Apixaban For Treatment Research Articles

Survival Implications of Thrombus Recurrence or Bleeding in Cancer Patients Receiving Anticoagulation for Venous Thromboembolism Treatment.

Study aims were to analyze prospectively collected data from patients with cancer-associated venous thromboembolism (VTE) to determine the impact of VTE recurrence and anticoagulant-related bleeding on all-cause mortality. Consecutive cancer patients with acute VTE treated with anticoagulants (March 1, 2013-November 30, 2021) were included in this analysis. Anticoagulant therapy-associated VTE recurrences, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) were assessed for their impact on all-cause mortality outcomes. This study included 1,812 cancer patients with VTE. Of these, there were 97 (5.4%) with recurrent VTE, 98 (5.4%) with major, and 104 (5.7%) with CRNMB while receiving anticoagulants. Recurrent VTE (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.16-2.00; p = 0.0028), major bleeding (HR: 1.82; 95% CI: 1.41-2.31; p = 0.006), and CRNMB (HR; 1.38; 95% CI: 1.05-1.81; p = 0.018) each adversely influenced mortality outcomes. Deep vein thrombosis as the incident thrombotic event type was associated with VTE recurrence (HR: 1.78; 95% CI: 1.08-2.89; p = 0.02). Neither cancer type nor stage, chemotherapy, or Ottawa risk category influenced VTE recurrence. Higher body weights (HR: 1.01; 95% CI: 1.00-1.01; p = 0.005) were associated with increased major bleeding, while high Ottawa scores (HR: 0.66; 95% CI: 0.46-0.96; p = 0.03) and apixaban treatment (HR: 0.62; 95% CI: 0.45-0.84; p = 0.002) were associated with fewer major bleeding outcomes. Among cancer patients receiving anticoagulant therapy for VTE, adverse outcomes such as VTE recurrence, major bleeding, or CRNMB increase mortality risk by 40 to 80%. Identifying variables predicting these outcomes may help risk-stratify patients with poor prognosis.

Conventional and synchronous spectrofluorometric determination of the recently administered drugs for treatment of COVID-19 favipiravir and apixaban

COVID-19 is a fast-spreading pandemic that is caused by SARS-CoV-2 viral pathogen. Combination therapy of the antiviral favipiravir and the anticoagulant apixaban is one of the efficient treatment regimens. Therefore, development of novel and sensitive methods for simultaneous analysis of such combination is highly advantageous. Herein, two eco-friendly, simple, rapid, and cost-effective spectrofluorometric methods were evolved for the estimation of favipiravir and apixaban in pharmaceutical and biological matrices. Method I was based on analysis of favipiravir and apixaban by the first-order derivative of the conventional fluorescence spectra obtained after excitation at 300 nm, where favipiravir and apixaban were detected at 468.8 and 432.0 nm, respectively. Method II relied on dual scan synchronous spectrofluorometry, in which favipiravir was determined at 364 nm using Δλ = 60 nm while apixaban was analyzed at 274 nm using Δλ = 200 nm. Method optimization was performed for selecting the optimum conditions at which maximum sensitivity and selectivity were obtained. This report is the first one that describes simultaneous analysis of favipiravir and apixaban by synchronous spectrofluorometry. The developed methods were successfully applied to evaluate favipiravir and apixaban in spiked human plasma and in pharmaceutical dosages with high %recoveries and low RSD.

Preliminary Result of a Pilot Study of Apixaban in the Treatment of Splanchnic Vein Thrombosis

