Impact of adherence on the cost-effectiveness of apixaban and rivaroxaban in stroke prevention among patients with atrial fibrillation in the United States.

OBJECTIVE: Despite the beneficial effects of DOACs, suboptimal adherence is widely documented, and real-world adherence is lower than in clinical trials. The objective of this study is to compare the cost-effectiveness of apixaban versus rivaroxaban for stroke prevention by incorporating real-world adherence from the US payer's perspective. METHODS: We developed a Markov model with three health states to evaluate the total costs and quality-adjusted life years (QALY) at a willingness to pay threshold of $100,000. The population was a hypothetical cohort of 65-year-old patients with moderate to high stroke risk. The transition probabilities of healthy adherent, nonadherent, and stroke were obtained from a Medicare Advantage Plan. The utilities and costs were obtained from prior clinical studies. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Apixaban was cost-effective than rivaroxaban at a willingness to pay threshold of $100,000. Apixaban yielded an additional 0.12 QALYs at a cost of $1904.39, resulting in an incremental cost-effectiveness ratio (ICER) of $16,279.25 per QALY gained. The Monte Carlo simulations indicated that apixaban was cost-effective at 89.67% of simulations. The ICER results were impacted by the medical costs among nonadherent patients. CONCLUSION: After incorporating adherence, apixaban 5 mg was a cost-effective alternative to rivaroxaban 20 mg for stroke prevention among elderly atrial fibrillation (AF) patients.

Due to the improved safety and efficacy profile, DOACs are preferred over warfarin for stroke prevention in AF patients. Suboptimal adherence to DOACs is commonly reported in real-world settings, leading to poorer patient outcomes. Prior pharmacoeconomic analyses have not incorporated real-world adherence data. The findings suggest that apixaban 5 mg is a cost-effective alternative to rivaroxaban 20 mg for stroke prevention. Apixaban was identified as the cost-effective option compared with rivaroxaban for stroke prevention among elderly AF patients after incorporating adherence data in the cost-effectiveness analysis. Healthcare decision-makers can utilize the findings of this study to inform formulary decisions and treatment guidelines.

Real-World Use and Outcomes of Apixaban for Early Post-Surgical Fontan Thromboprophylaxis.

Patients with Fontan physiology are at heightened risk of thrombosis related to passive venous return leading to increased stasis, as well as acquired thrombophilia from congestive hepatopathy. Variability exists for post-Fontan thromboprophylaxis, with no consensus on best practices. Direct oral anticoagulants offer advantages over conventional anticoagulants including fewer drug-drug interactions, no dietary restrictions, and less frequent monitoring. Herein, we report our single center experience utilizing apixaban thromboprophylaxis in children post-Fontan procedure. Single center, retrospective, cohort study evaluating apixaban thromboprophylaxis dosing strategies, efficacy, and safety in children admitted post-Fontan procedure at Boston Children's Hospital. Between September 2019 and December 2023, 62 children, median age 3.2 years (2.1-10.5 years), weight 13.9 kg (9.5-56.3 kg) received apixaban at a median of 93 days post-Fontan (7-1421 days). Over a total of 93 days of apixaban exposure, there was 1 treatment-related thrombosis event (0.07 per 1000 person-days on apixaban) and 3 combined treatment-related clinically relevant non-major (CRNM) and major bleeding events (0.22 per 1000 person-days on apixaban). Apixaban for post-Fontan thromboprophylaxis was feasible with low rates of bleeding and thrombosis.

Assays for Monitoring Apixaban and Rivaroxaban in Emergency Settings, State-of-the-Art Routine Analysis, and Volumetric Absorptive Microsamples Deliver Discordant Results.

Our aim was to compare the performance of complementary clinical laboratory approaches to monitoring exposure to apixaban and rivaroxaban, the most prescribed direct-acting oral anticoagulants (DOAC's): an automated commercial anti-Xa chromogenic assay suitable for emergency and pre-surgery testing and a laboratory-developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) method employed for non-emergency analysis in plasma and in dried blood volumetric absorptive microsamples (VAMS) collectible by the patients in their homes. The full validation of the LC-MS/MS method was performed. Cross-validation of the methodologies was accomplished by processing 60 specimens collected for whole blood count and DOAC monitoring in a central clinical laboratory. For VAMS samples, dried plasma and whole blood calibrators were found to be suitable, and a cycle run for seven days could be implemented for rational and economic sample processing. The anti-Xa chromogrenic assay and the LC-MS/MS method delivered discordant plasma analyte concentrations. Moreover, the lack of agreement between plasma and VAMS concentrations was observed. Clinical laboratories must be aware of the differences between the performance of apixaban and rivaroxaban LC-MS/MS and anti-Xa assays. Hematocrit must always be measured along with VAMS samples to obtain accurate results.

