Use Of Apixaban Research Articles

Risk for Bleeding-Related Hospitalizations During Use of Amiodarone With Apixaban or Rivaroxaban in Patients With Atrial Fibrillation : A Retrospective Cohort Study.

Amiodarone, the most effective antiarrhythmic drug in atrial fibrillation, inhibits apixaban and rivaroxaban elimination, thus possibly increasing anticoagulant-related risk for bleeding. For patients receiving apixaban or rivaroxaban, to compare risk for bleeding-related hospitalizations during treatment with amiodarone versus flecainide or sotalol, antiarrhythmic drugs that do not inhibit these anticoagulants' elimination. Retrospective cohort study. U.S. Medicare beneficiaries aged 65 years or older. Patients with atrial fibrillation began anticoagulant use between 1 January 2012 and 30 November 2018 and subsequently initiated treatment with study antiarrhythmic drugs. Time to event for bleeding-related hospitalizations (primary outcome) and ischemic stroke, systemic embolism, and death with or without recent (past 30 days) evidence of bleeding (secondary outcomes), adjusted with propensity score overlap weighting. There were 91590 patients (mean age, 76.3 years; 52.5% female) initiating use of study anticoagulants and antiarrhythmic drugs, 54977 with amiodarone and 36613 with flecainide or sotalol. Risk for bleeding-related hospitalizations increased with amiodarone use (rate difference [RD], 17.5 events [95% CI, 12.0 to 23.0 events] per 1000 person-years; hazard ratio [HR], 1.44 [CI, 1.27 to 1.63]). Incidence of ischemic stroke or systemic embolism did not increase (RD, -2.1 events [CI, -4.7 to 0.4 events] per 1000 person-years; HR, 0.80 [CI, 0.62 to 1.03]). The risk for death with recent evidence of bleeding (RD, 9.1 events [CI, 5.8 to 12.3 events] per 1000 person-years; HR, 1.66 [CI, 1.35 to 2.03]) was greater than that for other deaths (RD, 5.6 events [CI, 0.5 to 10.6 events] per 1000 person-years; HR, 1.15 [CI, 1.00 to 1.31]) (HR comparison: P= 0.003). The increased incidence of bleeding-related hospitalizations for rivaroxaban (RD, 28.0 events [CI, 18.4 to 37.6 events] per 1000 person-years) was greater than that for apixaban (RD, 9.1 events [CI, 2.8 to 15.3 events] per 1000 person-years) (P= 0.001). Possible residual confounding. In this retrospective cohort study, patients aged 65 years or older with atrial fibrillation treated with amiodarone during apixaban or rivaroxaban use had greater risk for bleeding-related hospitalizations than those treated with flecainide or sotalol. National Heart, Lung, and Blood Institute.

Experience in the treatment of patients with pulmonary embolism using apixaban and ultrasound inhalations of unfractionated heparin

Introduction. Pulmonary embolism (PE) is one of the leading causes of death even in hospitalized patients. The standard treatment results are disappointing. Since 2004, we have tested a new method for the treatment of hemodynamically insignificant PE (own patent RU2224525C1) by using unfractionated heparin (UFH) in ultrasound inhalations with a nebulizer, since 2014 – in combination with apixaban. Aim. To improve the treatment of PE. Materials and methods. The hospital mortality rate of 713 patients of the cardiac intensive care unit with hemodynamically insignificant PE (from January 1, 2002 to December 31, 2017) was studied. Since 2004, patients have received ultrasound UFH (5000 units twice a day). Since 2014, nebulased UFH has been supplemented with the use of apixaban (10 mg twice a day for 7 days and 5 mg twice a day thereafter). Results and discussion. There is a distinct tendency to the PE hospital mortality decrease, coinciding with the nebulased UFH use (illustrated by a diagram). Neither the systemic bleeding nor the heparin-induced thrombocytopenia were observed. Clinical cases show first reduction of perfusion disorders are seeing scintigraphicaly in 7 days. Unlike LMWH UFH is recommended in severe kidney damage and obesity, thus ultrasound technique has advantages in such patients. Conclusions. Nebulased UFH is an available, simple, safe and effective in treatmtnt of hemodynamically insignificant PE, especially with the use of apixaban. A real improvement in lung perfusion takes 1 week, as shown scintigraphically.

