RÉSUMÉ
Patients with peripheral artery disease (PAD) who undergo lower extremity revascularization (LER) are at high risk for cardiovascular and limb-related ischemic events. The role of antithrombotic therapy is to prevent thrombotic complications, but this requires balancing increased risk of bleeding events. The dual pathway inhibition (DPI) strategy including aspirin and low-dose rivaroxaban after LER has been shown to reduce major adverse cardiovascular and limb-related events without significant differences in major bleeding. There is now a need to implement the broad adoption of DPI therapy in PAD patients who have undergone LER in routine practice.
Sujet(s)
Fibrinolytiques , Maladie artérielle périphérique , Humains , Maladie artérielle périphérique/chirurgie , Fibrinolytiques/usage thérapeutique , Thrombose/prévention et contrôle , Antiagrégants plaquettaires/usage thérapeutique , Antiagrégants plaquettaires/administration et posologie , Membre inférieur/vascularisation , Membre inférieur/chirurgie , Hémorragie/induit chimiquement , Hémorragie/prévention et contrôle , Acide acétylsalicylique/usage thérapeutique , Acide acétylsalicylique/administration et posologie , Rivaroxaban/usage thérapeutique , Rivaroxaban/administration et posologieRÉSUMÉ
BACKGROUND: This study aimed to evaluate the application value and safety of Warfarin, Rivaroxaban, and Dabigatran in elderly patients with atrial fibrillation. METHODS: A total of 180 elderly patients with atrial fibrillation admitted to our hospital were retrospectively analyzed. According to their anticoagulant treatment regimen, patients were divided into three groups: Warfarin (57 cases), Rivaroxaban (61 cases), and Dabigatran (62 cases). General demographic information was collected, and coagulation function indicators-including fibrinogen (FIB), thrombin time (PT), activated partial thrombin time (APTT), and D-dimer (D-D)-as well as liver function indexes-including total bilirubin (TbiL), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine transferase (ALT)-were compared before and after 4 weeks of treatment. RESULTS: There were no significant differences in demographic characteristics such as gender, age, body mass index, or disease course among the three groups. The total effective rate in the Warfarin group (84.21%) was significantly lower than in the Rivaroxaban (98.36%) and Dabigatran (96.77%) groups (p < 0.05). However, there was no significant difference in the total effective rate between the Rivaroxaban and Dabigatran groups (p > 0.05). Additionally, no significant differences were found in the effects of the three drugs on coagulation function, liver function, or the incidence of bleeding (p = 0.052). CONCLUSION: Warfarin, Rivaroxaban, and Dabigatran can effectively prevent thrombosis in elderly patients with atrial fibrillation, with Rivaroxaban and Dabigatran showing superior effectiveness. All three drugs demonstrated similar low rates of bleeding events and had no significant impact on coagulation and liver function.
Sujet(s)
Anticoagulants , Fibrillation auriculaire , Coagulation sanguine , Dabigatran , Rivaroxaban , Warfarine , Humains , Dabigatran/effets indésirables , Dabigatran/usage thérapeutique , Fibrillation auriculaire/traitement médicamenteux , Fibrillation auriculaire/complications , Rivaroxaban/effets indésirables , Rivaroxaban/usage thérapeutique , Mâle , Femelle , Sujet âgé , Études rétrospectives , Warfarine/effets indésirables , Warfarine/usage thérapeutique , Anticoagulants/effets indésirables , Anticoagulants/usage thérapeutique , Coagulation sanguine/effets des médicaments et des substances chimiques , Résultat thérapeutique , Sujet âgé de 80 ans ou plus , Antithrombiniques/effets indésirables , Antithrombiniques/usage thérapeutique , Hémorragie/induit chimiquement , Hémorragie/épidémiologieRÉSUMÉ
BACKGROUND: Direct oral anticoagulants (DOACs) have been the drug of choice for preventing ischemic stroke in patients with atrial fibrillation since 2014. In previous studies, the stroke risk while taking warfarin was 2 per 100 patient-years and 1.5% per year while taking DOACs. We hypothesized that even if ischemic stroke occurred during anticoagulation therapy with DOACs, the prognosis was likely to be better than that with warfarin. METHODS AND RESULTS: Data from 2002 to 2019, sourced from a nationwide claims database, were used to identify atrial fibrillation patients using International Classification of Diseases codes. Patients who experienced an ischemic stroke during anticoagulation were categorized by the drugs used (warfarin, dabigatran, apixaban, rivaroxaban, and edoxaban). The primary outcome was mortality within 3 months and 1 year after the ischemic stroke. Among the 9578 patients with ischemic stroke during anticoagulation, 3343 received warfarin, and 6235 received DOACs (965 dabigatran, 2320 apixaban, 1702 rivaroxaban, 1248 edoxaban). The DOACs group demonstrated lower risks of 3-month (adjusted hazard ratio [HR], 0.550, [95% CI, 0.473-0.639]; P<0.0001) and 1-year mortality (adjusted HR, 0.596 [95% CI, 0.536-0.663]; P<0.0001) than the warfarin group. Apixaban and edoxaban within the DOAC group exhibited particularly reduced 1-year mortality risk compared with other DOACs (P<0.0001). CONCLUSIONS: Our study confirmed that DOACs have a better prognosis than warfarin after ischemic stroke. The apixaban and edoxaban groups had a lower risk of death after ischemic stroke than the other DOAC groups.