Introduction: Recently, direct oral anticoagulants (DOACs) are widely used in patients with venous thromboembolism. However, there is no sufficient data of DOACs in treatment of splanchnic vein thrombosis (SVT). In this study, we aimed to investigate the safety and efficacy of apixaban in treatment of SVT. Methods: PAINT-SVT study was a prospective pilot study of the patients with newly diagnosed symptomatic acute SVT. Patients should not have contraindication to DOACs, and appropriate liver and renal function. Patients with chronic SVT, which includes evidence of cavernous formation, collateral circulation, or known SVT within 6 months were excluded. Apixaban was administered at a dose of 10mg bid for 7 days, followed by 3 months of 5mg bid for initial treatment. With physicians’ decision, patients could be treated for 3 more months with apixaban at a dose of 2.5mg bid. Primary objective of this study was major bleeding (MB) according to International Society on Thrombosis and Haemostasis criteria. Key secondary objectives included clinically relevant non-major bleeding (CRNMB) and overall response rate (ORR). Results: From Mar 2021 to Jun 2022, a total of 21 patients were enrolled in this study. Median age was 67 (range, 44 - 81) years and 12 patients (57.1%) were males. This study included 17 patients (81.0%) with liver cirrhosis (LC), and all but one patient had child-push score of A. Four patients (19.0%) had underlying malignancies (1 lymphoproliferative disease, 1 gastrointestinal stromal tumor, 1 hepatocellular carcinoma, and 1 follicular lymphoma). With median time on anticoagulation of 92 (range, 3.0 - 184.0) days, 3 patients experienced MB and 6 patients experienced CRNMB. CRNMB occurred mostly within 1 month of anticoagulation, while MB occurred more wide range of time point during anticoagulation. Although the interpretation is limited due to the small number of samples, bleeding event occurred exclusively in LC patients. Of 21 patients, 18 patients were evaluable except for 2 patients who discontinued before the completion of initial treatment due to bleeding and 1 patient who did not completed 3 months of anticoagulation at the time of analysis. Radiologically, ORR was 61.1% including 5 patients (27.8%) with complete remission (CR) and 6 patients (33.3%) with partial remission (PR). Among 17 patients with LC, 15 patients were evaluable and ORR was 66.7% (CR, 26.7% and PR, 40.0%). Among patients who completed 3 months of initial treatment, 14 patients received additional 3 months of extended treatment and 11 patients completed extended treatment. So far, 2 patients showed improvement of response (PR to CR) and 1 patient showed thrombus progression during the treatment. Conclusions: In patients with SVT, apixaban can be used effectively and safely. However, caution is warranted for bleeding complications especially in patients with underlying LC, even in the early stage. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Effects Of Rivaroxaban And Apixaban On Intimal Hyperplasia In Rabbits

Aim: Intimal hyperplasia causes vascular occlusion and its optimal treatment is unknown. In this study, we evaluated the effectiveness of Apixaban and Rivaroxaban treatment for preventing intimal hyperplasia in rabbits. Material and Methods: The rabbits (n = 15) were randomly divided into three groups. Reanastomoses are applied to the carotid artery. All groups received 100 U/kg heparin sodium during the operation period. Group A (n = 5) as a control group had no medication. Group B (n = 5) was given Rivaroxaban 3 mg/kg/day. In-group C (n = 5) Apixaban was administered per orally 10 mg/kg. At the end of the treatment on the 28th day, carotid artery specimens were excised and evaluated histologically. Results: Increased intima thickness was observed in the control group than the drug groups (P=0.019, P=0.007). It was found that there was no difference between groups in terms of lumen diameter, lumen area, tunica media area and tunica media thickness. There was difference between groups in terms of caspase 3 or TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining (p<0.05). Conclusion: Apixaban and Rivaroxaban may have protective efficacy against intimal hyperplasia after vascular surgical intervention.

Bleedings in Cancer Patients Treated with Apixaban for Venous Thromboembolism

Background: Recently, direct oral anticoagulants (DOACs) have been investigated as an alternative to low-molecular-weight heparin (LMWH) for the treatment of cancer-associated venous thromboembolism (VTE). Apixaban, edoxaban, and rivaroxaban showed non-inferiority in preventing recurrent VTE compared with the dalteparin. However, it was reported higher risk of bleeding in gastrointestinal (GI) cancers in patients treated with edoxaban and rivaroxaban compared with dalteparin, but not with apixaban. It has been suggested that non-resected GI cancers have higher risk of bleeding than resected ones. The CAP study investigated apixaban as a treatment for cancer associated VTE (1). In this subanalysis, we aimed to investigate risk factors for bleedings and to find out if reducing the dose of apixaban influenced bleedings. Methods: The CAP study was a prospective, single-arm, interventional study conducted in Norway to assess the efficacy and safety of apixaban as a treatment for cancer-associated VTE. Patients received initially 7 days with 10 mg apixaban twice daily followed by 5 mg twice daily ("full dose") from baseline to 6 months, and 2.5 mg twice daily ("low dose") from 7 to 36 months. Bleedings were categorized as major bleedings or clinically relevant non-major bleedings (CRNMB). The combination of major bleedings and CRNMB is referred to as "clinically relevant bleedings” (CRBs). We investigated the following risk factors for bleeding: age, gender, low BMI, metastasis, unresected tumor, low thrombocyte count, cancer type, low hemoglobin, and concomitant use of anti-platelet therapy. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to assess the association between risk factors and bleedings. Results: Patient characteristics and bleeding events by type of cancer are shown in table 1. We found that CRBs were associated with high age (above 74 years old, OR 2.0, 95% CI 1.0-4.1), low BMI (below 21.7, OR 2.3, 95% CI 1.1-4.8), and low hemoglobin (below 10.5 for females, OR 2.8, 95% CI 1.1-7.3 and 11.1 for males, OR 3.3, 95% CI 1.3-8.4), during full dose apixaban treatment period. Having GI or urogenital cancer were not associated with CRB compared with other cancers. In general, patients with unresected cancers did not have more bleedings than resected cancers. However, unresected GI cancer had increased risk of bleeding (OR 3.4, 95% CI 1.0-11.6) compared with resected GI cancer. Within the group of urogenital cancer, resected cancers were apparently associated with bleeding (OR 11.1, 95% CI 1.3-94.0), although with a large confidence interval. We did not find any risk factors associated with CRB from 7-36 months except for having breast cancer (OR 3.2, 95% CI 1.0-10.0). The frequency of major bleeding events was higher in full-dose period compared to the low-dose period but the frequency of CRNMB was not influenced by the reduction in apixaban dose (figure 1). There was one fatal bleeding in the full-dose period. Conclusion: Risk factors for bleeding in treatment with full dose apixaban were high age, low BMI, low hemoglobin. Low dose apixaban apparently reduced major bleeding events, but not CRNMB. Reference: 1. Larsen TL, Garresori H, Brekke J, Enden T, Frøen H, Jacobsen EM, et al. Low dose apixaban as secondary prophylaxis of venous thromboembolism in cancer patients - 30 months follow-up. J Thromb Haemost. 2022;20(5):1166-81. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Spontaneous rectus sheath hematoma associated with apixaban in an elderly gentleman with chronic obstructive airway disease – a case report