502 The effects of removing the requirement for prior reimbursement approval on anticoagulant use in Ireland: A cross sectional study

Abstract Introduction Prior approval for reimbursement is a cost containment policy, aimed at reducing demand (1). It has been used temporarily in the Irish Healthcare system to deal with the initial financial challenges posed by the shift in use towards the Direct Oral Anticoagulants (DOACs) (apixaban, rivaroxaban, edoxaban and dabigatran) from warfarin. Improved safety of DOACs use was a secondary aim of this policy. The use of prior approval policies is increasing in Ireland but studies assessing their effectiveness are limited. Aim To examine the effect of removing the cost containment policy of prior approval for reimbursement of apixaban and rivaroxaban using a national pharmacy claims database. Methods The Health Service Executive-Primary Care Reimbursement Service database in Ireland was used in this cross-sectional study. The prescribing frequencies and associated costs of the oral anticoagulants; ((OACs) apixaban, rivaroxaban, and warfarin) listed in the top 100 most frequently prescribed drugs on the Community Drug Schemes (CDS), between 2018 and 2021 were examined. Levothyroxine was used as a negative control to detect any external deviances in the prescribing data records. Interrupted time series Poisson regression was used to assess the impact of removing the approval requirement of apixaban in September 2019 followed by the other DOACs in November 2020. Results The prescribing frequency of OACs increased by almost 20% during the study period. Figure1 shows the prescribing frequencies of apixaban , rivaroxaban , warfarin and levothyroxine on each of the three community drug schemes – General medical scheme (GMS), Drug payments scheme (DPS) and Long term illness scheme (LTI) during the study period.Timelines at September 2019 and November 2020 show the removal of prior approval for apixaban and all DOACs respectively. This study showed there were significant differences in the proportion of OACs prescribed among the CDS. A statistically significant decreased use of apixaban (<1%, p<0.05) occurred when prior approval was removed for all DOACs. Conclusion The removal of prior approval for reimbursement of DOACs in Ireland had a minimal impact on the prescribing frequency trends of the OACs. Future use of these potentially useful policies by healthcare systems requires careful consideration of drug type, approval criteria and length of time the policy remains in place.

The effect of frailty in older community-dwelling outpatients with atrial fibrillation: a new score HAS-BLED-F (rail).

This study aims to determine the effect of frailty on thromboembolic events (TEE) and bleeding in older patients with non-valvular atrial fibrillation (AF). Patients aged ≥65 years who were diagnosed as having non-valvular AF in a geriatric outpatient clinic between June 2015 and February 2021 were included in the study. Frailty, the risk of thrombosis secondary to AF, and the risk of bleeding as a complication of AF treatment were evaluated using the FRAIL scale, and CHA2DS2-VASc and HAS-BLED scores, respectively. Out of 83 patients included in the study, 72.3% were frail and 21.7% were pre-frail. TEE was observed in 14.5% (n=12) and bleeding was observed in 25.3% (n=21) of the patients. A total of 21 (25.3%) patients had a history of bleeding. There was no difference between the normal, pre-frail, and frail groups in terms of TEE and bleeding history (p=0.112 and p=0.571, respectively). In multivariate analysis, mortality decreased with the use of apixaban; frailty and malnutrition were found to increase mortality (p=0.014, p=0.023, and p=0.020, respectively). HAS-BLED-F score was obtained as a result of the sum of the patients' HAS-BLED and FRAIL scores to predict the bleeding risk. A HAS-BLED-F score of ≥6 predicted the risk of bleeding with 90.5% sensitivity and 40.3% specificity. Frailty is not associated with a statistically significant increase in the risk of thromboembolic events or bleeding in patients with non-valvular AF. HAS-BLED-F score can be used to better predict the risk of bleeding in frail patients.

Comparative Effectiveness and Safety of Oral Anticoagulants by Dementia Status in Older Patients With Atrial Fibrillation