Sujet(s)
Anticoagulants , Fibrillation auriculaire , Inhibiteurs du facteur Xa , Accident vasculaire cérébral ischémique , Warfarine , Humains , Warfarine/usage thérapeutique , Warfarine/effets indésirables , Accident vasculaire cérébral ischémique/prévention et contrôle , Accident vasculaire cérébral ischémique/mortalité , Accident vasculaire cérébral ischémique/diagnostic , Mâle , Femelle , Sujet âgé , Anticoagulants/effets indésirables , Anticoagulants/usage thérapeutique , Anticoagulants/administration et posologie , Fibrillation auriculaire/traitement médicamenteux , Fibrillation auriculaire/complications , Fibrillation auriculaire/mortalité , Pronostic , Administration par voie orale , Inhibiteurs du facteur Xa/usage thérapeutique , Inhibiteurs du facteur Xa/effets indésirables , Inhibiteurs du facteur Xa/administration et posologie , Adulte d'âge moyen , Sujet âgé de 80 ans ou plus , Pyridones/effets indésirables , Pyridones/usage thérapeutique , Pyridones/administration et posologie , Études rétrospectives , Pyrazoles/usage thérapeutique , Pyrazoles/effets indésirables , Dabigatran/usage thérapeutique , Dabigatran/effets indésirables , Dabigatran/administration et posologie , Rivaroxaban/usage thérapeutique , Rivaroxaban/effets indésirables , Rivaroxaban/administration et posologie , Facteurs de risque , Appréciation des risques , Taïwan/épidémiologie , Pyridines , ThiazolesRÉSUMÉ
BACKGROUND: Direct oral anticoagulants (DOACs) have high potency against their therapeutic target and are widely used in the treatment of atrial fibrillation (AF). Most DOACs are often claimed to have adverse effects due to off-target inhibition of essential proteins. Human serum paraoxonase 1 (PON1), one of the essential proteins, known for its anti-inflammatory and antioxidant properties, could be affected by DOACs. Thus, a comparative evaluation of DOACs and their effect on PON1 protein will aid in recommending the most effective DOACs for AF treatment. This study aimed to assess the impact of DOACs on PON1 through a combination of computational and experimental analyses. METHODS: We focus on apixaban, dabigatran, and rivaroxaban, the most recommended DOACs in AF treatment, for their impact on PON1 through molecular docking and molecular dynamics (MD) simulation to elucidate the binding affinity and drug-protein structural stability. This investigation revealed the most influential DOACs on the PON1 protein. Then experimental validation was performed in DOAC-treated AF participants (n = 42; 19 treated with dabigatran and 23 treated with rivaroxaban) compared to a healthy control group (n = 22) through gene expression analysis in peripheral blood mononuclear cells (PBMC) and serum enzyme concentration. RESULTS: Our computational investigation showed rivaroxaban (-4.24 kcal/mol) exhibited a lower affinity against the PON1 protein compared to apixaban (-5.97 kcal/mol) and dabigatran (-9.03 kcal/mol) through molecular docking. Dabigatran holds complex interactions with PON1 at GLU53, TYR197, SER193, and ASP269 by forming hydrogen bonds. Additionally, MD simulation revealed that dabigatran disrupts PON1 stability, which may contribute functional changes. Further experimental validation revealed a significant down-regulation (p < 0.05) of PON1 gene expression in PBMC and decreased serum PON1 enzyme concentration on DOAC treatment. Rivaroxaban as about 48% has inhibitory percentage and dabigatran as about 75% of inhibitory percentage compared to healthy control. CONCLUSION: Overall, our computational and experimental results clearly show the higher inhibitory effect of dabigatran than rivaroxaban. Hence, rivaroxaban will be a better drug candidate for improving the outcome of AF.
Sujet(s)
Aryldialkylphosphatase , Fibrillation auriculaire , Dabigatran , Simulation de docking moléculaire , Simulation de dynamique moléculaire , Pyridones , Rivaroxaban , Humains , Fibrillation auriculaire/traitement médicamenteux , Fibrillation auriculaire/métabolisme , Aryldialkylphosphatase/sang , Rivaroxaban/usage thérapeutique , Mâle , Pyridones/usage thérapeutique , Pyrazoles/pharmacologie , Pyrazoles/usage thérapeutique , Pyrazoles/composition chimique , Administration par voie orale , Anticoagulants/pharmacologie , Anticoagulants/composition chimique , Femelle , Sujet âgé , Adulte d'âge moyenSujet(s)
Fibrillation auriculaire , Diltiazem , Hémorragie , Métoprolol , Pyrazoles , Pyridones , Rivaroxaban , Humains , Fibrillation auriculaire/traitement médicamenteux , Fibrillation auriculaire/complications , Rivaroxaban/effets indésirables , Rivaroxaban/usage thérapeutique , Pyridones/effets indésirables , Pyridones/usage thérapeutique , Pyrazoles/effets indésirables , Pyrazoles/usage thérapeutique , Hémorragie/induit chimiquement , Hémorragie/prévention et contrôle , Diltiazem/effets indésirables , Diltiazem/usage thérapeutique , Métoprolol/effets indésirables , Métoprolol/usage thérapeutique , Femelle , Mâle , Inhibiteurs du facteur Xa/effets indésirables , Inhibiteurs du facteur Xa/usage thérapeutique , Sujet âgé , Adulte d'âge moyenRÉSUMÉ
OBJECTIVE: Patients with thromboembolic problems, prosthetic valves, or coagulation issues are commonly prescribed anticoagulants and antiplatelets. Anticoagulant and antiplatelet medication might constitute a challenge for dentists and dental hygienists since possible prolonged bleeding might interfere with dental procedures. The aim of the present study was to examine the bleeding durations associated with various anticoagulants and antiplatelets during professional dental hygiene sessions, utilizing a modified Ivy test adapted for the oral context. MATERIALS AND METHODS: Ninety-three consecutive patients undergoing professional oral hygiene were recruited. Debridement during oral hygiene was performed using ultrasonic mechanical instrumentation, and bleeding sites were assessed and treated with gentle pressure using sterile gauzes. The time for bleeding cessation was recorded. Patients were categorized into six groups based on their drug intake, Control: no anticoagulants or antiplatelets DTI: direct thrombin inhibitors (dabigatran) AntiXa: directa factor Xa inhibitors (endoxaban, apixaban, rivaroxaban) VKA: vitamin K antagonists (warfarin, acenocoumarol) SAPT: single anti-platelet therapy (acetylsalicylic acid or clopidogrel) DAPT: dual anti-platelet therapy (acetylsalicylic acid and clopidogrel). Bleeding time was measured in seconds and mean values were assessed among the different groups. Differences between groups were investigated with Kruskal-Wallis test followed by Dunn's post-hoc correction for multiple comparisons or two-way ANOVA followed by Dunnett post-hoc; RESULTS: Control patients presented the lowest bleeding time 50 s, followed by AntiXa (98), SAPT (105), DTI (120), DAPT (190) and VKA (203). A statistically significant difference was present among control and DTI (p = 0.004), VKA (p < 0.001), DAPT (p < 0.001). CONCLUSIONS: Based on the present outcomes, an increased risk of prolonged bleeding emerged in patients taking VKA and DAPT. CLINICAL SIGNIFICANCE: bleeding did not interfere with the oral hygiene session The optimal period for dental treatment of these patients should be 2-3 h before the next dose, without the need to temporarily suspend the medication.
