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Objective: The incidence of splanchnic vein thrombosis (SVT) is reported to be <25 times lower than that of deep vein thrombosis and pulmonary emboli, which occur in 70 to 270/100,000 cases in the general population. Current guidelines recommend initial treatment with therapeutic low-molecular-weight heparin followed by a transition to a vitamin K antagonist (VKA) or a direct oral anticoagulant (DOAC) in patients with cirrhosis who develop SVT without severe liver dysfunction. This, however, is based on observational data. This study aimed to evaluate the efficacy and safety of anticoagulant therapy in patients with cirrhosis who present with SVT and receive either a DOAC or a VKA. Methods: This multicenter retrospective cohort study was conducted from December 2021 to November 2022. Patients between the ages of 18 and 75 years with cirrhosis and acute SVT who received either a VKA or a DOAC between July 2019 and July 2021 were eligible for inclusion. The primary outcome was the efficacy of treatment, defined as a new thrombotic event. The secondary outcome was the safety of treatment, defined as the development of major bleeding. Readmission data were followed up at 6 and 10 months. Bivariate analysis was conducted to assess the relationship between the medication groups and each outcome and summarized as odds ratios (ORs) with 95% confidence intervals (Cis). Statistical significance was set at 5% for all of the comparisons. Results: A total of 80 patients from 50 hospitals were included in this study. Sixty-one patients (59.02% male) received DOACs and 19 (57.89% male) received a VKA. Of the patients who received DOACs, 41 (67.21%) received apixaban, one (1.64%) received dabigatran, and 19 (31.15%) received rivaroxaban. The results from the bivariate analysis revealed no significant differences between DOACs and warfarin for both the efficacy (OR 1.46,95% CI 0.44-4.84, P = 0.53) and safety outcomes (OR 1.03, 95% CI 0.04-26.43, P = 1) at 10 months. Conclusions: The use of DOACs in patients with cirrhosis who present with SVT may be efficacious and safe compared with warfarin. The findings from our study may inform power analyses for well-conducted randomized trials to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Although there are reports on the recurrence prevention in the chronic phase using direct oral anticoagulants (DOACs) for deep vein thrombosis (DVT) in patients with cancer, acute thrombus regression effect using DOACs has not been assessed. This study aimed to assess the thrombus regression effect of initial treatment using edoxaban for acute lower-extremity DVT in patients with active cancer. Methods and Results: In this observational study, among the inpatients with cancer and lower-extremity DVT who underwent initial treatment with edoxaban at our hospital from November 2019 to December 2021, 34 consenting patients were recruited in this study. The quantitative ultrasound thrombus (QUT) score of thrombus volume was calculated at baseline (before administration) and 7–14 days after the start of edoxaban administration, using lower-extremity venous ultrasound to evaluate changes in thrombus volume. The primary and secondary endpoints were the acute thrombus regression effect of edoxaban and the impact of patients' clinical frailty on the thrombus regression effect, respectively. Anticoagulant therapy with edoxaban significantly reduced QUT score (p < 0.001). In addition, regardless of the Clinical Frailty Scale scores, QUT score decreased significantly. Conclusion: Initial treatment with edoxaban was effective for lower-extremity DVT in patients with cancer. In addition, the effect was the same independent of the degree of frailty. [ABSTRACT FROM AUTHOR]

Background Hypothesis Animals Methods Results Conclusions and Clinical Importance Comparative pharmacokinetics and pharmacodynamics (PK/PD) of apixaban and rivaroxaban have not been studied in dogs and the propensity of these drugs to cause hypercoagulability after discontinuation is unknown.Compare the PK/PD of clinical dosing regimens of PO apixaban and rivaroxaban administered repeatedly to healthy dogs and assess the effect of abrupt drug discontinuation on coagulation.Six University‐owned, purpose‐bred, middle‐aged, mixed‐breed dogs (4 male, 2 female).Dogs were given apixaban or rivaroxaban PO at 0.5 mg/kg q12h for 7 days with a 14‐day washout period between drugs. Plasma drug concentrations were quantitated, and anticoagulant effects were measured using clotting times, calibrated anti‐Xa bioactivity assays, and measurements of thrombin generation. The potential for rebound hypercoagulability was assessed by measuring D‐dimers, thrombin‐antithrombin (TAT) complexes, and antithrombin activity after drug discontinuation.Plasma drug concentrations and anti‐Xa bioactivities were closely correlated for both drugs, but drug concentrations varied considerably among dogs, despite consistent dose regimens. Thrombin generation variables were significantly correlated with the anti‐Xa bioactivity of both drugs and no significant differences in the effects of apixaban and rivaroxaban on thrombin generation were observed. Drug discontinuation had no effect on D‐dimer concentrations. The concentration of TAT complexes decreased after apixaban discontinuation and did not change after rivaroxaban discontinuation.Repeated PO administration of apixaban or rivaroxaban to healthy dogs produced comparable anticoagulant effects measured by inhibition of thrombin formation. Rebound hypercoagulability after drug discontinuation was not observed and weaning of these drugs in clinical patients might not be necessary. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are the leading cause of death globally, making the use of oral anticoagulants for prevention increasingly important. Historically, warfarin has played a significant role in this context. In recent years, introduction of new oral anticoagulants, such as rivaroxaban, apixaban, dabigatran, and edoxaban, has been seen. This study evaluates the risk associated with the use of oral anticoagulants by analyzing spontaneous adverse drug reactions reported to the Portuguese Pharmacovigilance System from 2012 to 2021. The study includes 951 adverse drug reactions reports, with the majority (n = 770; 80.97%) classified as serious. Of the 770 serious adverse drug reactions reports, the most commonly reported seriousness criterion was "Clinically Important" (n = 350; 45.45%). In terms of demographics, there was a higher reporting rate among the elderly population, with a greater prevalence of females. The System Organ Class group with the highest number of adverse drug reactions was "Gastrointestinal disorders," with the most commonly reported Preferred Term being "Gastrointestinal hemorrhage," and dabigatran was the most frequently reported drug. In summary, oral anticoagulants have adverse drug reactions that require continuous monitoring. Accurate identification and monitorization of adverse drug reactions is an important starting point to improve drug safety in population. [ABSTRACT FROM AUTHOR]

Background Clinical trials of direct oral anticoagulants (DOAC) are scarce and inconclusive in patients who are receiving dialysis, for whom DOAC are not labelled in Europe. In a French nationwide registry study of patients on chronic dialysis, we compared the effectiveness and safety of off-label DOAC use vs approved vitamin K antagonist (VKA). Methods Data on patients on dialysis were extracted from the French Renal Epidemiology and Information Network (REIN) registry and merged with data from the French national healthcare system database (Système National des Données de Santé, SNDS). Patients on dialysis who had initiated treatment with an oral anticoagulant between 1 January 2012 and 31 December 2020, were eligible for inclusion. The primary safety outcome was the occurrence of major bleeding events and the primary effectiveness outcome was the occurrence of thrombotic events. Using propensity score–weighted cause-specific Cox regression, we compared the safety and effectiveness outcomes for DOAC and VKA. Results A total of 8954 patients received an oral anticoagulant (483 DOAC and 8471 VKA) for the first time after the initiation of dialysis. Over a median (interquartile range) follow-up period of 1.7 (0.8–3.2) years, 2567 patients presented a first thromboembolic event and 1254 patients had a bleeding event. After propensity score adjustment, the risk of a thromboembolic event was significantly lower in patients treated with a DOAC than in patients treated with a VKA {weighted hazard ratio (wHR) [95% confidence interval (CI)] 0.66 (0.46; 0.94)}. A non-significant trend toward a lower risk of major bleeding events was found in DOAC-treated patients, relative to VKA-treated patients [wHR (95% CI) 0.68 (0.41; 1.12)]. The results were consistent across subgroups and in sensitivity analyses. Conclusions In a large group of dialysis patients initiating an oral anticoagulant, the off-label use of DOACs was associated with a significantly lower risk of thromboembolic events and a non-significantly lower risk of bleeding, relative to VKA use. This provides reassurance regarding the off-label use of DOACs in people on dialysis. [ABSTRACT FROM AUTHOR]

Objectives: Bleeding after endoscopic submucosal dissection (ESD) for gastric tumors in patients taking antithrombotic drugs, in particular direct oral anticoagulants (DOACs), remains unresolved; therefore, we evaluated the risk factors for post‐ESD bleeding and drug differences in patients taking DOACs. Methods: We included 278 patients taking antithrombotic drugs who underwent gastric ESD between January 2017 and March 2022. Antithrombotic drugs were withdrawn following the 2017 guidelines (Appendix on anticoagulants including DOACs). To further clarify differences in antithrombotic agents' effects, the peri‐cancerous mucosa in the resected specimen was pathologically evaluated according to the Updated Sydney System. Multivariate analysis was performed to assess the risk of post‐ESD bleeding. Results: The incidence of post‐ESD bleeding in patients taking DOACs was 19.6% (10/51). Among patients taking antithrombotic drugs, DOACs were identified as a possible factor involved in post‐ESD bleeding (odds ratio [OR] 4.92). Among patients taking DOACs, possible factors included resection length diameter ≥30 mm (OR 3.72), presence of neutrophil infiltration (OR 2.71), lesions occurring in the lower third of stomach (OR 2.34), and preoperative antiplatelet use (OR 2.22). Post‐ESD bleeding by DOAC type was 25.0% of patients (4/16) receiving apixaban, in 20.0% (3/15) receiving edoxaban, in 21.4% (3/14) receiving rivaroxaban, and in none of those receiving dabigatran. Conclusions: The administration of DOACs was shown to be a possible factor involved in post‐ESD bleeding, and risk factors for patients taking DOACs included neutrophil infiltration. The pharmacological differences in the effects of DOACs contributing to bleeding in gastric ulcers suggest comparatively less bleeding with dabigatran after ESD. [ABSTRACT FROM AUTHOR]