The development of an optimal stroke prevention strategy, including the use of oral anticoagulant (OAC) therapy, is particularly important for patients with atrial fibrillation (AF) who are living with dementia, a condition that increases the risk of adverse outcomes. However, data on the role of dementia in the safety and effectiveness of OACs are limited. To assess the comparative safety and effectiveness of specific OACs by dementia status among older patients with AF. This retrospective comparative effectiveness study used 1:1 propensity score matching among 1 160 462 patients 65 years or older with AF. Data were obtained from the Optum Clinformatics Data Mart (January 1, 2013, to June 30, 2021), IBM MarketScan Research Database (January 1, 2013, to December 31, 2020), and Medicare claims databases maintained by the Centers for Medicare & Medicaid Services (inpatient, outpatient, and pharmacy; January 1, 2013, to December 31, 2017). Data analysis was performed from September 1, 2021, to May 24, 2022. Apixaban, dabigatran, rivaroxaban, or warfarin. Composite end point of ischemic stroke or major bleeding events over the 6-month period after OAC initiation, pooled across databases using random-effects meta-analyses. Among 1 160 462 patients with AF, the mean (SD) age was 77.4 (7.2) years; 50.2% were male, 80.5% were White, and 7.9% had dementia. Three comparative new-user cohorts were established: warfarin vs apixaban (501 990 patients; mean [SD] age, 78.1 [7.4] years; 50.2% female), dabigatran vs apixaban (126 718 patients; mean [SD] age, 76.5 [7.1] years; 52.0% male), and rivaroxaban vs apixaban (531 754 patients; mean [SD] age, 76.9 [7.2] years; 50.2% male). Among patients with dementia, compared with apixaban users, a higher rate of the composite end point was observed in warfarin users (95.7 events per 1000 person-years [PYs] vs 64.2 events per 1000 PYs; adjusted hazard ratio [aHR], 1.5; 95% CI, 1.3-1.7), dabigatran users (84.5 events per 1000 PYs vs 54.9 events per 1000 PYs; aHR, 1.5; 95% CI, 1.2-2.0), and rivaroxaban users (87.4 events per 1000 PYs vs 68.5 events per 1000 PYs; aHR, 1.3; 95% CI, 1.1-1.5). In all 3 comparisons, the magnitude of the benefits associated with apixaban was similar regardless of dementia diagnosis on the HR scale but differed substantially on the rate difference (RD) scale. The adjusted RD of the composite outcome per 1000 PYs for warfarin vs apixaban users was 29.8 (95% CI, 18.4-41.1) events in patients with dementia vs 16.0 (95% CI, 13.6-18.4) events in patients without dementia. The corresponding adjusted RD estimates of the composite outcome were 29.6 (95% CI, 11.6-47.6) events per 1000 PYs in patients with dementia vs 5.8 (95% CI, 1.1-10.4) events per 1000 PYs in patients without dementia for dabigatran vs apixaban users and 20.5 (95% CI, 9.9-31.1) events per 1000 PYs in patients with dementia vs 15.9 (95% CI, 11.4-20.3) events per 1000 PYs in patients without dementia for rivaroxaban vs apixaban users. The pattern was more distinct for major bleeding than for ischemic stroke. In this comparative effectiveness study, apixaban was associated with lower rates of major bleeding and ischemic stroke compared with other OACs. The increased absolute risks associated with other OACs compared with apixaban were greater among patients with dementia than those without dementia, particularly for major bleeding. These findings support the use of apixaban for anticoagulation therapy in patients living with dementia who have AF.

Ovarian Vein Thrombosis: A Sequela of COVID-Associated Coagulopathy.

Coronavirus disease 2019 (COVID-19) causes endothelial damage, blood stasis, and an overall state of hypercoagulability. This makes COVID a huge risk factor for venous thromboembolism (VTE) and arterial thromboembolism (ATE). Twenty percent of COVID-19 patients suffer from coagulation abnormalities like pulmonary embolism, myocardial infarction, stroke, deep vein thrombosis, etc. Ovarian vein thrombosis (OVT) has been previously linked to post-partum period, pregnancy, hypercoagulable state, or malignancy. We analyzed PubMed and Google Scholar databases for research and publications regarding OVT in patients with COVID-19. The search yielded nine case reports.These case reports were found to implicate COVID-associated coagulopathy (CAC) as an additional risk factor for ovarian vein thrombosis (OVT). OVT most commonly presents with abdominal pain and fever, making it difficult to diagnose, owing to the similarity in presentation with multiple other pathologies. OVT can be diagnosed radiologically with ultrasound, magnetic resonance imaging (MRI) scan, or CT scan with IV contrast. CT has been used as the modality of choice for diagnosing OVT. Although rare, OVT can cause life-endangering complications by extension of thrombus into systemic veins or pulmonary artery embolization. Therefore, early diagnosis and treatment are vital. There is no official guideline for the treatment of OVT post-COVID. However, the literature supports the use of apixaban or enoxaparin/acenocoumarol.

Real-world use of apixaban for the treatment and prevention of thrombosis in children with cardiac disease