Sujet(s)
Anticoagulants , Antiagrégants plaquettaires , Humains , Anticoagulants/usage thérapeutique , Femelle , Mâle , Antiagrégants plaquettaires/usage thérapeutique , Antiagrégants plaquettaires/effets indésirables , Adulte d'âge moyen , Temps de saignement , Hémorragie buccale/prévention et contrôle , Hémorragie buccale/étiologie , Sujet âgé , Adulte , Hygiène buccodentaire , Dabigatran/usage thérapeutique , Dabigatran/effets indésirables , Inhibiteurs du facteur Xa/usage thérapeutique , Warfarine/usage thérapeutique , Warfarine/effets indésirables , Clopidogrel/usage thérapeutique , Clopidogrel/effets indésirables , Pyrazoles/usage thérapeutique , Acide acétylsalicylique/effets indésirables , Acide acétylsalicylique/usage thérapeutique , Rivaroxaban/usage thérapeutique , Rivaroxaban/effets indésirablesSujet(s)
Tumeurs , Rivaroxaban , Rivaroxaban/usage thérapeutique , Humains , Tumeurs/complications , Tumeurs/traitement médicamenteux , Résultat thérapeutique , Thromboembolisme veineux/traitement médicamenteux , Inhibiteurs du facteur Xa/usage thérapeutique , Médecine factuelle , Anticoagulants/usage thérapeutique , Thromboembolie/prévention et contrôle , Thromboembolie/étiologie , Thromboembolie/traitement médicamenteux , Comorbidité , Prévalence , Facteurs de risqueRÉSUMÉ
INTRODUCTION: Heavy menstrual bleeding affects up to two thirds of women on oral anticoagulation. The rates of heavy menstrual bleeding, its impact on quality of life and associated risk factors in women attending anticoagulation clinics in South Africa are largely unknown. MATERIALS AND METHODS: A prospective cohort study was performed over an eight-month period in women on Warfarin (n = 30) and Rivaroxaban (n = 27) for a median [interquartile range] duration of 15.5 [78.0] months attending an anticoagulation clinic in Johannesburg, South Africa. Heavy menstrual bleeding was assessed over one menstrual cycle using the validated pictorial blood loss assessment charts (PBAC) and the menstrual bleeding questionnaire (MBQ). RESULTS: In this population of predominantly African ethnicity, with a median age of 39 [8] years, 39 (68.4%) women experienced heavy menstrual bleeding, defined as a PBAC score of >100. Median cycle length on anticoagulation and MBQ scores were significantly higher among women with a PBAC score of >100 (p > 0.05). Univariate analysis identified Rivaroxaban as a risk factor for heavy menstrual bleeding (OR 5.03, 95% CI 1.40-18.12). Heavy menstrual bleeding required treatment in 29 (74.4%) women which included management of iron deficiency, anti-fibrinolytics, modification of anticoagulation and hormonal contraception. CONCLUSION: Heavy menstrual bleeding was associated with a considerable negative impact on quality of life. This was most significant for women on Rivaroxaban as compared to Warfarin. It is essential to monitor and appropriately treat heavy menstrual bleeding in at risk women on anticoagulant treatment.
Sujet(s)
Anticoagulants , Ménorragie , Qualité de vie , Humains , Femelle , Ménorragie/traitement médicamenteux , Anticoagulants/usage thérapeutique , Anticoagulants/effets indésirables , Anticoagulants/administration et posologie , Adulte , Études prospectives , Adulte d'âge moyen , Incidence , Warfarine/usage thérapeutique , Warfarine/effets indésirables , Administration par voie orale , Rivaroxaban/usage thérapeutique , Rivaroxaban/effets indésirables , Rivaroxaban/administration et posologie , République d'Afrique du Sud , Facteurs de risqueRÉSUMÉ
BACKGROUND: The combination of rivaroxaban plus aspirin compared with aspirin alone reduces the risk of major adverse cardiovascular and limb events for high-risk patients with peripheral artery disease. It is unknown whether rivaroxaban plus aspirin improves intermittent claudication for adults with lower-risk peripheral arterial disease. METHODS: In this randomized, open-label, multicenter, 24-week clinical trial, we randomly assigned patients with peripheral artery disease and intermittent claudication to receive either 2.5 mg of rivaroxaban twice daily plus 100 mg of aspirin once daily or 100 mg of aspirin once daily. The primary outcome was a 24-week change in total walking distance, measured by the 6-minute walking test. The primary safety outcome was the incidence of major bleeding or clinically relevant nonmajor bleeding. RESULTS: Eighty-eight patients were randomly assigned to either rivaroxaban plus aspirin (n=46) or aspirin alone (n=42). The mean age was 67 years, and 54% were female. The total walking distance measured by 6-minute walk test improved by 89 ± 18 m (mean±standard error) in the rivaroxaban-plus-aspirin group versus 21 ± 16 m in the aspirin-alone group. This corresponded to an absolute difference of 68 ± 24 m (95% confidence interval [CI], 19 to 116 m; P=0.007) and a relative improvement over the aspirin-alone group of 327% (95% CI, 94 to 560%). No major bleeding events were observed in either group. CONCLUSIONS: In patients with peripheral artery disease and intermittent claudication, 2.5 mg of rivaroxaban twice daily plus 100 mg of aspirin daily improved the total walking distance by a 6-minute walking test compared with 100 mg of aspirin daily alone. (Funded by Bayer S.A.; Clinicaltrials.gov number, NCT04853719.).