Evaluation of Apixaban Use in Patients With Advanced Kidney Disease.

Background: Current guidelines and literature suggest apixaban may be used in patients with severe kidney disease and atrial fibrillation (AF) for stroke and systemic embolism risk reduction (SSE) or patients with acute venous thromboembolism (VTE). Limited data is available for long-term safety and efficacy outcomes in this patient population. Objective: Evaluate the use of apixaban for AF or VTE in patients with advanced kidney disease. Methods: This single-center, retrospective, Investigational Review Board approved study evaluated patients ≥18 years of age with severe kidney disease on apixaban therapy for VTE or AF from March 1, 2018, to December 31, 2020. The primary outcome was major bleeding from apixaban initiation/continuation until 12 months after discharge. The secondary outcomes included a composite bleed (major bleeding, clinically relevant non-major bleeding, and minor bleeding), the occurrence of VTE or SSE, and death during hospitalization from any cause other than bleeding. Results: Overall, 156 patients met inclusion criteria. Six patients experienced major bleeding (3.8%). Composite bleeding occurred in 16 patients (10.3%); no patients had SSE or VTE, and 4 patients died from causes other than bleeding (2.6%). Limitations included the small sample size and retrospective nature of the study. Conclusion: This study demonstrated that patients with advanced chronic kidney disease on apixaban for AF or VTE had low major bleeding and similar overall bleeding rates compared with previously published literature. When considering the use of apixaban in this population, risks and benefits should be weighed in addition to the consideration of FDA-label dosing guidance.

Risk of ocular neovascular conversion and systemic bleeding complications in patients with AMD on DOACs or Warfarin.

PURPOSE: Conversion to neovascular disease in patients with non-neovascular age-related macular degeneration (AMD) initiated on direct oral anticoagulants (DOAC) compared to matched patients treated with warfarin. DESIGN: Retrospective cohort study. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: The study included 20,300 patients and 13,387 patients with non-neovascular AMD initiated on DOACs or warfarin, respectively, before propensity score matching (PSM). METHODS, INTERVENTION, OR TESTING: TriNetX (Cambridge, MA, USA), was used to identify patients diagnosed with non-neovascular AMD stratified by treatment with DOACs or warfarin with at least six months of follow-up. Propensity score matching was performed to control for baseline demographics and medical comorbidities. MAIN OUTCOME MEASURES: Relative risk (RR) of developing neovascular AMD, macular hemorrhage (MH), vitreous hemorrhage (VH), and requiring an ocular intervention (intravitreal anti-vascular endothelial growth factor (VEGF) therapy or pars plana vitrectomy (PPV)) within six months and one year. Patients with chronic atrial fibrillation (AF) on anticoagulation were separately evaluated for the same measures within 5 years after initiating therapy. RESULTS: Treatment with warfarin was associated with higher risk of developing neovascular AMD at six months (RR,1.24, 95% CI, 1.12 - 1.39; P<.001) and one year (RR, 1.26, 95% CI, 1.14 - 1.40; P<.001) when compared to matched patients treated with DOACs. There was an increased risk of requiring intravitreal anti-VEGF therapy (6 months: RR, 1.30; 95% CI, 1.13-1.49; P<.001; 1 year: RR, 1.31, 95% CI, 0.72 - 2.05; P<.001) and PPV (6 months: RR, 1.16; 95% CI, 1.16-3.94; P = .01; 1 year: RR, 2.29, 95% CI, 1.30 - 4.05; P=.003). Among patients with AMD and AF treated with warfarin, there was an increased risk of ocular complications (neovascular AMD: RR, 1.25; 95% CI, 1.14-1.38; P<.001; MH: RR, 1.86; 95% CI, 1.47-2.35; P<.001; VH: RR, 2.22; 95% CI, 1.51-3.26; P<.001) and need for intravitreal anti-VEGF therapy (RR, 1.34; 95% CI, 1.18-1.52; P<.001) over an extended 5-year period. There was no significant difference in the development of major systemic hemorrhagic events between the two cohorts over five years. CONCLUSIONS: Patients with non-neovascular AMD treated with warfarin were more likely to develop neovascular disease and require ocular intervention for hemorrhagic complications when compared to matched patients initiated on DOACs.

