rivaroxaban and Aortic-Aneurysm--Abdominal

Abdominal aortic aneurysm (AAA) is a fatal disease due to the tendency to rupture. The drug treatment for small AAA without surgical indications has been controversial. Previous studies showed that high-sensitivity C-reactive protein (hs-CRP) had become a potential biomarker of the disease, and the anti-inflammatory effect of rivaroxaban for AAA had been well established. Thus, we hypothesized that rivaroxaban could control the progression of AAA in patients with hs-CRP elevation.. The study is a prospective, open-label, randomized, controlled clinical trial. Sixty subjects are recruited from the General Hospital of Northern Theatre Command of China. Subjects are randomly assigned (1:1) to the intervention arm (rivaroxaban) or control arm (aspirin). The primary efficacy outcome is the level of serum hs-CRP at 6 months. The secondary outcomes include imaging examination (the maximal diameter of AAA, the maximal thickness of mural thrombus, and the length of aneurysm), major adverse cardiovascular and cerebrovascular events (MACCE, including AAA transformation, non-fatal myocardial infarction, acute congestive heart failure, stent thrombosis, ischemia-driven target vessel revascularization, vascular amputation, stroke, cardiovascular death, and all-cause death), and other laboratory tests (troponin T, interleukin 6, D-dimer, and coagulation function).. The BANBOO trial tested the effect of rivaroxaban on the progression of AAA in patients with elevated Hs-CRP for the first time.. ChiCTR2100051990, ClinicalTrials.gov, registered on 12 October 2021.

Topics: Aortic Aneurysm, Abdominal; Aspirin; C-Reactive Protein; Humans; Prospective Studies; Randomized Controlled Trials as Topic; Rivaroxaban; Thrombosis; Treatment Outcome

Rivaroxaban is a specific factor Xa (FXa) inhibitor for venous thromboembolism treatment. Recently, increasing evidence have reported the beneficial effects of rivaroxaban on treating cardiovascular disorders such as coronary and peripheral artery disease. However, its potential influence on abdominal aortic aneurysm (AAA) remains unclear. This study aims to investigate whether rivaroxaban treatment could attenuate experimental AAA progression and its related mechanisms.. Rivaroxaban attenuated both angiotensin II- and calcium chloride-induced abdominal aortic aneurysm (AAA) progressions, through inhibiting aortic remodeling and inflammation. Rivaroxaban could be a promising therapeutic agent in attenuating AAA development by counteracting FXa-induced aortic wall inflammation.

Topics: Angiotensin II; Animals; Anti-Inflammatory Agents; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Aortitis; Calcium Chloride; Cell Adhesion Molecules; Cytokines; Dilatation, Pathologic; Disease Models, Animal; Disease Progression; Factor Xa Inhibitors; Humans; Inflammation Mediators; Male; Mice, Knockout, ApoE; Retrospective Studies; Rivaroxaban; Signal Transduction; Vascular Remodeling

The presence of intraluminal thrombus and mitochondrial dysfunction in human abdominal aortic aneurysms (AAAs) have been associated with aneurysmal growth and rupture. The objective of the study was to study if endogenous factor Xa (FXa) may modulate mitochondrial functionality and expression of proteins associated with mitophagy in human AAAs.. AAA sites with intraluminal thrombus were obtained from 6 patients undergoing elective AAA surgery repair. Control samples were collected from 6 organ donors. The effect of FXa was analyzed by in vitro incubation of AAA with 50 nmol/L rivaroxaban, an oral FXa inhibitor.. The enzymatic activities of citrate synthase, a biomarker of mitochondrial density, and cytochrome C oxidase, a biomarker of mitochondrial respiratory chain functionality, were significantly reduced in the AAA sites with respect to the healthy aorta (citrate synthase activity in μU/min/μg protein: control: 3.51 ± 0.22 vs. AAA: 0.37 ± 0.15.; P < 0.01; cytochrome C oxidase activity in μOD/min/μg protein: control: 8.05 ± 1.57 vs. AAA: 3.29 ± 1.05; P < 0.05). The addition of rivaroxaban to AAA reverted the activity of both citrate synthase and cytochrome C oxidase to similar values to control. Mitochondrial Drp-1 expression was higher in AAA sites than in either control aortas or rivaroxaban-incubated AAA sites. Cytosolic content of Drp-1 phosphorylated at Ser637, mitochondrial Parkin, and mitochondrial PINK1-Parkin interaction were significantly reduced in the AAA sites with respect to control aortas. For all these parameters, rivaroxaban-incubated AAA showed similar values compared with control aortas.. In human AAA, rivaroxaban improved mitochondrial functionality that was associated with changes in proteins related to mitophagy. Its opens possible new effects of endogenous FXa on the mitochondria in the human AAA site.

