Effectiveness of Novel Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) is a common cardiac arrhythmia associated with an increased risk of stroke and systemic embolism (SE). Anticoagulation therapy, particularly with vitamin K antagonists (VKA) or novel oral anticoagulants (NOACs), is essential for stroke prevention in patients with AF. However, the comparative effectiveness of NOACs and warfarin remains debatable. Of the 34 studies included, 14 studies involving 166,845 patients were included in the meta-analysis and 20 studies were included in the systematic review. Our findings indicate that NOACs were associated with a significantly lesser risk of stroke/SE with a relative risk (RR) of 0.84 and p=0.0005, and all-cause mortality RR=0.88 and p=0.006. There were no significant differences between major bleeding events with an RR of 0.87 and p=0.22, and serious adverse events (SAE) with RR=1.01 and p=0.35, compared to warfarin in patients with AF. Our meta-analysis demonstrates strong evidence for the superiority in reducing stroke/SE and all-cause mortality of NOACs compared to warfarin. However, no significant differences were identified in the bleeding outcomes or SAEs between the two groups.

Avoiding the needle: A quality improvement program introducing apixaban for extended thromboprophylaxis after major gynecologic cancer surgery.

OBJECTIVE: Patients undergoing gynecologic cancer surgery at our centre are recommended up to 28 days of enoxaparin for extended post-operative thromboprophylaxis (EP). Baseline survey revealed 92% patient adherence, but highlighted negative effects on patient experience due to the injectable route of administration. We aimed to improve patient experience by reducing pain and bruising by 50%, increasing adherence by 5%, and reducing out-of-pocket cost after introducing apixaban as an oral alternative for EP. METHODS: In this interrupted time series quality improvement study, gynecologic cancer patients were offered a choice between apixaban (2.5 mg orally twice daily) or enoxaparin (40 mg subcutaneously once daily) at time of discharge. A multidisciplinary team informed project design, implementation, and evaluation. Process interventions included standardized orders, patient and care team education programs. Telephone survey at 1 and 6 weeks and chart audit informed outcome, process, and balancing measures. RESULTS: From August to October 2022, 127 consecutive patients were included. Apixaban was chosen by 84%. Survey response rate was 74%. Patients who chose apixaban reported significantly reduced pain, bruising, increased confidence with administration, and less negative impact of the medication (p < 0.0001 for all). Adherence was unchanged (92%). The proportion of patients paying less than $125 (apixaban cost threshold) increased from 45% to 91%. There was no difference in bleeding and no VTE events. CONCLUSIONS: Introduction of apixaban for EP was associated with significant improvement in patient-reported quality measures and reduced financial toxicity with no effect on adherence or balancing measures. Apixaban is the preferred anticoagulant for EP at our centre.

Prothrombin complex concentrate for emergency surgery in patients on oral Xa-inhibitors.

BACKGROUND: It is uncertain whether prothrombin complex concentrate (PCC) improves hemostasis in patients on treatment with oral factor Xa-inhibitors (XaI) who require emergency surgery. OBJECTIVES: To evaluate whether, in patients with therapeutic levels of oral XaI, preoperative PCC prevents excessive bleeding during and after emergency surgery and is not associated with thrombotic complications. METHODS: We conducted a prospective cohort study wherein a fixed 2000 IU dose of 4-factor PCC was given to patients taking oral XaI with plasma XaI levels of at least 75 ng/mL before the emergency surgery with an expected blood loss of at least 50 mL. Patients were followed for 30 days. The primary efficacy outcome was the incidence of normal or mildly abnormal surgical hemostasis, as assessed by the surgeon; primary safety outcome was the incidence of thromboembolic events within 7 days. RESULTS: We included 20 patients, 50% were female, on apixaban (75%) or rivaroxaban (25%) with median XaI level of 128 ng/mL (range 77-497). The median duration of surgery was 2h 42 min (15 min to 8h 17 min). Normal or mildly abnormal hemostasis was observed in 16 patients (80%), 2 patients had moderately abnormal and 2 had severely abnormal hemostasis, 1 each of those was considered due to local or technical factors. There were 4 deaths (20%) secondary to underlying disease and 1 incidental pulmonary embolism in a patient with cancer. CONCLUSION: A fixed dose PCC appears to control hemostasis in patients with therapeutic plasma levels of apixaban or rivaroxaban requiring emergency surgery.