Sujet(s)
Acide acétylsalicylique , Inhibiteurs du facteur Xa , Claudication intermittente , Maladie artérielle périphérique , Rivaroxaban , Humains , Rivaroxaban/usage thérapeutique , Rivaroxaban/administration et posologie , Rivaroxaban/effets indésirables , Claudication intermittente/traitement médicamenteux , Femelle , Mâle , Sujet âgé , Acide acétylsalicylique/usage thérapeutique , Acide acétylsalicylique/administration et posologie , Acide acétylsalicylique/effets indésirables , Adulte d'âge moyen , Inhibiteurs du facteur Xa/usage thérapeutique , Inhibiteurs du facteur Xa/administration et posologie , Inhibiteurs du facteur Xa/effets indésirables , Inhibiteurs du facteur Xa/pharmacologie , Maladie artérielle périphérique/traitement médicamenteux , Antiagrégants plaquettaires/usage thérapeutique , Antiagrégants plaquettaires/administration et posologie , Antiagrégants plaquettaires/effets indésirables , Association de médicaments , Résultat thérapeutique , Hémorragie/induit chimiquementRÉSUMÉ
INTRODUCTION: Venous thromboembolism (VTE) is a major concern following total knee arthroplasty (TKA). The optimal pharmacological prophylaxis remains, however, controversial. The present investigation compared several non-vitamin K antagonist oral anticoagulants commonly employed as VTE prophylaxis following TKA. A Bayesian network meta-analysis was conducted to compare apixaban, aspirin, dabigatran, edoxaban, enoxaparin, fondaparinux, and rivaroxaban. The outcomes of interest were to compare the rate of deep venous thrombosis (DVT), pulmonary embolism (PE), and major and minor haemorrhages. METHODS: This study was conducted according to the PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-Analyses of Health Care Interventions. In March 2024, PubMed, Web of Science, and Google Scholar were accessed with no time constraints. All randomised controlled trials (RCTs) comparing two or more drugs for the prevention of VTE following TKA were considered for inclusion. RESULTS: Data from 29,678 patients were collected. Of them, 67% (19,884 of 29,678 patients) were women. The mean age of the patients was 66.8 ± 2.8 years, and the mean BMI was 29.2 ± 1.5 kg/m2. There was comparability in age, sex, and BMI at baseline. Apixaban 5 mg, dabigatran 220 mg, and rivaroxaban 10 mg were the most effective in reducing the rate of DVT. Apixaban 5 mg, enoxaparin 60 mg, and rivaroxaban 40 mg were the most effective in reducing the rate of PE. Apixaban 5 mg, rivaroxaban 10 mg, and apixaban 10 mg were associated with the lowest rate of major haemorrhages. Apixaban 5 mg and 20 mg, and dabigatran 220 mg were associated with the lowest rate of minor haemorrhages. CONCLUSION: Administration of apixaban 5 mg demonstrated the best balance between VTE prevention and haemorrhage control following TKA. LEVEL OF EVIDENCE: Level I, network meta-analysis of RCTs.
Sujet(s)
Arthroplastie prothétique de genou , Théorème de Bayes , Méta-analyse en réseau , Thromboembolisme veineux , Humains , Arthroplastie prothétique de genou/effets indésirables , Thromboembolisme veineux/prévention et contrôle , Thromboembolisme veineux/étiologie , Rivaroxaban/usage thérapeutique , Rivaroxaban/administration et posologie , Pyridones/administration et posologie , Pyridones/usage thérapeutique , Anticoagulants/usage thérapeutique , Anticoagulants/administration et posologie , Complications postopératoires/prévention et contrôle , Complications postopératoires/étiologie , Dabigatran/usage thérapeutique , Dabigatran/administration et posologie , Pyrazoles/usage thérapeutique , Acide acétylsalicylique/usage thérapeutique , Acide acétylsalicylique/administration et posologie , Fibrinolytiques/usage thérapeutique , Fibrinolytiques/administration et posologie , Embolie pulmonaire/prévention et contrôle , Embolie pulmonaire/étiologie , Énoxaparine/administration et posologie , Énoxaparine/usage thérapeutique , Hémorragie/induit chimiquement , Femelle , Fondaparinux/usage thérapeutique , Pyridines , ThiazolesRÉSUMÉ
BACKGROUND: Rivaroxaban 2.5 mg plus aspirin reduced limb and cardiovascular events and increased bleeding in patients with symptomatic peripheral artery disease (PAD) after lower extremity revascularization in the VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) study. Fragile patients are at heightened risk for ischemic and bleeding events. OBJECTIVES: The purpose of this study was to investigate the safety and efficacy of rivaroxaban 2.5 mg in fragile patients from VOYAGER PAD. METHODS: Patients were categorized as fragile based on prespecified criteria (age >75 years, weight ≤50 kg, or baseline estimated glomerular filtration rate <50 mL/min/1.73 m2). The primary efficacy outcome was the composite of acute limb ischemia, major amputation of a vascular etiology, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was TIMI major bleeding. RESULTS: Of 6,564 randomized patients, a total of 1,674 subjects were categorized as fragile at baseline. In the placebo arm, fragile patients were at higher risk of the primary outcome (HR: 1.34; 95% CI: 1.12-1.61) and TIMI major bleeding (HR: 1.57; 95% CI: 0.83-2.96), compared with nonfragile patients. The effect of rivaroxaban on the primary endpoint was not modified by frailty status (fragile HR: 0.93; 95% CI: 0.75-1.15; nonfragile HR: 0.83; 95% CI: 0.72-0.97; P interaction = 0.37). Rivaroxaban increased TIMI major bleeding in fragile (HR: 1.54; 95% CI: 0.82-2.91) and nonfragile patients (HR: 1.37; 95% CI: 0.84-2.23; P interaction = 0.65). CONCLUSIONS: Patients with PAD after lower extremity revascularization meeting fragile criteria are at higher risk of ischemic complications and bleeding. Rivaroxaban reduces ischemic risk and increases bleeding regardless of frailty status. These data may assist in personalization of antithrombotic therapy in fragile population.