BackgroundDirect oral anticoagulants use in pediatric cardiology is poorly defined. ObjectiveWe present the largest experience of apixaban use in children with heart disease, using weight- and level-based dosing. MethodsRetrospective single-center analysis of cardiac patients ≤19 years treated with apixaban. Patients were evaluated for safety (clinically relevant non-major [CRNM] or major bleeding; thrombotic events) and effectiveness (thrombus improvement by imaging). Peak drug-specific anti-Xa chromogenic assay results (“apixaban levels”) were analyzed. ResultsOver 3 years (5/2018-9/2021), 219 children, median age 6.8 years (0.3-19), median weight 20.8 kg (4.8-160) received apixaban, totaling 50,916 patient days. Of them, 172 (79%) warranted thromboprophylaxis and 47 (21%) thrombosis treatment (with 10 arterial, 19 venous, 15 intracardiac, and 3 pulmonary). The median initial peak apixaban level was 165 ng/mL (23-474; n = 125) in the prophylaxis subgroup and 153 ng/mL (30-450; n = 33) in the treatment subgroup; dosage was adjusted in response to levels in 25% of the patients. There were 4 bleeding safety events (3 CRNM; 1 major, hemoptysis complicating empyema); the serious bleeding event rate was 2.9 per 100 patient-years of apixaban. Minor bleeding events (42) were noted in 18 patients, with an additional 2 having leukopenia, 1 transaminitis, and 3 rashes. An improvement in thrombosis was seen in 95% of the treated patients with available follow-up imaging (37/39 patients). ConclusionApixaban use was feasible with a low rate of adverse events across a diverse pediatric cardiac population using commercially available tablets dosed to weight and adjusted based on peak apixaban levels.

Comparative pharmacoeconomic analysis of the use of apixaban, rivaroxaban and dabigatran for prevention of stroke and embolism in the vessels of the systemic circulation in patients with non-valvular atrial fibrillation

Aim . To compare the effectiveness of direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (AF) for preventing stroke and systemic thromboembolism (embolism in the vessels of the systemic circulation, systemic embolism) in terms of pharmacoeconomic indicators. Materials and Methods . The economic assessment was carried out from the standpoint of the healthcare system of the Russian Federation. We used published data on the clinical efficacy and safety of DOACs, which were obtained earlier in clinical trials. The efficacy of therapy was assessed by the incidence of ischemic stroke (IS) of systemic embolism (SE), while the safety was assessed by the incidence of major bleeding (MB) and clinically signifi cant minor bleeding (CSNMB). The total cost of patient management for each alternative treatment option included both the cost of drug therapy and the cost of managing adverse events over a study horizon of 12 months. The conclusion about the most preferred alternative was made on the basis of the ratio of effectiveness and cost of treating the patient. Results . The use of apixaban to prevent IS or SE in patients with AF was accompanied by a decrease in the incidence of their development (HR 0.80, 95 % CI 0.73–0.89; HR 0.72, 95 % CI 0.60–0.85 — compared with rivaroxaban and dabigatran, respectively), as well as a decrease in the frequency of MB compared with other DOACs (HR 0.55, 95 % CI 0.53–0.59; HR 0.78, 95 % CI 0.70–0.87 — compared with rivaroxaban and dabigatran, respectively). Since apixaban was more effective and safer than rivaroxaban and dabigatran, a cost-effectiveness approach was applied in this study. The least expensive treatment regimen included apixaban, the direct cost was 33,263 roubles per patient. The advantage was achieved both due to the lower of therapy with apixaban (29.6–34.0 % lower than other DOACs) and the minimum cost of managing the adverse events: for MB and CSNMB, it was reduced by 20.7 % compared to dabigatran and by 44.7 % compared to rivaroxaban; for stroke/SE, it was reduced by 25.9 % and 20.6 %, respectively. Conclusion . In patients with AF, apixaban was more cost-effective compared with rivaroxaban or dabigatran for preventing IS and SE, as it led to higher clinical efficacy and safety while requiring less healthcare system costs.

Pharmacoeconomic evaluation of apixaban use for the treatment and prevention of venous thromboembolism in the general population and patients with oncological diseases

