Use Of Apixaban Research Articles

Apixaban in Patients With Post-Myocardial Infarction Left Ventricular Thrombus: A Randomized Clinical Trial

BackgroundDirect oral anticoagulants are frequently used to treat post-myocardial infarction (MI) left ventricular thrombus (LVT). This study was conducted to evaluate the efficacy and safety of use of apixaban, compared to the standard warfarin therapy, in post-MI LVT. MethodsThis open-label, randomized controlled trial included patients with post-acute or recent anterior wall MI with transthoracic echocardiography-confirmed LVT. Patients were randomized to receive either apixaban 5 mg twice daily or warfarin to achieve an international normalized ratio of 2-3, in addition to dual antiplatelet therapy. The primary endpoint was LVT resolution at 3 months, with a noninferiority margin of 95% for apixaban compared to warfarin. The secondary endpoint was major adverse cardiovascular events (MACE) or any relevant bleeding according to the Bleeding Academic Research Consortium (BARC) classification. ResultsFifty patients were enrolled from 3 centres. The use of dual or single antiplatelet agents was similar in the 2 groups. The number of 1-, 3-, and 6-month LVT resolutions were 10 (40.0%), 19 (76.0%), and 23 (92.0%) in the apixaban group, and 14 (56%), 20 (80.0%), and 24 (96.0%) in the warfarin group, respectively, without significant differences (P < 0.036 for noninferiority at 3 months). Patients taking warfarin required longer hospital stays and more outpatient visits. Multivariate adjustment analysis revealed left ventricular aneurysm, larger baseline LVT area and lower left ventricular ejection fraction to be independent predictors of LVT persistence at 3 months. No MACE occurred in either group; 1 BARC-2 bleeding event occurred with warfarin. ConclusionsApixaban was not inferior to warfarin in the resolution of post-MI LVT.

Effectiveness and Safety of Anticoagulants in Cancer Patients with VTE and Kidney Disease

Introduction: Cancer patients with kidney disease are at increased risk for having venous thromboembolism (VTE) and bleeding than those without kidney disease. There is a lack of evidence about the effectiveness and safety of anticoagulants in cancer patients with VTE and kidney disease. Purpose: To evaluate the effectiveness and safety of different anticoagulants among VTE cancer patients with or without kidney disease. Methods: Adult VTE patients with any active cancer identified between 01SEP2014 and 29SEP2020 who initiated apixaban, low molecular weight heparin (LMWH), or warfarin within 30-days following a VTE were identified from 4 commercial databases and Medicare database. Cancer status was identified in the 6-months prior through 30-days post VTE. Kidney disease (chronic kidney disease plus acute kidney disease) was defined based on diagnosis codes and was identified in the 6-months prior to VTE. Stabilized inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. After IPTW, VTE cancer patients were stratified by those with and without kidney disease. Incidence rates (IRs) were determined for major bleeding (MB), clinically relevant non-major (CRNM) bleeding and recurrent VTE events within the first 6-months of follow-up. Cox proportional hazard models were used to evaluate interactions between treatments (apixaban or warfarin or LMWH) and kidney disease status on the risk of MB, CRNM bleeding and recurrent VTE events. Interactions with P<0.10 were considered statistically significant. Results: Among the 30,586 VTE cancer patients who met all study criteria 8,858 (29.0%) had kidney disease. Use of warfarin, LMWH and apixaban was similar between those with kidney disease (40.2%, 31.6%, and 28.1%) and without kidney disease (36.9%, 38.6%, and 24.4%, respectively). After IPTW, patient characteristics were balanced between treatment cohorts. Analyses stratified by kidney disease status showed that treatment effects were not significantly different for patients with and without kidney disease (figure). The incidence rates of major bleeding, CRNM bleeding and recurrent VTE events trended lower in the apixaban cohort compared to warfarin or LMWH for both kidney disease and no kidney disease patients (figure). Generally, there were no significant interactions between kidney disease status and treatments on any of the outcomes (figure). Conclusion: Effects of apixaban, LMWH and warfarin on recurrent VTE and bleeding were generally consistent in VTE cancer patients with or without kidney disease. Additional research is needed to identify optimal anticoagulant treatment strategy for VTE cancer patients with kidney disease. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 15728: Apixaban Use in Patients Supported by Durable Left Ventricular Assist Device