BackgroundRectus sheath hematoma (RSH) is a relatively uncommon cause of acute abdominal pain and can be mistaken as other surgical causes of acute abdomen. A diagnosis requires high index of suspicion especially in susceptible patients, for example, in patients on anticoagulation. While anticoagulation is the commonest risk factor for RSH, direct-acting oral anticoagulants have only been very recently implicated as a potential cause with fewer than ten cases reported in the literature.Case presentation.An 82-year-old Chinese man with chronic obstructive airway disease, ischemic heart disease, heart failure and atrial fibrillation on apixaban presenting with acute onset of lower abdominal pain. Physical examination showed peritoneal signs with tenderness and guarding over the lower quadrants with hypotension. Computed tomography (CT) of the abdomen confirmed a large rectus sheath hematoma (RSH) without active extravasation. He was given fluid resuscitation and was managed successfully with supportive treatment and cessation of apixaban. A follow-up CT two months later showed resolving hematoma and aspirin was resumed primarily for ischemic heart disease. The patient tolerated anti-platelet therapy without recurrence of RSH. The risk factors, treatment options, prognosis and issue related to anticoagulation resumption after an episode of RSH are discussed. Reported cases of RSH associated with direct-acting oral anticoagulants are reviewed.ConclusionsDirect-acting oral anticoagulant-associated rectus sheath hematoma is rare. With increasing use of direct-acting oral anticoagulants in multiple clinical settings, clinicians should remain vigilant of this potentially life-threatening bleeding complication when a patient presents with acute abdominal pain. Conservative treatment with cessation of anti-coagulant and supportive transfusion remains the mainstay of treatment.

Apixaban Prophylactic Anticoagulation in Patients with Nephrotic Syndrome.

Background Nephrotic syndrome (NS) is associated with an increased risk of thromboembolic events (TEs), due to hemostatic derangements. The use of direct oral anticoagulants (DOACs) in the prevention of TE has not been studied intensively in patients suffering from NS. Methods The method included retrospective analysis of consecutive incident patients with NS due to glomerular disease, receiving apixaban for thromboprophylaxis. It is an uncontrolled, single-center study. Results We identified 27 patients treated with apixaban for the prevention of TEs, in the context of NS. During follow-up, apixaban minimal blood concentration (trough level; Cmin) and maximum blood concentration (Cmax) levels were measured. The mean duration of the anticoagulant treatment was 153 days (±132). Patients were followed for a mean of 14.7 months (±8.4) since the introduction of apixaban. Three patients had a TE at the time of NS diagnosis. Two patients had pulmonary embolism (PE) and one patient presented a stroke in a lupus membranous nephropathy context. One patient developed PE approximately 2 months after the introduction of apixaban treatment. No minor or major bleeding events were noticed. Conclusion The present study shows that patients, suffering from severe NS under anticoagulant therapy with apixaban had a reduced risk of venous and arterial TEs compared with patients previously described in the literature, without increased risk of bleeding.