Effects of the antitumor drugs adagrasib and asciminib on apixaban metabolism in vitro and in vivo.

Apixaban is an oral anticoagulant that directly inhibits the target Factor Xa (FXa). In this study, we focused on the in vivo and in vitro effects of adagrasib and asciminib on apixaban metabolism, to discover potential drug-drug interactions (DDI) and explore their inhibitory mechanisms. The levels of apixaban and its metabolite, O-desmethyl-apixaban (M2), were determined by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). In vitro evaluation, the maximum half inhibitory concentration (IC50) of adagrasib in rat liver microsomes (RLM) and human liver microsomes (HLM) against apixaban was 7.99 µM and 117.40 µM, respectively. The IC50 value of asciminib against apixaban in RLM and HLM was 4.28 µM and 18.42 µM, respectively. The results of the the analysis on inhibition mechanisms showed that adagrasib inhibited the metabolism of apixaban through a non-competitive mechanism, while asciminib inhibited the metabolism of apixaban through a mixed mechanism. Moreover, the interaction of apixaban with adagrasib and asciminib in Sprague-Dawley (SD) rats was also investigated. It was found that the pharmacokinetic characteristics of apixaban were significantly changed when combined with these two antitumor drugs, where AUC(0-t), AUC(0-∞), t1/2, Tmax, and Cmax were increased, while CLz/F was significantly decreased. But both drugs did not appear to affect the metabolism of M2 in a significant way. Consistent results from in vitro and in vivo demonstrated that both adagrasib and asciminib inhibited the metabolism of apixaban. It provided reference data for the future clinical individualization of apixaban.

Direct oral anticoagulants vs Vitamin-K antagonists in solid organ transplant recipients: A systematic review and meta-analysis.

Objective: Oure review aimed to examine evidence on the safety and efficacy of direct oral anticoagulants (DOAC) vs Vitamin K antagonists (VKA) in patients with solid organ transplants. Methods: PubMed, Embase, and Web of Science libraries were searched from inception to 25th November 2023 for all studies comparing DOAC with VKA in solid organ recipients. Results: Nine studies were included with patients who had undergone kidney, heart, or liver transplants. Meta-analysis showed that patients receiving DOAC had a significantly reduced risk of composite bleeding as compared to those with VKA (RR: 0.45 95% CI: 0.30, 0.68 I2=25%). However, the risk of major bleeding was not significantly different between the two groups (RR: 0.76 95% CI: 0.40, 1.42 I2=37%). Pooled analysis showed that the risk of VTE (RR: 0.90 95% CI: 0.72, 1.13 I2=0%) and ischemic stroke (RR: 0.87 95% CI: 0.39, 1.94 I2=12%) was not significantly different between DOAC and VKA groups. Conclusion: Limited data shows that DOAC are safe and effective in patients with solid organ transplants. The overall risk of bleeding may be reduced with the use of DOAC. There is a need for randomized controlled trials comparing DOAC and VKA in such patients to obtain high-quality evidence.

Differences in coagulation responses to vascular injury between uninterrupted dabigatran and apixaban - a clinical prospective randomized study.

