Apixaban-Induced Spontaneous Hemorrhagic Cardiac Tamponade.

Direct oral anticoagulants (DOACs), such as apixaban, are used for the prevention and management of thromboembolic diseases. Here, we present a case of a 72-year-old African American woman who presented to the hospital with shortness of breath and precordial chest pain for three days. The patient was diagnosed with volume overload associated with the progression of chronic kidney disease (CKD) and subsequently admitted to the hospital. Since the patient failed to adequately respond to diuretics, hemodialysis was initiated. During the hospital stay, she developed paroxysmal atrial fibrillation. Along with amiodarone, apixaban was started for primary stroke prophylaxis. Within 72 hours, the patient developed worsening chest pain. An echocardiogram revealed a large pericardial effusion with cardiac tamponade. She was taken for an emergent open pericardial window placement to relieve cardiac tamponade, where 600 mL of blood was drained. Considering the timeline of the development of a large bloody pericardial effusion following initiation of apixaban, spontaneous hemorrhagic cardiac tamponade attributed to the use of apixaban was diagnosed. The patient was eventually taken off all anticoagulants. In considering potential mechanisms, impaired hepatic and renal metabolism of apixaban could be factored in this case. In addition, CKD can increase bleeding risk, due to platelet dysfunction and impaired interaction of von Willebrand factor with GPIIb-IIIa. Moreover, renal secretion of apixaban is mediated by p-glycoprotein and amiodarone is an inhibitor of this protein. Although extremely rare, spontaneous hemorrhagic cardiac tamponade can occur with the use of DOACs, such as apixaban. Prompt recognition and urgent treatment remain keys to avoiding adverse patient outcomes.

Vintage Victory: Warfarin Versus Apixaban in the Antiphospholipid Arena.

This case report explores the efficacy of warfarin compared to apixaban in managing antiphospholipid syndrome (APS), an autoimmune disorder characterized by recurrent thrombosis. We emphasize the constraints of direct oral anticoagulants (DOACs) such as apixaban in APS management. This case discusses a 41-year-old female patient with APS who did not respond to apixaban therapy. The report details her transition to warfarin, resulting in symptom resolution and no further complications, thus alluding to warfarin's effectiveness in APS management over apixaban. The case contributes to the ongoing debate on the suitability of modern DOACs in APS treatment.

A real-world exploration into clinical outcomes of direct oral anticoagulant therapy in people with chronic kidney disease: a large hospital-based study.

BACKGROUND: There is limited evidence to support definite clinical outcomes of direct oral anticoagulant (DOAC) therapy in chronic kidney disease (CKD). By identifying the important variables associated with clinical outcomes following DOAC administration in patients in different stages of CKD, this study aims to assess this evidence gap. METHODS: An anonymised dataset comprising 97,413 patients receiving DOAC therapy in a tertiary health setting was systematically extracted from the multidimensional electronic health records and prepared for analysis. Machine learning classifiers were applied to the prepared dataset to select the important features which informed covariate selection in multivariate logistic regression analysis. RESULTS: For both CKD and non-CKD DOAC users, features such as length of stay, treatment days, and age were ranked highest for relevance to adverse outcomes like death and stroke. Patients with Stage 3a CKD had significantly higher odds of ischaemic stroke (OR 2.45, 95% Cl: 2.10-2.86; p = 0.001) and lower odds of all-cause mortality (OR 0.87, 95% Cl: 0.79-0.95; p = 0.001) on apixaban therapy. In patients with CKD (Stage 5) receiving apixaban, the odds of death were significantly lowered (OR 0.28, 95% Cl: 0.14-0.58; p = 0.001), while the effect on ischaemic stroke was insignificant. CONCLUSIONS: A positive effect of DOAC therapy was observed in advanced CKD. Key factors influencing clinical outcomes following DOAC administration in patients in different stages of CKD were identified. These are crucial for designing more advanced studies to explore safer and more effective DOAC therapy for the population.

Clinical guidelines for prevention and treatment of CAT in Japan and other countries.

Cancer-associated thrombosis (CAT) is an important prognostic factor for an increasing number of cancer patients. Understanding of CAT among cancer care providers has grown in recent years, and guidelines for the prevention and treatment of CAT have been published in Japan and around the world. In this article, we introduce these major guidelines and discuss differences we identified between the Japanese guidelines and those of other countries, with a focus on problems and issues. Insurance coverage of low-molecular-weight heparin and indications for primary prevention with direct oral anticoagulants in particular require urgent consideration.