Sujet(s)
Acide acétylsalicylique , Association de médicaments , Inhibiteurs du facteur Xa , Membre inférieur , Maladie artérielle périphérique , Rivaroxaban , Humains , Rivaroxaban/administration et posologie , Rivaroxaban/usage thérapeutique , Femelle , Mâle , Sujet âgé , Maladie artérielle périphérique/chirurgie , Acide acétylsalicylique/administration et posologie , Acide acétylsalicylique/usage thérapeutique , Membre inférieur/vascularisation , Membre inférieur/chirurgie , Inhibiteurs du facteur Xa/administration et posologie , Inhibiteurs du facteur Xa/usage thérapeutique , Antiagrégants plaquettaires/administration et posologie , Antiagrégants plaquettaires/usage thérapeutique , Méthode en double aveugle , Sujet âgé de 80 ans ou plus , Procédures de chirurgie vasculaire , Adulte d'âge moyenRÉSUMÉ
Non-vitamin K oral anticoagulants (NOACs) have revolutionized anticoagulant therapy, offering improved safety and efficacy over traditional agents like warfarin. This review comprehensively examines the dual roles of NOACs-apixaban, rivaroxaban, edoxaban, and dabigatran-not only as anticoagulants, but also as modulators of inflammation via protease-activated receptor (PAR) signaling. We highlight the unique pharmacotherapeutic properties of each NOAC, supported by key clinical trials demonstrating their effectiveness in preventing thromboembolic events. Beyond their established anticoagulant roles, emerging research suggests that NOACs influence inflammation through PAR signaling pathways, implicating factors such as factor Xa (FXa) and thrombin in the modulation of inflammatory responses. This review synthesizes current evidence on the anti-inflammatory potential of NOACs, exploring their impact on inflammatory markers and conditions like atherosclerosis and diabetes. By delineating the mechanisms by which NOACs mediate anti-inflammatory effects, this work aims to expand their therapeutic utility, offering new perspectives for managing inflammatory diseases. Our findings underscore the broader clinical implications of NOACs, advocating for their consideration in therapeutic strategies aimed at addressing inflammation-related pathologies. This comprehensive synthesis not only enhances understanding of NOACs' multifaceted roles, but also paves the way for future research and clinical applications in inflammation and cardiovascular health.
Sujet(s)
Anticoagulants , Inflammation , Récepteurs activés par la protéinase , Transduction du signal , Humains , Inflammation/traitement médicamenteux , Inflammation/métabolisme , Anticoagulants/usage thérapeutique , Anticoagulants/pharmacologie , Anticoagulants/administration et posologie , Récepteurs activés par la protéinase/métabolisme , Transduction du signal/effets des médicaments et des substances chimiques , Administration par voie orale , Animaux , Rivaroxaban/usage thérapeutique , Rivaroxaban/pharmacologie , Rivaroxaban/administration et posologie , Pyridones/pharmacologie , Pyridones/usage thérapeutique , Pyridones/administration et posologieRÉSUMÉ
BACKGROUND: The objective of this study is to compare and assess the efficacy and safety of low-molecular-weight heparin calcium (LMWH-Ca), followed by either warfarin or rivaroxaban, as treatment options for portal vein thrombosis (PVT) in patients with cirrhosis. METHODS: In this pilot study, cirrhotic (with liver function score of Child-Pugh A) patients diagnosed with PVT who were not on anticoagulant therapy received 2 weeks of subcutaneous injections of LMWH-Ca. They were then randomized to either warfarin (a full course of oral warfarin for 6 months) or rivaroxaban (a full course of oral rivaroxaban for 2 months), with 30 cases in each group. After a treatment period of up to 6 months, a comparative analysis was performed to assess the efficacy and safety of both groups. Volumetric changes in PVT were monitored dynamically using enhanced computed tomography scans before treatment at week 2 and month 6. RESULTS: There were no statistically significant differences in the clinical characteristics of the patients between the two groups. Rivaroxaban treatment reduced PVT median volume from 1.83 cm3 at week 2 to 0.0 cm3 at month 6 and prevented the worsening of PVT after 6 months of treatment with LMWH-Ca (Pâ <â 0.001). On the other hand, warfarin treatment increased PVT median volume from 1.95 cm3 at week 2 to 3.78 cm3 at month 6 (Pâ =â 0.002). None of the 30 patients in the rivaroxaban group had clinically significant gastrointestinal bleeding, while 2 of the 30 patients (7%) in the warfarin group had gastrointestinal bleeding (Pâ =â 0.317). CONCLUSION: Rivaroxaban followed by LMWH-Ca is an effective anticoagulant treatment strategy for PVT in cirrhosis.