The efficacy and safety of direct oral anticoagulants (DOAC) in patients with embolic stroke of undetermined source (ESUS) remains unclear. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCT) comparing DOACs versus aspirin in patients with ESUS. Risk ratios (RR) and 95% confidence intervals (CI) were computed for binary endpoints. Four RCTs comprising 13,970 patients were included. Compared with aspirin, DOACs showed no significant reduction of recurrent stroke (RR 0.95; 95% CI 0.84–1.09; p = 0.50; I2 = 0%), ischemic stroke or systemic embolism (RR 0.97; 95% CI 0.80–1.17; p = 0.72; I2 = 0%), ischemic stroke (RR 0.92; 95% CI 0.79–1.06; p = 0.23; I2 = 0%), and all-cause mortality (RR 1.11; 95% CI 0.87–1.42; p = 0.39; I2 = 0%). DOACs increased the risk of clinically relevant non-major bleeding (CRNB) (RR 1.52; 95% CI 1.20–1.93; p < 0.01; I2 = 7%) compared with aspirin, while no significant difference was observed in major bleeding between groups (RR 1.57; 95% CI 0.87–2.83; p = 0.14; I2 = 63%). In a subanalysis of patients with non-major risk factors for cardioembolism, there is no difference in recurrent stroke (RR 0.98; 95% CI 0.67–1.42; p = 0.90; I2 = 0%), all-cause mortality (RR 1.24; 95% CI 0.58–2.66; p = 0.57; I2 = 0%), and major bleeding (RR 1.00, 95% CI 0.32–3.08; p = 1.00; I2 = 0%) between groups. In patients with ESUS, DOACs did not reduce the risk of recurrent stroke, ischemic stroke or systemic embolism, or all-cause mortality. Although there was a significant increase in clinically relevant non-major bleeding, major bleeding was similar between DOACs and aspirin. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) are commonly co-prescribed with amiodarone/diltiazem/verapamil, but whether there is a drug interaction between these drugs is unclear. The purpose of this study was to investigate the risk of clinical outcomes associated with concomitant use of DOACs and amiodarone/diltiazem/verapamil. We identified DOAC users in the Clinical Practice Research Datalink Aurum from January 1, 2011, to December 31, 2019. We used a cohort design to estimate hazard ratios for ischemic stroke, myocardial infarction, venous thromboembolism, intracranial bleeding, gastrointestinal bleeding, other bleeding, cardiovascular mortality, and all-cause mortality, comparing DOACs + amiodarone/diltiazem/verapamil users and DOACs + beta-blocker users. A case-crossover design comparing odds of exposure to different drug initiation patterns for all outcomes in hazard window vs referent window within an individual also was conducted. Of 397,459 DOAC users, we included 9075 co-prescribed amiodarone, 9612 co-prescribed diltiazem, and 2907 co-prescribed verapamil. There was no difference in risk of any outcomes between DOACs + amiodarone/diltiazem/verapamil users vs DOACs + beta-blocker users in the cohort design. However, in the case-crossover design, we observed an odds ratio (OR) of 2.09 (99% confidence interval [CI] 1.37–3.18) for all-cause mortality associated with initiation of a DOAC while taking amiodarone, which was greater than that observed for DOAC monotherapy (OR 1.30; 99% CI 1.25–1.35). Similar findings were observed for cardiovascular mortality and all-cause mortality respectively with diltiazem. Our study showed no evidence of higher bleeding or cardiovascular risk associated with co-prescribed DOACs and amiodarone, diltiazem, or verapamil. Elevated risks of cardiovascular and all-cause mortality were only observed during DOAC initiation when diltiazem/amiodarone were being taken. [ABSTRACT FROM AUTHOR]

Background: Little is known how individual time-in-therapeutic-range (TTR) impacts the effectiveness and safety of warfarin therapy compared to direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF). Objective: To compare the effectiveness and safety of standard dose DOACs to warfarin in patients with AF, while categorizing warfarin treated patients into quartiles based on their individual TTR. Materials and methods: We conducted a nationwide study including all patients with new-onset AF between 2011 and 2018 in Finland. Hazard ratios (HR) were calculated using Cox regression analysis with the inverse probability of treatment weighted method to assess the risks of ischaemic stroke (IS), intracranial haemorrhage (ICH) and mortality for users of apixaban (n = 12,426), dabigatran (n = 4545), rivaroxaban (n = 12,950) and warfarin (n = 43,548). Results: The median TTR for warfarin users was 72%. Compared to the second best TTR quartile (reference), the risk of IS was higher in the two poorest TTR quartiles, and lower in the best TTR quartile and on rivaroxaban [2.35 (95% confidence interval, 1.85-2.85), 1.44 (1.18-1.75), 0.60 (0.47-0.77) and 0.72 (0.56-0.92)]. These differences were non-significant for apixaban and dabigatran. HR of ICH was 6.38 (4.88-8.35) and 1.87 (1.41-2.49) in the two poorest TTR groups, 1.44 (1.02-1.93) on rivaroxaban, and 0.58 (0.40-0.85) in the best TTR group compared to the reference group. Mortality was higher in the two poorest TTR groups and lowest in the best TTR group. Conclusions: The outcome was unsatisfactory in the two lowest TTR quartiles - in half of the patients treated with warfarin. The differences between the high TTR groups and standard dose DOACs were absent or modest. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Direct oral anticoagulants (DOACs) reflect anticoagulation agents given to treat or prevent thrombosis, having largely replaced vitamin K antagonists (VKAs) such as warfarin. DOACs are given in fixed daily doses and generally do not need monitoring. However, there may be a variety of reasons that justify measurement of plasma DOAC levels in individual patients. Methods: We report updated findings for DOAC testing in our geographic region, using recent data from the RCPAQAP, an international external quality assessment (EQA) program, currently with some 40–60 participants in each of the different DOAC (rivaroxaban, apixaban, dabigatran) modules, to assess laboratory performance in this area. Data has been assessed for the past 5 years (2019–2023 inclusive), with 20 samples each per DOAC. Results: Data shows a limited repertoire of assays in use, and mostly consistency in reported numerical values when assessing proficiency samples. Available assays mostly comprised reagents from four manufacturing suppliers. There was good consistency across what participants identified as 'DOAC detected', but some variability when participants attempted to grade DOAC levels as low vs moderate vs high. Inter‐laboratory/method coefficient of variation (CVs) were generally <15% for each DOAC, when present at >100 ng/mL. Conclusion: We hope our findings, reflecting on mostly consistent reporting of DOAC levels and interpretation provides reassurance for clinicians requesting these measurements, and helps support their implementation in regions where there is a paucity of test availability. [ABSTRACT FROM AUTHOR]

Introduction: There is a paucity of real-world studies examining the risks of stroke/systemic embolism (SE) and major bleeding (MB) among non-valvular atrial fibrillation (NVAF) patients switching from warfarin to a direct oral anticoagulant (DOAC). This retrospective study was conducted to compare the stroke/SE and MB risks between patients switched from warfarin to apixaban, dabigatran, or rivaroxaban in real-world clinical practice. Materials and methods: This study used data from four United States commercial claims databases from January 1, 2012 to June 30, 2019. The study population included NVAF patients initially treated with warfarin and switched to apixaban, dabigatran, or rivaroxaban within 90 days of their warfarin prescription ending. Patients were matched 1:1 between the DOACs in each database using propensity scores and then pooled for the final analysis. Cox proportional hazards models were used to calculate the risk of stroke/SE and MB. Results and conclusions: The final population consisted of 2,611 apixaban-dabigatran, 12,165 apixaban-rivaroxaban, and 2,672 dabigatran-rivaroxaban pairs. Apixaban vs. dabigatran was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.39–0.96) and MB (HR: 0.67; 95% CI: 0.50–0.91). Apixaban vs. rivaroxaban was associated with a similar risk of stroke/SE (HR: 0.88; 95% CI: 0.73–1.07) and a lower risk of MB (HR: 0.60; 95% CI: 0.52–0.68). There was no significant difference in either risk between dabigatran and rivaroxaban. These results provide important insights into how the risks of stroke/SE and MB for NVAF patients vary when switching from warfarin to different DOACs. Key point: • Patients with NVAF may switch to DOACs for effectiveness, safety, or convenience. • Risk of stroke/SE and MB may vary among patients with NVAF who switch to DOACs. • Switching to apixaban had a lower risk of MB than dabigatran/rivaroxaban. • Results may inform DOAC prescribing decisions after warfarin in patients with NVAF. [ABSTRACT FROM AUTHOR]

Background: Patients who sustain a hip fracture whilst taking direct oral anticoagulants (DOACs) experience delays to surgery, which can increase morbidity and mortality. Achievement of the prompt surgery aspect of the National Hip Fracture Database (NHFD) best practice tariff (BPT) stipulates surgery within 36 h, which these patients often fail to meet. Patients and methods: Our protocol for expedited hip fracture surgery in patients taking DOACs was implemented. We compared surgery within 36 h (primary outcome) and peri-operative blood transfusions, 30-day mortality, wound leakage, return to theatre and length of hospital stay (secondary outcomes) with standard care of 80 matched non-anticoagulated controls. Results: Median times to theatre were 26.0 h (IQR 16.2 h) in DOAC patients and 22.4 h (IQR 16.9 h) in controls: bootstrapped 95% CI for the difference (−0.935, 7.52). Bias-corrected related samples bootstrapped t -test revealed no evidence for a group difference on the primary outcome (p = 0.133) or any secondary outcome, including post-operative transfusions (χ2(1) = 0.533; p = 0.465, 95% CI for the difference −18.3% to 8.37%); death within 30 days (χ2(1) = 0.667; p = 0.414, 95% CI for the difference −3.48% to 8.48%); wound leakage (χ2(1) = 0.571; p = 0.450, 95% CI −1.79% to 0.792%); return to theatre (χ2(1) = 0.00; p = 1.00); and median length of hospital stay (p = 0.678, bias-corrected bootstrapped 95% CI for the difference −4.47 to 6.68). Discussion: Our protocol is simple, does not require plasma DOAC level testing and can be used to achieve the NHFD recommendation of surgery within 36 h without increasing peri-operative transfusions, wound leakage, return to theatre, length of stay or mortality. [ABSTRACT FROM AUTHOR]