Topics: Adult; Aged; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Case-Control Studies; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Mitochondria; Mitochondrial Proteins; Mitophagy; Rivaroxaban; Thrombosis

Direct oral anticoagulants are commonly used instead of vitamin K antagonists in patients needing long-term anticoagulant treatment. As their use has become more popular, there is an increase possibility to perform a major surgery on an urgent or emergency basis on patients under nonvitamin-K antagonist oral anticoagulants.. We report a case of a ruptured abdominal aortic aneurysm on a male patient under rivaroxaban and clopidogrel. Emergency open repair of the aneurysm was performed. No anti-Xa antidote was administered. The patient had an uneventful recovery.. An open repair of a ruptured abdominal aortic aneurysm under rivaroxaban is feasible. However, an antidote should be available in cases of uncontrolled diffused bleeding. To the best of our knowledge, this is the first reported case of successful open repair of a ruptured abdominal aortic aneurysm on a patient under rivaroxaban and clopidogrel.

Topics: Aortic Aneurysm, Abdominal; Aortic Rupture; Aortography; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Clopidogrel; Computed Tomography Angiography; Drug Administration Schedule; Emergencies; Factor Xa Inhibitors; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Rivaroxaban; Treatment Outcome

The authors describe a case of unfractionated heparin (UFH) unresponsiveness in the operating room secondary to reversal of rivaroxaban with coagulation factor Xa (recombinant) inactivated-zhzo (andexanet alfa). A 70-year-old man with a known 4.5- to 5.0-cm abdominal aortic aneurysm and atrial fibrillation managed with rivaroxaban presented with severe right-sided flank pain radiating to the left side of his abdomen. Computed tomography-angiography on arrival demonstrated a left retroperitoneal hematoma and a suspected ruptured abdominal aortic aneurysm. He received andexanet alfa to reverse rivaroxaban prior to an emergent endovascular aneurysm repair. During surgery, he received a total of 14,000 units (167 units/kg) of UFH with minimal changes in activated clotting time (132-144 sec; baseline 135 sec [reference range 74-137 sec]). This case highlights the potential complications of using UFH anticoagulation following reversal of factor Xa inhibitors with andexanet alfa and underscores the importance of peri-procedural anticoagulation planning. For patients who require intra-operative anticoagulation, providers should consider anticoagulation reversal with prothrombin complex concentrate instead of andexanet alfa or administration of a parenteral direct thrombin inhibitor, such as argatroban or bivalirudin during the surgical procedure.

Topics: Aged; Anticoagulants; Aortic Aneurysm, Abdominal; Aortic Rupture; Factor Xa; Heparin; Humans; Intraoperative Period; Male; Recombinant Proteins; Rivaroxaban; Treatment Failure

To evaluate if rivaroxaban, an oral factor Xa (FXa) inhibitor, could modify the expression in vitro of inflammatory and oxidative stress biomarkers in abdominal aortic aneurysmal (AAA) sites showing intraluminal thrombus.. AAA sites with intraluminal mural thrombus were obtained from six patients undergoing elective AAA repair. In addition, control abdominal aortic samples were obtained from six organ donors. AAA sites were incubated in the presence and absence of 50 nmol l. AAA sites showing thrombus demonstrated higher content of FXa than control. Interleukin-6 levels released from AAA [Control: median: 23.45 (interquartile range: 16.17-37.15) vs. AAA: median: 153.07 (interquartile range: 100.80-210.69) pg ml. FXa inhibition by rivaroxaban exerted anti-inflammatory and antioxidative stress properties in human AAA sites, suggesting a role of FXa in these mechanisms associated with the pathogenesis of AAA.

Topics: Adult; Aged; Anti-Inflammatory Agents; Antioxidants; Aortic Aneurysm, Abdominal; Biomarkers; Blood Coagulation; Case-Control Studies; Factor Xa Inhibitors; Female; Humans; In Vitro Techniques; Inflammation Mediators; Interleukin-6; Male; Matrix Metalloproteinase 9; Middle Aged; NADPH Oxidase 2; Nitric Oxide Synthase Type II; Oxidative Stress; Phosphoproteins; Rivaroxaban

A 67-year-old man with non-valvular atrial fibrillation (AF) and previous myocardial and cerebral infarctions had uncontrollable bleeding after undergoing dental extraction because of an exacerbation of chronic disseminated intravascular coagulation (DIC) due to an abdominal aortic aneurysm. After successful treatment of the bleeding with the transfusion of fresh frozen plasma and platelets, nafamostat mesilate was used to treat the chronic DIC. Finally, rivaroxaban (an oral direct Factor Xa inhibitor) was prescribed for chronic DIC, as well as non-valvular AF. Following the initiation of rivaroxaban, the chronic DIC gradually improved, and the patient was discharged.

Topics: Aged; Anticoagulants; Aortic Aneurysm, Abdominal; Benzamidines; Blood Platelets; Blood Transfusion; Disseminated Intravascular Coagulation; Guanidines; Humans; Male; Rivaroxaban; Tooth Extraction