Introduction: Coumadin is currently the standard of care for long-term anticoagulation in patients supported with a left ventricular assist device (LVAD). Coumadin requires frequent testing and is associated with adverse events. The aim of this study was to evaluate the routine use of Apixaban in contemporary LVAD patients. Methods: A single center LVAD database was retrospectively queried to identify HeartMate 3 (HM3) patients between January 2016 and May 2022. Patients were divided into 2 groups based on anticoagulation received: Coumadin vs Apixaban. The primary outcome was 1-year mortality and secondary events of freedom from bleeding and stroke at 1 year. Univariate statistics and Kaplan-Meier curves were used for data analysis. Results: A total of 67 consecutive patients underwent HM3 implant during the study period: 20 (30%) coumadin and 47 (70%) apixaban. There was no difference in gender, age, BMI, creatinine, previous stroke or INTERMACS level between groups (Tabe1). Total days of support: Coumadin 25,750 days and Apixaban 16,556 days. The mortality at one year was comparable (5% v. 6%, p=0.12). The coumadin group had higher overall bleeding events (55% v. 17%, p&lt;.01) and freedom bleeding at 1 year was better in apixaban group (86% v. 64%, p=0.04). Freedom from stroke at 1 year was comparable between the groups (95% v. 97%, p=026). Survival at 1 year with no stroke or bleeding was similar (Figure 1). Conclusion: In this single center retrospective analysis, Apixaban in patients with a durable LVAD has shown reduced bleeding events and comparable stroke and survival outcomes. This early experience demonstrates that Apixaban is a possible alternative to Coumadin.

Comparative Effectiveness and Safety Between Apixaban, Dabigatran, Edoxaban, and Rivaroxaban Among Patients With Atrial Fibrillation : A Multinational Population-Based Cohort Study.

Current guidelines recommend using direct oral anticoagulants (DOACs) over warfarin in patients with atrial fibrillation (AF), but head-to-head trial data do not exist to guide the choice of DOAC. To do a large-scale comparison between all DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) in routine clinical practice. Multinational population-based cohort study. Five standardized electronic health care databases, which covered 221 million people in France, Germany, the United Kingdom, and the United States. Patients who were newly diagnosed with AF from 2010 through 2019 and received a new DOAC prescription. Database-specific hazard ratios (HRs) of ischemic stroke or systemic embolism, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), and all-cause mortality between DOACs were estimated using a Cox regression model stratified by propensity score and pooled using a random-effects model. A total of 527226 new DOAC users met the inclusion criteria (apixaban, n = 281320; dabigatran, n = 61008; edoxaban, n = 12722; and rivaroxaban, n = 172176). Apixaban use was associated with lower risk for GIB than use of dabigatran (HR, 0.81 [95% CI, 0.70 to 0.94]), edoxaban (HR, 0.77 [CI, 0.66 to 0.91]), or rivaroxaban (HR, 0.72 [CI, 0.66 to 0.79]). No substantial differences were observed for other outcomes or DOAC-DOAC comparisons. The results were consistent for patients aged 80 years or older. Consistent associations between lower GIB risk and apixaban versus rivaroxaban were observed among patients receiving the standard dose (HR, 0.72 [CI, 0.64 to 0.82]), those receiving a reduced dose (HR, 0.68 [CI, 0.61 to 0.77]), and those with chronic kidney disease (HR, 0.68 [CI, 0.59 to 0.77]). Residual confounding is possible. Among patients with AF, apixaban use was associated with lower risk for GIB and similar rates of ischemic stroke or systemic embolism, ICH, and all-cause mortality compared with dabigatran, edoxaban, and rivaroxaban. This finding was consistent for patients aged 80 years or older and those with chronic kidney disease, who are often underrepresented in clinical trials. None.

Comparative effectiveness and safety of extended anticoagulant therapy among Medicare beneficiaries with venous thromboembolism.

Guidelines recommend an extended course of anticoagulation therapy for patients who experienced venous thromboembolism (VTE) without transient provocation, however, optimal duration remains uncertain. We assessed effectiveness and safety of extended use of apixaban and warfarin greater than 6months of initial treatment in patients with VTE. We conducted a retrospective cohort study of Medicare beneficiaries aged greater than or equal to 18 years with deep vein thrombosis or pulmonary embolism. Patients were required to have initiated anticoagulants within 30 days of their first VTE diagnosis, completed 6months of initial anticoagulant treatment, and received extended phase treatment with apixaban (the apixaban group) or warfarin (the warfarin group) or no extended therapy. Multivariable Cox proportional hazards modeling with inverse probability treatment weighting was used to compare recurrent VTE, mortality, and major bleeding risks among the three groups. Mean extended-treatment duration was up to 10months and 14 months in apixaban and warfarin groups, respectively. Compared with no extended treatment, apixaban use was associated with decreased risks of recurrent VTE (hazard ratio [HR]=0.08, [95% confidence interval [CI]: 0.01-0.41]) and mortality (HR=0.37, [95% CI: 0.27-0.51]) without increased major bleeding risk (HR=1.29, [95% CI: 0.68-2.45]); warfarin use was associated not with recurrent VTE risk change but with increased major bleeding risk (HR=2.14, [95% CI: 1.26-3.65]) and decreased mortality risk (HR=0.39, [95% CI: 0.29-0.51]). Compared with warfarin, apixaban use was associated with decreased recurrent VTE (HR=0.13, [95% CI: 0.03-0.63]) and major bleeding (HR=0.56, [95% CI: 0.32-0.98]) risks. Subgroup and sensitivity analyses (e.g., intention-to-treat) findings remained consistent. Compared with warfarin or no extended therapy, extended-apixaban use was associated with reduced risk of recurrent VTE without increased major bleeding risk. Continuing anticoagulant therapy with apixaban greater than 6months may be effective and safe.