BACKGROUND: The coagulation response during vascular injury with uninterrupted administration of direct oral anticoagulants (DOACs) has not been elucidated. OBJECTIVE: Our aim was to evaluate differences in coagulation responses after vascular injury between uninterrupted direct thrombin inhibitor and direct factor Xa inhibitor recipients. METHODS: Patients scheduled for catheter ablation for atrial fibrillation were randomly assigned to receive dabigatran or apixaban in this prospective, randomized, comparative, parallel-group study. Venous blood was collected three times: 180 minutes after taking the anticoagulant on the day before the procedure, before vascular punctures of the ablation procedure, and 10-15 minutes after the start of vascular punctures. RESULTS: Forty-two patients were enrolled. The prothrombin fragment 1+2 (F1+2) level, the primary endpoint, was much larger after vascular puncture in the uninterrupted dabigatran recipients (median: 83 pmol/L; interquartile range: 56-133 pmol/L) than in the uninterrupted apixaban recipients (median: 1 pmol/L; interquartile range: -3-19 pmol/L; P < 0.001). Antithrombin levels decreased after vascular puncture in dabigatran recipients, and both protein C and antithrombin levels decreased after vascular puncture in apixaban recipients. CONCLUSIONS: Unlike uninterrupted apixaban, uninterrupted dabigatran does not inhibit thrombin generation in response to vascular injury.

Apixaban vs Aspirin According to CHA2DS2-VASc Score in Subclinical Atrial Fibrillation: Insights From ARTESiA.

BACKGROUND: ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation) demonstrated that apixaban, compared with aspirin, significantly reduced stroke and systemic embolism (SE) but increased major bleeding in patients with subclinical atrial fibrillation. OBJECTIVES: To help inform decision making, the authors evaluated the efficacy and safety of apixaban according to baseline CHA2DS2-VASc score. METHODS: We performed a subgroup analysis according to baseline CHA2DS2-VASc score and assessed both the relative and absolute differences in stroke/SE and major bleeding. RESULTS: Baseline CHA2DS2-VASc scores were <4 in 1,578 (39.4%) patients, 4 in 1,349 (33.6%), and >4 in 1,085 (27.0%). For patients with CHA2DS2-VASc >4, the rate of stroke was 0.98%/year with apixaban and 2.25%/year with aspirin; compared with aspirin, apixaban prevented 1.28 (95% CI: 0.43-2.12) strokes/SE per 100 patient-years and caused 0.68 (95% CI: -0.23 to 1.57) major bleeds. For CHA2DS2-VASc <4, the stroke/SE rate was 0.85%/year with apixaban and 0.97%/year with aspirin. Apixaban prevented 0.12 (95% CI: -0.38 to 0.62) strokes/SE per 100 patient-years and caused 0.33 (95% CI: -0.27 to 0.92) major bleeds. For patients with CHA2DS2-VASc =4, apixaban prevented 0.32 (95% CI: -0.16 to 0.79) strokes/SE per 100 patient-years and caused 0.28 (95% CI: -0.30 to 0.86) major bleeds. CONCLUSIONS: One in 4 patients in ARTESiA with subclinical atrial fibrillation had a CHA2DS2-VASc score >4 and a stroke/SE risk of 2.2% per year. For these patients, the benefits of treatment with apixaban in preventing stroke/SE are greater than the risks. The opposite is true for patients with CHA2DS2-VASc score <4. A substantial intermediate group (CHA2DS2-VASc =4) exists in which patient preferences will inform treatment decisions. (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; NCT01938248).

Unveiling May-Thurner Syndrome in a Case of Recurrent Deep Venous Thrombosis With Bilateral Pulmonary Embolism.

May-Thurner syndrome (MTS) is a rare cause of deep venous thrombosis (DVT), characterized by the external compression of the left common iliac vein by the right common iliac artery against bony structures. Risk factors for MTS include female sex (postpartum, multiparous, and using oral contraceptive pills), spinal abnormalities like scoliosis, prior aortoiliac vascular stent placement, dehydration, and hypercoagulability. MTS patients with partial obstruction can be asymptomatic, but progression to extensive symptomatic DVT and/or chronic venous insufficiency can occur. MTS can be diagnosed by non-invasive imaging studies including ultrasound (US), computed tomography (CT) scan, magnetic resonance imaging (MRI), venogram, catheter-based venogram, and intravascular US. For MTS patients with moderate to severe symptoms, we suggest thrombectomy, angioplasty, and stenting of the affected segment. In this case report, we highlight a 44-year-old male with a recent diagnosis of left-sided DVT on apixaban who presented with worsening leg swelling. DVT, pulmonary embolism (PE), and MTS were diagnosed with a lower extremity US, chest CT angiography, and abdominal/pelvic CT scan and venography, respectively. The patient underwent interventional radiology-guided local thrombolysis, thrombectomy, and venoplasty along with stent placement in the left common iliac vein. Subsequently, the patient was discharged on rivaroxaban.