Apixaban versus low molecular weight heparin in patients with cancer-associated venous thromboembolism: a systematic review and meta-analysis.

Background: The optimal treatment regimen for patients with cancer-associated venous thromboembolism (CA-VTE) remains unclear. Therefore, the authors sought to compare the outcomes of (VKAs) versus direct apixaban and low molecular weight heparin (LMWH) in patients with CA-VTE. Methods: MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials (RCTs) and observational studies comparing the efficacy and safety of apixaban and LMWH in patients with CA-VTE. Major bleeding, clinically relevant non-major bleeding (CRNMB), recurrence of pulmonary embolism (PE), deep venous thrombosis (DVT) and bleeding-related mortality were among outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95% CIs. Results: The analysis included 12 011 patients from 3 RCTs and 2 observational studies. Compared to LMWH, apixaban significantly decreased the risk of major bleeding [RR 0.67 (95% CI 0.54, 0.83); P=0.0003, I2=0%] without significantly changing the risk of clinically relevant non-major bleeding [RR 0.96 (95% CI 0.64, 0.1.45); P=0.85, I2=57%]. Patients on apixaban had a noticeably reduced the risk of recurrence of PE than those taking LMWH, according to a meta-analysis [RR 0.56 (95% CI 0.32, 0.99); P=0.05, I2=0%]. There was no discernible difference between apixaban and LMWH in bleeding-related mortality events [RR 0.20 (95% CI 0.01, 4.18); P=0.30, I2=NA%], and recurrence of DVT [RR 0.60 (95% CI 0.22, 1.59); P=0.23, I2=32%]. Conclusion: Due to its lower risk of severe bleeding and reduced PE recurrence, apixaban may be a preferable treatment option for CA-VTE, but additional research is required to validate these conclusions and evaluate its long-term efficacy and safety.

Dried plasma spot as an innovative approach to therapeutic drug monitoring of apixaban: Development and validation of a novel liquid chromatography-tandem mass spectrometry method.

Apixaban, a direct oral anticoagulant drug (DOAC), typically does not require routine therapeutic drug monitoring (TDM), yet recent guidelines propose its use in specific clinical scenarios. While various antifactor Xa (anti-FXa) chromogenic assays serve as useful proxies for measuring plasma exposure to apixaban in emergencies, they lack specificity compared with chromatographic methods. This research project is intended to the development and validation of a standardized protocol of liquid chromatography-tandem mass spectrometry (LC-MS/MS) in conformity with the ICH guidelines M10 for the measurement of apixaban in both plasma and dried plasma spots (DPSs). Samples preparation included protein precipitation after the addition of a deuterated internal standard (IS), and the chromatographic separation was carried out on a Thermo Scientific™ Accucore™ Polar Premium column (50 mm × 2.1 mm, i.d. 2.6 m). The newly developed LC-MS/MS method for apixaban mesurement from both plasma and DPS resulted linear over a wide concentration range (31.25-500 ng/mL), accurate, and reproducible without matrix effects, allowing for specific and rapid quantification. Stability was assessed on quality controls and a real sample, allowing the setting up of a robust TDM protocol that was applied to five anonymized plasma samples obtained from adult patients undergoing apixaban treatment at steady-state. In conclusion our novel LC-MS/MS method is adequate for accurate apixaban quantitation from both plasma and DPS matrixes, and may thus facilitate the guidelines suggested implementation of apixaban TDM, even in peripheral hospitals through shipment of DPS at reference laboratories.

Comparison of perioperative bleeding risk between direct oral anticoagulants in transurethral resection of prostate.

OBJECTIVES: To evaluate the perioperative morbidity and mortality associated with direct oral anticoagulants (DOACs) and warfarin for patients receiving transurethral resection of prostate (TURP). PATIENTS AND METHODS: This was a single-centre, retrospective cohort analysis of patients who underwent TURP for benign prostate hyperplasia from April 2019 to December 2023. The primary objective was to evaluate the perioperative bleeding and thromboembolic risk between anticoagulated (AC) vs no-AC patients. The secondary objective was to evaluate perioperative bleeding and thromboembolic risk between different formulations of DOACs. Patient demographics, prior treatment, prostate size, baseline bleeding risk, and operative details were collected. Bleeding and thromboembolic-related morbidity were captured within a 3-month postoperative period. Perioperative management of AC therapy was recorded, and all patients had their AC therapy withheld. Cohort characteristic between the AC vs no-AC, and DOAC groups were analysed with two-sided t-test, and chi-square test. Further logistic regression analyses were carried out to identified significant variables between the groups. These significant variables were used for adjustment in inverse probability-weighted treatment effect analysis to evaluate bleeding risk. RESULTS: There were 629 patients in the cohort, and 113 (18%) patients were receiving AC therapy. The AC patients were at 1.6 times statistically significant increased risk of acute bleeding, and 11 times increased risk of prolonged haematuria for >14 days. When compared to apixaban, patients on rivaroxaban conferred a statistically significant increased risk of acute bleeding by 2.21 times. Patients receiving AC therapy had a statistically significant increased risk of stroke in the perioperative setting (no-AC vs AC: 0.4% vs 2.7%, P = 0.01). CONCLUSION: This is the first study to evaluate risk of bleeding for TURP patients receiving DOACs. The AC patients are more likely to experience haematuria and stroke in the perioperative period despite withholding therapy. Apixaban appears to cause less bleeding-related complications than rivaroxaban.