The Risk of Major Bleeding With Apixaban Administration in Patients With Acute Kidney Injury.

Apixaban is eliminated by the kidneys and in acute kidney injury (AKI) there is potential for an increase in apixaban exposure and bleeding events. In one instance, data have shown higher than normal bleed risk in patients with AKI, unless calibrated anti-factor Xa monitoring is used, which is not widely available. To evaluate bleeding with apixaban administration to hospitalized patients with an AKI in an unmonitored real-world scenario. We conducted a retrospective study of patients admitted to a large urban academic teaching hospital from April 2015 to March 2022, who received apixaban for venous thromboembolism or nonvalvular atrial fibrillation (NVAF). The primary outcome evaluated major bleeding when apixaban was administered to patients with or without an AKI. A total of 232 patients were evaluated (116 per group). Most patients (79.7%) were on apixaban for NVAF, 32.7% had chronic kidney disease, 58.2% were on a medication increasing bleed risk, and HAS-BLED score was a median of 2 in both groups. No differences were noted between groups for bleeding (AKI group 7.8% vs non-AKI 3.4%; P = 0.15), and on regression analysis, coadministration of a P2Y12 inhibitor was predictive of major bleeding (odds ratio = 5.9; 95% confidence interval = 1.4-23.6). Although no differences between groups were noted, apixaban use in the AKI group resulted in a higher than normally reported incidence of apixaban-associated major bleeding, and concomitant antiplatelet use increased bleed risk as well. Cautious use of apixaban and further investigation with larger studies are warranted in this area.

Major Hemorrhage Risk Associated with Direct Oral Anticoagulants in Non-Valvular Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Real-world, observational studies have investigated the safety profile of Direct Oral Anticoagulants (DOACs) on Major Hemorrhage (MH) used for stroke prevention in Non-Valvular Atrial Fibrillation (NVAF). We performed a systematic review and meta-analysis to investigate the comparative safety of DOACs versus other DOACs and versus Vitamin K Antagonists (VKAs) adhering to PRISMA guidelines. We defined MH according to the International Society on Thrombosis and Haemostasis statement or as the composite outcome of intracranial, gastrointestinal, genitourinary, respiratory, cavitary and musculoskeletal bleeding in case of studies using International Statistical Classification of Diseases codes for patient selection. We systematically investigated two databases (Medline, Embase) until April of 2021, gathered observational studies and extracted hazard ratios (HRs) with 95% confidence intervals (CI) on our outcome of interest. Additional subgroup analyses according to DOAC dosing, prior diagnosis of chronic kidney disease, prior diagnosis of stroke, history of previous use of VKA, the users' age, the users' gender and study population geographic region were conducted. All analyses were performed with a random-effects model. From this search, 55 studies were included and 76 comparisons were performed. The MH risk associated with Rivaroxaban use was higher than the risk with Dabigatran use (HR: 1.32, 95% CI: 1.21-1.45, : 12.39%) but similar to VKA use (HR: 0.94, 95% CI: 0.87-1.02, : 76.57%). The MH risk associated with Dabigatran use was lower than the risk with VKA use (HR: 0.75, 95% CI: 0.64-0.90, : 87.57%). The MH risk associated with Apixaban use was lower than the risk with Dabigatran use (HR: 0.75, 95% CI: 0.64-0.88, : 58.66%), with Rivaroxaban use (HR: 0.58, 95% CI: 0.50-0.68, : 74.16%) and with VKA use (HR: 0.60, 95% CI: 0.55-0.65, : 58.83%). Our aforementioned subgroup analyses revealed similar results. All in all, Apixaban was associated with a reduced MH risk compared to Dabigatran, Rivaroxaban and VKA. Dabigatran was associated with a reduced MH risk compared to both Rivaroxaban and VKA.

Nine-Year Trends in Prevention of Thromboembolic Complications in Elderly Patients with Atrial Fibrillation Treated with NOACs.