Aim: Atezolizumab and bevacizumab (Atezo/Bev) combination immunotherapy regimens and direct oral anticoagulants (DOACs) are both associated with bleeding. Therefore, combining Atezo/Bev regimens with DOACs may exacerbate the bleeding risk. This study investigated the feasibility of the Atezo/Bev regimen in patients taking DOACs. Methods: This retrospective study included 141 patients with unresectable hepatocellular carcinoma (HCC) or advanced lung cancer (LC) treated with Atezo/Bev regimens. Patients who used antithrombotic agents other than DOACs were excluded. Bleeding events during the Atezo/Bev regimen were analyzed. Results: The incidence rates of bleeding of any grade in the DOAC (n = 11) and no antithrombotic agent (NAA) (n = 130) groups were 9.1% and 10.8%, respectively, with no significant differences. Moreover, no significant difference was found in the frequency of bleeding of grade ≥3 between the DOAC and NAA groups. No patients in the DOAC group discontinued the Atezo/Bev regimen because of severe bleeding. Although serum albumin levels, with a hazard ratio (HR) of 0.298 (95% confidence interval [CI]: 0.105–0.847), independently contributed to bleeding events (p = 0.023), DOAC administration did not (HR: 1.357; 95% CI: 0.157–10.54; p = 0.770). Among only patients with HCC (n = 59), none of the five patients taking DOACs experienced bleeding events. A high albumin–bilirubin score (HR: 9.083, 95% CI: 1.118–73.76) was associated with bleeding events (p = 0.039). Conclusions: DOACs did not have a considerable effect on bleeding events in the Atezo/Bev regimens for HCC or LC. Under careful surveillance for bleeding, Atezo/Bev regimens may be feasible in patients receiving DOACs. [ABSTRACT FROM AUTHOR]

Background: Off-label dosing of direct oral anticoagulants (DOACs) is both common and associated with adverse patient outcomes. Evidence describing best practices to support optimal direct oral anticoagulant (DOAC) dosing is limited. Objective: To describe the impact of clinical pharmacist intervention on DOAC prescribing. Methods: This retrospective study was a descriptive analysis conducted within an integrated healthcare system with a centralized, pharmacist-led Anticoagulation Management Service (AMS). Patients prescribed a DOAC between January 1, 2020 and December 31, 2020 were included. Pharmacy dispensing reports were generated for pharmacist review and anticoagulant drug therapy changes were recommended to physicians where appropriate. The primary objective was to describe the number and type of recommendations made. Secondary objectives were to determine the provider acceptance rate based on the intervention type and on clinical vs formulary recommendations. Results: Clinical pharmacists made 147 recommendations for 2331 unique patients included in the analysis. Twenty-three recommendations (16%) were to decrease the dose, 46 (31%) were to increase the dose, 14 (10%) were to change the medication due to clinical scenario, 62 (42%) were to change the medication due to cost, and 2 (1%) were another issue. One hundred twenty-three (84%) recommendations were accepted. The provider acceptance rate was similar for clinical and formulary recommendations (85% and 82% respectively). Conclusion: Implementation of report-driven clinical pharmacist intervention led to an improvement in appropriate DOAC medication selection and dosing. [ABSTRACT FROM AUTHOR]

Background: Apixaban is commonly used to prevent stroke in older adults with nonvalvular atrial fibrillation (AF). Although its package insert has specific dose reduction criteria, providers may dose reduce outside of these parameters based on clinical scenarios. Objective: The primary objective was to determine the incidence of apixaban off-label reduced dosing, while secondarily determining the safety and efficacy outcomes associated with such dosing. Methods: A retrospective analysis of patients aged 65 and older with orders for apixaban for AF was institutional review board (IRB)-approved and conducted across 3 academic medical centers. Patients receiving off-label reduced-dose apixaban (ie, "underdosed") were matched to a cohort of patients dosed according to the package insert at the standard dosing (5 mg twice daily) using stratified random sampling. Secondary outcomes included 1-year incidence of major bleeding, clinically relevant non-major bleeding (CRNMB), stroke or transient ischemic attack (TIA), and mortality. The Fisher exact tests were used to compare between-group differences. Results: Of the 1172 patients meeting initial inclusion criteria, 201 (17%) were dosed off-label, with 175 (15%) "underdosed." The 147 "underdosed" patients with documented follow-up were matched with 139 patients receiving standard Food and Drug Administration (FDA)-labeled dosing. There were no significant differences in incidence of stroke (2.7% vs 2.2%), major bleeding (0% vs 0.7%), and CRNMB (2.7% vs 1.4%) in the off-label reduced dosing versus standard dosing groups. All-cause mortality was higher in the off-label reduced-dose group (16 [10.9%] vs 2 [1.4%], P < 0.05). Conclusion and Relevance: Older adults with nonvalvular AF are commonly prescribed lower-than-recommended doses of apixaban. However, no significant association was found between empiric off-label reduced dosing and stroke or bleeding outcomes. [ABSTRACT FROM AUTHOR]

Anticoagulants play a vital role as part of the antithrombotic therapy of myocardial infarction and are complementary to antiplatelet therapies. In the acute setting, the rationale for their use is to antagonize the ongoing clotting cascade including during percutaneous coronary intervention. Anticoagulation may be an important part of the longer-term antithrombotic strategy especially in patients who have other existing indications (e.g. atrial fibrillation) for their use. In this narrative review, the authors provide a contemporary summary of the anticoagulation strategies of patients presenting with NSTEMI, both in terms of anticoagulation during the acute phase as well as suggested antithrombotic regimens for patients who require long-term anticoagulation for other indications. Patients presenting with non-ST-elevation myocardial infarction (NSTEMI) should be initiated on anticoagulation (e.g. heparin/low molecular weight heparin) for the initial hospitalization period for those medically managed or until percutaneous coronary intervention. Longer term management of NSTEMI for patients with an existing indication for long-term anticoagulation should comprise triple antithrombotic therapy of anticoagulant (preferably DOAC) with aspirin and clopidogrel for up to 1 month (typically 1 week or until hospital discharge), followed by DOAC plus clopidogrel for up to 1 year, and then DOAC monotherapy thereafter. [ABSTRACT FROM AUTHOR]

Abstract Cardiovascular diseases are the leading cause of death globally, making the use of oral anticoagulants for prevention increasingly important. Historically, warfarin has played a significant role in this context. In recent years, introduction of new oral anticoagulants, such as rivaroxaban, apixaban, dabigatran, and edoxaban, has been seen. This study evaluates the risk associated with the use of oral anticoagulants by analyzing spontaneous adverse drug reactions reported to the Portuguese Pharmacovigilance System from 2012 to 2021. The study includes 951 adverse drug reactions reports, with the majority (n = 770; 80.97%) classified as serious. Of the 770 serious adverse drug reactions reports, the most commonly reported seriousness criterion was “Clinically Important” (n = 350; 45.45%). In terms of demographics, there was a higher reporting rate among the elderly population, with a greater prevalence of females. The System Organ Class group with the highest number of adverse drug reactions was “Gastrointestinal disorders,” with the most commonly reported Preferred Term being “Gastrointestinal hemorrhage,” and dabigatran was the most frequently reported drug. In summary, oral anticoagulants have adverse drug reactions that require continuous monitoring. Accurate identification and monitorization of adverse drug reactions is an important starting point to improve drug safety in population.

Background: The incidence of cardiovascular diseases is increasing in persons with hemophilia A (HA). Therefore, anticoagulant therapy based on direct oral anticoagulants (DOACs) may be needed, despite the bleeding risk. In case of surgery or bleeding, such patients may be concomitantly treated with emicizumab (routine prophylaxis), factor (F)VIII products, and DOAC. Their concomitant presence constitutes a hemostatic challenge. Recent international guidelines stated that data are scarce on the hemostatic balance of plasma samples from patients with HA receiving emicizumab and DOAC. Objectives: The aim of this observational study was to assess the coagulation of FVIII-deficient plasma spiked with DOAC and emicizumab and to evaluate the effects of FVIII addition. Methods: Prothrombin time, activated partial thromboplastin time, and thrombin generation (TG) using the calibrated automated thrombogram method were evaluated in aliquots of a commercial severe HA plasma supplemented with emicizumab (0, 12.5, 25, 50, and 100 ng/mL), DOAC (0, 50, 100, 200, and 400 ng/mL of apixaban, rivaroxaban, edoxaban, or dabigatran) and FVIII (0%, 5%, 15%, 50%, and 100%). Results: DOAC rapidly induced a TG decrease. Emicizumab could counter this effect only for the lowest DOAC dose. FVIII addition to the FVIII-deficient plasma containing a DOAC and emicizumab improved TG and countered the anticoagulant effect of DOAC at ≤100 ng/mL. Conclusion: Our findings indicate that FVIII can be safely used with emicizumab to counter the anticoagulant effect of DOAC at ≤100 ng/mL. The TG assay is an efficient tool to monitor plasma containing anti-FXa DOAC, but not dabigatran (anti-FIIa).

