POSSIBILITIES OF USING EDOXABAN IN STROKE PREVENTION IN PATIENTS WITH ATRIAL FIBRILLATION

Применение антикоагулянтов у пациентов с фибрилляцией предсердий (ФП) - краеугольный камень профилактики инсульта. Обзор включает современные данные доказательной медицины по эффективности и безопасности применения Эдоксабана - ингибитора Xa фактора - для предупреждения инсульта при ФП, включая больных с чрескожными коронарными вмешательствами. The use of anticoagulants in patients with atrial fibrillation (AF) is the cornerstone of stroke prevention. The review includes modern evidence-based medicine data on the efficacy and safety of the use of Edoxaban, a factor Xa inhibitor, for the prevention of stroke in AF, including in patients with percutaneous coronary interventions.

Factor Xa inhibitor for venous thromboembolism management in patient with cancer: a systematic review and meta-analysis

Background: An earlier systematic review reported no differences in the incidence of recurrent venous thromboembolism and major bleeding between factor Xa inhibitors and standard anticoagulation. The present meta-analysis aimed to assess the effectiveness of factor Xa inhibitors for the management of venous thromboembolism (VTE), specifically in patients with cancer, as there were more randomized clinical trials (RCTs) available. Methods: The PubMed and Cochrane Library databases were systematically screened for all RCTs assessing factor Xa inhibitor efficacy for VTE management in cancer patients. Using RevMan 5.3, we performed a Mantel–Haenszel fixed-effects meta-analysis of the following outcomes: recurrent VTE, VTE events, and major bleeding rates. Results: We identified 11 studies involving 7,965 patients. Factor Xa inhibitors were superior in preventing VTE recurrence, compared to low-molecular-weight heparin (LMWH) (OR 0.60; 95% CI 0.45–0.80; P < 0.01) and vitamin K antagonists (VKA) (OR 0.51; 95% CI 0.33–0.78; P < 0.01). As prophylaxis, factor Xa inhibitors had a similar rate of VTE compared to VKAs (OR 1.08 [95% CI 0.31–3.77]; P = 0.90) and a lower rate compared to placebo (OR 0.54 [95% CI 0.35–0.81]; P < 0.01). Major bleeding rates were higher with factor Xa inhibitors than with LMWHs (OR 1.34 [95% CI 0.83–2.18]; P = 0.23), but significantly lower than VKAs (OR 0.71 [95% CI 0.55–0.92]; P < 0.01). Conclusions: Factor Xa inhibitors are effective for VTE management in patients with cancer; however, they are also associated with an increased bleeding risk compared to LMWH, but decreased when compared to VKA.

Abstract 1122‐000165: Endovascular Intervention for a Thrombotic Adverse Event During Andexanet Alfa Infusion

Introduction : Andexanet alfa is the only specific reversal agent for factor Xa inhibitors and received FDA approval in 2018. Here we report an early infusion adverse event in a patient with acute intraventricular hemorrhage (IVH) that received Andexanet alfa, with an unfavorable outcome. Methods : A 73‐year‐old male presented to our emergency department (ED) after he developed sudden onset of severe headache without other associated neurological symptoms. An outpatient brain MRI showed IVH, that remained stable in size (2.4 cm3) on a follow‐up head CT performed in our ED. CT angiogram showed a 60% stenosis of the left supraclinoid internal carotid artery. The patient was taking apixaban 5 mg twice daily for atrial fibrillation (last dose 5.5 hours prior to presentation). Results : The anticoagulation was reversed with Andexanet alfa, 400 mg bolus given at 18:30, followed by 480 mg infusion over 2 hours started at 19:00 (12 hours from last apixaban dose). At 19:00, he developed left middle cerebral artery (MCA) ischemic stroke symptoms (global aphasia) that resolved with head‐of‐the‐bed flattening. CT perfusion demonstrated left ICA territory mismatch (342 ml) and 76 ml core. Shortly after CT perfusion, the patient developed a persistent complete left MCA stroke syndrome with NIH stroke scale (NIHSS) score 23. Decision was made to perform emergent cerebral angiogram which demonstrated a large, fresh thrombus in the left cervical ICA. Thrombectomy was successful with TICI score 2B. Patient’s neurological status initially improved. However, despite this intervention, patient developed a large territory infarct. As neurologic status remained poor, family withdrew care and patient died. Conclusions : ANNEXA‐A and ANNEXA‐R were parallel trials of Andexanet alfa for factor Xa inhibitor reversal that demonstrated a transient increase in prothrombotic factors post Andexanet alfa infusion. Neither of these phase 3 trials nor the previous phase 2 trials reported a clinical thrombotic event very early during the infusion. The ANNEXA‐4 trial (Phase 3) enrolled subjects with active major bleeding on a factor Xa inhibitor and 10% developed a thrombotic event during the 30‐day follow‐up period. 41% of the thrombotic complications were acute ischemic stroke (AIS), 35% (5 patients) experienced an AIS in the first six days post‐administration and the earliest reported thrombotic event occurred day 1 post infusion. Our case report illustrates an early cerebrovascular thrombotic event with dismal outcome despite timely and effective mechanical reperfusion therapy, which could be due to vessel re‐obstruction in setting of a hypercoagulable state. We aim to make vascular neurologists, neurointensivists and neurosurgeons aware of this possible occurrence when reversing patients with factor Xa‐related intracranial hemorrhages.

