Outcomes of direct oral anticoagulants with aspirin vs warfarin with aspirin: a registry-based cohort study.

Background: For patients anticoagulated with direct oral anticoagulants (DOACs) or warfarin and on aspirin (ASA) for nonvalvular atrial fibrillation and/or venous thromboembolism, it is unclear if bleeding outcomes differ. Objectives: To assess bleeding rates for ASA with DOACs vs warfarin and one another. Methods: Registry-based cohort study of patients followed by a 6-center quality improvement collaborative in Michigan using data from 2009 to 2022. The study included adults on ASA with warfarin or DOACs for atrial fibrillation and/or venous thromboembolism without a recent myocardial infarction or heart valve replacement. Results: After propensity matching by anticoagulant class, we compared 2 groups of 1467 patients followed for a median of 18.0 months. Any bleeding and nonmajor bleeding was increased with DOACs + ASA compared with warfarin + ASA (32.2 vs 27.8 and 27.1 vs 22.9 events/100 patient-years; relative risks [RRs], 1.1 and 1.2; 95% CIs, 1.1-1.2 and 1.1-1.3, respectively). After matching by drug, patients on apixaban + ASA vs warfarin + ASA had more bleeding (31.2 vs 27.8 events/100 patient-years; RR, 1.1; 95% CI, 1.0-1.2) and nonmajor bleeding but less major bleeding (3.8 vs 4.7 events/100 patient-years; RR, 0.8; 95% CI, 0.6-1.0) and emergency room visits for bleeding. Patients on rivaroxaban + ASA vs warfarin + ASA had more bleeding (39.3 vs 26.3 events/100 patient-years, RR, 1.5; 95% CI, 1.3-1.6), nonmajor bleeding, and thrombosis. Patients on apixaban + ASA vs rivaroxaban + ASA had significantly less bleeding (22.5 vs 39.3/100 patient-years; RR, 0.6; 95% CI, 0.5-0.7), nonmajor bleeding, major bleeding (2.1 vs 5.5 events/100 patient-years; RR, 0.4; 95% CI, 0.2-0.6), emergency room visits for bleeding, and thrombotic events. Conclusion: Patients on DOAC + ASA without a recent myocardial infarction or heart valve replacement had more nonmajor bleeding but otherwise similar outcomes compared with warfarin + ASA. Patients treated with rivaroxaban + ASA experienced more adverse clinical events compared with warfarin + ASA or apixaban + ASA.

The comparative efficacy and safety of factor Xa inhibitors and warfarin for primary thromboprophylaxis in multiple myeloma patients undergoing immunomodulatory therapy.

There are limited data on the optimal choice of anticoagulation in multiple myeloma (MM) patients receiving immunomodulatory drugs (IMiDs). We conducted a propensity score-matched cohort study using the TriNetX database to compare the efficacy and safety of factor Xa inhibitors and warfarin in this patient population. Compared to warfarin, factor Xa inhibitors had a similar risk of deep vein thrombosis (hazard ratio [HR]: 1.11 [95% CI: 0.50-2.46]) or pulmonary embolism (HR: 1.08 [95% CI: 0.59-2.00]). There were no differences in the risk of gastrointestinal or intracranial bleeding. Factor Xa inhibitor-treated patients had lower all-cause mortality (HR: 0.56 [95% CI: 0.36-0.86]) compared with warfarin. These data suggest that factor Xa inhibitors had similar safety and efficacy compared with warfarin for MM patients on IMiDs.

Andexanet Alfa versus Four-Factor Prothrombin Complex Concentrate for the Reversal of Factor Xa (FXa) Inhibitor-Associated Intracranial Hemorrhage: A Systematic Review of Retrospective Studies.