Sujet(s)
Anticoagulants , Héparine bas poids moléculaire , Cirrhose du foie , Veine porte , Rivaroxaban , Thrombose veineuse , Warfarine , Humains , Projets pilotes , Anticoagulants/administration et posologie , Anticoagulants/effets indésirables , Anticoagulants/usage thérapeutique , Mâle , Rivaroxaban/administration et posologie , Rivaroxaban/effets indésirables , Rivaroxaban/usage thérapeutique , Veine porte/imagerie diagnostique , Femelle , Thrombose veineuse/traitement médicamenteux , Thrombose veineuse/imagerie diagnostique , Adulte d'âge moyen , Cirrhose du foie/complications , Cirrhose du foie/traitement médicamenteux , Warfarine/administration et posologie , Warfarine/effets indésirables , Héparine bas poids moléculaire/administration et posologie , Héparine bas poids moléculaire/usage thérapeutique , Héparine bas poids moléculaire/effets indésirables , Administration par voie orale , Résultat thérapeutique , Sujet âgé , Inhibiteurs du facteur Xa/effets indésirables , Inhibiteurs du facteur Xa/administration et posologie , Inhibiteurs du facteur Xa/usage thérapeutique , Adulte , Injections sous-cutanées , Tomodensitométrie , Association de médicamentsRÉSUMÉ
BACKGROUND: Patients with atrial fibrillation and severe chronic kidney disease have higher risks of bleeding, thromboembolism, and mortality. However, optimal anticoagulant choice in these high-risk patients remains unclear. METHODS AND RESULTS: Using deidentified electronic health records from the Optum Labs Data Warehouse, adults with atrial fibrillation and severe chronic kidney disease (estimated glomerular filtration rate <30 mL/min per 1.73 m2) initiating warfarin, apixaban, or rivaroxaban between 2011 and 2021 were included. Using inverse probability of treatment weighting, adjusted risks of major bleeding, stroke/systemic embolism, and death were compared among agents. A total of 6794 patients were included (mean age, 78.5 years; mean estimated glomerular filtration rate, 24.7 mL/min per 1.73 m2; 51% women). Apixaban versus warfarin was associated with a lower risk of major bleeding (incidence rate, 1.5 versus 2.9 per 100 person-years; subdistribution hazard ratio [sub-HR], 0.53 [95% CI, 0.39-0.70]), and similar risks for stroke/systemic embolism (incidence rate, 1.9 versus 2.4 per 100 person-years; sub-HR, 0.80 [95% CI, 0.59-1.09]) and death (incidence rate, 4.6 versus 4.5 per 100 person-years; HR, 1.03 [95% CI, 0.82-1.29]). Rivaroxaban versus warfarin was associated with a higher risk of major bleeding (incidence rate, 4.9 versus 2.9 per 100 person-years; sub-HR, 1.65 [95% CI, 1.10-2.48]), with no difference in risks for stroke/systemic embolism and death. Apixaban versus rivaroxaban was associated with a lower risk of major bleeding (sub-HR, 0.53 [95% CI, 0.36-0.78]). CONCLUSIONS: These real-world findings are consistent with potential safety advantages of apixaban over warfarin and rivaroxaban for patients with atrial fibrillation and severe chronic kidney disease. Further randomized trials comparing individual oral anticoagulants are warranted.
Sujet(s)
Anticoagulants , Fibrillation auriculaire , Embolie , Hémorragie , Pyrazoles , Pyridones , Insuffisance rénale chronique , Rivaroxaban , Accident vasculaire cérébral , Warfarine , Humains , Fibrillation auriculaire/traitement médicamenteux , Fibrillation auriculaire/complications , Fibrillation auriculaire/mortalité , Femelle , Mâle , Sujet âgé , Insuffisance rénale chronique/complications , Insuffisance rénale chronique/mortalité , Hémorragie/induit chimiquement , Hémorragie/épidémiologie , Accident vasculaire cérébral/prévention et contrôle , Accident vasculaire cérébral/épidémiologie , Accident vasculaire cérébral/étiologie , Accident vasculaire cérébral/mortalité , Anticoagulants/effets indésirables , Anticoagulants/usage thérapeutique , Anticoagulants/administration et posologie , Warfarine/effets indésirables , Warfarine/usage thérapeutique , Rivaroxaban/effets indésirables , Rivaroxaban/usage thérapeutique , Rivaroxaban/administration et posologie , Embolie/prévention et contrôle , Embolie/épidémiologie , Embolie/étiologie , Pyrazoles/effets indésirables , Pyrazoles/usage thérapeutique , Pyridones/effets indésirables , Pyridones/usage thérapeutique , Pyridones/administration et posologie , Administration par voie orale , Appréciation des risques , Sujet âgé de 80 ans ou plus , Facteurs de risque , Études rétrospectives , Indice de gravité de la maladie , Incidence , Inhibiteurs du facteur Xa/effets indésirables , Inhibiteurs du facteur Xa/usage thérapeutique , Inhibiteurs du facteur Xa/administration et posologieRÉSUMÉ
BACKGROUND: This retrospective cohort study aims to compare the effectiveness and safety of warfarin, rivaroxaban, and dabigatran in atrial fibrillation (AF) patients with different CHA2DS2-VASc scores in northern China. METHODS: A retrospective cohort study was performed to evaluate anticoagulation in AF patients at the second affiliated hospital of Harbin Medical University from September 2018 to August 2019. Patients included in this study (n = 806) received warfarin (n = 300), or rivaroxaban (n = 203), or dabigatran (n = 303). Baseline characteristics and follow-up data including adherence, bleeding events and ischemic stroke (IS) events were collected. RESULTS: Patients receiving rivaroxaban (73.9%) or dabigatran (73.6%) showed better adherence than those receiving warfarin (56.7%). Compared with warfarin-treated patients, dabigatran-treated patients had lower incidence of bleeding events (10.9% vs 19.3%, χ2 = 8.385, P = 0.004) and rivaroxaban-treated patients had lower incidence of major adverse cardiovascular events (7.4% vs 13.7%, χ2 = 4.822, P = 0.028). We classified patients into three groups based on CHA2DS2-VASc score (0-1, 2-3, ≥ 4). In dabigatran intervention, incidence of bleeding events was higher in patients with score 0-1 (20.0%) than those with score 2-3 (7.9%, χ2 = 5.772, P = 0.016) or score ≥ 4 (8.6%, χ2 = 4.682, P = 0.030). Patients with score 0-1 in warfarin or rivaroxaban therapy had a similar but not significant increase of bleeding compared with patients with score 2-3 or score ≥ 4, respectively. During the follow-up, 33 of 806 patients experienced IS and more than half (19, 57.6%) were patients with score ≥ 4. Comparing patients with score 0-1 and 2-3, the latter had an significant reduction of IS in patients prescribed warfarin and non-significant reduction in rivaroxaban and dabigatran therapy. CONCLUSION: Compared with warfarin therapy, patients with different CHA2DS2-VASc scores receiving either rivaroxaban or dabigatran were associated with higher persistence. AF patients with score ≥ 4 were more likely to experience IS events while hemorrhagic tendency preferred patients with low score 0-1.