A Unique Case of Unprovoked Pulmonary Venous Thrombosis in a Postpartum Female Following COVID-19 Infection.

SARS-CoV-2 can induce a hypercoagulable state, occasionally resulting in pulmonary venous thrombosis (PVT) due to inflammation and endothelial injury. Documented cases of PVT with active COVID-19 and post-COVID are rare. We report a 40-year-old postpartum female with unprovoked PVT following a recent nonhospitalized COVID-19 infection. She presented with cough, right pleuritic chest pain, and worsening dyspnea. Imaging confirmed right lower lobe PVT with ground glass infiltrates. Despite a negative hypercoagulable workup, the patient's postpartum and post-COVID status suggest an unprovoked PVT. Treated with a high-intensity heparin drip and transition to apixaban, she showed resolution of the thrombus. This case underscores the importance of considering COVID-19 as a potential risk factor for venous thromboembolism and highlights the need for vigilant monitoring in post-COVID-19 patients.

Assessing Direct Oral Anticoagulants in the Clinical Laboratory.

Direct oral anticoagulants (DOACs) have significant advantages over vitamin K antagonists including lack of need for routine laboratory monitoring. However, assessment of DOAC effect and concentration may be important to guide clinical management including need for DOAC reversal, particularly in acute or emergent situations. In this manuscript, the authors describe tests to screen for DOAC presence and tests that have demonstrated equivalence to gold standard testing for quantifying DOAC exposure. They also discuss the effect of DOACs on other coagulation assays and strategies for monitoring unfractionated heparin in patients with concomitant DOAC exposure.

Apixaban vs rivaroxaban in patients with atrial fibrillation at high or low bleeding risk: A population-based cohort study.

BACKGROUND: Despite many atrial fibrillation (AF) patients being at risk of bleeding, very limited data are available on bleeding rates of different direct oral anticoagulants based on the spectrum of bleeding risk. OBJECTIVE: We aimed to compare the risk of major bleeding and thromboembolic events with apixaban vs rivaroxaban for AF patients stratified by bleeding risk. METHODS: We conducted a population-based, retrospective cohort study of all adult patients (66 years or older) with AF in Ontario, Canada, who were treated with apixaban or rivaroxaban between April 1, 2011, and March 31, 2020. Bleeding risk was estimated by the HAS-BLED score, with high bleeding risk defined as a score of ≥3. The primary safety outcome was major bleeding, and the primary efficacy outcome was thromboembolic events. Comparisons were adjusted for baseline comorbidities by inverse probability of treatment weighting. RESULTS: This study included 18,156 AF patients with high bleeding risk and 55,186 AF patients with low bleeding risk. Apixaban use was more common in patients with high bleeding risk; 63% of high-risk patients used apixaban compared with 56% of low-risk patients. Apixaban users had lower rates of major bleeding in high-risk patients (2.9% vs 4.2% per year; hazard ratio [HR], 0.69; 95% CI, 0.58-0.81) and in low-risk patients (1.8% vs 2.9% per year; HR, 0.63; 95% CI, 0.56-0.70) compared with rivaroxaban. There were no differences in rates of thromboembolic events, 3.1% vs 3.0% per year (HR, 1.02; 95% CI, 0.86-1.22) in high-risk patients and 1.9% vs 1.9% per year (HR, 1.00; 95% CI, 0.89-1.14) in low-risk patients. CONCLUSION: In older AF patients with high or low bleeding risk, treatment with apixaban was associated with lower rates of major bleeding with no difference in risk for thromboembolic events compared with rivaroxaban.

Formulation Optimization and Characterization of Solid Lipid Nanoparticles of Apixaban.

