p) was less than 0.05 was considered statistically significant. BenjaminiHochberg was used to correct for significance levels in multiple hypothesis tests. All calculations were performed using Rprogramming language v3.6.3. RESULTS: For all polymorphisms there was no association with the level of platelets, protein, creatinine, alanine transaminase, prothrombin, international normalized ratio, activated partial thromboplastin time and fibrinogen. Carriers of rs1128503 (TT) had a significant decrease of hematocrit (p = 0.001), red blood count and hemoglobin (p = 0.015) while receiving dabigatran therapy during the postoperative period compared to the CC, CT. Carriers of rs2032582 (TT) had a significant decrease of hematocrit (p = 0.001), red blood count and hemoglobin (p = 0.006) while receiving dabigatran therapy during the postoperative period compared to the GG, GT phenotypes. These differences were not observed in carriers of rs4148738. CONCLUSION: It might be necessary to reconsider thromboprophylaxis with dabigatran in carriers of rs1128503 (TT) or rs2032582 (TT) polymorphisms in favor of other new oral anticoagulants. The long-term implication of these findings would be the reduction of bleeding complications after total joint arthroplasty.