Background: Atrial fibrillation (AF) is the most common disease in elderly patients and thromboembolic complication prophylaxis significantly improves the prognosis in these patients. The study assessed the frequency of individual non-vitamin K antagonist oral anticoagulant (NOAC) use among patients ≥75 years and attempted to identify factors predisposing to their prescription. Methods: The data of patients with non-valvular AF hospitalized in the reference cardiology center between 2011 and 2019 were analyzed. Results: Out of 1443 analyzed patients, 329 (22.8%) received apixaban, 618 (42.8%) dabigatran, and 496 (34.4%) rivaroxaban. The entire population mean age was 82.3 ± 5 years, and 57.9% were females. Independent predictors of apixaban use were age, and bleeding history. Hospitalization for the implantation/reimplantation of a cardiac implantable electronic device (CIED) reduced the chance of apixaban use. Hypertension was a predictor of dabigatran prescription. The chance of using dabigatran decreased with age. Hypertension and bleeding history decreased the chance of rivaroxaban application. Conclusions: In hospitalized AF patients ≥75 years, dabigatran was the most frequently used NOAC. Age, comorbidities and bleeding risk determined the selection of individual NOACs.

Do Patients with Atrial Fibrillation and a History of Ischemic Stroke Overuse Reduced Doses of NOACs?-Results of the Polish Atrial Fibrillation (POL-AF) Registry.

Background: The aim of our study was to assess if patients with AF (atrial fibrillation) and a history of ischemic stroke (IS) excessively receive reduced doses of NOACs (non-vitamin K antagonist oral anticoagulants). Methods: The Polish AF (POL-AF) registry is a prospective, observational, multicenter study, including patients with AF from 10 cardiology hospital centers. In this study we focused on patients with IS in their past. Results: Among 3999 patients enrolled in the POL-AF registry, 479 (12%) had a previous history of IS. Compared to patients without IS history, post-stroke subjects had a higher CHA2DS2-VASc score (median score 7 vs. 4, p < 0.05). Of these subjects, 439 (92%) had anticoagulation therapy, 83 (18.9%) were treated with a vitamin K antagonist (VKA), 135 (30.8%) with rivaroxaban, 112 (25.5%) with dabigatran, and 109 (24.8%) with apixaban. There were a significant number of patients after IS with reduced doses of NOACs (48.9% for rivaroxaban, 45.5% for dabigatran, and 36.7% for apixaban). In many cases, patients were prescribed reduced doses of NOACs without any indication for reduction (28.8% of rivaroxaban use, 56.9% of dabigatran use, and 60.0% of apixaban use—out of reduced dosage groups, p = 0.06). Conclusions: A significant proportion of AF patients received reduced doses of NOAC after ischemic stroke in a sizeable number of cases, without indication for dose reduction.

A Description of Apixaban Dosing Patterns for Treatment or Prevention of Thrombotic Events in Hospitalized Patients on Dialysis.

Introduction: Apixaban is currently the only oral direct factor Xa inhibitor approved for treatment and prevention of venous thromboembolism (VTE) in patients on hemodialysis. Exclusion of dialysis patients from major clinical trials results in prescriber uncertainty regarding the optimal dose of apixaban for VTE treatment in this population. This study sought to characterize the variance in apixaban prescribing patterns for thrombotic indications other than atrial fibrillation. Methods: This retrospective, multi-center, descriptive study analyzed apixaban dosing patterns for hospitalized chronic dialysis patients with history of thrombosis. The primary outcome was incidence of deviation from manufacturer recommendations for dosing, assessed for either a new start or receipt prior to hospitalization. Secondary outcomes included observation of recurrent thrombotic and bleeding event rates during subsequent hospitalizations. Patients were analyzed into subgroups according to type of thrombotic indication for treatment. Data are reported with descriptive statistics. Results: A total of 101 patients were included. Deviations in recommended dosing were observed in 53 of 80 (66.2%) patients receiving apixaban for treatment of acute or chronic thrombosis. Of 44 patients started on apixaban during hospitalization for the indication of acute VTE, a dose deviation was observed in 79.5% of patients. Rates of rehospitalization for recurrent thrombotic events and bleeding were 11.8% and 9.9%, respectively. Conclusion: Variation in apixaban prescribing practices for the treatment of VTE in dialysis patients is common, suggesting an urgent need for prospective studies and updated dosing guidance to optimize safety with apixaban use in this population.