Efficacy and Safety of a DOAC Compared to Unfractionated Heparin and A Low Molecular Weight Heparin in the Prevention of Thromboembolism in Hematopoietic Stem Cell Transplant Recipients.

Background: Hematopoietic stem cell transplantation (HSCT) patients are at risk of thromboembolic events, making thromboprophylaxis crucial. Objectives: This study aimed to compare apixaban, a direct factor Xa inhibitor (DOAC), with dalteparin and unfractionated heparin for thromboprophylaxis in HSCT recipients. The safety outcome included the assessment of hemorrhagic events. Methods: In this open-label randomized clinical trial, 182 HSCT recipients were divided into three groups: Apixaban (n = 61, 2.5 mg two times a day), dalteparin (n = 59, 5000 IU daily), and unfractionated heparin (n = 62, 5000 IU twice daily). These anticoagulant regimens were administered after central vein catheterization and during hospitalization. The primary clinical outcome was the risk of thrombosis, and the secondary outcome was the rate of bleeding. Relevant laboratory results were analyzed using appropriate statistical tests. Results: Among the 61 patients in the apixaban group, six experienced thrombosis (9.83%), with four (6.65%) of them on anticoagulants. In the dalteparin group, three patients (5%) developed thrombosis, two of whom (3.38%) were on anticoagulants. In the heparin group, all four thrombosis cases (6.4%) occurred in patients on anticoagulants (P = 0.543 overall and P = 0.776 in anticoagulant users). Only two cases of bleeding were reported (1.09% overall), one in the dalteparin group (1.69%) and the other in the apixaban group (1.63%). Conclusions: Apixaban, dalteparin, and heparin demonstrated similar effectiveness in preventing thromboembolism in HSCT recipients. Furthermore, the comparison of bleeding rates across the study groups did not reveal significant differences. Larger studies with higher event rates may yield more precise conclusions.

Spontaneous Hemopericardium Associated With Apixaban Use With Newly Diagnosed Malignancy and Acute Kidney Injury: A Case Report.

Direct oral anticoagulants have simplified the use of anticoagulation for patients and clinicians. These medications now have indications for non-valvular atrial fibrillation and venous thromboembolism and carry a lower risk of bleeding than warfarin. While bleeding complications are common amongst all anticoagulants, spontaneous hemopericardium is a rarely reported side effect of direct oral anticoagulants, previously reported in patients with concomitant malignancy or kidney injury. We present a case of a patient with recently diagnosed renal malignancy and atrial fibrillation on apixaban who developed a spontaneous hemopericardium that required a pericardial window.

Persistent Peril: Recurrent Deep Vein Thrombosis and Pulmonary Embolism in a Patient With Protein S Deficiency Despite Optimal Anticoagulation Therapies.

The clotting system has evolved as an adaptive mechanism to prevent blood loss during vascular damage. However, the intricate nature of the clotting cascade and the complexities of human life can sometimes lead to the unnatural activation of this delicate cascade. This can result in blood clot formation within the cardiovascular system, contributing to a wide range of pathological conditions. Abnormal intravascular coagulation most commonly occurs in the deep veins of the lower extremities, and can emboli to other organs, hence, it is termed "venous thromboembolism" (VTE). In this report, we introduce a challenging case of VTE that poses a dilemma for current medical management. The patient with possible protein S deficiency underwent various guideline-directed medical treatments, yet experienced recurrent VTE episodes, including deep vein thrombosis (DVT) and pulmonary embolism (PE), leading to hospital readmissions. This case report sheds light on our challenges in effectively treating VTE.