Background/Objectives: There are limited data on the risks and benefits of using Andexanet alfa (AA) compared with four-factor prothrombin complex concentrate (4F-PCC) for the reversal of factor Xa inhibitor-associated intracranial hemorrhage (ICH). Our aim was to describe a compilation of the information available in the literature to date. Methods: PubMed, Embase, Web of Science (Clarivate Analytics) and the Cochrane Central Register of Controlled Trials were searched until December 2023. Following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" guidelines, our systematic literature review included studies that were retrospective in design and evaluated both drugs to control bleeding and complications (death and thromboembolic events). Two researchers re-examined the studies for relevance, extracted the data and assessed the risk of bias. No meta-analyses were performed for the results. Results: In this limited patient sample, we found no differences between published articles in terms of neuroimaging stability or thrombotic events. However, some studies show significant differences in mortality, suggesting that one of the AAs may be superior to 4F-PCC. Conclusions: Our qualitative analysis shows that AA has a better efficacy profile compared with 4F-PCC. However, further studies monitoring these patients and a multicenter collaborative network dedicated to this topic are needed.

External validation of the PE-SARD bleeding score for early major bleeding in patients with acute pulmonary embolism: From the COMMAND VTE Registry-2.

BACKGROUND: There is no established risk score for anticoagulant-related bleeding during the acute phase in patients with pulmonary embolism (PE). The Syncope, Anemia, Renal Dysfunction (PE-SARD) bleeding score was developed to predict early major bleeding, but has not yet been fully externally validated. OBJECTIVES: To externally validate the PE-SARD bleeding score. PATIENTS/METHODS: Using the COMMAND VTE Registry-2 database, which enrolled 5197 consecutive acute symptomatic venous thromboembolism patients among 31 centers in Japan between January 2015 and August 2020, we identified acute PE patients. We divided those into 3 groups by the score: high-risk (>2.5 points), intermediate-risk (1-2.5 points), and low-risk (0 points). The discriminating and calibration performances of the score for 30-day major bleeding were assessed. Subgroup analyses based on active cancer were also performed. RESULTS: Of 2781 eligible patients, the high-risk group accounted for 557 patients (20%), intermediate-risk group for 1412 (51%), and low-risk group for 812 (29%). Major bleeding occurred in 121 patients within 30 days. The cumulative 30-day incidence of major bleeding substantially increased in the higher risk categories by the score (high-risk group: 8.2% [95%CI, 5.9%-10.5%], intermediate-risk group: 4.6% [95%CI, 3.5%-5.7%], and low-risk group: 1.8% [95%CI, 0.8%-2.7%]). The discriminating power of the score was modest with a C-statistic of 0.65 (95%CI, 0.61-0.70) with a good calibration performance with a score of <4 points except for in active cancer patients. CONCLUSIONS: The PE-SARD bleeding score had a modest discriminating performance with a limited calibration performance in acute PE patients without active cancer.

Design and rationale for REVERXaL: A real-world study of patients with factor Xa inhibitor-associated major bleeds.

BACKGROUND: The prevalence of anticoagulation treatment is increasing as an aging global population faces a high burden of cardiovascular comorbidities. Direct oral anticoagulants, including factor Xa inhibitors (FXai), are replacing vitamin K antagonists as the most commonly prescribed treatment for reducing risk of thrombotic events. While the risk of FXai-associated spontaneous bleeds is established, less is understood about their management and the effect of treatment on clinical and patient-reported outcomes. The primary objectives of the REVERXaL study are to describe patient characteristics, health care interventions during the acute-care phase, in-hospital outcomes, and associations between timing of reversal/replacement agent administration and in-hospital outcomes. Secondary/exploratory objectives focus on clinical assessments and patient-reported outcome measures (PROMs) at 30 and 90 days. METHODS: REVERXaL is a multinational, observational study of hospitalized patients with FXai-associated major bleeds in Germany, Japan, the United Kingdom, and the United States. The study includes 2 cohorts of approximately 2000 patients each. Cohort A is a historic cohort for whom medical chart data will be collected from hospitalization to discharge for patients admitted for major bleeds during FXai use within 2 years prior to enrollment of Cohort B. Cohort B will prospectively enroll patients administered any reversal/replacement agent during hospitalization to manage FXai-associated major bleeds and will include the collection of clinical outcomes and PROMs data over 3 months. CONCLUSIONS: REVERXaL will generate insights on patient characteristics, treatment approaches, and associated outcomes in patients hospitalized with FXai-associated major bleeds. These data may inform clinical practice and streamline treatment pathways in this population. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; unique identifier: NCT06147830.