Background In direct oral anticoagulant (DOAC) users with stroke due to large artery occlusion, endovascular thrombectomy is an effective treatment when intravenous thrombolytic therapy is unsuitable. The purpose of this study is to investigate the association between emergent DOAC levels and endovascular thrombectomy outcomes. Methods Participants with atrial fibrillation, who had a premorbid modified Rankin Scale score of ≤3 and had undergone endovascular thrombectomy for acute stroke, were enrolled. Drug levels upon hospital arrival were measured in the prestroke DOAC users. Head noncontrast computed tomography and computed tomographic angiography images were used to quantify thrombus permeability. The primary outcome was functional independence at 3 months (modified Rankin Scale 0–2 or a return to premorbid status for patients with a premorbid modified Rankin Scale of 3). Results The study included 250 patients (antithrombotic agent nonusers, 42.0%; oral anticoagulant users, 34.0%; and antiplatelet users, 24.0%). The primary outcomes did not differ among the 3 groups. Among oral anticoagulant users, 78.8% were DOAC users. Of the 59 DOAC users with available drug level measurements, 62.7% had low levels (

Partial thrombosis of the corpus cavernosum is an extremely rare and likely underdiagnosed urologic condition. We discuss a case of a 25-year-old male who presented with severe perineal pain and was diagnosed with idiopathic proximal partial thrombosis of the corpus cavernosum via ultrasound and MRI. The patient experienced symptom resolution with evidence of disease regression on follow up MRI after treatment with direct oral anticoagulation. Further studies are needed to fully delineate the pathophysiology of this condition to facilitate development of standardized diagnostic and treatment algorithms.

BackgroundOral anticoagulants (OACs) mitigate stroke risk in patients with atrial fibrillation (AF). The study aim was to analyze prevalence and predictors of OAC underutilization.MethodsNewly diagnosed AF patients with a CHA2DS2-VASc score ≥ 2 were identified from the US CMS Database (January 1, 2013-December 31, 2017). Patients were stratified based on having an OAC prescription versus not and the OAC prescription group was stratified by direct OAC (DOACs) versus warfarin. Multivariable logistic regression models were used to examine predictors of OAC underutilization.ResultsAmong 1,204,507 identified AF patients, 617,611 patients (51.3%) were not prescribed an OAC during follow-up (mean: 2.4 years), and 586,896 patients (48.7%) were prescribed an OAC during this period (DOAC: 388,629 [66.2%]; warfarin: 198,267 [33.8%]). Age ≥ 85 years (odds ratio [OR] 0.55, 95% confidence interval [CI] 0.55-0.56), female sex (OR 0.96, 95% CI 0.95-0.96), Black race (OR 0.78, 95% CI 0.77-0.79) and comorbidities such as gastrointestinal (GI; OR 0.43, 95% CI 0.41-0.44) and intracranial bleeding (OR 0.29, 95% CI 0.28-0.31) were associated with lower utilization of OACs. Furthermore, age ≥ 85 years (OR 0.92, 95% CI 0.91-0.94), Black race (OR 0.78, 95% CI 0.76-0.80), ischemic stroke (OR 0.77, 95% CI 0.75-0.80), GI bleeding (OR 0.73, 95% CI 0.68-0.77), and intracranial bleeding (OR 0.72, 95% CI 0.65-0.80) predicted lower use of DOACs versus warfarin.ConclusionsAlthough OAC therapy prescription is the standard of care for stroke prevention in AF patients, its overall utilization is still low among Medicare patients ≥ 65 years old, with specific patient characteristics that predict underutilization.

Abstract Aims Atrial fibrillation (AF) and heart failure (HF) often coexist. Older age is strongly associated with stroke, HF, and mortality. The association between coexistence of HF and a risk of clinical outcomes and the effectiveness of anticoagulation therapy including direct oral anticoagulants (DOACs) in elderly patients with AF and HF have not been investigated. We aimed to evaluate 2 years of outcomes and to elucidate the efficacy of DOACs or warfarin in elderly AF patients in the All Nippon AF In the Elderly (ANAFIE) Registry with and without a history of HF. Methods and results The ANAFIE Registry is a multicentre, prospective observational study following elderly non‐valvular AF patients aged ≥75 years for 2 years. Hazard ratios (HRs) were calculated based on the presence or absence of an HF diagnosis and DOAC or warfarin use at enrolment. Among 32 275 eligible patients, 12 116 (37.5%) had been diagnosed with HF. Patients with HF had significantly higher rates of HF hospitalization or cardiovascular death (HR 1.94, P

Background Little is known how individual time-in-therapeutic-range (TTR) impacts the effectiveness and safety of warfarin therapy compared to direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF).Objective To compare the effectiveness and safety of standard dose DOACs to warfarin in patients with AF, while categorizing warfarin treated patients into quartiles based on their individual TTR.Materials and methods We conducted a nationwide study including all patients with new-onset AF between 2011 and 2018 in Finland. Hazard ratios (HR) were calculated using Cox regression analysis with the inverse probability of treatment weighted method to assess the risks of ischaemic stroke (IS), intracranial haemorrhage (ICH) and mortality for users of apixaban (n = 12,426), dabigatran (n = 4545), rivaroxaban (n = 12,950) and warfarin (n = 43,548).Results The median TTR for warfarin users was 72%. Compared to the second best TTR quartile (reference), the risk of IS was higher in the two poorest TTR quartiles, and lower in the best TTR quartile and on rivaroxaban [2.35 (95% confidence interval, 1.85–2.85), 1.44 (1.18–1.75), 0.60 (0.47–0.77) and 0.72 (0.56–0.92)]. These differences were non-significant for apixaban and dabigatran. HR of ICH was 6.38 (4.88–8.35) and 1.87 (1.41–2.49) in the two poorest TTR groups, 1.44 (1.02–1.93) on rivaroxaban, and 0.58 (0.40–0.85) in the best TTR group compared to the reference group. Mortality was higher in the two poorest TTR groups and lowest in the best TTR group.Conclusions The outcome was unsatisfactory in the two lowest TTR quartiles – in half of the patients treated with warfarin. The differences between the high TTR groups and standard dose DOACs were absent or modest.

Purpose: Polypharmacy is a frequent situation in older adults that increases the risk of drug-drug interactions (DDIs), both pharmacokinetic (PK) and pharmacodynamic (PD). Direct oral anticoagulants (DOACs) are frequently prescribed in older adults, mainly because of the high prevalence of atrial fibrillation (AF). DOACs are subject to cytochrome P450 3A4 (CYP3A4)- and/or P-glycoprotein (P-gp)-mediated PK DDIs and PD DDIs when co-administered with drugs that interfere with platelet function. The aim of our study was to assess the prevalence of DDIs involving DOACs in older adults and the associated risk factors at admission and discharge. Methods: This was a cross-sectional study conducted in an acute geriatric unit between January 1, 2018 and December 31, 2022, including patients over 75 years of age treated with DOACs at admission and/or discharge, for whom a comprehensive collection of co-medications was performed. Results: From 909 hospitalizations collected, the prevalence of PK DDIs involving DOACs was 16.9% at admission and 20.7% at discharge, and the prevalence of PD DDIs was 20.7% at admission and 20.2% at discharge. Factors associated with DDIs were bleeding history [adjusted odds ratio (ORa) 1.74, 95% confidence interval (CI) 1.13–2.68], number of drugs > 6 (ORa 2.54, 95% CI 1.88–3.46) and reduced dose of DOACs (ORa 0.39, 95% CI 0.28–0.54) at admission and age > 87 years (ORa 0.74, 95% CI 0.55–0.99), number of drugs > 6 (ORa 2.01, 95% CI 1.48–2.72) and reduced dose of DOACs (ORa 0.41, 95% CI 0.30–0.57) at discharge. Conclusion: This study provides an indication of the prevalence of DDIs as well as the profile of DDIs and patients treated with DOACs. [ABSTRACT FROM AUTHOR]

Background: Although renal dysfunction is associated with adverse clinical outcomes in patients with atrial fibrillation (AF) following stroke, the impact of renal function variability is unclear. Aim: This study aimed to assess the association between renal function variability and various adverse clinical outcomes in patients with transient ischemic attack (TIA)/ischemic stroke and atrial fibrillation (AF). Methods: We conducted a population-based study and retrospectively identified patients hospitalized with a diagnosis of TIA/ischemic stroke and AF during 2016-2020 using the Clinical Data Analysis and Reporting System of Hong Kong. Serial serum creatinine tested upon the onset of TIA/ischemic stroke and during their subsequent follow-up was collected. Renal function variability was calculated using the coefficient of variation of the estimated glomerular filtration rate (eGFR). Clinical endpoints that occurred during the study period were captured and included ischemic stroke/systemic embolism, intracerebral hemorrhage (ICH), total bleeding, major adverse cardiovascular events (MACE), cardiovascular, non-cardiovascular, and all-cause mortality. Competing risk regression and Cox proportional hazard regression models were used to assess the associations of renal function variability with the outcomes of interest. Results: A total of 3,809 patients (mean age 80 ± 10 years, 43% men) who satisfied the inclusion and exclusion criteria were followed up for a mean of 2.5 ± 1.5 years (9,523 patient-years). The mean eGFR was 66 ± 22 mL/min/1.73 m2 at baseline, and the median number of renal function tests per patient during the followup period was 20 (interquartile range 11-35). After accounting for potential confounders, a greater eGFR variability was associated with increased risks of recurrent ischemic stroke/systemic embolism [fully adjusted subdistribution hazard ratio 1.11, 95% confidence interval (CI) 1.03-1.20], ICH (1.17, 1.01-1.36), total bleeding (1.13, 1.06-1.21), MACE (1.22, 1.15-1.30), cardiovascular (1.49, 1.32-1.69), non-cardiovascular (1.43, 1.35-1.52), and all-cause mortality (fully adjusted hazard ratio 1.44, 1.39-1.50). Conclusion: Visit-to-visit renal function variability is independently associated with adverse clinical outcomes in TIA/ischemic stroke patients with AF. Further large-scale studies are needed to validate our results. [ABSTRACT FROM AUTHOR]