Antithrombotic Strategies According to Age: Insights From the AUGUSTUS Trial.

OBJECTIVE: We aimed to evaluate the safety and efficacy of antithrombotic strategies by age in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention in AUGUSTUS. METHODS: Patients were stratified into 3 age groups: <65, 65-74, and ≥75 years. Outcomes of interest were major or clinically relevant non-major bleeding, major bleeding, death or rehospitalization, and ischemic events. Treatment effects of apixaban vs. vitamin K antagonist (VKA) and aspirin vs. placebo were assessed across age groups using Cox models. RESULTS: Of 4614 patients, 1267 (27.5%) were <65, 1802 (39.0%) were 65-74, and 1545 (33.5%) were ≥75 years. Apixaban was associated with lower rates of major or clinically relevant non-major bleeding than VKA (<65: HR 0.69 [0.47-1.00]; 65-74: HR 0.57 [0.43-0.75]; ≥75: HR 0.81 [0.63-1.04]). Death or hospitalization occurred less often with apixaban, regardless of age. No differences were observed in rates of ischemic events between apixaban and VKA according to age. Aspirin was associated with higher rates of bleeding than placebo (<65: HR 1.67 [1.15-2.43]; 65-74: HR 2.32 [1.73-3.10]; ≥75: HR 1.69 [1.31-2.19]). Rates of death or rehospitalization and ischemic events were similar among patients receiving aspirin or placebo across age groups. CONCLUSIONS: Apixaban was associated with greater absolute reduction in bleeding than VKA in older age groups, reflecting their higher hemorrhagic risk. Aspirin increased bleeding in all age groups vs. placebo. Our findings support the use of apixaban plus a purinergic receptor P2Y12(P2Y12) inhibitor without aspirin in patients with atrial fibrillation and recent acute coronary syndrome/percutaneous coronary intervention, regardless of age.

Adverse events of direct factor Xa inhibitors: a disproportionality analysis of the FAERS database.

OBJECTIVES: Direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, commonly used direct oral anticoagulant (DOAC), are widely used to prevent and treat stroke and venous thromboembolic events in patients with atrial fibrillation (AF). This study aimed to assess and compare reports of adverse events associated with rivaroxaban, apixaban, and edoxaban, including hemorrhagic and non-hemorrhagic events. METHODS: Reporting odds ratio (ROR), proportional reporting ratio (PRR), Medications and Health Care Products Regulatory Agency (MHRA), and the information component (IC) were used to perform a risk assessment of adverse event reports in the FDA Adverse Event Reporting System (FAERS) database for the years 2018-2022. RESULTS: Combined with disproportionality analysis in different backgrounds, the salient risks of the three-factor Xa inhibitors varied. Rivaroxaban had the most significant risk of hemorrhage, apixaban had a higher incidence and risk of death, cardiac and cerebral adverse events, and edoxaban showed a more prominent risk in the kidneys and urinary system. CONCLUSION: Hemorrhage is a common risk with factor Xa inhibitors, with rivaroxaban being the most significant. Apixaban and edoxaban also showed significant association with non-hemorrhagic adverse events, and increased attention to non-hemorrhagic adverse events is needed in clinical use.

Clinical characteristics of apixaban prescription in AF patients with single dose-reduction criterion: the ASPIRE (efficAcy and safety of aPixaban in rEal-world practice in Korean frail patients with atrial fibrillation) study.