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.

Safety and Efficacy of Direct Oral Anticoagulants vs Warfarin in Patients With Obesity and Venous Thromboembolism: A Retrospective Analysis.

BACKGROUND: Current venous thromboembolism guidelines recommend using direct oral anticoagulants (DOACs) over warfarin regardless of obesity status; however, evidence remains limited for the safety and efficacy of DOAC use in patients with obesity. This retrospective analysis sought to demonstrate the safety and efficacy of DOACs compared with warfarin in a diverse population of patients with obesity in light of current prescribing practices. METHODS: A retrospective cohort study was conducted at a large academic health system between July 2014 and September 2019. Adults with an admission diagnosis of deep vein thrombosis (DVT) or pulmonary embolism, with weight greater than 120 kg or a body mass index greater than 40, and who were discharged on an oral anticoagulant were included. Outcomes included occurrence of a thromboembolic event (DVT, pulmonary embolism, or ischemic stroke), bleeding event requiring hospitalization, and all-cause mortality within 12 months following index admission. RESULTS: Out of 787 patients included, 520 were in the DOAC group and 267 were in the warfarin group. Within 12 months of index hospitalization, thromboembolic events occurred in 4.23% of patients in the DOAC group vs 7.12% of patients in the warfarin group (hazard ratio, 0.6 [95% CI, 0.32-1.1]; P = .082). Bleeding events requiring hospitalization occurred in 8.85% of DOAC patients vs 10.1% of warfarin patients (hazard ratio, 0.93 [95% CI, 0.57-1.5]; P = .82). A DVT occurred in 1.7% and 4.9% of patients in the DOAC and warfarin groups, respectively (hazard ratio, 0.35 [95% CI, 0.15-0.84]; P = .046). CONCLUSION: No significant differences could be determined between DOACs and warfarin for cumulative thromboembolic or bleeding events, pulmonary embolism, ischemic stroke, or all-cause mortality. The risk of DVT was lower with apixaban and rivaroxaban. Regardless of patient weight or body mass index, physicians prescribed DOACs more commonly than warfarin.

Evaluation of the Hemocompatibility of the Direct Oral Anticoagulant Apixaban in Left Ventricular Assist Devices: The DOAC LVAD Study.

BACKGROUND: Patients receiving left ventricular assist device (LVAD) support require long-term anticoagulation to reduce the risk of thromboembolic complications. Apixaban is a direct oral anticoagulant that has become first-line therapy; however, its safety in LVAD recipients has not been well described. OBJECTIVES: This study sought to investigate whether, in patients with a fully magnetically levitated LVAD, treatment with apixaban would be feasible and comparable with respect to safety and freedom from the primary composite outcome of death or major hemocompatibility-related adverse events (HRAEs) (stroke, device thrombosis, major bleeding, aortic root thrombus, and arterial non-central nervous system thromboembolism) as compared with treatment with warfarin. METHODS: The DOAC LVAD (Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices) trial was a phase 2, open label trial of LVAD recipients randomized 1:1 to either apixaban 5 mg twice daily or warfarin therapy. All patients were required to take low-dose aspirin. Patients were followed up for 24 weeks to evaluate the primary composite outcome. RESULTS: A total of 30 patients were randomized: 14 patients to warfarin and 16 patients to apixaban. The median patient age was 60 years (Q1-Q3: 52-71 years), and 47% were Black patients. The median time from LVAD implantation to randomization was 115 days (Q1-Q3: 56-859 days). At 24 weeks, the primary composite outcome occurred in no patients receiving apixaban and in 2 patients (14%) receiving warfarin (P = 0.12); these 2 patients experienced major bleeding from gastrointestinal sources. CONCLUSIONS: Anticoagulation with apixaban was feasible in patients with an LVAD without an excess of HRAEs or deaths. This study informs future pivotal clinical trials evaluating the safety and efficacy of apixaban in LVAD recipients. (Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices [DOAC LVAD]; NCT04865978).