Given the growing number of patients receiving direct oral anticoagulant (DOAC), patients requiring rapid neutralization is also increasing in case of major bleedings or urgent surgery/procedures. Idarucizumab is commercialized as a specific antidote to dabigatran while andexanet alfa has gained the Food and Drug Administration and the European Medicines Agency approval as an oral anti-factor Xa inhibitors antidote. Other antidotes or hemostatic agents are still under preclinical or clinical development, the most advanced being ciraparantag. DOAC plasma levels measurement allows to appropriately select patient for antidote administration and may prevent unnecessary prescription of expensive molecules in some acute clinical settings. However, these tests might be inconclusive after some antidote administration, namely andexanet alfa and ciraparantag. The benefit of laboratory monitoring following DOAC reversal remains unclear. Here, we sought to provide an overview of the key studies evaluating the safety and efficacy of DOAC reversal using the most developed/commercialized specific antidotes, to discuss the potential role of the laboratory monitoring in the management of patients receiving DOAC specific antidotes and to highlight the areas that deserve further investigations in order to establish the exact role of laboratory monitoring in the appropriate management of DOAC specific antidotes. Anticoagulation monitoring and specific reversal agent targets DOAC: direct oral anticoagulant; dTT: diluted thrombin time; ECA: ecarin chromogenic assay; ECT: ecarin cloting time. [Display omitted] • Antidotes for direct oral anticoagulant (DOAC) reversal have been developed. • The role of laboratory monitoring in DOAC reversal using antidotes is unclear. • Dabigatran level prior to idarucizumab could predict reversal outcome. • Oral FXa inhibitor levels cannot be easily measured following andexanet alfa. • DOAC measurement using commercialized assays is not possible after ciraparantag. [ABSTRACT FROM AUTHOR]

Background: Anticoagulation (AC) is used for stroke prevention in atrial fibrillation (AF). Direct Oral Anticoagulants (DOACs) are safe in patients with AF without cirrhosis, they are hardly studied in patients with advanced cirrhosis. Our study evaluates the safety and outcomes of DOACs in patients with Child‐Pugh class C cirrhosis (CPC). Methods: We queried TriNetX Database. Patients with CPC and AF were divided into three cohorts: patients on DOACs, no AC, and warfarin. Three study arms were created using a 1:1 propensity score matching system (PSM). Results: Totally 16 029 patients met the inclusion criteria. Of those, 20.2% (n = 3235) were on DOACs, 47.1% (n = 7552) were not on AC, and 32.7% (n = 5242) were on warfarin. First arm comparing AC versus no AC, a statistically significant benefit was identified in 3‐year mortality risk (47% vs 71%, P < 0.0001) and transplant status (17% vs 5%, p < 0.0001) with AC. However, no significant difference was identified regarding intracranial hemorrhage and GI bleeding risk. Second arm comparing patients on DOACs versus no AC, we identified mortality benefit (40% vs 72%, P < 0.0001) and a higher transplant rate (9% vs 3.2%, P < 0.0001) with DOACs. Intracranial hemorrhage rates (6% vs 4%, P = 0.03) were higher in patients on DOACs. Third arm comparing patients on DOACs versus Warfarin, a statistically significant lower risk of intracranial hemorrhage (6.6% vs 8.7%, P = 0.004) and GI bleed (2% vs 2.4%, P < 0.0001) were identified in patients on DOACs. Conclusion: Anticoagulation is safe in patients with CPC with AF and may provide a mortality benefit. DOACs are a safer alternative to warfarin. [ABSTRACT FROM AUTHOR]

Patients with hematologic malignancies are often complicated not only by severe bleeding due to thrombocytopenia and disseminated intravascular coagulation but also by thromboembolic events, just like in patients with solid cancers, and these events can negatively impact patient outcomes. Nevertheless, the prevention and treatment of cancer-associated thrombosis (CAT) in hematologic malignancies has not been adequately investigated due to the limited size, heterogeneity, and unique pathophysiology of the patient population. This article summarizes the current understanding, risk factors, prediction models, and optimal prevention and treatment strategies of CAT in hematologic malignancies on a disease-by-disease basis, including acute leukemia, lymphoma, myeloma, and myeloproliferative neoplasms. Specific considerations of novel molecular targeted therapeutics introduced in recent years, such as immunomodulatory drugs and tyrosine kinase inhibitors, are also discussed based on the latest clinical trials. [ABSTRACT FROM AUTHOR]

Background: Toxicity or treatment failure related to drug-drug interactions (DDIs) are known to significantly affect morbidity and hospitalization rates. Despite the availability of numerous databases for DDIs identification and management, their information often differs. Oral anticoagulants are deemed at risk of DDIs and a leading cause of adverse drug events, most of which being preventable. Although many databases include DDIs involving anticoagulants, none are specialized in them. Aim and method: This study aims to compare the DDIs information content of four direct oral anticoagulants and two vitamin K antagonists in three major DDI databases used in Switzerland: Lexi-Interact, Pharmavista, and MediQ. It evaluates the consistency of DDIs information in terms of differences in severity rating systems, mechanism of interaction, extraction and documentation processes and transparency. Results: This study revealed 2'496 DDIs for the six anticoagulants, with discrepant risk classifications. Only 13.2% of DDIs were common to all three databases. Overall concordance in risk classification (high, moderate, and low risk) was slight (Fleiss' kappa = 0.131), while high-risk DDIs demonstrated a fair agreement (Fleiss' kappa = 0.398). The nature and the mechanism of the DDIs were more consistent across databases. Qualitative assessments highlighted differences in the documentation process and transparency, and similarities for availability of risk classification and references. Discussion: This study highlights the discrepancies between three commonly used DDI databases and the inconsistency in how terminology is standardised and incorporated when classifying these DDIs. It also highlights the need for the creation of specialised tools for anticoagulant-related interactions. [ABSTRACT FROM AUTHOR]

There is limited data on the safety of direct oral anticoagulants (DOACs) in fragile patients with venous thromboembolism (VTE). We used the COMMAND VTE Registry-2 enrolling patients with acute symptomatic VTE. The study population consisted of 3928 patients receiving DOACs, who were divided into fragile (2136 patients) and non-fragile groups (1792 patients). Fragility was defined as patients of age ≥ 75 years, creatinine clearance level ≤ 50 ml/min, and/or body weight ≤ 50 kg. The fragile group significantly more often received reduced doses of DOACs compared to the non-fragile group (51 % and 19 %, P < 0.001). The cumulative 5-year incidence of major bleeding was numerically higher in the fragile group than the non-fragile group (15.0 % and 11.1 %, P = 0.052), even with no significant excess risk after adjusting for confounders (HR 1.03, 95%CI 0.81–1.31, P = 0.78). The cumulative 5-year incidence of clinically relevant bleeding was significantly higher in the fragile group than the non-fragile group (28.6 % and 19.6 %, P < 0.001), even after adjusting for confounders (HR 1.28, 95%CI 1.08–1.53, P = 0.005). There was no significant difference in cumulative 5-year incidence of recurrent VTE between the groups (9.6 % and 8.9 %, P = 0.68), which was consistent after adjusting for confounders (HR 1.13, 95%CI 0.84–1.51, P = 0.41). Among VTE patients receiving DOACs, fragile patients were associated with a numerically higher rate of major bleeding and a significantly increased risk of clinically relevant bleeding, but not an increased risk of recurrent VTE. • There is limited data on the safety of DOACs in fragile patients with VTE. • Fragility was not associated with an increased risk of recurrent VTE. • Fragility showed a numerically higher rate of occurrence of major bleeding. • Fragility had a significantly increased risk of clinically relevant bleeding. [ABSTRACT FROM AUTHOR]

Aims: Atrial fibrillation (AF) and heart failure (HF) often coexist. Older age is strongly associated with stroke, HF, and mortality. The association between coexistence of HF and a risk of clinical outcomes and the effectiveness of anticoagulation therapy including direct oral anticoagulants (DOACs) in elderly patients with AF and HF have not been investigated. We aimed to evaluate 2 years of outcomes and to elucidate the efficacy of DOACs or warfarin in elderly AF patients in the All Nippon AF In the Elderly (ANAFIE) Registry with and without a history of HF. Methods and results: The ANAFIE Registry is a multicentre, prospective observational study following elderly non‐valvular AF patients aged ≥75 years for 2 years. Hazard ratios (HRs) were calculated based on the presence or absence of an HF diagnosis and DOAC or warfarin use at enrolment. Among 32 275 eligible patients, 12 116 (37.5%) had been diagnosed with HF. Patients with HF had significantly higher rates of HF hospitalization or cardiovascular death (HR 1.94, P < 0.001), cardiovascular events (HR 1.59, P < 0.001), cardiovascular death (HR 1.49, P < 0.001), all‐cause death (HR 1.32, P < 0.001), and net clinical outcome including stroke/systemic embolism, major bleeding, and all‐cause death (HR 1.23, P < 0.001), compared with those without HF; however, HRs for stroke/systemic embolism (HR 0.96, P = 0.56) and major bleeding (HR 1.14, P = 0.13) were similar. DOAC use was associated with a low risk of stroke/systemic embolism (HR 0.86, P = 0.19 in HF; HR 0.79, P = 0.016 in non‐HF; P for interaction = 0.56), major bleeding (HR 0.71, P = 0.008 in HF; HR 0.75, P = 0.016 in non‐HF; P for interaction = 0.74), HF hospitalization or cardiovascular death (HR 0.81, P < 0.001 in HF; HR 0.78, P < 0.001 in non‐HF; P for interaction = 0.26), cardiovascular events (HR 0.83, P < 0.001 in HF; HR 0.82, P = 0.001 in non‐HF; P for interaction = 0.65), cardiovascular death (HR 0.84, P = 0.12 in HF; HR 0.75, P = 0.035 in non‐HF; P for interaction = 0.18), all‐cause death (HR 0.89, P = 0.082 in HF; HR 0.80, P = 0.001 in non‐HF; P for interaction = 0.091), and net clinical outcome (HR 0.88, P = 0.019 in HF; HR 0.81, P < 0.001 in non‐HF; P for interaction = 0.21) compared with warfarin, irrespective of the presence or absence of HF. Analysis using the propensity score matching method showed similar associations. Conclusions: Non‐valvular AF patients aged ≥75 years with a history of HF had higher risks of cardiovascular events and mortality. DOACs were favourable to warfarin regardless of the coexistence of HF. These results might encourage the use of DOACs in elderly patients with non‐valvular AF with or without HF. [ABSTRACT FROM AUTHOR]