Impact of apixaban treatment discontinuation on the risk of hospitalization among patients with nonvalvular atrial fibrillation and COVID-19

Introduction This study evaluated the risk of hospitalization among nonvalvular atrial fibrillation (NVAF) patients with an outpatient COVID-19 diagnosis who discontinued vs continued apixaban treatment. Methods Adult patients with NVAF with an apixaban prescription prior to an outpatient COVID-19 diagnosis were identified from Optum Clinformatics claims database (1 April 2020–31 March 2021). Continuers were those who continued apixaban as of the index date (date of initial outpatient COVID-19 diagnosis) and discontinuers were those who had the last day of apixaban supply on or before index. Patients were followed from COVID-19 diagnosis to change of continuation/discontinuation status, switch, death, end of continuous coverage or study end, whichever occurred first. Inverse probability treatment weighting (IPTW) was performed to balance cohorts. Cox proportional hazard models were used to compare the risk of all-cause hospitalization and hospitalization for ischemic stroke (IS), venous thromboembolism (VTE), myocardial infarction (MI), bleeding and mortality. Results A total of 7869 apixaban patients with COVID-19 were included: 6676 continuers (84.8%) and 1193 discontinuers (15.2%). Compared with continuers, discontinuers had a higher risk of all-cause hospitalization (hazard ratio [HR]: 1.23; 95% confidence interval [CI]: 1.08–1.40), IS (HR: 2.00; 95% CI: 1.03–3.87), VTE (HR: 2.37; 95% CI: 1.06–5.27) and mortality (HR: 2.28; 95% CI: 1.85–2.80). There were no significant differences in the risk of MI (HR: 1.01; 95% CI: 0.54–1.90) or bleeding-related hospitalization (HR: 1.13; 95% CI: 0.73–1.76). Conclusion NVAF patients with COVID-19 who discontinued apixaban had a higher risk of hospitalization and thrombotic events vs those who continued apixaban, with no significant difference in bleeding-related hospitalization.

Rapid Detection of Apixaban by a ROTEM-Based Approach and Reversibility with Andexanet Alfa or DOAC-Stop.

Background A rapid test to detect apixaban treatment would be useful in acute situations such as major bleeding, urgent surgery, or in acute thrombosis. Objective This article aims to study if the viscoelastic test rotational thromboelastometry (ROTEM) can rapidly detect apixaban in whole blood using modified triggers based on factor Xa (FXa) or Russell viper venom (RVV). Method ROTEM clotting time (CT) was measured in samples from 40 patients on apixaban treatment, and in vitro in samples spiked with apixaban (20–500 ng/mL). Commercially available trigger Ex-tem was compared with modified triggers based on FXa or RVV. Reversibility of apixaban in the samples was studied; CT was measured with and without addition of DOAC-Stop or andexanet alfa, respectively, and the difference in CT was calculated (CT diff ). Results Using FXa as trigger, we detected apixaban concentrations at 20 ng/mL and above with 100% sensitivity and 100% specificity in patient samples and in vitro. Corresponding data for Ex-tem were 92% sensitivity and 100% specificity in patients, and 94% sensitivity and 100% specificity in vitro, and for RVV 97% sensitivity and 94% specificity in patients, and 97% sensitivity and 100% specificity in vitro, respectively. CT diff data were similar. Patient sample data were obtained within 20 minutes from sampling. Conclusion Apixaban at low therapeutic concentrations was detected within 20 minutes, and with high sensitivity and specificity. A trigger based on FXa outperformed the commercial trigger Ex-tem and a trigger based on RVV. ROTEM with a FXa-based trigger is a promising method to detect apixaban bedside in acute settings.

Effectiveness and Safety of Extended Oral Anticoagulant Therapy in Patients with Venous Thromboembolism: A Retrospective Cohort Study.

Limited real-world evidence exists for effectiveness and safety of extended oral anticoagulation beyond 6months of initial treatment in prevention of recurrent venous thromboembolism (VTE) and adverse major bleeding events among patients with VTE. Using MarketScan Commercial and Medicare Supplemental databases (2013-2019), we conducted a retrospective cohort study to compare the risk of recurrent VTE and major bleeding events during extended treatment among patients with VTE who completed the 6-month initial treatment and received extended oral anticoagulant treatment with apixaban, warfarin, or no extended treatment. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards modeling with inverse probability treatment weighting. We identified 14,818 patients with extended treatment of apixaban (n=4,338), warfarin (n=5,298), or no extended treatment (n=5,182). Compared with no extended treatment, apixaban use was associated with decreased risk of recurrent VTE (HR: 0.10, 95% CI: 0.04-0.26) without increased risk of major bleeding events (HR: 1.06, 95% CI: 0.52-2.17); warfarin use was associated with decreased risk of recurrent VTE (HR: 0.23, 95% CI: 0.12-0.44) but with increased risk of major bleeding events (HR: 2.64, 95% CI: 1.51-4.59). Compared with warfarin, apixaban use was associated with decreased risk of major bleeding events (HR: 0.42, 95% CI: 0.22-0.80) but no difference in risk of recurrent VTE (HR: 0.46, 95% CI: 0.15-1.36). In a real-world clinical setting, extended anticoagulation with apixaban or warfarin was associated with decreased risk of recurrent VTE compared with no extended treatment, and apixaban had a better safety profile with fewer major bleeding events compared with warfarin among commercially insured patients with VTE.