Hematoma Expansion and Clinical Outcomes in Patients With Factor-Xa Inhibitor–Related Atraumatic Intracerebral Hemorrhage Treated Within the ANNEXA-4 Trial Versus Real-World Usual Care

Background and Purpose: It is unestablished whether andexanet alfa, compared with guideline-based usual care including prothrombin complex concentrates, is associated with reduced hematoma expansion (HE) and mortality in patients with factor-Xa inhibitor–related intracerebral hemorrhage (ICH). We compared the occurrence of HE and clinical outcomes in patients treated either with andexanet alfa or with usual care during the acute phase of factor-Xa inhibitor–related ICH. Methods: Data were extracted from the multicenter, prospective, single-arm ANNEXA-4 trial (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors) and a multicenter observational cohort study, RETRACE-II (German-Wide Multicenter Analysis of Oral Anticoagulant-Associated Intracerebral Hemorrhage - Part Two). HE was based on computed tomography scans performed within 36 hours from baseline imaging. Inverse probability of treatment weighting was performed to adjust for baseline comorbidities and ICH severity. Patients presenting with atraumatic ICH while receiving apixaban or rivaroxaban within 18 hours of admission were included. Patients with secondary ICH or not fulfilling the inclusion criteria for the ANNEXA-4 trial were excluded. We compared ANNEXA-4 patients, who received andexanet alfa for hemostatic treatment, with RETRACE-II patients who were treated with usual care, primarily administration of prothrombin complex concentrates. Primary outcome was rate of HE defined as relative increase of ≥35%. Secondary outcomes comprised mean absolute change in hematoma volume, as well as in-hospital mortality and functional outcome. Results: Overall, 182 patients with factor-Xa inhibitor–related ICH (85 receiving andexanet alfa versus 97 receiving usual care) were selected for analysis. There were no relevant differences regarding demographic or clinical characteristics between both groups. HE occurred in 11 of 80 (14%) andexanet alfa patients compared with 21 of 67 (36%) usual care patients (adjusted relative risk, 0.40 [95% CI, 0.20–0.78]; P =0.005), with a reduction in mean overall hematoma volume change of 7 mL. There were no statistically significant differences among in-hospital mortality or functional outcomes. Sensitivity analysis including only usual care patients receiving prothrombin complex concentrates demonstrated consistent results. Conclusions: As compared with usual care, andexanet alfa was associated with a lower rate of HE in atraumatic factor-Xa inhibitor–related ICH, however, without translating into significantly improved clinical outcomes. A comparative trial is needed to confirm the benefit on limiting HE and to explore clinical outcomes across patient subgroups and by time to treatment.

Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients

Background Maintenance drugs are used to treat chronic conditions. Several classes of maintenance drugs have attracted attention because of their potential to affect susceptibility to and severity of COVID-19. Methods Using claims data on 20% random sample of Part D Medicare enrollees from April to December 2020, we identified patients diagnosed with COVID-19. Using a nested case-control design, non-COVID-19 controls were identified by 1:5 matching on age, race, sex, dual-eligibility status and geographical region. We identified usage of angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), warfarin, direct factor Xa inhibitors, clopidogrel, famotidine and hydroxychloroquine based on Medicare prescription claims data. Using extended Cox regression models with time-varying propensity score adjustment we examined the independent effect of each study drug on contracting COVID-19. For severity of COVID-19, we performed extended Cox regressions on all COVID-19 patients, using COVID-19-related hospitalization and all-cause mortality as outcomes. Covariates included gender, age, race, geographic region, low-income indicator and co-morbidities. To compensate for indication bias related to the use of hydroxychloroquine for the prophylaxis or treatment of COVID-19, we censored patients who only started on hydroxychloroquine in 2020. Results Up to December 2020, our sample contained 374,229 Medicare patients over 65 who were diagnosed with COVID-19. Among the COVID-19 patients, 209,208 (55.9%) were on at least one study drug. The three most common study drugs were ACEI 97,872 (26.1%), ARB 83,329 (22.3%) and clopidogrel 38,203 (10.2%). Current users of ACEI, ARB, warfarin, direct factor Xa inhibitor and clopidogrel were associated with reduced risk of getting COVID-19 (3-13%), and reduced risk of dying after a COVID-19 diagnosis (8-19%). Famotidine did not show consistent significant effects. Hydroxychloroquine did not show significant effects after censoring of recent starters. Conclusions Maintenance use of ACEI, ARB, warfarin, direct factor Xa inhibitor and clopidogrel was associated with reduction in risk of acquiring COVID-19 and dying from it.

Treatment of Deep Vein Thrombosis Using Factor Xa Inhibitor Concurrent with Platinum Based Chemotherapy Regimen: A Case Report

Deep Vein Thrombosis (DVT) is a common treatment-related complication following surgery and chemotherapy. We are reporting a case of colorectal cancer-associated thrombosis during platinum-based chemotherapy. The patient was treated with Rivaroxaban (Xarelto), a highly selective direct Factor Xa inhibitor. This case report highlights the concurrent use of novel oral anticoagulants, which does not interrupt the chemotherapy schedule among patients receiving cytotoxic agents.