Background: Direct oral anticoagulants (DOACs) are the mainstay of treatment for venous thromboembolism (VTE) and non-valvular atrial fibrillation (AF), with or without an underlying cancer. Patients with cancer have a 2-3-fold increase in risk for bleeding complications compared to non-cancer patients taking anticoagulant therapy, however the incidence of bleeding for urogenital and gynecological cancers on DOACs are uncertain. Aims: To assess the bleeding risk associated with the use of DOACs in patients with urogenital and/or gynecological cancers. Method: We conducted a systematic review of randomized controlled trials (RCTs) and prospective cohort studies to address the safety of DOACs for VTE and AF when used in patients with urogenital and/or gynecological malignancy. The primary outcomes assessed were major and clinically relevant non-major (CRNMB) bleeding, with minor bleeding considered as a secondary outcome. MEDLINE, EMBASE and COCHRANE Central Registry of Controlled Trials were searched up to and including Oct 28, 2022. The study protocol was registered in PROSPERO (CRD42022370981). Studies were independently assessed for inclusion and data extracted in duplicate. Result: Seven studies met our inclusion criteria (Fig. 1): 2 RCTs and 5 prospective cohort studies. A total of 676 patients treated with DOACs were included, 628 (92.8%) had VTE and 48 (7.1%) had AF. In patients with VTE treated with DOACs, the pooled major bleeding rate was 2.1%, 95% confidence intervals (CI) 0.9–3.3% (Fig. 2). Pooled estimates could not be determined for AF patients given small event and patient numbers. Conclusion: Major bleeding rates in urogenital and/or gynecological cancer patients treated with DOACs are similar to that of the general cancer population. [ABSTRACT FROM AUTHOR]

DOACs have emerged as first-line treatment in most cancer-associated thrombosis (CAT), representing a paradigm shift in its management. However, CAT management remains challenging and requires careful risk–benefit considerations. A retrospective analysis of CAT presentations to a tertiary referral centre from January 2011 to December 2020. Outcomes in CAT patients were compared to VTE patients without malignancy. Subgroup analysis was also conducted for CAT according to anticoagulation type. 514 CAT cases from 491 patients were identified from 3230 total VTE cases. CAT patients had higher rates of major VTE (PE and/or proximal DVT) compared to patients without malignancy (78.4% vs. 66.8%, p < 0.001). CAT patients also had higher rates of VTE recurrence (HR 1.66, 95%CI 1.23–2.26), major bleeding (HR 3.41, 95%CI 2.36–4.93), VTE-related mortality (HR 2.59, 95%CI 1.46–4.62) and bleeding-related mortality (HR 2.66, 95%CI 1.05–6.73). There were no significant differences in rates of VTE recurrence, major bleeding, VTE-related mortality or fatal bleeding between CAT patients treated with DOACs, enoxaparin or warfarin. In the subgroup of CAT treated with DOACs, there was no significant difference in rates of GI bleeding compared to the enoxaparin subgroup (HR 0.17, 95%CI 0.02–1.26). CAT was associated with a larger clot burden and higher rates of VTE recurrence, major bleeding and mortality compared to VTE patients without malignancy in this large real-world study. This study demonstrated no significant differences in complication rates for CAT patients treated with DOACs over enoxaparin, suggesting that DOACs can be safely used in most cases of CAT. [ABSTRACT FROM AUTHOR]

Background and Aims: An increasing number of patients are undergoing gastric endoscopic submucosal dissection (ESD) with active prescriptions of direct oral anticoagulants (DOACs). Only a few reports have described the effects of DOAC intake on postoperative bleeding. We aimed to investigate the bleeding risk associated with DOACs after gastric ESD. Methods: Clinical studies published up to April 2022 showing bleeding rates after gastric ESD in patients taking DOACs were identified using electronic searches. The primary outcome was the rate of bleeding after gastric ESD in patients receiving DOACs compared to those not receiving antithrombotic therapy. In this meta-analysis, odds ratios (ORs) were calculated and pooled using a random effects model. The secondary outcome was the difference in the bleeding rate between patients treated with DOACs and those treated with warfarin and antiplatelet drugs. Results: Seven studies were included in this meta-analysis. The pooled analysis showed that DOACs had a higher bleeding rate than non-thrombotic therapy (17.0% vs. 3.4%; OR 5.72; 95% confidence interval [CI], 4.33–7.54; I2 = 0%). The bleeding risk associated with DOAC administration was similar to that associated with warfarin (17.0% vs. 20.0%; OR 0.83; 95% CI 0.59–1.18; I2 = 0%), whereas it was higher than that associated with antiplatelet administration (16.9% vs. 11.0%; OR 1.63; 95% CI 1.14–2.34; I2 = 8%). Conclusions: This meta-analysis reveals that the bleeding risk of DOACs is higher than that of non-antithrombotics and antiplatelets, whereas it is comparable to that of warfarin. Gastric ESD in patients on anticoagulants requires careful postoperative management. [ABSTRACT FROM AUTHOR]

To evaluate the safety of direct oral anticoagulants (DOACs) versus low-molecular weight heparin (LMWH) in patients with central nervous system (CNS) malignancies and secondary metastases. All adult patients with CNS malignancies and secondary metastases who were treated with a DOAC or LMWH for any indication from 2018 to 2022 were included. The primary outcome was the incidence of any intracranial hemorrhage (ICH) after anticoagulation initiation. Secondary outcomes included non-ICH bleeding events and thromboembolic events. Tolerability was assessed by any changes in anticoagulant therapy during study period. 153 patients were included; 48 patients received enoxaparin and 105 received DOACs, of which apixaban was used most commonly. The population was predominantly White (74%) and male (59%) with a median age of 65. Data was censored for immortal time bias for outcomes evaluated beyond 3 months. ICH occurred in 7.7% of the population, more frequently in the enoxaparin group (DOACs 4, 4% vs. enoxaparin 7, 16%, p = 0.037). Non-ICH bleeds were predominantly minor and more common in the DOAC group (DOACs 13, 13% vs. enoxaparin 1, 2%, p = 0.037). Thromboembolic events were not different between groups (DOACs 9. 9% vs, enoxaparin 2, 4%, p = 0.503). Anticoagulant switches occurred more in the enoxaparin group (DOACs 12, 12.4% vs. enoxaparin, 37.8%, p < 0.001), primarily due to patient or provider preference. Our data supports DOACs to be preferred over LMWH for the treatment of VTE or for stroke prevention with AF to prevent ICH in patients with brain tumors or metastases. [ABSTRACT FROM AUTHOR]

Background: While anticoagulation therapy is highly effective at treating venous thromboembolism, some patients can develop rapidly progressive thrombosis in multiple organs or sites despite therapeutic anticoagulation. Effective strategies to manage life-threatening thrombosis in these patients are elusive. Objectives: We describe our experience using dual direct oral anticoagulant (DOAC) therapy with a factor (F)Xa inhibitor (such as rivaroxaban or apixaban) and a FIIa inhibitor (dabigatran) for refractory cases of thrombosis. Methods: A retrospective chart review of all patients treated with simultaneous dabigatran and an oral FXa inhibitor at our institution was conducted. We included all patients over the age of 18. The study was approved by the University of British Columbia Research Ethics Board (REB number: H23-02575). Results: Eight patients were included. All patients initiated standard therapeutic anticoagulation upon diagnosis of acute venous thromboembolism with a median of 3 breakthrough thrombotic events prior to dual DOAC use. Five patients had a positive heparin-induced thrombocytopenia screen, but only 2 had heparin-induced thrombocytopenia confirmed on serotonin release assay testing. There were no recurrent deep vein thrombosis, pulmonary embolism, or bleeding events during dual DOAC use. Most patients ultimately transitioned to a single oral FXa inhibitor. Conclusion: Dual DOAC therapy may be a useful strategy for managing challenging thrombosis cases resistant to conventional anticoagulation. Further research is warranted to validate these findings and explore the broader applicability of dual DOAC therapy in challenging thrombotic scenarios.