European expert consensus recommendations on the primary care use of direct oral anticoagulants in patients with venous thromboembolism.

BACKGROUND: Direct oral anticoagulants for the treatment of venous thromboembolism are supported by robust clinical trial evidence. Despite published guidance, general practitioners are faced with increasingly complex decisions and implementation remains sub-optimal in certain real-world scenarios. METHODS: A two stage formal consensus exercise was performed to formulate consensus statements and a summary guide, facilitating optimal management of direct oral anticoagulants in venous thromboembolism patients by generalist physicians across Europe. An online questionnaire distributed to a broad panel (Phase 1), followed by a virtual panel discussion by an expert group (Phase 2) were conducted. Phase 1 statements covered nine management domains, and were developed via a literature review and expert steering committee. Participants rated statements by their level of agreement. Phase 1 responses were collated and analysed prior to discussion and iterative refinement in Phase 2. RESULTS: In total 56 participants from across Europe responded to Phase 1. The majority had experience working as general practitioners. Consensus indicated that direct oral anticoagulants are the treatment of choice for managing patients with venous thromboembolism, at initiation and for extended treatment, with a review at three to six months to re-assess treatment effect and risk profile. Direct oral anticoagulant choice should be based on individual patient factors and include shared treatment choice between clinicians and patients; the only sub-group of patients requiring specific guidance are those with cancer. CONCLUSION: Results demonstrate an appreciation of best practices, but highlight challenges in clinical practice. The patient pathway and consensus recommendations provided, aim to highlight key considerations for general practice decision making, and aid optimal venous thromboembolism treatment.

Secondary Prophylaxis of Venous Thromboembolism (VTE) with Low Dose Apixaban or Rivaroxaban: Results from a Patient Population with More than 2 Years of Median Follow-up.

Background: Direct oral anticoagulants (DOACs) are widely used for the treatment and secondary prophylaxis of venous thromboembolism (VTE). Nowadays, DOACs represent the gold standard for long-term anticoagulation, with low-intensity DOACs administration becoming increasingly used worldwide in such scenario. Albeit low-intensity apixaban and rivaroxaban are approved for clinical usage as secondary VTE prophylaxis, there are few literature data regarding their efficacy and safety with a long follow-up. Objectives: The aim of our study was to evaluate the efficacy and safety of low-dose DOACs for VTE secondary prophylaxis in patients at high risk of VTE recurrence. Methods: We retrospectively evaluated patients who required long-term anticoagulant secondary prophylaxis to prevent recurrent VTE, treated with apixaban 2.5 mg BID or rivaroxaban 10 mg daily with a follow-up ≥ 12 months. Results: The examined patients were 323. The median low-dose DOAC administration time was 25.40 months (IQR 13.93-45.90). Twelve (3.7%) VTE recurrences were observed; 21 bleeding events were registered (6.5%), including one episode of Major bleeding (MB) (0.3%), 8 Clinically relevant nonmajor bleeding (CRNMB) (2.5%) and 12 minor bleeding (3.7%). No statistically significant difference in the rate of VTE recurrence and/or bleeding events emerged between the rivaroxaban and apixaban groups. Patients included in the study for multiple episodes of VTE presented a significantly higher risk of a new VTE recurrence during low-intensity DOAC. Conclusions: Our data suggest that low-dose DOACs may be effective and safe in secondary VTE prophylaxis in patients at high risk of VTE recurrence; however, attention might be needed in their choice in such a scenario for patients who experienced multiple episodes of VTE.

Management of patients with proximal femur fractures under DOACs.