Aim . To conduct a pharmacoeconomic analysis of the use of the drug Eliquis® (apixaban), belonging to direct oral anticoagulants (DOACs), for the treatment and prevention of deep vein thrombosis (DVT) and/or pulmonary embolism (PE), including in patients suffering from cancer disease compared with other anticoagulants. Materials and Methods . The economic assessment was made from the standpoint of the healthcare of the Russian Federation. Comparative evaluation of the effectiveness of DOACs was carried out on the basis of the combined rate of the incidence of VTE and death from VTE, as well as death from any cause. Safety assessment — based on the rate of major bleeding (MB) and clinically significant non-severe bleeding (CSNSB). The evaluation was performed on the basis of data obtained in the course of previously performed meta-analyses, the results of which were published. The total cost of patient management for each of the compared alternative treatment tactics was estimated by calculating the cost of a course of drug therapy, as well as the cost of managing adverse events in the study horizon, which was 12 months. The conclusion about the most preferred alternative was made on the basis of data on the relationship between the effectiveness and cost of treating the patient. Results . Apixaban compared with dabigatran and rivaroxaban was associated with a lower risk of developing MB and CSNSB. In addition, in patients taking apixaban, there was a trend towards a decrease in the risk of death from any cause compared with patients who used dabigatran and rivaroxaban, which did not reach statistical significance, which in turn led to the choice of the method of pharmacoeconomic analysis — “cost minimization”. It has been established that the use of apixaban is characterized by the lowest costs, the cost of managing one patient amounted to 59 271,89 rubles per year, which is 28,8 % and 27,2 % lower than similar costs for treatment regimens with the original drugs dabigatran and rivaroxaban, respectively. The difference in costs was due to both the cost of treating complications (1362.8 rubles vs. 2536.3 rubles vs. 3170.9 rubles for apixaban, rivaroxaban and dabigatran, respectively), and the cost of treatment and prophylaxis of DOACs (31 514,20 RUB vs 46 434,8 RUB vs 46 790,6 RUB, respectively). Similar results were achieved in the group of patients suffering from oncological diseases, as DOACs also allowed to reduce costs by 4–5 times compared with the use of LMWH. Conclusion . Among the original DOACs and traditional LMWH therapies, the apixaban regimen has the best cost-effectiveness ratio and is the most preferred alternative in terms of pharmacoeconomic analysis.

Outcomes with direct-acting oral anticoagulants in patients with a history of bariatric surgery: a retrospective cohort study

<h2>Abstract</h2><h3>Background</h3> Patients who undergo bariatric surgery have major physiologic changes in their gastrointestinal tract, which can theoretically alter drug absorption and pharmacokinetics. This is especially concerning for drugs with a narrow therapeutic index, as small changes in absorption can have significant effects on safety and efficacy. One class of interest is direct-acting oral anticoagulants (DOACs), for which there is a paucity of data in this population. <h3>Objective</h3> To characterize the use of DOACs (apixaban, dabigatran, rivaroxaban) in patients with a history of bariatric surgery and incidence of clotting and bleeding events. <h3>Setting</h3> Public healthcare system/university hospital, United States. <h3>Methods</h3> This retrospective cohort study included adult patients who were prescribed a DOAC for the prophylaxis or treatment of venous thromboembolism or for stroke and systemic embolism prevention in atrial fibrillation between January 2011 and December 2018. <h3>Results</h3> A total of 191 patients with a history of bariatric surgery were included. Clotting events occurred in 11 of 191 patients (5.8%) receiving DOAC therapy, with a calculated clotting rate of 3.9 clots per 100 person-years. Bleeding events occurred in 42 of 191 patients (22%) receiving a DOAC, with a calculated bleeding rate of 17.1 bleeds per 100 person-years. The use of rivaroxaban versus apixaban was associated with a statistically significant increased risk of bleeding in patients with a history of bariatric surgery. <h3>Conclusion</h3> In this retrospective cohort of bariatric surgery patients receiving DOACs, we found clotting rates consistent with expected rates and bleeding rates above expected rates based on historical data. We also found an increased risk of bleeding in rivaroxaban users compared with apixaban users. Careful evaluation of bleeding risks in bariatric surgery patients is encouraged.

Comparing the risk of dementia in subjects with atrial fibrillation using non-vitamin K antagonist oral anticoagulants versus vitamin K antagonists: a Belgian nationwide cohort study

Atrial fibrillation (AF) is associated with cognitive decline, with anticoagulated subjects potentially having a reduced risk compared with non-anticoagulated subjects. However, whether non-vitamin K antagonist oral anticoagulants (NOACs) may reduce the risk of dementia compared with vitamin K antagonists (VKAs) is unclear yet. Therefore, the risk of dementia was compared between AF subjects on NOACs versus VKAs. AF subjects initiating anticoagulation between 2013 and 2019 were identified in Belgian nationwide data. Inverse probability of treatment weighted Cox regression was used to investigate cognitive outcomes. Among 237,012 AF subjects (310,850 person-years (PYs)), NOAC use was associated with a significantly lower risk of dementia (adjusted hazard ratio (aHR) 0.91, 95% confidence interval (CI) (0.85-0.98)) compared with VKAs. A trend towards a lower risk of vascular dementia (aHR 0.89, 95%CI (0.76-1.04)) and significantly lower risk of other/unspecified dementia (aHR 0.91, 95%CI (0.84-0.99)) were observed with NOACs compared with VKAs, whereas the risk of Alzheimer's disease was similar (aHR 0.99, 95%CI (0.88-1.11)). Apixaban (aHR 0.91, 95%CI (0.83-0.99)) and edoxaban (aHR 0.79, 95%CI (0.63-0.99)) were associated with significantly lower risks of dementia compared with VKAs, while risks were not significantly different with dabigatran (aHR 1.02, 95% CI (0.93-1.12)) and rivaroxaban (aHR 0.97, 95% CI (0.90-1.05)). Comparable risks of dementia were observed between individual NOACs, except for significantly lower risks of dementia (aHR 0.93, 95% CI (0.87-0.98)) and other/unspecified dementia (aHR 0.90 (0.84-0.97)) with apixaban compared with rivaroxaban. NOACs were associated with a significantly lower risk of dementia compared with VKAs, likely driven by apixaban and edoxaban use.