Background: Hip fractures primarily occur in older people and represent a significant public health issue due to their high incidence and mortality rate. The concurrent occurrence of venous thromboembolism (VTE) during the perioperative period exacerbates the threat to patient health. Methods: We retrieved all articles related to hip fracture surgery and venous VTE from the Web of Science core collection database from 2000 to 2023. For bibliometric analysis, we extracted relevant information, including year of publication, country, institution, journal, impact factor, title, author, category, reference, keywords, number of citations, average number of citations, and H-index. Results: A total of 1079 articles were retrieved, with 67 countries, 341 institutions, and 256 journals participating in research on hip fracture surgery and venous thromboembolism. The overall research showed an increasing trend. The United States, Harvard University, Injury-International Journal of The Care of The Injured, and Lassen MR are the leading country, institution, journal, and author respectively, in terms of publication. Research directions in this field mainly include the impact of preoperative anticoagulation on fracture surgery, intraoperative blood protection strategies, and postoperative prevention and treatment of VTE. Hotspots and trends in research include the relationship between direct oral anticoagulants and surgical timing, perioperative blood protection, intertrochanteric fractures, and geriatric traumatic fractures. Conclusions: This study constructed the knowledge structure of hip fracture surgery and VTE and identified research hotspots and trends. Future research should focus on developing a prediction system for VTE in hip fracture surgery to guide individualized prevention and treatment.

Background There have been limited data on the changes in clinical outcomes after the introduction of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) in real clinical practice. We evaluated the changes in management strategies and long‐term outcomes from the warfarin era to the DOAC era. Methods and Results We compared the 2 series of multicenter COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) registries in Japan enrolling consecutive patients with acute symptomatic VTE: Registry 1: 3027 patients in the warfarin era (2010–2014) and Registry 2: 5197 patients in the DOAC era (2015–2020). The prevalence of DOAC use increased more in Registry 2 than in the Registry 1 (Registry 1: 2.6% versus Registry 2: 79%, P

Background Direct oral anticoagulants (DOACs) have been the drug of choice for preventing ischemic stroke in patients with atrial fibrillation since 2014. In previous studies, the stroke risk while taking warfarin was 2 per 100 patient‐years and 1.5% per year while taking DOACs. We hypothesized that even if ischemic stroke occurred during anticoagulation therapy with DOACs, the prognosis was likely to be better than that with warfarin. Methods and Results Data from 2002 to 2019, sourced from a nationwide claims database, were used to identify atrial fibrillation patients using International Classification of Diseases codes. Patients who experienced an ischemic stroke during anticoagulation were categorized by the drugs used (warfarin, dabigatran, apixaban, rivaroxaban, and edoxaban). The primary outcome was mortality within 3 months and 1 year after the ischemic stroke. Among the 9578 patients with ischemic stroke during anticoagulation, 3343 received warfarin, and 6235 received DOACs (965 dabigatran, 2320 apixaban, 1702 rivaroxaban, 1248 edoxaban). The DOACs group demonstrated lower risks of 3‐month (adjusted hazard ratio [HR], 0.550, [95% CI, 0.473–0.639]; P

Abstract Aim Atezolizumab and bevacizumab (Atezo/Bev) combination immunotherapy regimens and direct oral anticoagulants (DOACs) are both associated with bleeding. Therefore, combining Atezo/Bev regimens with DOACs may exacerbate the bleeding risk. This study investigated the feasibility of the Atezo/Bev regimen in patients taking DOACs. Methods This retrospective study included 141 patients with unresectable hepatocellular carcinoma (HCC) or advanced lung cancer (LC) treated with Atezo/Bev regimens. Patients who used antithrombotic agents other than DOACs were excluded. Bleeding events during the Atezo/Bev regimen were analyzed. Results The incidence rates of bleeding of any grade in the DOAC (n = 11) and no antithrombotic agent (NAA) (n = 130) groups were 9.1% and 10.8%, respectively, with no significant differences. Moreover, no significant difference was found in the frequency of bleeding of grade ≥3 between the DOAC and NAA groups. No patients in the DOAC group discontinued the Atezo/Bev regimen because of severe bleeding. Although serum albumin levels, with a hazard ratio (HR) of 0.298 (95% confidence interval [CI]: 0.105–0.847), independently contributed to bleeding events (p = 0.023), DOAC administration did not (HR: 1.357; 95% CI: 0.157–10.54; p = 0.770). Among only patients with HCC (n = 59), none of the five patients taking DOACs experienced bleeding events. A high albumin–bilirubin score (HR: 9.083, 95% CI: 1.118–73.76) was associated with bleeding events (p = 0.039). Conclusions DOACs did not have a considerable effect on bleeding events in the Atezo/Bev regimens for HCC or LC. Under careful surveillance for bleeding, Atezo/Bev regimens may be feasible in patients receiving DOACs.

Introduction: Non-adherence to recommended secondary preventive anticoagulation in stroke patients with atrial fibrillation (AF) is a common phenomenon, although the introduction of direct oral anticoagulants (DOACs) has simplified anticoagulation management for physicians as well as for patients. Methods: We examined the adherence of secondary preventive anticoagulation in AF patients after re-integration in their social environment 6–12 weeks after stroke unit and rehabilitation clinic treatment and analyzed for predictors for adherence and non-adherence. We conducted a telephone survey in consecutive patients treated between January 2013 and December 2021 at our institutional stroke unit with an acute cerebrovascular ischemic event, and we analyzed discharge letters of rehabilitation clinics of those patients not anticoagulated at follow-up. All patients had known or newly diagnosed AF, and in all, we had recommended secondary preventive anticoagulation. Results: Follow-up information about anticoagulant intake could be obtained in 1,348 of 1,685 patients (80.0%) treated within the study period. Anticoagulation rate was 91.5%, with 83.6% of patients receiving DOACs and 7.9% receiving vitamin K antagonists (VKAs). Adherence to recommended anticoagulation was associated with intake of the recommended anticoagulant already at discharge (adjusted odds ratio [OR], 18.357; confidence interval [CI], 9.637–34.969), recommendation of a specific DOAC and dose (in contrast to “DOAC” as drug category) (adjusted OR, 2.971; CI, 1.173–7.255), a lower modified Rankin Scale at discharge (per point; adjusted OR, 0.813; CI, 0.663–0.996), younger age (per year; OR, 0.951; CI, 0.926–0.976), and the absence of peripheral vascular disease (adjusted OR, 0.359; CI, 0.173–0.746). In patients already anticoagulated at discharge, adherence was 98.5%, irrespective of a patient’s age, functional deficit at discharge, and peripheral vascular disease. Avoidable obstacles for non-adherence in patients not on anticoagulants at stroke unit discharge were (1) non-implementation of recommended anticoagulation by rehabilitation physicians predominantly in patients with moderate-severe or severe stroke disability (2.1%), (2) delegation of anticoagulation start from rehabilitation physicians to general practitioners/resident radiologists (1.3%), and (3) rejection of recommended anticoagulation because of patients’ severe stroke disability (0.5%). Non-avoidable obstacles were contraindications to anticoagulation (2.1%) and patients’ refusal (0.7%). Conclusions: Commencing drug administration already during stroke unit hospitalization and providing an explanation for the selection of the recommended anticoagulant in discharge letters ensures high adherence at patients’ re-integration in their social environment after acute stroke treatment. If drug administration cannot be commenced before discharge, education of rehabilitation physicians by stroke physicians and the involvement of stroke physicians into the post-stroke decision process might hinder avoidable obstacles.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong anticoagulant therapy. The safety and efficacy of direct oral anticoagulant (DOAC) in the chronic and transitional management of CTEPH has not been investigated. We performed a retrospective analysis of 405 consecutive pulmonary endarterectomy (PEA) cases at the University of California, San Diego, from July 2015 through July 2017. PEA specimen was reviewed for the presence of acute or subacute thrombotic material distinct from the expected chronic disease removed at the time of PEA by two investigators blinded to the patient information. Of 405 PEA cases, 166 patients (41.0%) were anticoagulated with one of three available DOACs; 239 (59.0%) presented on either oral vitamin-K antagonist or chronic injectable therapy. There were no significant differences in baseline characteristics between DOAC and non-DOAC groups. Evidence of recent thrombus was observed in 22 (13.3%) in the DOAC group versus 16 (6.7%) within the non-DOAC group. The odds ratio of DOACs usage and evidence of recent thrombus was 2.34 (95% confidence interval: 1.1-5.0, p = 0.03) after adjusting for age, gender, race, body mass index, and history of antiphospholipid antibody syndrome. CTEPH patients referred for PEA while on DOAC therapy were twice as likely to have associated acute or subacute thrombi present at the time of surgery compared with those on more traditional, non-DOAC anticoagulant therapies. This raises questions of the safety and efficacy of DOACs in the chronic management of CTEPH.