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

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. Retrospective cohort study. Patients receiving dialysis represented in the US Renal Data System database 2013-2018 who had AF and were treated with apixaban or warfarin. First prescribed treatment with apixaban dosed according to the label, apixaban dosed below the label, or warfarin. Ischemic stroke/systemic embolism, major bleeding, and all-cause mortality. 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. 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. Study limited to US Medicare beneficiaries; reliance on administrative claims to ascertain outcomes of AF, stroke, and bleeding; likely residual confounding. 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.

Aspects of anticoagulant therapy in venous thromboembolism, pulmonary embolism. Focus on elderly patients

The prevalence and mortality due to venous thromboembolism (VTE) occupies a leading position among the population throughout the world. The incidence and severity of VTE increases the older the patient. The emergence of a new group of direct oral anticoagulants significant changed the management of these groups of patients. The article touches upon the problem of choice, efficacy and safety of oral anticoagulants in elderly and senile patients with VTE, in particular in pulmonary embolism (PE). An analysis of randomized clinical trials and prospective cohort studies is given. In addition, rational recommendations are given on the optimal choice of oral anticoagulant in these categories of patients. Apixaban and rivaroxaban are highly effective drugs of choice with a reliable safety profile in patients of the senile age group in the prevention and treatment of VTE, including PE, and apixaban has the most optimal profile and safety class among all other oral anticoagulants when used in elderly and senile patients.

Přímé náklady na léčbu pacientů s nevalvulární fibrilací síní nově indikovaných k léčbě apixabanem: retrospektivně prospektivní jednoramenná kohortová studie

Atrial fibrillation (AF) affects 46.3 million people; its prevalence has tripled over the last 50 years. AF leads to formation of blood clots increasing four-fold the risk of a stroke. Preventive anticoagulant therapy with warfarin has been well established for over 50 years but has efficacy and safety limitations. New anticoagulants do not require laboratory monitoring of prothrombin time, have low risk of adverse events, yet are more costly.This non-interventional (Act 378/2007 Coll.) retrospective-prospective single-arm cohort study consisted of 3 visits. The primary objective was to compare the total direct cost of treatment with warfarin and apixaban. Patients with non-valvular AF were enrolled at the time of discontinuation of warfarin and switching to apixaban. Costs were derived from the care provided and the list of medical procedures (Decrees 268/ 2019 Coll.). Satisfaction was assessed using SAFUCA® questionnaire.Between February 2017 and June 2019, 499 patients were enrolled in 29 Czech internal medicine clinics. The mean age of the patients was 73.6 ± 10.2 years, 36.5% were at high risk of bleeding (HAS-BLED score). Previous warfarin treatment lasted 5.9 ± 2.7 months, 63% were unable to achieve target prothrombin time, 18% switched due to adverse reactions. New apixaban treatment was followed for the first 6 months. Treatment with warfarin was associated with higher rates of major bleeding and adverse events (22 vs. 2), stroke (17 vs. 0), ischemic heart attack (11 vs. 0), and minor bleeding (173 vs. 2). The average daily cost following the switch to apixaban decreased from CZK 65.2 to CZK 4.8 (p.

Cardiac Calcified Amorphous Tumor Presenting with Thromboembolism in a Patient Under Apixaban Treatment

Cardiac Calcified Amorphous Tumor Presenting with Thromboembolism in a Patient Under Apixaban Treatment

Comparative Safety and Effectiveness of Apixaban vs. Warfarin in Oral Anticoagulant-Naïve Japanese Patients With Non-Valvular Atrial Fibrillation - A Retrospective Chart Review Study.

The risk of bleeding and stroke/systemic embolism (SE) events associated with apixaban vs. warfarin among oral anticoagulant-naïve Japanese patients with non-valvular atrial fibrillation (NVAF) has not been well studied in daily clinical practice.Methods and Results:Clinical data for 12,090 patients were retrospectively extracted from the medical records of patients with NVAF (aged ≥20 years, creatinine clearance [CrCl] ≥15 mL/min) newly initiated to apixaban or warfarin treatment between January 1, 2010, and December 31, 2017, at 315 general practitioner clinics and 87 hospitals across Japan. After applying propensity score matching, patient characteristics were well-balanced between the apixaban and warfarin groups (4,523 patients each). The incidence rate (per 100 person-years) of major bleeding was lower in the apixaban vs. warfarin group (1.17 vs. 1.64; hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.54-0.93; P=0.01), as was that of stroke/SE (1.14 vs. 1.73; HR, 0.65; 95% CI, 0.50-0.85; P<0.01). When patients were stratified by CrCl (≥50 mL/min and <50 mL/min), the P value for interaction was not statistically significant between subgroups (P=0.31 for major bleeding and P=0.32 for stroke/SE). The benefit of apixaban over warfarin for the reduction in risk of major bleeding and stroke/SE could be generalizable to daily clinical practice and to patients with reduced renal function.