PURPOSE: In the past, preinjury direct oral anticoagulant (DOAC) intake has led to delays in time to surgery (TTS) in patients with proximal femur fractures and delays in surgery have been associated with impaired outcomes. Although healthcare institutions/federal committees have set rules for treatment within 24 h of injury, comprehensive guidelines for the perioperative management of these patients, in particular when on preinjury DOACs, are still lacking. This contribution aims to summarize the current evidence on the safe time window for surgery in patients with proximal femur fractures on preinjury DOACs and to outline therapeutic options if emergency DOAC reversal becomes necessary. METHODS: Narrative review based upon selective review of the pertinent literature. RESULTS: For the majority of patients with proximal femur fractures and on preinjury DOACs, early surgery appears safe as soon as medical clearance has been obtained. There may be an increase in the need for blood products but with data not yet conclusive. Work-up including assessment of remaining anticoagulant activity and potential reversal should be restricted to patients at risk for bleeding complications, in particular in the presence of renal/hepatic impairment. Methodology for rapid assessment of DOACs including quantitative/qualitative concentration levels is work in progress. In the case of bleeding, rapidly acting reversal agents are available. CONCLUSION: Preinjury DOAC use should not routinely delay surgery in patients with proximal femur fractures.

Spontaneous hemothorax caused by rivaroxaban treatment for pulmonary embolism: A case report.

Hemothorax is a rare and potentially fatal condition characterized by pleural effusion containing over 50% of the patient's hematocrit. A massive hemothorax involves blood loss exceeding 1.5 L. Common causes include chest trauma, invasive thoracic procedures, anticoagulant medications, vascular anomalies, malignancies, and hematologic abnormalities. Spontaneous hemothorax may be seen in conjunction with pulmonary infarction and spontaneous pneumothorax. Anticoagulation is a key therapeutic strategy for certain thromboembolic events, such as pulmonary embolism. Historically, these events were treated with vitamin K antagonists (VKAs), which have demonstrated variable plasma concentrations and an increased risk of hemorrhage. With the advent of direct oral anticoagulants (DOACs), treatment has become as effective as VKAs while significantly reducing the risk of hemorrhage. However, some researchers have speculated that hemorrhagic complications in certain cases could be worse with DOACs than with VKAs. In the case presented here, we identified a genuine association between the use of rivaroxaban and spontaneous hemothorax following the initiation of treatment for pulmonary embolism.

Clinical comprehensive evaluation of direct oral anticoagulants for patients with atrial fibrillation in China.

BACKGROUND: Direct oral anticoagulants (DOACs) are increasingly recommended over warfarin in stroke prevention for patients with non-valvular atrial fibrillation (AF). However, there is an important evidence gap in choosing the most appropriate DOAC for Chinese patients in clinical practice. METHODS: A multi-criteria decision analysis (MCDA) was adopted to build a scoring framework. Attributes and criteria were identified and determined by a scoping literature review, two rounds of Delphi surveys, and a consensus meeting. Weights of each attribute and criterion in the framework were determined using analytic hierarchy process (AHP). Evidence was collected based on the domestic or at least Asian data. Scoring methods for each criterion were developed depended on their characteristics and determined with an expert consensus meeting. Comprehensive scores of each DOAC were calculated based on the utility scores of each criterion and their corresponding weights. RESULTS: A total of 5 attributes, including safety, efficacy, costs/cost-effectiveness, suitability, and accessibility, were determined, and 16 criteria were under the 5 attributes. The safety and efficacy were ranked as the top two important attributes with the weights of 38.8% and 35.9%, respectively, while the suitability received the lowest weight of 7.9%. The comprehensive score for edoxaban was the highest (72.3), followed by dabigatran (49.7), rivaroxaban (37.9), and apixaban (35.8). CONCLUSIONS: This study provided a scoring framework developed for comprehensive evaluation of DOACs in China. The ranking of DOACs could help to support the decision-making in clinical practice. The framework could provide a reference for comprehensive evaluation of other drugs.

Management of Patients Treated with Direct Oral Anticoagulants in Clinical Practice and Challenging Scenarios.

It is well established that direct oral anticoagulants (DOACs) are the cornerstone of anticoagulant strategy in atrial fibrillation (AF) and venous thromboembolism (VTE) and should be preferred over vitamin K antagonists (VKAs) since they are superior or non-inferior to VKAs in reducing thromboembolic risk and are associated with a lower risk of intracranial hemorrhage (IH). In addition, many factors, such as fewer pharmacokinetic interactions and less need for monitoring, contribute to the favor of this therapeutic strategy. Although DOACs represent a more suitable option, several issues should be considered in clinical practice, including drug-drug interactions (DDIs), switching to other antithrombotic therapies, preprocedural and postprocedural periods, and the use in patients with chronic renal and liver failure and in those with cancer. Furthermore, adherence to DOACs appears to remain suboptimal. This narrative review aims to provide a practical guide for DOAC prescription and address challenging scenarios.