Introduction: Existing randomised controlled trials assessing the safety and efficacy of left atrial appendage occlusion (LAAO) in atrial fibrillation (AF) were of relatively small sample size or included patients who could receive oral anticoagulant treatment after device implantation. We compared the outcomes of patients with newly diagnosed AF who received percutaneous LAAO or direct oral anticoagulant (DOAC) treatment, in a large population from a global federated health network (TriNetX). Methods: Patients with AF treated with percutaneous LAAO were matched with those treated with DOAC between December 1, 2010, and October 1, 2018. Outcomes were all-cause mortality, ischaemic stroke, and intracranial haemorrhage (ICH) at 5 years. Results: We included 200 patients with AF, who received either LAAO or DOAC. The risk of all-cause mortality, ischaemic stroke, and ICH at 5 years was not significantly different between the two groups (risk ratio [RR] for all-cause mortality: 1.52, 95% confidence interval (CI): 0.97–2.38, RR for ischaemic stroke: 1.09, 95% CI: 0.51–2.36, and RR for ICH: 1.0, 95% CI: 0.44–2.30). Conclusion: Patients newly diagnosed with AF, eligible for DOAC, showed similar 5-year risk of death, ischaemic stroke, and ICH when comparing those who underwent percutaneous LAAO to those receiving DOAC. Future randomised controlled trials are needed to confirm the findings and advise changes in guidelines. [ABSTRACT FROM AUTHOR]

Background: Patients with atrial fibrillation (AF) and heart failure (HF) have a high risk of thromboembolism and other outcomes and anticoagulation is recommended. Hypothesis: This study was aimed to explore the risk factors associated with HF worsening in patients with AF and HF taking rivaroxaban in Spain. Methods: Multicenter, prospective, observational study that included adults with AF and chronic HF, receiving rivaroxaban ≥4 months before entering. HF worsening was defined as first hospitalization or emergency visit because of HF exacerbation. Results: A total of 672 patients from 71 Spanish centers were recruited, of whom 658 (97.9%) were included in the safety analysis and 552 (82.1%) in the per protocol analysis. At baseline, mean age was 73.7 ± 10.9 years, 64.9% were male, CHA2DS2‐VASc was 4.1 ± 1.5, HAS‐BLED was 1.6 ± 0.9% and 51.3% had HF with preserved ejection fraction. After 24 months of follow‐up, 24.9% of patients developed HF worsening, 11.6% died, 2.9% had a thromboembolic event, 3.1% a major bleeding, 0.5% an intracranial bleeding and no patient had a fatal hemorrhage. Older age, the history of chronic obstructive pulmonary disease, the previous use of vitamin K antagonists, and restrictive or infiltrative cardiomyopathies, were independently associated with HF worsening. Only 6.9% of patients permanently discontinued rivaroxaban treatment. Conclusions: Approximately one out of four patients with HF and AF treated with rivaroxaban developed a HF worsening episode after 2 years of follow‐up. The identification of those factors that increase the risk of HF worsening could be helpful in the comprehensive management of this population. [ABSTRACT FROM AUTHOR]

There is currently no established recommendation for antithrombotic treatment following transcatheter mitral valve replacement (TMVR). However, based on the analogy with surgical mitral bioprosthesis, vitamin K antagonists (VKAs) are predominantly used. The purpose of this study was to compare bleeding and thrombotic events associated with direct oral anticoagulants (DOACs) or VKAs in a prospective cohort of TMVR patients. We enrolled consecutive patients who underwent transseptal TMVR using a SAPIEN family prosthesis at our center between 2011 and 2023. The primary outcome was the occurrence of bleeding. VKAs were administered to patients until October 2019, after which DOACs were prescribed. The median follow-up was 4.7 months (Q1-Q3: 2.6-6.7 months). A total of 156 patients were included. The mean age was 65 ± 18.5 years, and 103 patients (66%) were women. The median EuroSCORE II was 7.48% (Q1-Q3: 3.80%-12.97%). Of the participants, 20.5% received DOACs and 79.5% were treated with VKAs. The primary outcome was observed in 50 (40%) patients in the VKA group and 3 (9%) patients in the DOAC group (adjusted HR: 0.21; 95% CI: 0.06-0.74; P = 0.02). Treatment with DOAC was associated with a shorter length of hospital stay. No significant differences were found in terms of thrombotic events, major vascular complications, stroke, or death. The use of DOACs after TMVR, compared with VKAs, appears to reduce the risk of bleeding complications and decrease the length of hospital stay for patients, without a significant increase in the risk of thrombotic events. [Display omitted] [ABSTRACT FROM AUTHOR]

Left atrial appendage occlusion (LAAO) provides an alternative for poor candidates of long-term oral anticoagulant (OAC) therapy; however, anticoagulant therapy after surgical procedures has limited use due to associated uncertainties. We aimed to evaluate the effectiveness and safety of the short-term use of direct oral anticoagulant (DOAC) and warfarin after LAAO. Electronic databases such as PubMed, Embase, Medline, and Cochrane Library databases were searched up to November 11, 2022. Our study compared DOAC therapy and warfarin in patients after LAAO. A meta-analysis was conducted with the Review Manager software (version 5.4). The meta-analysis included 13 cohort studies with a total of 32,607 patients. Our findings indicated that the incidence of stroke/TIA/SE, peri-device leaks>5 mm, device-related thrombosis , and all-cause mortality were not significantly different between the two groups after LAAO (P > 0.05). The DOAC group had a significantly lower incidence of major bleeding (OR = 0.83, 95 % CI: 0.74–0.94, P = 0.003), any bleeding (OR = 0.34, 95 % CI: 0.23–0.51, P < 0.001), stroke/TIA/SE and major bleeding (OR = 0.57, 95 % CI: 0.34–0.95, P = 0.03), and any major adverse event (OR = 0.89, 95 % CI:0.82–0.97, P = 0.010) than the warfarin group. The subgroup analysis revealed that the rate of stroke/TIA/SE was similar in the two groups in terms of the different regions, follow-up time, study type, anticoagulant strategy, and bleeding risk. The incidence of major bleeding in the DOAC group was significantly lower than that in the warfarin group in North America, as well as at follow-up period ≤6 months, retrospective cohort, HAS-BLED average score ≥ 3. In addition, the risk of major bleeding was higher with the combination of OAC and single antiplatelet therapy (SAPT) than with OAC alone. Finally, in the North American region, retrospective cohort, and HAS-BLED average score ≥ 3, the incidence of any serious adverse event in the DOAC group was still significantly lower than that in the warfarin group. Compared to warfarin, DOAC reduced the risk of major bleeding and any serious adverse event in patients after LAAO. This advantage was particularly notable in North America and high-risk populations for bleeding. In addition, the incidence of device-related thrombosis, peri-device leaks, stroke/TIA/SE and all-cause mortality were similar in both groups. The risk of major bleeding was lower in patients taking OAC alone compared with those taking OAC plus SAPT, without increasing the risk of thrombosis. • There is currently no unified standard for anticoagulation after left atrial appendage occlusion (LAAO) surgery. • In 13 studies revealed that the incidence of stroke/TIA/systemic embolism and all-cause mortality were similar between direct oral anticoagulant (DOAC) compared to warfarin. However, the incidence of bleeding and any major adverse event were higher among those who received warfarin. • The risk of major bleeding was lower among patients who received OAC alone compared to those who received OAC plus single antiplatelet therapy, without an increased risk of thrombosis. [ABSTRACT FROM AUTHOR]

• During the first 14 days of Direct oral anticoagulant (DOAC) therapy, a slight increase in serum levels of tacrolimus and cyclosporine can be found; • Serum Levels and concentration/dose ratio of Tacrolimus and cyclosporin were stable at 18 months follow-up in patients treated with DOAC; • DOACS have a similar safety and efficacy profile when compared to antagonist of vitamin K and no difference in terms of bleeding, thromboembolic events and renal function decline was found. direct oral anticoagulants (DOACs) are an alternative to conventional antagonist of vitamin-K (AVK). However, immune suppressive drugs (ISDs) may interfere with DOACs pharmacokinetic. evaluate safety and efficacy profile of DOACs compared to AVK in kidney transplant recipients (KTRs) treated with ISDs. a multi-center study from 4 Italian University hospitals enrolling consecutive KTRs on DOACs or AVK was carried out. Sixty-six patients on DOACs were compared with fifty patients on AVK with similar clinical features. Serial evaluation of renal function and serum levels of ISDs during 18 months follow-up (FU) was performed. Mean age of DOACs patients was 67±9 and mean eGFR was 58,3± 30,4mL/min/1.73m2. ISDs included tacrolimus (n=47, 71%), cyclosporin (n=13, 20%), everolimus (n=10, 7%) and sirolimus (n=4, 6%). After 14 days of DOACs therapy initiation there was a slight increase of serum levels of tacrolimus (+0.19±0.67 p=0.80) and cyclosporine (+0.12±0.25 p=0.94) not statistically significant. Levels of Tacrolimus and cyclosporin were stable at serial evaluation during 18-months follow-up. There were no thromboembolic events among patients treated with DOACs or AVK and no differences in term of major bleeding (6% vs 4% p=0.69), at long-term follow-up. There was no difference in term of eGFR decline from start therapy to 18 months FU between DOACs vs AVK therapy (-3.9±1 vs -3.8±2 p=0.82). DOACs have similar safety and efficacy than AVK among KTRs treated with ISDs. However, careful evaluation of potential drug interaction and ISDs serum levels is needed. [Display omitted] [ABSTRACT FROM AUTHOR]

The direct anticoagulants (DOACs), apixaban and rivaroxaban, are used for extended-phase treatment of venous thromboembolism (VTE) and have labeling for dose reduction for this indication. The objective of this study was to better understand primary care clinician prescribing patterns of apixaban and rivaroxaban for extended-phase anticoagulation. We conducted a 21-question survey targeting members of the American College of Physicians and United States Veterans Administration anticoagulation management services. Survey questions covered prescribing behaviors for dose reduction of apixaban and rivaroxaban for extended VTE treatment, as well as questions related to the respondent's practice setting. We used logistic regression to assess associations between demographics and prescribing behaviors. We used k-means clustering to identify distinct groups of prescribing patterns. Among 227 respondents, most were attending physicians (60%) and one-third (34%) practiced in internal medicine or primary care. Most (59%) indicated they dose-reduced DOACs. Hospitalists (no outpatient care) were least likely to dose-reduce (OR 0.09 [95% CI 0.03–0.22]), as well as early-career clinicians (0.53 [0.30–0.91]). Pharmacists and clinicians who treat over 500 VTE patients annually were most likely to dose reduce (6.4 [2.9–16.3]), (2.9 [1.5–6.0]), respectively. We identified five clusters of dosing behaviors and characterized clinician makeup. Clusters were primarily differentiated by frequency of dose reduction, DOAC preference, and temporary re-escalation of doses. We identified clinician characteristics that are associated with dose-reduction prescribing behaviors; these analyses provide insight into where targeted interventions, such as protocolization and education, would be most beneficial. [ABSTRACT FROM AUTHOR]