Adverse events in low versus normal body weight patients prescribed apixaban for atrial fibrillation.

Safety and efficacy of direct oral anticoagulants (DOAC) in low weight patients with atrial fibrillation (AF) is unclear due to few low body weight patients enrolled in clinical trials. To assess bleeding and thrombotic event rates for patients with AF that are prescribed apixaban and have a low versus normal body weight. We analyzed patients with AF prescribed apixaban from 2017 to 2020 with at least 12 months of follow-up. Patients were divided into low [< 60kg (kg)] and normal (60-100kg) weight cohorts. Bleeding and thrombotic event rates were compared. Poisson regression and Cox proportional hazard models were used to estimate adjusted adverse event rates. A total of 545 patients met inclusion criteria. In the unadjusted analysis, there was an increase in non-major bleeding events requiring an Emergency Department visit more often in the low versus normal weight cohort (10.8 versus 7.4 per 100 patient-years, p = 0.15). Thrombotic event rates also occurred more often in the lower versus normal weight cohort (2.4 versus 0.9 per 100 patient-years, p = 0.09). However, adjusted analysis found no statistically significant difference in bleeding or thrombotic events between low and normal weight cohorts. The adjusted hazard ratio for bleeding was similar between the two weight cohorts. The use of apixaban in low body weight patients was not associated with higher rates of bleeding or thrombotic events, compared to those with normal body weight, after adjusting for potential confounding covariates. Larger studies may offer further insight into the overall safety and efficacy of DOAC therapy in these patients.

Long-term Anticoagulation with Apixaban in Patients with Cerebral Venous Thrombosis.

Introduction: Cerebral venous thrombosis (CVT) is a life-threatening neurological condition. There is limited evidence for the use of direct oral anticoagulants (DOAC) for long-term anticoagulation in this patient population. We report a case series of patients treated with apixaban and their clinical course. Methods: This was a retrospective cohort study. Patients diagnosed with CVT in a defined time period at our institution were screened for long-term anticoagulation and patients who were treated with apixaban were included in this study. Results: A total of nine patients were included in this study. The mean age was 36 years and 56% of the patients included were women. All received initial anticoagulation with unfractionated heparin (UFH) infusion for at least twenty-four hours, except for one patient who had anti-thrombin III deficiency and was treated with argatroban infusion. For long-term anticoagulation, 56% of patients received apixaban 10 mg twice daily for the first five to seven days followed by 5 mg twice daily, while the remaining 44% were transitioned from IV anticoagulation to apixaban 5 mg twice daily. There were no adverse events reported, except for one patient who developed anemia after 7 months of treatment and required a blood transfusion. Complete recanalization was achieved in 78% while 22% had partial recanalization. Follow-up time ranged from six to twenty-three months. Conclusion: The use of apixaban for long-term anticoagulation in CVT resulted in recanalization in all of the patients in this case series without any major side effects. This case series adds to the emerging studies demonstrating the utility of apixaban for CVT.

Over-the-Counter Product-Apixaban Interactions: Patient Perspectives on Information-Seeking.

CONTEXT: Patients taking direct-acting oral anticoagulants (DOACs) may be at risk for bleeding if they take interacting over-the-counter (OTC) products, yet little information exists about why patients may or may not seek information about potential interactions. OBJECTIVE: To investigate perspectives of patients taking apixaban (a commonly prescribed DOAC) regarding seeking information about OTC products. STUDY DESIGN and ANALYSIS: Semi-structured interviews were analyzed using thematic analysis. SETTING: Two large academic medical centers. POPULATION: English-, Mandarin-, Cantonese-, or Spanish-speaking adults taking apixaban. OUTCOME MEASURES: Themes associated with information-seeking about potential apixaban-OTC product interactions. RESULTS: Forty-six patients aged 28-93 years (35% Asian, 15% Black, 24% Hispanic, and 20% White; 58% women), were interviewed. Respondents took 172 total OTC products, of which the most common were: vitamin D and/or calcium (15%), non-vitamin non-mineral dietary supplements (13%), acetaminophen (12%), NSAIDS/aspirin (9%), and multivitamins (9%). Themes related to lack of information-seeking about OTC products included: 1) failure to recognize that apixaban-OTC product interactions might exist; 2) beliefs that providers are responsible for disseminating information about interactions; 3) previous suboptimal interactions with providers; 4) infrequent OTC product use; and 5) lack of prior problems with OTC product use (with or without concomitant apixaban use). Conversely, themes associated with seeking information included: 1) believing that patients are responsible for their own medication-related safety; 2) greater trust in providers; 3) unfamiliarity with the OTC product; and 4) prior medication-related problems. Patients noted that information sources ranged from in-person sources (e.g., physicians, pharmacists) to online and written materials. CONCLUSIONS: Patients taking apixaban raised reasons for information-seeking about OTC products related to their perceptions of OTC products, provider-patient interactions, and their prior experiences with and frequency of OTC product use. Greater patient education about the need for information-seeking about potential DOAC-OTC product interactions may be needed at the time of prescribing.