Implementation of a pharmacist-developed, indication-based order panel for outpatient prescribing of direct-acting oral anticoagulants.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Minimally modified human blood coagulation factor X to bypass direct factor Xa inhibitors.

BACKGROUND: Direct oral factor (F)Xa inhibitors are widely used as alternatives to conventional vitamin K antagonists in managing venous thromboembolism and nonvalvular atrial fibrillation. Unfortunately, bleeding-related adverse events remain a major concern in clinical practice. In case of bleeding or emergency surgery, rapid-onset reversal agents may be required to counteract the anticoagulant activity. OBJECTIVES: The ability of FXa variants to bypass the direct oral FXa inhibitors was assessed. METHODS: Human FXa variants were generated through substitution of phenylalanine 174 (F174) for either alanine, isoleucine, or serine. FXa variants were stably expressed in HEK293 cells and purified to homogeneity using ion-exchange chromatography. RESULTS: F174-substituted human FX variants demonstrated efficacy in restoring thrombin generation in plasma containing direct FXa inhibitors (apixaban, rivaroxaban, edoxaban). Their ability to bypass the anticoagulant effects stems from a significantly reduced sensitivity for the direct FXa inhibitors due to a decrease in binding affinity determined using molecular dynamics simulations and free energy computation. Furthermore, F174 modification resulted in a partial loss of inhibition by tissue factor pathway inhibitor, enhancing the procoagulant effect of F174-substituted FX. Consequently, the F174A- and F174S-substituted FX variants effectively counteracted the effects of 2 widely used anticoagulants, apixaban and rivaroxaban, in plasma of atrial fibrillation and venous thromboembolism patients. CONCLUSION: These human FX variants have the potential to serve as a rescue reversal strategy to overcome the effect of direct FXa inhibitors in case of life-threatening bleeding events or emergency surgical interventions.

Evaluation and treatment of gastrointestinal bleeding in patients taking anticoagulants presenting to the emergency department.

This manuscript is a consensus document of an expert panel on the Evaluation and Treatment of Gastrointestinal Bleeding in Patients Taking Anticoagulants Presenting to the Emergency Department, sponsored by the American College of Emergency Physicians.

Does in vitro hemolysis affect measurements of plasma apixaban concentration by UPLC-MS and anti-Xa assay?

INTRODUCTION: Hemolytic interference may impact various laboratory tests, including coagulation analyses. Apixaban is the most commonly used direct oral anticoagulant in Norway, and there is lacking knowledge on how apixaban concentration measurements might be influenced by hemolysis. Moreover, hemolysis-induced alterations in apixaban levels could potentially impact the risk of bleeding in specific clinical scenarios. We wanted to study whether hemolysis would increase apixaban concentration and investigate the impact of hemolytic interference on apixaban concentration measurements. METHODS: Blood samples from 20 apixaban-treated patients and 8 healthy controls were hemolyzed in vitro by a freeze method. The degree of hemolysis was measured with plasma free hemoglobin (PfHb) at baseline and two levels of hemolysis. Apixaban concentration was measured in plasma using both the chromogenic anti-Xa method and the ultraperformance liquid chromatography mass spectrometry (UPLC-MS). Thrombin generation assay was performed to assess coagulability. RESULTS: UPLC-MS measurements showed a mean concentration change of -1.66% (±3.2%, p = 0.005) and anti-Xa assay showed a mean concentration change of 3.37% (±6.5%, p = 0.09) with increasing hemolysis. Thrombin generation lagtime decreased, and endogenous thrombin potential and peak thrombin increased with increasing hemolysis in both the control group and the apixaban group. CONCLUSION: Apixaban concentration measurements by anti-Xa assay and UPLC-MS were not affected by hemolysis to a clinically relevant extent. Furthermore, hemolysis did not lead to hypocoagulability when assessed by thrombin generation.