BACKGROUND: Unpredictable situations such as clotting of blood, deep vein thrombosis, and pulmonary embolism arise in the body, which is the leading cause of mortality. Such conditions generally arise after surgery as well as after treatment with oral anticoagulant agents. Apixaban is a novel oral anticoagulant widely recommended for the prevention and treatment of strokes and blood clots suffering from nonvalvular atrial fibrillation by suppressing factor Xa. Apixaban has a log P of 2.71 with poor solubility and reported maximum bioavailability of approximately 50%. OBJECTIVE: Hence, the current research mainly focused on the improvement of solubility, bioavailability, and therapeutic efficacy of Apixaban via solid lipid nanoparticles (SLN). METHODS: The SLN was developed using the hot-homogenization method using a high-pressure homogenizer. The drug-lipid compatibility study was assessed by the FTIR, and the thermal analysis was performed using differential scanning calorimetry (DSC). During the scrutiny of lipids, the highest solubility of Apixaban was estimated in the glyceryl monostearate, hence selected for the formulation. Moreover, the colloidal solution was stabilized by the polyethylene glycol 200. The Design of Expert software (Version 13, Stat-Ease) was implemented for the optimization analysis by considering the 3-independent factors and 2-dependent parameters. The Patents on the SLN are Indian 202321053691, U.S. Patent, 10,973,798B2, U.S. Patent, U.S. Patent 2021/0069121A1, U.S. Patent 2022/0151945A1. RESULTS: Box-Behnken design was applied along with ANOVA, which showed a p-value less than 0.05 for the dependent parameters such as particle size and entrapment efficiency (p-value: 0.0476 and 0.0379). The optimized batch F10 showed a particle size of 167.1 nm, -19.5 mV zeta potential, and an entrapment efficiency of 87.32%. The optimized batch F10 was lyophilized and analyzed by Scanning electron microscopy (SEM), which showed a particle size of 130 nm. The solid powder was filled into the capsule for oral delivery. CONCLUSION: The marked improvement in solubility and bioavailability was achieved with F10- loaded Apixaban via Solid lipid nanoparticles. Moreover, the sustained released profile also minimizes the unseen complications that occur due to the clotting of blood.

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).

Preparation of an anticoagulant polyethersulfone membrane by immobilizing FXa inhibitors with a polydopamine coating.

Anticoagulation treatment for patients with high bleeding risk during hemodialysis is challenging. Contact between the dialysis membrane and the blood leads to protein adsorption and activation of the coagulation cascade reaction. Activated coagulation Factor X (FXa) plays a central role in thrombogenesis, but anticoagulant modification of the dialysis membrane is rarely targeted at FXa. In this study, we constructed an anticoagulant membrane using the polydopamine coating method to graft FXa inhibitors (apixaban and rivaroxaban) on the membrane surface. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and atomic force microscopy (AFM) were used to characterize the membranes. The apixaban- and rivaroxaban-modified membranes showed lower water contact angles, decreased albumin protein adsorption, and suppressed platelet adhesion and activation compared to the unmodified PES membranes. Moreover, the modified membranes prolonged the blood clotting times in both the intrinsic and extrinsic coagulation pathways and inhibited FXa generation and complement activation, which suggested that the modified membrane enhanced biocompatibility and antithrombotic properties through the inhibition of FXa. Targeting FXa to design antithrombotic HD membranes or other blood contact materials might have great application potential.

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, of which 50% were female, on apixaban (75%) or rivaroxaban (25%) with median XaI level of 128 ng/mL (range, 77-497 ng/mL). The median duration of surgery was 2 hours 42 minutes (range, 15 minutes to 8 hours 17 minutes). 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 of 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 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.

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.

Clinical Implications of Co-administering Apixaban with Key Interacting Medications.

With many available data sources, clinicians need to consider the benefit-risk profile of individual anticoagulants when balancing the need for anticoagulation, including evaluating the risks in patients with comorbidities and potential drug-drug interactions. This narrative review presents clinical data across multiple phases of drug development for the use of apixaban, a selective factor Xa inhibitor, when taken concomitantly with other agents, and evaluates the benefit-risk profile of apixaban with these interacting medications. Key subgroup analyses from the phase 3 ARISTOTLE trial (NCT00412984) are presented using data from patients who received either concomitant inhibitors or inducers of cytochrome P450 3A4 and/or P­glycoprotein. We also review the available evidence for the use of apixaban in patients with cancer-associated thromboembolism, as well as the use of apixaban in patients with COVID-19.

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.

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.