Comparative Pharmacology of Direct Oral Anticoagulants and Vitamin K Antagonist

Background: The prevalence of thrombus and use of anticoagulants is routine in clinical cardiology practice. Vitamin K antagonist (VKA) and/or Direct oral anticoagulants (DOAC) are used for resolution of the thrombus. Despite similar anticoagulation efficacy, use of DOAC is preferred due to their superior safety margin and reduced risk of bleeding. Currently the following DOAC are available for the prevention of thrombosis, i.e., dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban. This study evaluates the comparative pharmacology of these DOAC and VKA to assess clinical preference. Materials and Methods: The human specific targets of DOAC and VKA (Warfarin) were identified from the SwissTargetPrediction server and analysed for their affinity. The targets were subclassified into functional categories and the relative proportion of each of the functional categories among the total number of targets was estimated. A novel concentration affinity (CA) ratio system was developed for the drugs to assess their safety margin and compared. Results: The following targets were identified has high affinity targets of DOAC or VKA i.e., coagulation factor X, hERG, matriptase, multidrug and toxin extrusion protein 1, plasminogen, quinone reductase 1 and 2, serine protease hepsin, solute carrier family 22 member 2 and thrombin. Apixaban and rivaroxaban were observed to have superior anticoagulation pharmacology compared to the other DOAC or VKA. Edoxaban and betrixaban were observed to have affinity against hERG, which carries the risk of prolonging QT interval and triggering ventricular tachyarrhythmia. Conclusion: This study shows the comparative pharmacology of DOAC and VKA and suggests preferential use of apixaban or rivaroxaban due to their superior pharmacodynamic effects and wider safety margin.

570 FRAILTY AND DISABILITY IN OLDER PATIENTS AND THE EFFECTS OF APIXABAN ON QUALITY OF LIFE AND DEPRESSIVE SYMPTOMS. THE EXPERIENCE OF THE APULEIO STUDY