Comparison of Fixed Versus Weight-Based Prothrombin Complex Concentrate Dosing Strategies for Factor Xa Inhibitor Reversal.

Background: Our institution introduced fixed-dose prothrombin complex concentrate (PCC) to streamline order verification and medication administration. Previous studies using fixed-dose PCC for vitamin K antagonist reversal showed comparable efficacy to weight-based dosing. Objective: To compare fixed versus weight-based PCC dosing for reversal of Factor Xa Inhibitor (FXaI) effects. Methods: Retrospective cohort study conducted at a tertiary care academic medical center. Patients who received PCC to reverse the effects of apixaban or rivaroxaban were eligible. Subjects in the fixed-dose group (5000 units or 2000 units) were compared to weight-based PCC (50 units/kg). The primary outcome was time between order entry and medication administration. Secondary outcomes included: average PCC dose, postadministration procedures, achieved hemostasis, 30-day mortality, hospital length of stay, and adverse drug events. Results: 72 patients received fixed-dose PCC and 101 received weight-based PCC. Median time between order entry and administration was 4.5 min shorter in the fixed-dose group compared to weight-based (34.5 vs 39 min, P = .10). In patients who received fixed-dose, 79.2% achieved hemostasis versus 71.3% in the weight-based group (RR = 1.11, 95% CI = 0.94-1.32). There was no difference in the number of subsequent hemorrhage-related surgeries (29.2% vs 36.7%, RR = 0.80, 95% CI = 0.51-1.24) or mortality rate (26.4% vs 35.6%, RR = 0.73, 95% CI = 0.46-1.17). There were zero adverse drug events reported. Rates of thrombosis were 2.8% and < 1% (P = .57) in the fixed and weight-based groups, respectively. Conclusion and Relevance: The fixed-dosing strategy did not reduce time to PCC administration nor impact hemostasis or mortality. These data support that the fixed-dosing method is a viable option.

Efficacy and Safety of Direct Oral Anticoagulants for Acute Treatment of Venous Thromboembolism in Older Adults: A Network Meta-Analysis of Randomised Controlled Trials.

OBJECTIVE: This systematic review and network meta-analysis aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in adults aged 75 and over undergoing acute venous thromboembolism (VTE) treatment. METHODS: PubMed, Embase and the CENTRAL were searched up to 25 December 2023. The incidence of VTE recurrence and bleeding events was assessed. Employing a frequentist network meta-analysis approach, interventions not directly compared could be indirectly assessed through the 95% confidence interval (CI), enhancing the interpretability of the search results. The surface under the cumulative ranking curves (SUCRA) was utilized to generate the relative ranking probabilities for each group. RESULTS: Our study, analysing 6 randomised controlled trials with 3665 patients, compares direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in adults aged 75 and over with acute venous thromboembolism. Edoxaban reduces VTE recurrence risk compared with VKAs (risk ratio [RR] .50, 95% CI 0.27 - .95), while apixaban significantly decreases bleeding risk compared with VKAs (RR .23, 95% CI 0.08 - .69), edoxaban (RR .28, 95% CI 0.09 - .86) and rivaroxaban (RR .28, 95% CI 0.09 - .86). Despite low overall evidence quality, apixaban consistently ranks highest for both efficacy and safety. Findings underscore the nuanced efficacy-safety balance in this population, emphasizing cautious interpretation due to evidence limitations. CONCLUSION: Apixaban emerges as a favourable choice for acute VTE treatment in the elderly, displaying reduced bleeding risk compared to other treatments while maintaining comparable efficacy. Future studies should explore diverse anticoagulants efficacy and safety in older populations. Additionally, clinical prediction models tailored to geriatric cohorts are crucial for guiding treatment duration decisions.