Sujet(s)
Anticoagulants , Fibrillation auriculaire , Dabigatran , Hémorragie , Rivaroxaban , Warfarine , Humains , Fibrillation auriculaire/traitement médicamenteux , Fibrillation auriculaire/diagnostic , Fibrillation auriculaire/complications , Dabigatran/effets indésirables , Dabigatran/usage thérapeutique , Dabigatran/administration et posologie , Rivaroxaban/effets indésirables , Rivaroxaban/usage thérapeutique , Rivaroxaban/administration et posologie , Études rétrospectives , Warfarine/effets indésirables , Warfarine/usage thérapeutique , Mâle , Femelle , Sujet âgé , Hémorragie/induit chimiquement , Adulte d'âge moyen , Résultat thérapeutique , Appréciation des risques , Facteurs de risque , Anticoagulants/effets indésirables , Anticoagulants/usage thérapeutique , Anticoagulants/administration et posologie , Chine/épidémiologie , Facteurs temps , Inhibiteurs du facteur Xa/effets indésirables , Inhibiteurs du facteur Xa/usage thérapeutique , Inhibiteurs du facteur Xa/administration et posologie , Antithrombiniques/effets indésirables , Antithrombiniques/usage thérapeutique , Antithrombiniques/administration et posologie , Sujet âgé de 80 ans ou plus , Adhésion au traitement médicamenteux , Techniques d'aide à la décision , Coagulation sanguine/effets des médicaments et des substances chimiquesRÉSUMÉ
OBJECTIVE: Deep vein thrombosis (DVT) provoked by orthopedic trauma is increasing in pediatric hospitalized patients. The purpose of our study is to identify the prevalence of acute DVT in pediatric and adolescent orthopedic trauma hospitalized patients and focus on evaluating the anticoagulation strategies and the clinical outcomes after a confirmed acute DVT. METHODS: Patients (age ≤18 years) with a confirmed acute DVT admitted for orthopedic trauma between September 2017 and December 2023 were included. Patients were classified into the non-anticoagulation (NA), the in-hospital anticoagulation (IHA), and the in-and-out-of-hospital anticoagulation (IOHA) groups based on their anticoagulation regimen. Efficacy outcomes were the venous thromboembolism (VTE) recurrence within 3 months and change in thrombus burden by repeat imaging at 2 weeks after discharge compared with baseline. Safety outcomes were major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) within 3 months. RESULTS: Of the 11,206 pediatric and adolescent orthopedic trauma inpatients, 94(median age,16 [15, 18] years) were diagnosed with acute DVT, with an incidence of 0.84 %, of which 8(8.5 %) received NA, 41(43.6 %) received IHA, and 45(47.9 %) received IOHA. After the diagnosis of DVT, of patients who received anticoagulation, 97.9 % were treated with rivaroxaban as an oral anticoagulant, and 71.7 % received an LMWH course of ≥5 days before starting rivaroxaban therapy. With a median anticoagulation course of 22(8, 37.3) days, the duration in the IOHA was significantly longer than the IHA (37 days vs. 8 days, p = 0.000). No patients experienced recurrent VTE and MB at 3 months, and 1 received IOHA had a CRNMB event (0 % vs. 0 % vs. 2.2 %, p = 1.000). Thrombus resolution was significantly higher in patients who received anticoagulation therapy (IOHA 91.1 % vs. IHA 80.5 % vs. NA 37.5 %, P = 0.002), and thrombus-no relevant change was significantly lower in patients who received the IOHA strategy compared with the other groups (4.4 % vs. 19.5 % vs. 62.5 %, P = 0.000). CONCLUSIONS: A rivaroxaban-predominant IOHA strategy significantly reduced the thrombotic burden without increasing the risk of bleeding for the treatment of DVT in adolescents with orthopedic trauma. Duration of anticoagulation therapy <6 weeks appears appropriate for adolescent orthopedic trauma-related DVT.