Acute Lower-Extremity Posterior Compartment Syndrome: A Rare Complication of Apixaban Use

Apixaban is an oral anticoagulant that directly inhibits factor Xa and is indicated for the prophylaxis and treatment of deep venous thrombosis and stroke prevention in nonvalvular atrial fibrillation. Acute lower-extremity posterior compartment syndrome is a rare complication of apixaban use. We present a 78-year-old man with significant medical morbidities taking apixaban for atrial fibrillation presenting with posttraumatic extensive hemorrhagic bullae on the left proximal pretibial region secondary to anticoagulation. We recommend that clinicians develop awareness of the potential for serious bleeding complications of anticoagulants and devise strategies to identify the need for early recognition and prompt management.

Using population health‐based strategies to optimize use of direct‐acting oral anticoagulants in atrial fibrillation

AbstractIntroductionPharmacists deploy a variety of population‐health strategies to identify needs related to pharmacotherapy. One area that deserves closer attention is medication management in atrial fibrillation (AF) since managing stroke prevention in older adults with AF requires delicately balancing the risk of thrombosis with the risk of bleeding.Objective(s)Evaluate direct‐acting oral anticoagulant (DOAC) prescribing trends and explore strategies for mitigating gastrointestinal bleeding (GIB) risk in older adults prescribed a DOAC for stroke prevention in AF.MethodsA quality improvement project was conducted and included Managed‐Medicare patients from a single primary care organization prescribed a DOAC for AF. Pharmacists estimated risk of benefit and harm from the prescribed DOAC using established algorithms and patient characteristics documented in the medical record. They then forecasted the change in net clinical benefit if the prescribed DOAC was switched to a different DOAC.ResultsOverall, 200 patients met the inclusion criteria. Based on distribution of DOACs in the original study population, 52% of patients were in the definitive benefit group (benefit in reducing stroke risk outweigh risk of bleeding by 2‐fold or greater), with 37% and 10.5% in the leaning benefit (reduction in stroke risk was up to 2‐fold greater than bleeding risk) and leaning risk (bleeding risk was up to 2‐fold greater than stroke risk reduction) groups, respectively. Calculation of risk should the prescribed DOAC be changed from rivaroxaban to apixaban was estimated to improve the net clinical benefit and reduce the risk of a patient falling in a negative clinical benefit group when compared to rivaroxaban and the original study population, respectively; 92% (relative risk [RR] 0.08 [0.026‐0.277; P &lt; 0.0001]) and 81% (RR 0.19 [0.067‐0.545; P = 0.0002]).ConclusionPopulation health‐based strategies centered on DOAC use in older adults can help identify prescribing trends and allow organizations to explore ways to mitigate risk of GIB. Preferential use of apixaban could reduce bleeding risk among older adults requiring anticoagulation for AF.

Trends in post-discharge prophylactic anticoagulant use among stroke patients in the United States between 2006 and 2019

BackgroundStroke is an independent risk factor for venous thromboembolism (VTE). Although the risk of VTE persists after hospital discharge, information on the utilization of anticoagulants among stroke patients after discharge remains limited. ObjectiveTo evaluate changes in post-discharge thromboprophylaxis among stroke patients between 2006 and 2019. MethodsWe conducted a retrospective repeated cross-sectional analysis using a commercial healthcare insurance database in the United States. We included patients aged ≥ 18 years with incident stroke diagnosis and assessed prophylactic use of anticoagulants in the 30 days following hospital discharge including low-molecular-weight heparin (enoxaparin ≤40 mg/day, dalteparin ≤5000 IU/day), unfractionated heparin ≤5000 IU/ twice daily or 3 times a day, apixaban 2.5 mg twice daily, and rivaroxaban 10 mg/day. Patients with atrial fibrillation, VTE, mechanical heart valves, cancer, antiphospholipid antibody syndrome, and users of therapeutic doses of anticoagulants were excluded. We used the Cochrane-Armitage test to assess changes in the use of anticoagulants across the study period. ResultsThere was a small increase in the overall use of post-discharge prophylactic anticoagulants among stroke patients between 2006 and 2019 from 0.5% to 1.9%. The use of heparin decreased from 0.5% in 2006 to 0.3% in 2019 (P-value for trend = 0.001). In contrast, the use of apixaban or rivaroxaban increased from 0.1% in 2013 to 1.6% in 2019 (P-value for trend < 0.001). Apixaban was more commonly used than rivaroxaban. ConclusionsIn this population-based study of stroke patients, we found that post-discharge anticoagulant use remains low through 2019. Prophylactic use of heparin or rivaroxaban was relatively low but the use of apixaban increased over the study period. Further research is needed to determine if these agents are safe and effective for VTE prevention in stroke patients.