Survival Benefit of Anticoagulation Therapy in End Stage Kidney Disease Patients with Atrial Fibrillation: A Single Center Retrospective Study.

Background and Objectives: Although the need for anticoagulation to prevent thromboembolism is increasing and non-vitamin K antagonist oral anticoagulants (NOACs) have been tried, there is still controversy about the efficacy of anticoagulation in patients with dialysis. Materials and Methods: We retrospectively analyzed the risk and benefit of anticoagulation in dialysis patients with atrial fibrillation (AF). We retrospectively analyzed all data of 89 patients who received dialysis therapy and were diagnosed with AF. Among them, 27 received anticoagulation (11 warfarin and 16 apixaban 2.5 mg twice a day), while 62 received no anticoagulation. Results: In multivariate Cox regression analysis, compared to no anticoagulation treatment, anticoagulation treatment was associated with a low incidence of all-cause mortality (hazard ratios (HR) 0.36; 95% confidence interval (CI) 0.15–0.88). Compared to no anticoagulation treatment, more anticoagulation treatment patients experienced severe bleeding (HR 4.67; 95% CI 1.26–17.25) and any bleeding (HR 2.79; 95% CI 1.01–7.74). Compared to no anticoagulation, warfarin treatment patients were associated with a low incidence of all-cause mortality (HR 0.26; 95% CI 0.09–0.81) and a high incidence of severe bleeding (HR 4.85; 95% CI 1.12–21.10). All-cause mortality and bleeding were not significantly different between no anticoagulation and apixaban treatment patients. Conclusions: In dialysis patients with AF, anticoagulation therapy is associated with an increased incidence of severe bleeding, but anticoagulation therapy is associated with a low incidence of all-cause mortality. Individualized anticoagulation therapy with careful bleeding monitoring is needed in dialysis patients with AF.

Association of Rivaroxaban vs Apixaban With Major Ischemic or Hemorrhagic Events in Patients With Atrial Fibrillation

The comparative effectiveness of rivaroxaban and apixaban, the most frequently prescribed oral anticoagulants for ischemic stroke prevention in patients with atrial fibrillation, is uncertain. To compare major ischemic and hemorrhagic outcomes in patients with atrial fibrillation treated with rivaroxaban or apixaban. Retrospective cohort study using computerized enrollment and claims files for US Medicare beneficiaries 65 years or older. Between January 1, 2013, and November 30, 2018, a total of 581 451 patients with atrial fibrillation began rivaroxaban or apixaban treatment and were followed up for 4 years, through November 30, 2018. Rivaroxaban (n = 227 572) and apixaban (n = 353 879), either standard or reduced dose. The primary outcome was a composite of major ischemic (stroke/systemic embolism) and hemorrhagic (intracerebral hemorrhage/other intracranial bleeding/fatal extracranial bleeding) events. Secondary outcomes were nonfatal extracranial bleeding and total mortality (fatal ischemic/hemorrhagic event or other death during follow-up). Rates, hazard ratios (HRs), and rate differences (RDs) were adjusted for baseline differences in comorbidity with inverse probability of treatment weighting. Study patients (mean age, 77.0 years; 291 966 [50.2%] women; 134 393 [23.1%] receiving reduced dose) had 474 605 person-years of follow-up (median [IQR] of 174 [62-397] days). The adjusted primary outcome rate for rivaroxaban was 16.1 per 1000 person-years vs 13.4 per 1000 person-years for apixaban (RD, 2.7 [95% CI, 1.9-3.5]; HR, 1.18 [95% CI, 1.12-1.24]). The rivaroxaban group had increased risk for both major ischemic events (8.6 vs 7.6 per 1000 person-years; RD, 1.1 [95% CI, 0.5-1.7]; HR, 1.12 [95% CI, 1.04-1.20]) and hemorrhagic events (7.5 vs 5.9 per 1000 person-years; RD, 1.6 [95% CI, 1.1-2.1]; HR, 1.26 [95% CI, 1.16-1.36]), including fatal extracranial bleeding (1.4 vs 1.0 per 1000 person-years; RD, 0.4 [95% CI, 0.2-0.7]; HR, 1.41 [95% CI, 1.18-1.70]). Patients receiving rivaroxaban had increased risk of nonfatal extracranial bleeding (39.7 vs 18.5 per 1000 person-years; RD, 21.1 [95% CI, 20.0-22.3]; HR, 2.07 [95% CI, 1.99-2.15]), fatal ischemic/hemorrhagic events (4.5 vs 3.3 per 1000 person-years; RD, 1.2 [95% CI, 0.8-1.6]; HR, 1.34 [95% CI, 1.21-1.48]), and total mortality (44.2 vs 41.0 per 1000 person-years; RD, 3.1 [95% CI, 1.8-4.5]; HR, 1.06 [95% CI, 1.02-1.09]). The risk of the primary outcome was increased for rivaroxaban in both those receiving the reduced dose (27.4 vs 21.0 per 1000 person-years; RD, 6.4 [95% CI, 4.1-8.7]; HR, 1.28 [95% CI, 1.16-1.40]) and the standard dose (13.2 vs 11.4 per 1000 person-years; RD, 1.8 [95% CI, 1.0-2.6]; HR, 1.13 [95% CI, 1.06-1.21]) groups. Among Medicare beneficiaries 65 years or older with atrial fibrillation, treatment with rivaroxaban compared with apixaban was associated with a significantly increased risk of major ischemic or hemorrhagic events.