Efficacy and safety of oral factor Xa inhibitors versus vitamin-K antagonists in the early phase after acute ischemic stroke or TIA in the real-world setting: The PRODAST study.

INTRODUCTION: Factor Xa (FXa) inhibitors are superior to vitamin K antagonists (VKAs) in terms of avoiding hemorrhagic complications. However, no robust data are available to date as to whether this also applies to the early phase after stroke. In this prospective registry study, we aimed to investigate whether anticoagulation with FXa inhibitors in the early phase after acute ischemic stroke or transient ischemic attack (TIA) is associated with a lower risk of major bleeding events compared with VKAs. MATERIALS AND METHODS: The Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA (PRODAST) study is a prospective, multicenter, observational, post-authorization safety study at 86 German stroke units between July 2015 and November 2020. Primary outcome was a major bleeding event during hospital stay. Secondary endpoints were recurrent strokes, recurrent ischemic strokes, TIA, systemic/pulmonary embolism, myocardial infarction, death and the composite endpoint of stroke, systemic embolism, life-threatening bleeding and death. RESULTS: In total, 10,039 patients have been recruited. 5,874 patients were treated with FXa inhibitors and 1,050 patients received VKAs and were eligible for this analysis. Overall, event rates were low. We observed 49 major bleeding complications during 33,297 treatment days with FXa-inhibitors (rate of 14.7 cases per 10,000 treatment days) and 16 cases during 7,714 treatment days with VKAs (rate of 20.7 events per 10,000 treatment days), translating into an adjusted hazard ratio (aHR) of 0.70 (95% confidence interval (95% CI): 0.37-1.32) in favor of FXa inhibitors. Hazards for ischemic endpoints (63 vs 17 strokes, aHR: 0.96 (95% CI: 0.53-1.74), mortality (33 vs 6 deaths, aHR: 0.87 (95% CI: 0.33-2.34)) and the combined endpoint (154 vs 39 events, aHR: 0.99 (95% CI: 0.65-1.41) were not substantially different. DISCUSSION AND CONCLUSION: This large real-world study shows that FXa inhibitors appear to be similarly effective in terms of bleeding events and ischemic endpoints compared to VKAs in the early post-stroke phase of hospitalization. However, the results need to be interpreted with caution due to the low precision of the estimates.

Direct oral anticoagulant-associated bleeding complications in patients with gastrointestinal cancer and venous thromboembolism.

BACKGROUND: Direct oral anticoagulants (DOACs) have become widely used for cancer-associated venous thromboembolism (VTE). However, DOAC-associated bleeding complications remain challenging, especially in patients with gastrointestinal (GI) cancer. This study aimed to compare the bleeding outcomes between patients with upper or lower GI cancers and those without GI cancer. METHODS: Using the COMMAND VTE Registry-2 database, which is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020, we identified 1149 active cancer patients with DOACs (upper GI cancer: N = 88; lower GI cancer: N = 114; non-GI cancer: N = 947). The primary outcome was major bleeding during anticoagulation therapy, which was evaluated in the competing risk regression model. RESULTS: The upper GI cancer group had a lower mean body weight, and most often had anemia. The cumulative 5-year incidence of major bleeding was higher in the upper GI cancer group (upper GI cancer: 22.4 %, lower GI cancer: 15.4 %, and non-GI cancer: 11.6 %, P = 0.015). The most frequent major bleeding site in the upper GI cancer group was the upper GI (53 %), followed by the lower GI (24 %). After adjusting for the confounders, the excess risk in upper GI cancer relative to non-GI cancer remained significant for major bleeding (adjusted subhazard ratio, 2.25; 95 %CI, 1.31-3.87, P = 0.003), but that in lower GI cancer was insignificant. CONCLUSIONS: Upper GI cancer, but not lower GI cancer, as compared to non-GI cancer was associated with a higher risk for major bleeding during anticoagulation therapy with DOACs. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000044816.