The Expanded Role of Apixaban in Cardiovascular Disease Management: A Literature Review

Direct Oral Anticoagulants (DOACs) are widely used for stroke prevention in non-valvular atrial fibrillation, treatment of deep venous thrombosis and pulmonary embolism, and prophylaxis of Venous Thromboembolism (VTE) after hip and knee surgery. Apixaban, a Factor Xa inhibitor, is one of the most efficacious DOACs with some of the lowest bleeding rates. It has therefore been widely adopted into clinical practice. In the recent years, its usefulness has been tested outside traditional clinical paradigms in coronary artery disease, VTE in malignancy, and deep venous thrombosis prophylaxis in acute medical illnesses. Other off label uses include treatment of left ventricular thrombus and transient post procedural use in transcatheter aortic valve replacement and left atrial appendage occlusion device placement. This review systematically evaluates the clinical evidence and knowledge gaps in expanded clinical use of apixaban.

Atraumatic splenic rupture in a patient after apixaban use and radiologically inserted gastrostomy – a case report

Andrius Račiūnas1 1Royal London Hospital, Barts Health NHS Trust, Ear, Nose & Throat Department, London, United Kingdom Abstract: Introduction. Atraumatic splenic rupture (ASR), also known as spontaneous splenic rupture, is a rare, potentially life-threatening condition that can be a result of infection, malignancy, inflammation, and a complication of various surgical procedures. There are not enough studies about patient characteristics, incidence rates, aetiology, and guidelines for management associated with ASR. Clinical case. A 53-year-old gentleman had a transoral robotic resection of the left tongue base/aryepiglottic fold carcinoma and level 2-4 neck dissection. Subsequently, he had a radiologically inserted gastrostomy (RIG) for his dysphagia and airway protection. Two days after RIG was inserted, the patient collapsed in the ward. Blood tests were done and showed a severe haemoglobin level drop from 123 g/L to 73 g/L. Computer Tomography (CT) of the abdomen showed splenic bleeding. He had emergency laparotomy with splenectomy which showed no signs of traumatic spleen rupture secondary to RIG insertion. A histopathology sample taken in theatre showed no pathological changes in the spleen. There were no other causes apart from apixaban which was stopped before the procedure and resumed 24 hours after RIG insertion. Conclusion. ASR is a rare event in healthcare and the symptoms are not specific. Abdominal pain on the left side that can spread to the shoulder, a decrease in haemoglobin level, and signs of haemorrhagic shock are all possible signs of bleeding in the spleen. Anticoagulant therapies such as apixaban, rivaroxaban, direct-acting oral anticoagulants (DOAC), and dabigatran are linked to instances of ASR. Keywords. Atraumatic splenic rupture, splenectomy, radiologically inserted gastrostomy, apixaban.

Non-vitamin K antagonist oral anticoagulants (NOAC) in nonvalvular atrial fibrillation – in-group comparison

&#x0D; Atrial fibrillation (AF) is a major and widespread health problem. Its main and most threatening complication, ischemic stroke, is responsible for a great number of deaths and disability worldwide. This makes anticoagulation a priority in AF management. Non-vitamin K antagonist oral anticoagulants (NOAC) are currently the most effective and safe option for patients with nonvalvular atrial fibrillation. Rivaroxaban, apixaban, edoxaban and dabigatran are non-inferior to warfarin in terms of stroke and systemic embolism prevention. However, warfarin use is associated with higher rates of major bleedings than any NOAC. Different drugs and mechanism of action among NOACs may result in differences in terms of efficacy and safety between them. This review aims to assess these differences by summarizing data available in online databases and European Society of Cardiology guidelines. There are major studies comparing each of NOACs to warfarin, however there is only limited data comparing apixaban, rivaroxaban and dabigatran directly. Both direct and indirect comparisons suggest that apixaban, rivaroxaban and dabigatran use is associated with similar reduction of stroke and systemic embolism risk. In terms of safety, anticoagulation with apixaban results in lower major bleeding risk relative to dabigatran and rivaroxaban. &#x0D;

Effectiveness and Safety of Apixaban versus Rivaroxaban in Patients with Atrial Fibrillation and Type 2 Diabetes Mellitus.