Cost-effectiveness of anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation in mainland China.

With the high cost, the long-term persistence of new oral anticoagulants (NOACs) was lower than that of warfarin in Chinese patients with non-valvular atrial fibrillation (NVAF) for a long time. The prices of NOACs (apixaban, rivaroxaban and dabigatran) decreased significantly over the past year in mainland China. The objective of this study was to evaluate the cost-effectiveness of NOACs versus warfarin for preventing stroke in patients with NVAF from a Chinese healthcare system perspective. A decision tree and Markov model were used to assess the treatment strategies of four NOACs versus warfarin over a lifetime horizon. For each treatment strategy, the total lifetime cost, quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER) were calculated. The impact of parameter uncertainties on base-case analysis results was evaluated using sensitivity analyses. In the base-case analysis, compared with warfarin, apixaban had a decreased total lifetime cost of USD 389 and rivaroxaban of USD 1482, while low-dose dabigatran had an increased total lifetime cost of USD 925 and high-dose dabigatran of USD 6641, with QALY increasing by 0.53, 1.32, 0.92 and 1.83, respectively. The ICER of low-dose dabigatran versus warfarin was USD 1005 per QALY gain, while those of apixaban (-USD 734 per QALY gain) and rivaroxaban (-USD 1123 per QALY gain) were negative. One-way and probabilistic sensitivity analyses indicated that the base-case results were robust by applying certain varying parameters to the model. These four NOAC (apixaban, rivaroxaban, low-dose dabigatran and high-dose dabigatran) treatment strategies were cost-effective compared with warfarin and recommended as substitutes for warfarin treatment for preventing stroke in patients with NVAF in the healthcare system of China, which might be driven by large drug price reductions in the past year.

Comparative Effectiveness and Safety of Extended Anticoagulant Therapy Among Medicare Beneficiaries with Venous Thromboembolism