Abstract Introduction The APULEIO study was designed to describe the psychological effects of apixaban in Italian elderly patients with non-valvular atrial fibrillation (NVAF), deep vein thrombosis (DVT) or pulmonary embolism (PE). The existence of implications of treatment on health-related quality of life (HRQL) and mood is among the most important knowledge gaps in cardiovascular care of older subjects. Real-world data on these issues, essential to improve therapy adherence, are lacking. Aim of the present analysis was to evaluate the presence of a different response to oral anticoagulation in the disabled, frail and robust subjects enrolled in the study. Methods APULEIO was a multicenter, prospective, observational study including apixaban eligible patients. The 12-Item Short Form Health Survey (SF-12), the Beck Depression Inventory-II (BDI-II) and the Frail non-Disabled (FiND) questionnaire were used to evaluate, respectively, HRQL, depressive symptoms and the presence of disability and frailty. The findings of the baseline and the 6-month evaluation - end of the study - will be presented. Results Overall, 376 patients had complete data. Of these, 163 (43.4%), 111 (29.5%) and 102 (27.1%) subjects were, respectively, defined disabled, frail and robust. No differences for reason to anticoagulate were observed by FiND category (p=0.797; overall, AF: 77.1%; DVT/PE: 22.9%). Patients with disability were older (Disabled – D: 79±11; Frail - F: 72±12; Robust – R: 72±12 years; p&amp;lt;0.0001), more frequently women (D: 66.9; F: 43.2; R: 24.5%; p&amp;lt;0.0001), with a greater clinical complexity, as expressed by the CHA2DS2-VASc score (D: 4.3±1.5; F: 3.2±1.5; R: 2.9±1.6; p&amp;lt;0.0001), and showed a higher heart rate (D: 82±17; F: 77±14; R: 77±15 bpm; p=0.0414). BMI (overall, 27.5±4.7 Kg/m2; p=0.328), left ventricular ejection fraction (overall, 53±10%; p=0.453), and systolic (overall, 129±15 mmHg; p=0.219) and diastolic (overall, 76±10 mmHg; p=0.285) arterial pressure were similar among groups. The incidence of any adverse event was higher in those with disability (D: 14.1; F: 8.1; R: 3.9%; p=0.0190), but the proportion of those with serious adverse events was similar among categories (overall, 6.9%; p=0.105). When studying HRQL, at enrollment, the Physical Health composite score of the SF-12 was significantly different among groups (D: 32.7±7.9; F: 42.4±9.3; R: 45.6±8.0; p&amp;lt;0.0001). At the 6-month evaluation (D: 37.0±10.1; F: 43.9±8.8; R: 47.2±7.3; p&amp;lt;0.0001), only the improvement for disabled subjects was significant (p=0.0020). At Baseline, the Mental Health composite score of the SF-12 was lower in disabled and frail patients, when compared to robust ones (D: 46.8±9.8; F: 47.7±9.2; R: 51.4±8.6; p&amp;lt;0.0001). After 6 months, once again, only the improvement for disabled subjects (D: 37.0±10.1; F: 43.9±8.8; R: 47.2±7.3; p=0.0004) was significant (p&amp;lt;0.0001) and statistically greater than that observed for frail and robust patients. Regarding depressive symptoms, at enrollment, the BDI-II score was worse in the disabled and frail groups (D: 14.7±9.8; F: 9.0±8.1; R: 4.7±4.5; p&amp;lt;0.0001). At the 6-month assessment, it was possible to observe an improvement (D: 10.5±8.5; F: 6.8±7.8; R: 4.2±4.5; p&amp;lt;0.0001) in disabled (p&amp;lt;0.0001) and frail subjects (p=0.0112), but not in robust ones (p=0.1705). Conclusions The APULEIO study demonstrates that disability and frailty are common conditions in older subjects anticoagulated for AF and DVT/PE. Disabled patients present a higher clinical complexity than frail and robust ones. After 6 months of therapy, the use of apixaban is associated with a significant improvement of HRQL in disabled individuals and of depressive symptoms in disabled and frail ones. No changes were found in robust subjects. No differences by group were observed in the incidence of serious adverse events. These findings confirm the efficacy and safety of apixaban also when applying a multidimensional approach to high-risk geriatric populations.

788: ANDEXANET ALFA (ANDEXXA) REVIEW OF EFFICACY, SAFETY, AND TIME TO PATIENT ADMINISTRATION

Introduction: The 2022 Management of Patients with Spontaneous Intracranial Hemorrhage guideline recommends the use of andexanet alfa as an option for patients taking apixaban or rivaroxaban to reverse the anticoagulant effects. In the ANNEXA-4 trial, 82% of the patients evaluated achieved either excellent or good hemostatic efficacy 12 hours after the andexanet alfa infusion. The use of andexanet alfa is restricted at our institution to the treatment of intracranial hemorrhage in patients previously on rivaroxaban or apixaban asordered by neurocritical care providers. The primary objectives for this evaluation were to determine the hemostatic efficacy 24 hours post andexanet alfa infusion and the time from andexanet alfa order to administration. Secondary endpoints included the rate of thromboembolic events, 30-day mortality, and adherence to prescribing restriction protocol. Methods: This was a single-center, retrospective medication use evaluation that assessed patients prescribed andexanet alfa from November 2018 to December 2021. Results: A total of 30 patients were prescribed andexanet alfa with 26 patients included in the analysis. Four patients were excluded due to the drug being ordered but not administered. Most patients were on apixaban prior to admission for atrial fibrillation indication (n=22, 85%). All included patients received low dose andexanet alfa, with the most common indication for reversal being intracranial hemorrhage (n=25, 96%).One patient received andexanet alfa for hemoperitoneum bleed reversal indication. Hemostatic efficacy was assessed and 61.5% achieved a rating of good or excellent as defined by the ANNEXA-4 trial. The average time from andexanet alfa order to administration was 53.2 minutes and the average door to needle time was 2.5 hours. Adverse events, including thromboembolic events and inpatient mortality, occurred in 0 and. Conclusions: In our study, patients admitted with intracranial hemorrhages secondary to apixaban or rivaroxaban use who received andexanet alfa for emergent reversal had excellent hemostatic outcomes with a low rate of adverse events. Most patients received andexanet alfa within an hour of order entry into the electronic health record and adhered to institutional prescribing restrictions.

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

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

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

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

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

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