Background: Data on off-label reduced dose risk among patients with atrial fibrillation (AF) who qualify for a single-dose reduction of apixaban is scarce. Objectives: We prospectively assessed apixaban dosing and clinical characteristics in AF patients meeting a dose reduction criterion. Methods: The multicentre, prospective cohort study, the efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE), encompasses patients with AF who met the criteria for a single-dose reduction of apixaban and were given varying doses of apixaban, either the on-label standard dose or the off-label reduced dose. Results: Of 2,000 patients (mean age 74.3 ± 7.9 years, 55.8% women), 29.7% were ≥80 years, 62.6% weighed ≤60 kg, and 7.8% had serum creatinine ≥1.5 mg/dL. Of these, 51.3% were prescribed an off-label reduced dose of apixaban. The off-label group was characterized with older age, more comorbidities, and antiplatelet agents, while the on-label group had more prior strokes. Physicians preferred off-label reduced dose in the "marginal zone," defined as age 75-80 years, weight 60-65 kg, and creatinine levels 1.2-1.5 mg/dL. Conclusions: In real-world clinical setting of the Korean population, off-label reduced dose apixaban was administered to nearly half of the patients who qualified for a single dose reduction. This reduced dosage was more commonly prescribed to patients with frail characteristics, while patients with a history of stroke were more often given the standard dose as per the label. A future study is planned to contrast the safety and effectiveness of the standard dose against the reduced dose of apixaban in this population.

The impact of ABCB1, CYP3A4 and CYP3A5 gene polymorphisms on apixaban trough concentration and bleeding risk in patients with atrial fibrillation.

OBJECTIVES: Apixaban, a direct oral anticoagulant, is increasingly used worldwide for the treatment and prevention of venous thromboembolism and ischemic stroke in patients with nonvalvular atrial fibrillation (AF). Obviously, one of the ways to enhance effectiveness and safety of drug therapy is a personalized approach to therapy, which involves pharmacogenetic and pharmacokinetic tests. The study aims to investigate the effect of CYP3A4*22, CYP3A5*3 and ABCB1 polymorphisms on the pharmacokinetics of apixaban and the risk of bleeding. METHODS: A total of 84 patients were enrolled in this prospective observational study. All patients received apixaban 5 or 2.5 mg twice daily. Real-time polymerase chain reaction was used to evaluate single-nucleotide polymorphisms of the ABCB1 gene (rs1045642 and rs4148738), CYP3A4*22 (rs35599367) C>T, CYP3A5*3 (rs776746) A>G. A plasma trough concentration/dose (C/D) ratio was used as a pharmacokinetic index. RESULTS: The C/D ratio was higher in patients aged >80 years (F(1)=11.209, p=0.00124) and was affected by serum creatinine (>133 µmol/L, F(1)=6.7, p=0.01124). ABCB1 (rs1045642 and rs4148738), CYP3A5 (rs776746) and CYP3A4 (rs35599367) polymorphisms did not show a correlation with C/D ratio of apixaban. Multivariate logistic regression analyses showed that none of the clinical or genetic factors predicted the fact of bleeding. CONCLUSIONS: We report no significant association between ABCB1 gene polymorphisms (rs1045642 and rs4148738), CYP3A4*22 (rs35599367) C>T, CYP3A5*3 (rs776746) A>G and bleeding events on apixaban treatment. Complementing the existing criteria with pharmacogenetic and pharmacokinetics information for the patients with AF will enable further individualization of apixaban.

Meta-analysis evaluating apixaban in patients with atrial fibrillation and end-stage renal disease requiring dialysis.