▪Introduction: Approximately 30% of patients with venous thromboembolism (VTE) experience a recurrence within 10 years of the initial event with their recurrence risk peaking during the first 6-12 months. Two large randomized clinical trials AMPLIFY-EXT and PADIS-PE reported that extended treatment with apixaban and warfarin beyond 6 months of initial treatment reduced recurrent VTE without increasing the rate of major bleeding compared to placebo, respectively. Little is known about real-world effectiveness and safety of extended oral anticoagulation beyond 6 months of initial treatment for Medicare beneficiaries with VTE, despite the fact that VTE disproportionately affects the elderly. We assessed the effectiveness and safety of extended use of apixaban and warfarin beyond 6 months of initial treatment for prevention of recurrent VTE and adverse major bleeding events among Medicare beneficiaries with newly diagnosed VTE.Methods: A retrospective cohort study using 2014-2018 Medicare data (5% samples in 2014-2016 and 15% samples of Medicare beneficiaries in 2017-2018) was conducted for patients aged ≥18 years with a diagnosis of deep vein thrombosis or pulmonary embolism ascertained from inpatient claims. Patients were included if they initiated anticoagulants within 30 days of their first VTE diagnosis, completed 6 months of therapy defined as ≥83% proportion days covered with oral anticoagulants during the initial 6-month period, and received extended treatment with either apixaban or warfarin or no extended therapy. We compared the risks of recurrent VTE and major bleeding between apixaban, warfarin, and no treatment groups. To adjust for differences in baseline characteristics and clinical factors (e.g., HAS-BLED score, active cancer, and provoked VTE) between groups, we used the stabilized inverse probability treatment weighting (IPTW) method. Follow-up continued until the occurrence of the first event, switch to the comparator, disenrollment, death, or end of the study period. Multivariable Cox proportional hazards modeling with IPTW was used to obtain adjusted hazard ratios (aHR) and 95% confidence intervals (95%CI).Results: The study cohort (mean age=74 ±12 years, 40% male, 76% White) consisted of 2,315 users of extended apixaban treatment (83% with 5 mg twice a day and 17% with 2.5 mg twice a day; mean duration=6.2 months), 2,757 users of extended warfarin treatment (mean duration=8.2 months), and 2,328 patients with no extended treatment following completion of an initial 6 months of anticoagulant treatment. The incidence rates of recurrent VTE were 0.42, 1.73, and 1.72 per 100 person-years, and those of major bleeding were 2.28, 3.62, and 1.43 per 100 person-years in the apixaban, warfarin, and no treatment groups, respectively (Table 1). Compared to no extended treatment, the use of apixaban was associated with an 80% decreased risk of recurrent VTE (aHR=0.19, 95%CI=0.06-0.55) without increasing the risk of major bleeding (aHR=1.19, 95%CI=0.65-2.19); the use of warfarin did not lower the risk of recurrent VTE (aHR=0.75, 95%CI=0.42-1.37) but increased the risk of major bleeding (aHR=1.92, 95%CI=1.13-3.25). Compared to the use of warfarin, the use of apixaban was associated with a decreased risk of recurrent VTE (aHR=0.26, 95% CI=0.09-0.76) and no difference in major bleeding risk (aHR=0.61, 95%CI=0.36-1.06). These findings remained consistent in subgroup (e.g., patients with provoked vs. unprovoked VTE, patients with active cancer vs. those without, and patients with chronic kidney diseases vs. those without) and sensitivity analyses (e.g., ≥92% proportion days covered with oral anticoagulants during the initial 6-month period).Conclusions: Compared to no extended therapy, extended anticoagulation with apixaban was associated with a reduced risk of recurrent VTE without increasing the risk of major bleeding, whereas warfarin did not lower risk of recurrent VTE but increased the risk of major bleeding among Medicare beneficiaries with VTE. In the head-to-head comparison, the use of apixaban was more effective than warfarin in preventing recurrent VTE, without increasing the risk of major bleeding events. Our findings suggest that apixaban is an effective and safer option for extended treatment of VTE when compared to warfarin or no treatment among Medicare beneficiaries with VTE. [Display omitted] DisclosuresPark: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Kang: BMS/Pfizer Alliance American Thrombosis InvestigatorInitiated Research Program: Research Funding. Huang: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Lo-Ciganic: MERCK: Research Funding; BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Dietrich: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Murphy: North American Thrombosis Foundation: Honoraria. DeRemer: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding; Portola Pharmaceuticals: Current equity holder in publicly-traded company; BMS advisory board attendee: Honoraria.

Apixaban vs. Warfarin in Atrial Fibrillation Patients With Chronic Kidney Disease.

Background and Objectives: Real-world evidence of apixaban treatment in patients with chronic kidney disease remains scarce. This study aimed to compare the relative risk of stroke or systemic embolism (SE) and major bleeding between apixaban and warfarin in atrial fibrillation (AF) patients with different degrees of kidney function.Design, Setting, Participants, and Measurements: We evaluated newly diagnosed AF patients between 2004 and 2018, who were receiving apixaban or warfarin. Electronic medical record data were collected from a large healthcare delivery network in Taiwan. The outcomes of hospitalization for stroke/SE and major bleeding were compared with propensity-score matched apixaban and warfarin cohorts. Stratified analyses according to initial apixaban dose (standard dose of 10 mg/day vs. lower dose of 2.5–5.0 mg/day) and baseline estimated glomerular filtration rate were performed.Results: Each cohort involved 1,625 matched patients. Apixaban was significantly associated with a lower risk of stroke/SE (adjusted hazard ratio [aHR]: 0.74; 95% confidence interval [CI]:0.57–0.97; p = 0.03). The risk of major bleeding was not increased whether in standard doses (aHR: 0.66; 95% CI: 0.45–0.96; p = 0.03) or reduced doses (aHR, 0.84; 95% CI, 0.63–1.12; p = 0.23) of apixaban. Regarding kidney function, apixaban reduced the risk of stroke/SE by 37% in those with an eGFR of <30 ml/min/1.73 m2 (aHR: 0.63; 95% CI: 0.40–0.98; p = 0.04).Conclusions: Compared to warfarin, apixaban is associated with a reduced risk of stroke/SE and is consistent with a subset of AF patients with eGFR <30 ml/min/1.73 m2. Both standard and reduced doses of apixaban showed lower risk of major bleeding than those of warfarin.