Low recurrent thrombosis rates in single positive antiphospholipid syndrome regardless of type of anticoagulation.

Thrombotic antiphospholipid syndrome (TAPS) is characterized by thrombosis and persistently positive tests for antiphospholipid antibodies or lupus anticoagulant (LAC). Triple-positive APS has the highest risk of recurrent thrombosis, but no studies have focused on recurrent thrombosis in patients with single-positive TAPS. We conducted a retrospective cohort study of patients with single-positive TAPS diagnosed at Lifespan Health System, Rhode Island, to determine the rates and risk factors for recurrent thrombosis. Between January 2001 and April 2022, 128 patients were assessed who had single-positive APS (LAC = 98, aCL = 21, aß2GPI = 9) and who had been followed for a total of 1453.8 patient-years (median follow-up 3.04 years). The initial antithrombotic regimen was warfarin in 44 %, a direct oral anticoagulant (DOAC) in 34 %, enoxaparin in 2 %, and no antithrombotic therapy or antiplatelet therapy only in 20 %. Recurrent thrombosis occurred in 16 (12.5 %) with a recurrent thrombosis rate of 3.08 per 100 patient-years. Systemic lupus erythematosus was the only variable significantly associated with recurrent thrombosis in a model adjusted for age, sex, body mass index, and type of positive APS test. All 16 patients with recurrent thrombosis were initially treated with warfarin, and, at the time of recurrent thrombosis, 13 patients remained on warfarin and three were off anticoagulation. In conclusion, the recurrent thrombosis rate in single-positive APS is low, and not all patients with a single-positive test may need indefinite anticoagulation with warfarin. Larger prospective studies are required to confirm this finding and establish optimal anticoagulation regimens for low-risk TAPS.

Clinical Characteristics and Incidence of Hemorrhagic Complications in Patients Taking Factor Xa Inhibitors in Spain: A Long-Term Observational Study.

Objective. To analyze the clinical characteristics of patients taking Factor Xa inhibitors (FXai), either direct FXai or enoxaparin (only in active cancer patients), and to estimate the incidence of and risk factors for major bleeding during FXai use. Methods. A retrospective cohort study, which included secondary data from computerized health records of primary care centers and hospitals in seven Spanish Autonomous Communities. Results. 9374 patients were analyzed, with 8972 taking direct FXai and 402 enoxaparin. At baseline, the mean age (SD) was 71.8 (9.4) years, 56.0% were women, 76.3% had hypertension, 33.6% had type 2 diabetes, and 25.5% had heart failure. The most common indication for FXai use was atrial fibrillation (72.3%), followed by venous thromboembolism (22.2%) and non-mechanical cardiac-valve replacement (5.6%). At the end of the follow-up period, the incidence rates of major bleeding overall, gastrointestinal, and intracranial were 10.2, 9.0, and 0.8 per 100 person-years, respectively. The total incidence of fatal major bleeding was 0.5 per 100 person-years. Incidence rates of all bleedings progressively decreased over time, with 62.5% of the first events occurring in the initial three months and reaching 76.8% within six months following initiation of treatment. Only 4.8% of the 1st major bleedings led to death, 2.3% in the case of major gastrointestinal bleeding, and 30.8% after an intracranial bleeding. 65.9% of patients discontinued anticoagulation after experiencing major bleeding. Conclusions. In Spain, patients taking FXai were old and had many comorbidities. Despite incidence rates of major bleeding were high, incidence rates of intracranial and fatal bleedings were low, but more efforts are required due to their relevant clinical impact.