Therapeutic Drug Monitoring of Direct Oral Anticoagulants in Patients with Extremely Low and High Body Weight-Pilot Study.

Phase III clinical trials for individual direct oral anticoagulants (DOACs) contained a limited representation of subjects with abnormal body weight, which were mostly limited to a BMI > 40 kg/m2, or body weight > 120 kg for obese subjects, and <50 kg for underweight subjects. Although low or high body weight is not a contraindication to DOACs therapy, it can significantly affect the safety and effectiveness of treatment. Due to the limited amount of clinical data on the use of DOACs in extremely abnormal weight ranges, optimal pharmacotherapy in this group of patients is a matter of controversy. The objective of this study was to evaluate the pharmacokinetics of DOAC properties in patients with abnormal body weight beyond the established cut-off points in the phase III studies for rivaroxaban, apixaban, and dabigatran. In total, 38 patients took DOACs for at least 12 months for non-valvular atrial fibrillation in 2019-2021. Blood samples were collected before the planned intake of the drug and 4 h after its administration. The determined concentrations of DOACs were statistically analyzed in relation to body weight, age, and eGFR (estimated Glomerular Filtration Rate). Among subjects taking apixaban, rivaroxaban, and dabigatran, the smallest representation of patients who achieved therapeutic concentrations were those treated with dabigatran. The population of people with abnormal body weight is a potential risk group of patients, in which some of them do not reach the therapeutic range of DOACs.

Effectiveness and safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation and advanced kidney disease.

BACKGROUND: The effectiveness and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and advanced kidney disease (AKD) has not been fully established. OBJECTIVES: To determine the effectiveness and safety related to pooled or specific DOACs to that with warfarin in patients with AF and AKD. METHODS: Patients with AF and AKD (estimated glomerular filtration rate < 30 mL/min) who received DOAC or warfarin from July 2011 to December 2020 were retrospectively identified in a medical center in Taiwan. Primary outcomes were hospitalized for stroke/systemic embolism and major bleeding. Secondary outcomes included any ischemia and any bleeding. RESULTS: A total of 1,011 patients were recruited, of whom 809 (80.0%) were in the DOACs group (15.3% dabigatran, 25.4% rivaroxaban, 25.2% apixaban, and 14.1% edoxaban), and 202 (20.0%) in the warfarin group. DOACs had considerably lower risks of stroke/systemic embolism (adjusted hazard ratio [aHR] 0.29; 95% CI, 0.09-0.97) and any ischemia (aHR, 0.42; 95% CI, 0.22-0.79), but had comparable risks of major bleeding (aHR, 0.99; 95% CI, 0.34-2.92) and any bleeding (aHR, 0.74; 95% CI, 0.50-1.09) than warfarin. Apixaban was linked to considerably lower risks of any ischemia (aHR, 0.13; 95% CI, 0.04-0.48) and any bleeding (aHR, 0.53; 95% CI, 0.28-0.99) than warfarin. CONCLUSION: Among patients with AF and AKD, DOACs were linked to a lower risk of ischemic events, and apixaban was linked to a lower risk of any ischemia and any bleeding than warfarin.

Patrones y resultados del cambio de anticoagulantes orales directos en la fibrilación auricular no valvular: experiencia en la práctica clínica en España / Patterns and outcomes of switching direct oral anticoagulants in non-valvular atrial fibrillation: A real-world experience from Spain