Background: Warfarin is considered the primary oral anticoagulant for patients with atrial fibrillation and end-stage renal disease (ESRD) requiring dialysis. Although warfarin can offer significant stroke prevention in this population, the accompanying major bleeding risks make warfarin nearly prohibitive. Apixaban was shown to be superior to warfarin in preventing stroke or systemic embolism, with a lower risk of bleeding and mortality in a large, randomized trial of individuals with mostly normal renal function but none with ESRD. Methods: We systematically reviewed evidence comparing apixaban versus warfarin for atrial fibrillation in this population, and evaluated outcomes of stroke or systemic embolism, and major bleeding using random-effects models. The main safety outcome was major bleeding, and the main effectiveness outcome was stroke or systemic embolism. Results: We found five observational studies of 10 036 patients (2638 receiving apixaban, and 7398 receiving warfarin) meeting inclusion criteria. Pooled analysis demonstrated a significant reduction in major bleeding with apixaban as compared to warfarin (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.42-0.61; p < .0001). Apixaban was also associated with a reduction in intracranial bleeding (OR 0.58, 95% CI 0.37-0.92; p = .02) and in gastrointestinal bleeding (OR 0.61, 95% CI 0.51-0.73; p < .0001). Furthermore, apixaban was associated with a reduction in stroke/systemic embolism (OR 0.64, 95% CI 0.50-0.82; p < .0001). Conclusion: Apixaban was associated with superior outcomes and reduced adverse events compared to warfarin in observational studies of patients with atrial fibrillation on dialysis. Randomized controlled studies are needed to confirm these findings.

Post-Discharge Treatment Patterns among Patients Treated with Apixaban or Warfarin during Hospitalization for Venous Thromboembolism (VTE).

Background: Oral anticoagulants (OACs), such as apixaban and warfarin, are indicated for reducing the risk of recurrent venous thromboembolism (VTE) and are often initiated in the hospital. The aim of this study was to evaluate OAC continuity from inpatient to outpatient settings and the risk of recurrent VTE among patients with an initial event. Methods: This retrospective cohort study utilized hospital charge data and medical and prescription claims from 1 July 2016 to 31 December 2022 to identify adults treated with apixaban or warfarin while hospitalized for VTE. Patients were followed to assess switching or discontinuation post-discharge and the risk of recurrent VTE. The index date was the date of the first apixaban or warfarin claim within 30 days post-discharge. Results: Of the 19,303 eligible patients hospitalized with VTE, 85% (n = 16,401) were treated with apixaban and 15% (n = 2902) received warfarin. After discharge, approximately 70% had ≥1 fill for their respective apixaban or warfarin therapy. The cumulative incidence of discontinuation over the 6 months following index was 50.5% and 52.2% for the apixaban and warfarin cohorts, respectively; the cumulative incidence of switching was 6.0% and 20.9%, respectively. The incidence rates of recurrent VTE were 1.2 and 2.5 per 100 person-years for the apixaban and warfarin cohorts, respectively. Conclusions: The majority of patients continued their apixaban or warfarin therapy following hospital discharge; however, a considerable proportion either switched or discontinued OAC upon transitioning from inpatient care. Among those who continued therapy, discontinuation, switch, and recurrent VTE occurred less often with apixaban vs. warfarin.

[Overdosing of direct oral anticoagulants]. / Überdosierung von direkten oralen Antikoagulanzien.

BACKGROUND: Direct oral anticoagulants (DOAC) are increasingly used for prophylaxis and treatment of thromboembolic events. Incorrectly dosed DOAC treatment is associated with excess mortality. PURPOSE: This article aims at raising awareness of DOAC overdosing and its causes as well as presenting a diagnostic and therapeutic work-up. MATERIAL AND METHODS: Based on a case presentation, a structured review of the current literature on DOAC overdosing was performed and treatment recommendations were extracted. RESULTS: In addition to wittingly or unwittingly increased DOAC intake, common causes of overdose are inadequate dose adjustment for concomitant medication or comorbidities. Global coagulation testing should be supplemented with DOAC-specific testing. Severe bleeding and the need for invasive diagnostics or urgent surgery represent indications for treating DOAC overdoses. Based on the cause of an DOAC overdose, active charcoal, endoscopic pill rescue, antagonization with idarucizumab or andexanet alfa and the targeted substitution of coagulation factors represent treatment options. CONCLUSION: The sensitization of clinicians is important to ensure a timely diagnosis and adequate treatment of DOAC overdosing. This report provides an overview of current knowledge on diagnostics and treatment; however, further studies are necessary to improve the existing algorithms.