To evaluate the effectiveness and safety of apixaban versus rivaroxaban among patients with nonvalvular atrial fibrillation (NVAF) and type 2 diabetes mellitus (T2DM). Using the United Kingdom's Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository, and the Office for National Statistics database, we identified a cohort of patients with NVAF and T2DM newly treated with apixaban or rivaroxaban between 2013 and 2020. Propensity scores with standardized mortality ratio weighting were used to control for confounding. We used weighted Cox proportional hazards models to estimate separately the hazard ratios (HRs) with 95% confidence intervals (CIs) of ischemic stroke, major bleeding, and major adverse limb events associated with the use of apixaban compared with rivaroxaban. We also evaluated whether the risk was modified by age, sex, duration of diabetes, microvascular and macrovascular complications of diabetes, nephropathy, CHA2DS2-VASc and HAS-BLED scores, and by dose (standard vs. low dose). The cohort included 11,561 apixaban and 8,265 rivaroxaban users. Apixaban was associated with a similar risk of stroke (HR: 0.99, 95% CI: 0.79-1.23), and a 32% reduced risk of major bleeding (HR: 0.68, 95% CI: 0.59-0.78), compared with rivaroxaban. The risk of major adverse limb events was similar between apixaban and rivaroxaban (HR: 0.75, 95% CI: 0.54-1.04). Overall, the risk of ischemic stroke and major bleeding was consistent in stratified analyses. Among patients with NVAF and T2DM, apixaban was associated with a similar risk of stroke and a lower risk of major bleeding compared with rivaroxaban.

Apixaban or Warfarin and Aspirin or Placebo After Acute Coronary Syndrome or Percutaneous Coronary Intervention in Patients With Atrial Fibrillation and Prior Stroke

Data are limited regarding the risk of cerebrovascular ischemic events and major bleeding in patients with atrial fibrillation (AF) and recent acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI). Determine the efficacy and safety of apixaban or vitamin K antagonists (VKA) and aspirin or placebo according to prior stroke, transient ischemic attack (TIA), or thromboembolism (TE). In this prospective, multicenter, 2-by-2 factorial, randomized clinical trial, post hoc parallel analyses were performed to compare randomized treatment regimens according to presence or absence of prior stroke/TIA/TE using Cox proportional hazards models. Patients with AF, recent ACS or PCI, and planned use of P2Y12 inhibitors for 6 months or longer were included; 33 patients with missing data about prior stroke/TIA/TE were excluded. Apixaban (5 mg or 2.5 mg twice daily) or VKA and aspirin or placebo. Major or clinically relevant nonmajor (CRNM) bleeding. Of 4581 patients included, 633 (13.8%) had prior stroke/TIA/TE. Patients with vs without prior stroke/TIA/TE were older; had higher CHA2DS2-VASC and HAS-BLED scores; and more frequently had prior bleeding, heart failure, diabetes, and prior oral anticoagulant use. Apixaban was associated with lower rates of major or CRNM bleeding and death or hospitalization than VKA in patients with (hazard ratio [HR], 0.69; 95% CI, 0.46-1.03) and without (HR, 0.68; 95% CI, 0.57-0.82) prior stroke/TIA/TE. Patients without prior stroke/TIA/TE receiving aspirin vs placebo had higher rates of bleeding; this difference appeared less substantial among patients with prior stroke/TIA/TE (P = .01 for interaction). Aspirin was associated with numerically lower rates of death or ischemic events than placebo in patients with (HR, 0.71; 95% CI, 0.42-1.20) and without (HR, 0.93; 95% CI, 0.72-1.21) prior stroke/TIA/TE (not statistically significant). The safety and efficacy of apixaban compared with VKA was consistent with the AUGUSTUS findings, irrespective of prior stroke/TIA/TE. Aspirin increased major or CRNM bleeding, particularly in patients without prior stroke/TIA/TE. Although aspirin may have some benefit in patients with prior stroke, our findings support the use of apixaban and a P2Y12 inhibitor without aspirin for the majority of patients with AF and ACS and/or PCI, regardless of prior stroke/TIA/TE status. ClinicalTrials.gov Identifier: NCT02415400.

Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data.

Relatively little is known about the influence of extreme body weight on the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of drugs used in many disease states. While direct oral anticoagulants (DOACs) have an advantage over warfarin in that they do not require routine drug monitoring, some may regard this convenience as less compelling in obese patients. Some consensus guidelines discourage using DOACs in patients weighing > 120 kg or with a body mass index > 35-40 kg/m2, given a sparsity of available data in this population and the concern that fixed dosing in obese patients might lead to decreased drug exposure and lower efficacy. Per the prescribing information, apixaban does not require dose adjustment in patients weighing above a certain threshold (e.g., ≥ 120 kg). Data from healthy volunteers and patients with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE) have shown that increased body weight has a modest effect on apixaban's PK. However, the paucity of exposure data in individuals > 120 kg and the lack of guideline consensus on DOAC use in obese patients continue to raise concerns about potential decreased drug exposure at extreme weight. This article is the first to comprehensively review the available PK data in obese individuals without NVAF or VTE, and PK, PD, efficacy, effectiveness, and safety data for apixaban in obese patients with either NVAF or VTE, including subgroup analyses across randomized controlled trials and observational (real-world) studies. These data suggest that obesity does not substantially influence the efficacy, effectiveness, or safety of apixaban in these patients. Trial Registration ARISTOTLE: NCT00412984; AVERROES: NCT00496769; AMPLIFY: NCT00643201; AMPLIFY-EXT: NCT00633893; ADVANCE-1: NCT00371683; ADVANCE-2: NCT00452530; ADVANCE-3: NCT00423319 Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data (MP4 161.22 MB).