Objetivos El objetivo consistía en evaluar un programa de gestión de anticoagulantes orales directos (ACOD) en pacientes con fibrilación auricular no valvular (FANV) según sus perfiles, idoneidad de la dosis, patrones de cambio de tratamiento, efectividad y seguridad Se trató de un estudio observacional, prospectivo y longitudinal en una cohorte de pacientes atendidos en la práctica clínica cotidiana en un hospital regional español con un plan de seguimiento de 3 años para pacientes que iniciaron el tratamiento con dabigatrán, rivaroxabán o apixabán entre enero de 2012 y diciembre de 2016. Métodos Se analizaron 490 episodios de tratamiento (apixabán 2,5mg, 9,4%; apixabán 5mg, 21,4%; dabigatrán 75mg, 0,6%; dabigatrán 110mg, 12,4%; dabigatrán 150mg, 19,8%; rivaroxabán 15mg, 17,8%; rivaroxabán 20mg, 18,6%) en 445 pacientes. En el 13,6% de los pacientes tratados con dabigatrán, el 9,7% de los tratados con rivaroxabán y el 3,9% de los tratados con apixabán se cambió a otros ACOD o se modificó la dosis. Resultados El ACOD al que se cambió con mayor frecuencia fue el apixabán. Los motivos más frecuentes para cambiar de tratamiento fueron toxicidad (23,8%), hemorragia (21,4%) y deterioro renal (16,7%). En el 23,8% de los episodios se constató una inadecuación de la dosis. Las tasas de ictus y accidentes isquémicos transitorios (AIT) fueron de 1,64 y 0,54 eventos/100 años/paciente, respectivamente, mientras que las de hemorragias importantes, no importantes, pero clínicamente relevantes (NICR) e intracraneales fueron de 2,4, 5 y 0,5 eventos/100 años/paciente, respectivamente. Las hemorragias digestivas y genitourinarias fueron el tipo más frecuente de eventos hemorrágicos. En el análisis multifactorial, el ictus previo y la edad fueron factores predictivos independientes de ictus/AIT. El uso concomitante de antiagregantes plaquetarios, el sexo masculino y la edad fueron factores predictivos independientes de eventos hemorrágicos (AU)

Aims The aim is to evaluate a management program for direct oral anticoagulants (DOACs) in non-valvular atrial fibrillation (NVAF) patients according to their profiles, appropriateness of dosing, patterns of crossover, effectiveness and safety. This is an observational and longitudinal prospective study in a cohort of patients attended in daily clinical practice in a regional hospital in Spain with 3-year a follow-up plan for patients initiating dabigatran, rivaroxaban or apixaban between Jan/2012 and Dec/2016. Methods We analyzed 490 episodes of treatment (apixaban 2.5, 9.4%; apixaban 5, 21.4%; dabigatran 75, 0.6%; dabigatran 110, 12.4%; dabigatran 150, 19.8%; rivaroxaban 15, 17.8% and rivaroxaban 20, 18.6%) in 445 patients. 13.6% of patients on dabigatran, 9.7% on rivaroxaban, and 3.9% on apixaban switched to other DOACs or changed dosing. Results Apixaban was the most frequent DOAC switched to. The most frequent reasons for switching were toxicity (23.8%), bleeding (21.4%) and renal deterioration (16.7%). Inappropriateness of dose was found in 23.8% of episodes. Rates of stroke/transient ischemic attack (TIA) were 1.64/0.54 events/100 patients-years, while rates of major, clinically relevant non-major (CRNM) bleeding and intracranial bleeding were 2.4, 5, and 0.5 events/100 patients-years. Gastrointestinal and genitourinary bleeding were the most common type of bleeding events (BE). On multivariable analysis, prior stroke and age were independent predictors of stroke/TIA. Concurrent platelet inhibitors, male gender and age were independent predictors of BE. Conclusion This study complements the scant data available on the use of DOACs in NVAF patients in Spain, confirming a good safety and effectiveness profil (AU)

Patterns and outcomes of switching direct oral anticoagulants in non-valvular atrial fibrillation: A real-world experience from Spain.

AIMS: The aim is to evaluate a management program for direct oral anticoagulants (DOACs) in non-valvular atrial fibrillation (NVAF) patients according to their profiles, appropriateness of dosing, patterns of crossover, effectiveness and safety. This is an observational and longitudinal prospective study in a cohort of patients attended in daily clinical practice in a regional hospital in Spain with 3-year a follow-up plan for patients initiating dabigatran, rivaroxaban or apixaban between JAN/2012-DEC/2016. METHODS: We analyzed 490 episodes of treatment (apixaban 2.5 9.4%, apixaban 5 21.4%, dabigatran 75 0.6%, dabigatran 110 12,4%, dabigatran 150 19.8%, rivaroxaban 15 17.8% and rivaroxaban 20 18.6%) in 445 patients. 13.6% of patients on dabigatran, 9.7% on rivaroxaban, and 3.9% on apixaban switched to other DOACs or changed dosing. RESULTS: Apixaban was the most frequent DOAC switched to. The most frequent reasons for switching were toxicity (23.8%), bleeding (21.4%) and renal deterioration (16.7%). Inappropriateness of dose was found in 23.8% of episodes. Rates of stroke/transient ischemic attack (TIA) were 1.64/0.54 events/100 patients-years, while rates of major, clinically relevant non-major (CRNM) bleeding and intracranial bleeding were 2.4, 5, and 0.5 events/100 patients-years. Gastrointestinal and genitourinary bleeding were the most common type of bleeding events (BE). On multivariable analysis, prior stroke and age were independent predictors of stroke/TIA. Concurrent platelet inhibitors, male gender and age were independent predictors of BE. CONCLUSION: This study complements the scant data available on the use of DOACs in NVAF patients in Spain, confirming a good safety and effectiveness profile.