Sujet(s)
Rivaroxaban , Thrombose veineuse , Humains , Adolescent , Rivaroxaban/usage thérapeutique , Rivaroxaban/effets indésirables , Femelle , Mâle , Thrombose veineuse/épidémiologie , Thrombose veineuse/traitement médicamenteux , Thrombose veineuse/prévention et contrôle , Incidence , Enfant , Inhibiteurs du facteur Xa/usage thérapeutique , Inhibiteurs du facteur Xa/effets indésirables , Études rétrospectives , Hospitalisation/statistiques et données numériques , Anticoagulants/usage thérapeutique , Anticoagulants/effets indésirables , Résultat thérapeutique , Hémorragie/induit chimiquement , Hémorragie/épidémiologieRÉSUMÉ
BACKGROUND: Preclinical animal studies have suggested that myeloid cell-synthesized coagulation factor X dampens antitumor immunity and that rivaroxaban, a direct factor Xa inhibitor, can be used to promote tumor immunity. This study was aimed at assessing whether patients with atrial fibrillation taking direct factor Xa inhibitors have lower risk of cancer and cancer-related mortality than patients taking the direct thrombin inhibitor dabigatran. METHODS AND FINDINGS: This nationwide population-based cohort study in Denmark included adult patients with atrial fibrillation and without a history of cancer, who started taking a factor Xa inhibitor or dabigatran between 2011 and 2015. Data on medical history, outcomes, and drug use were acquired through Danish healthcare registries. The primary outcome was any cancer. Secondary outcomes were cancer-related mortality and all-cause mortality. Outcome events were assessed during 5 years of follow-up in an intention-to-treat analysis. The propensity score-based inverse probability of treatment weighting was used to compute cumulative incidence and subdistribution hazard ratios (SHRs) and corresponding 95% confidence intervals (CIs), with death as a competing event. Propensity scores were estimated using logistic regression and including in the model sex, age group at index date, comorbidities, and use of comedications. A total of 11,742 patients with atrial fibrillation starting a factor Xa inhibitor and 11,970 patients starting dabigatran were included. Mean age was 75.2 years (standard deviation [SD] 11.2) in the factor Xa cohort and 71.7 years (SD 11.1) in the dabigatran cohort. On the basis of the propensity score-weighted models, after 5 years of follow-up, no substantial difference in the cumulative incidence of cancer was observed between the factor Xa inhibitor (2,157/23,711; 9.11%, 95% CI [8.61%,9.63%]) and dabigatran (2,294/23,715; 9.68%, 95% CI [9.14%,10.25%]) groups (SHR 0.94, 95% CI [0.89,1.00], P value 0.0357). We observed no difference in cancer-related mortality (factor Xa inhibitors cohort 1,028/23,711; 4.33%, 95% CI [4.02%,4.68%]. Dabigatran cohort 1,001/23,715; 4.22%, 95% CI [3.83%,4.66%]; SHR 1.03, 95% CI [0.94,1.12]), but all-cause mortality was higher in the factor Xa inhibitor cohort (factor Xa inhibitors cohort 7,416/23,711; 31.31%, 95% CI [30.37%,32.29%]. Dabigatran cohort 6,531/23,715; 27.56%, 95% CI [26.69%,28.45%]; HR 1.17, 95% CI [1.13,1.21]). The main limitations of the study were the possibility of residual confounding and the short follow-up period. CONCLUSIONS: In this population based cohort study, factor Xa inhibitor use was not associated with an overall lower incidence of cancer or cancer-related mortality when compared to dabigatran. We did observe an increase in all-cause mortality in the factor Xa inhibitor cohort.
Sujet(s)
Fibrillation auriculaire , Dabigatran , Inhibiteurs du facteur Xa , Tumeurs , Humains , Inhibiteurs du facteur Xa/usage thérapeutique , Inhibiteurs du facteur Xa/effets indésirables , Tumeurs/mortalité , Tumeurs/épidémiologie , Danemark/épidémiologie , Mâle , Femelle , Sujet âgé , Fibrillation auriculaire/traitement médicamenteux , Fibrillation auriculaire/mortalité , Fibrillation auriculaire/épidémiologie , Adulte d'âge moyen , Sujet âgé de 80 ans ou plus , Dabigatran/usage thérapeutique , Dabigatran/effets indésirables , Études de cohortes , Enregistrements , Rivaroxaban/usage thérapeutique , Rivaroxaban/effets indésirables , Facteurs de risque , Incidence , Antithrombiniques/usage thérapeutique , Antithrombiniques/effets indésirablesRÉSUMÉ
Vitamin K antagonists (VKA) remain the only option of anticoagulation for people with mechanical valve replacement and due to their wider availability and lower acquisition costs, VKA's remain widely used in low- and middle-income countries. It has been suggested that prolonged use of VKAs can increase the development of vascular and valvular calcification, though this effect has not been examined in larger randomized prospective trials. This investigator-initiated multicenter, prospective, randomized, open-label interventional trial randomized patients with baseline coronary or valvular calcification and an indication for prolonged oral anticoagulation therapy to Marcumar or Rivaroxaban. Patients were followed-up through repeat coronary computed tomographies to measure the progression of coronary and valvular calcification for up to 24 months. 192 patients were randomized between 2013 and 2018 to receive either Rivaroxaban or Marcumar and followed for up to 24 months. Coronary calcification significantly increased over time although there was no significant difference in progression between the groups after 12 and 24 months as measured by the Agatston score [360.7 (90.2; 1075.3) vs 380.4 (136.4; 1546.9) p = 0.69], the volume score [295.8 (93.0; 995.3) vs 335.5 (128.7; 1316.9) p = 0.95] and the mass score [58.5 (15.9; 172.0) vs 71.1 (24.8; 257.3) p = 0.5]. Dephosphorylated, uncarboxylated matrix Gla Protein (Dp-ucMGP) significantly decreased in the VKA group [Δ dp-uc MGP - 95.2 (- 554.1; 156.0) vs 231.3 (- 59.7; 388.1) p < 0.001]. There does not appear to be a relevant effect of vitamin K inhibition by the vitamin K antagonist marcumar upon coronary calcification.