MO420: Effects of Indoxyl Sulfate and Apixaban in Liver Gene Expression

Abstract BACKGROUND AND AIMS Uraemic toxins accumulate in the blood and tissues of patients with chronic kidney disease (CKD). Previous animal studies have shown that chronic kidney disease (CKD) not only alters the elimination of drugs excreted by the kidneys, but it also impacts the metabolism of drugs subject to non-renal clearance, which involves mainly the liver and the gut. The use of apixaban, an oral anticoagulant, has been approved in the USA for dialysis patients. However, the coexistence of thrombotic and haemorrhagic risk in patients with CKD makes dose adjustment difficult. The liver has a major role in drug metabolization. Hepatocytes express high levels of AhR, a ligand-inducible transcription factor that mediates the induction of various liver cytochrome P450 enzymes by xeno and endobiotic. Tryptophan-derived uraemic toxins (TDUT) are AhR agonists. Indoxyl sulfate (IS) is the main TDUT involved in uraemic syndrome. IS increases the expression and activity of P-glycoprotein (P-gp) in the liver. Apixaban metabolism is mediated by P-gp and Cyp3a4 (Cyp3a11 in mice). We aim to study the effect of apixaban and IS in the expression of drug metabolism genes. Our hypothesis is that AhR activation by IS could severely modify drug metabolism during CKD. METHOD C57BL/6J Wild-type mice purchased from The Jackson Laboratory were fed ad libitum with a standard diet. At 10 weeks of age, mice drinking water was substituted with a 5% sucrose water solution with either 0.1% indoxyl sulphate or KCl (control) added at equivalent concentrations. 48-h before sacrifice some mice were gavaged with an apixaban solution (0.6 mg/mL) twice a day with the last dose given 4 h prior to sacrifice. All mice were sacrificed at 11 weeks of age. Liver samples were stored in an RNA-later solution at −20°C. Samples were thawed and lysed in Trizol using the Tissue-Ruptor system (Qiagen). RNA was extracted and purified with chloroform and precipitated with isopropanol. RNA concentration was estimated by spectrophotometry. Gene expression was analysed by q-RT-PCR using Gusb as a housekeeping gene. Apixaban levels were quantified by LC-MS. Kruskal–Wallis followed by a two-stage linear step-up procedure of Benjamini, Krieger and Yekutieli (q &amp;lt; 0.05) was performed using GraphPad Prism 9.2.1. RESULTS Four groups of mice per sex were thus created: WT-KCl, WT-IS, WT-KCl Apix, WT-IS Apix. In the IS/KCl model we observe higher mRNA basal expression of Abcb1a (q = 0.008) and Sult1a1 (q = 0.006) and lower basal expression of Abcg2 (q = 0.0005) in females compared to males when treated with KCl. IS treatment increases Cyp1a2 expression in females (q = 0.0139) and Cyp1a1 in both males (q = 0.0145) and females (q = 0.026). In the IS/KCl-Apix model the same sex-related differences are maintained for Abcb1a (q = 0.0031), Sult1a1 (q = 0.0316) and Abcg2 (q &amp;lt; 0.0001). In males, CYP2e1 expression is increased by apixaban in KCl (q = 0.067) and IS (q = 0.0278) treated mice. Moreover, apixaban counteracts the increased expression of Cyp1a1 induced by IS (q = 0.0177). The expression of Cyp3a11 is augmented in males treated with KCl-apixaban (q = 0.0143), an effect that seems to be reversed by IS (q = 0.0066). In females, apixaban has no effect in gene expression. Apixaban serum concentration is higher in KCl (q = 0.0350) and IS (q = 0.0019) treated females when compared to males. CONCLUSION The effect of IS as an agonist of AhR in the liver is confirmed by the increased expression of Cyp1a1. Apixaban provokes a remarkable increase of Cyp3a11 in male mice, which could lead to higher degradation rates decreasing its activity. IS seems to reverse this effect. This could lead to increased activity of apixaban during CKD which could derive in an increased risk of bleeding. Higher BCRP rates could explain lower rates of apixaban in male serum. Apixaban did not alter gene expression in females. Clinical trials in CKD are generally biased regarding sex (fewer women represented) possibly masking important sex-dependent drug adverse effects. Our results show great differences in basal expression of various genes, confirming the importance to study men and women separately with respect to drug metabolism.