Retrospective analysis of gastrointestinal bleedings with direct oral anticoagulants reported to EudraVigilance.

Direct oral anticoagulants (DOACs) are increasingly used and are an important cornerstone in antithrombotic therapy. Adverse drug reactions (ADRs) such as bleedings have only partially been investigated during clinical trials. The primary goal was to analyse pharmacovigilance data based on spontaneous reports of gastrointestinal (GI) bleedings with DOACs reported to EudraVigilance. A second goal was to compare GI safety profiles between DOACs based on these signals. All DOAC related GI bleedings mentioned in individual case safety reports (ICSRs) from 2012 till 2017 in the European Economic Area were classified in four GI categories based on the reported site of occurrence of the haemorrhage. Age group and gender of the patient, seriousness and ADR outcome, and the reporter's qualification were assessed per category and per DOAC. Disproportionality analyses were performed to evaluate whether or not the reported ADRs were more prevalent with a given DOAC. ICSRs were bleeding-related in about half of the cases (n = 28,992/53,471). Of these bleedings, >25% was GI-related. Most patients experiencing GI bleedings were between 65 and 85 years old, with no obvious differences between men and women. Stomach, ulcer-related duodenal, and rectal bleedings were the most reported GI bleedings with a fatal outcome in 5.8%, 7.5%, and 9.8% of the cases for rivaroxaban, apixaban, and dabigatran, respectively. The disproportionality data suggest that dabigatran is more frequently involved in GI bleeding events than the other DOACs. DOACs were significantly associated with GI bleedings. Although the data should be interpreted with caution, it seems that dabigatran was associated more often than other DOACs with GI bleedings based on the analysis of spontaneous pharmacovigilance reports.

Trends in utilization, reimbursement, and price for DOACs and warfarin in the US Medicaid population from 2000 to 2020.

The use of direct oral anticoagulants (DOACs) is widely increasing in the United States (US). Warfarin has been the conventional anticoagulant used in the past few decades, but it has been gradually replaced by DOACs. The objective of the study was to analyze trends in utilization, reimbursement, and price for those anticoagulants in the US Medicaid population. Retrospective data analysis was conducted using the National Summary Files for the Medicaid State Drug Utilization Data. Study drugs included dabigatran, rivaroxaban, apixaban, edoxaban and warfarin. The study assessed secular trends of utilization, reimbursement, and per-prescription price. The data was collected from the first quarter of 2000 through to the second quarter of 2020 restricted for outpatient prescriptions only. During the 21-year study period, a substantial rise in total expenditures on warfarin and DOACs was observed from $144 million in 2000 to $694 million in 2020. Moreover, the utilization of DOACs has increased significantly since the first approval of Xarelto in 2010 from 1079 in 2011 to 1.5 million in 2019. The per-prescription price of DOACs increased from an average of $200 in 2011 to $407 in 2020. Conversely, the total number of prescriptions of Warfarin and branded Coumadin decreased from 2.4 million to 1.4 million and from 3.9 million to less than a million, respectively. The present study demonstrated a change in the trends of US expenditure and utilization for warfarin and DOACs with DOACs representing the majority of market share of both spending per prescription and reimbursement.

Direct oral anticoagulants in pediatric venous thromboembolism: Review of approved products rivaroxaban and dabigatran.

Venous thromboembolism is a major hospital acquired complication in the pediatric population over the last two-decades, with a 130% increase in the past decade. Direct oral anticoagulants (DOACs) are a newer class of anticoagulant medication for the treatment and prophylaxis of VTEs that provide the primary advantages of an oral route of administration without a requirement to adjust dosing to achieve a therapeutic level. It is anticipated that these medications will quickly replace parenteral anticoagulants and clinicians should familiarize themselves with DOACs. In this article, we provide an overview of the pharmacological properties of DOACs, with a specific focus on rivaroxaban and dabigatran, which have been approved for use in pediatric patients. Each drug's characteristics are discussed along with data from their respective clinical trials.

Complexity and clinical significance of drug-drug interactions (DDIs) in oncology: challenging issues in the care of patients regarding cancer-associated thrombosis (CAT).

Cancer patients have an increased risk of developing venous thromboembolic events. Anticoagulation management includes prophylactic or therapeutic doses of low molecular weight heparins (LMWHs) or direct oral anticoagulants (DOACs). However, the management of thrombosis in patients with cancer is complex due to various individual and disease-related factors, including drug-drug interactions (DDIs). Furthermore, DDIs may impact both, cancer and venous thrombosis, treatment effectiveness and safety; their relevance is highlighted by the advances in cancer therapeutics. Given that these new oncology drugs are extensively used, more attention should be given to monitoring potential DDIs to minimize risks. Recognition of DDIs is of utmost importance in an era of rapid developments in cancer treatments and introduction of novel treatments and protocols. When managing cancer-associated thrombosis (CAT), the concomitant use of a DOAC and a moderate or strong modulator (inhibitor or inducer) of CYP3A4 or a P-glycoprotein (P-gp) is most likely to be associated with significant DDIs. Therefore, LMWHs remain the first-line option for the long-term management of CAT under these circumstances and physicians must consider utilizing LMWHs as first line. This review describes the risk of DDIs and their potential impact and outcomes in patients with cancer associated thrombosis (CAT) receiving anticoagulation.

Apixaban Dosing Patterns Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation Receiving Dialysis: A Retrospective Cohort Study.

BACKGROUND & OBJECTIVES: Comparison of clinical outcomes across anticoagulation regimens using different apixaban dosing or warfarin is not well-defined in patients with nonvalvular atrial fibrillation (AF) who are receiving dialysis. This study compared these outcomes in a US national cohort of patients with kidney failure receiving maintenance dialysis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Patients receiving dialysis represented in the US Renal Data System database 2013-2018 who had AF and were treated with apixaban or warfarin. EXPOSURE: First prescribed treatment with apixaban dosed according to the label, apixaban dosed below the label, or warfarin. OUTCOME: Ischemic stroke/systemic embolism, major bleeding, and all-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards models with inverse probability of treatment weighting. Analyses simulating an intention-to-treat (ITT) approach as well as those incorporating censoring at drug switch or discontinuation (CAS) were also implemented. Inverse probability of censoring weighting was used to account for possible informative censoring. RESULTS: Among 17,156 individuals, there was no difference in risk of stroke/systemic embolism among the label-concordant apixaban, below-label apixaban, and warfarin treatment groups. Both label-concordant (HR, 0.67 [95% CI, 0.55-0.81]) and below-label (HR, 0.68 [95% CI, 0.55-0.84]) apixaban dosing were associated with a lower risk of major bleeding compared with warfarin in ITT analyses. Compared with label-concordant apixaban, below-label apixaban was not associated with a lower bleeding risk (HR, 1.02 [95% CI, 0.78-1.34]). In the ITT analysis of mortality, label-concordant apixaban dosing was associated with a lower risk versus warfarin (HR, 0.85 [95% CI, 0.78-0.92]) while there was no significant difference in mortality between below-label dosing of apixaban and warfarin (HR, 0.97 [95% CI, 0.89-1.05]). Overall, results were similar for the CAS analyses. LIMITATIONS: Study limited to US Medicare beneficiaries; reliance on administrative claims to ascertain outcomes of AF, stroke, and bleeding; likely residual confounding. CONCLUSIONS: Among patients with nonvalvular AF undergoing dialysis, warfarin is associated with an increased risk of bleeding compared with apixaban. The risk of bleeding with below-label apixaban was not detectably less than with label-concordant dosing. Label-concordant apixaban dosing is associated with a mortality benefit compared to warfarin. Label-concordant dosing, rather than reduced-label dosing, may offer the most favorable benefit-risk trade-off for dialysis patients with nonvalvular AF.