RESUMEN
Concomitant direct oral anticoagulants (DOACs) and tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (anti-VEGF TKI) have been associated with a higher risk of bleeding. Nevertheless, concomitant administration seems frequent in clinical practice in patients with cancer-associated thrombosis and appears to be safe according to the retrospective study by Boileve A. et al. But the risk of an additional pharmacokinetic interaction between anti-VEGF TKI and DOACs must be considered, in case of P-glycoprotein (P-gp) inhibition by the TKI. We describe a case report with a major bleeding event in a renal metastatic cancer patient treated with cabozantinib and rivaroxaban. This case highlights the difficult therapeutic decision in a complex patient with cancer-associated thrombosis, who refused the anticoagulant subcutaneous route. Accumulation of bleeding risk factors (genito-urinary tumor localization) was additive to several pharmacodynamic interactions (acetylsalicylic acid, venlafaxine) and a potential pharmacokinetic interaction between cabozantinib and rivaroxaban. Indeed, cabozantinib-related P-glycoprotein inhibition could have led to a supratherapeutic level of rivaroxaban, contributing partly to the bleeding event. Before combining an anti-VEGF TKI and DOACs, a multidisciplinary pretherapeutic assessment seems crucial to evaluate the patient's bleeding risk factors, pharmacodynamic interactions, and the risk of pharmacokinetic interactions mediated by P-gp.
Asunto(s)
Anticoagulantes , Interacciones Farmacológicas , Piridinas , Rivaroxabán , Humanos , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Estudios Retrospectivos , Piridinas/efectos adversos , Piridinas/administración & dosificación , Piridinas/uso terapéutico , Piridinas/farmacocinética , Rivaroxabán/administración & dosificación , Rivaroxabán/efectos adversos , Rivaroxabán/farmacocinética , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Anilidas/administración & dosificación , Anilidas/efectos adversos , Anilidas/farmacocinética , Hemorragia/inducido químicamente , Neoplasias Renales/tratamiento farmacológico , Masculino , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacocinética , Trombosis/inducido químicamente , Trombosis/etiología , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Administración Oral , AncianoRESUMEN
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.
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Fibrinolíticos , Enfermedad Arterial Periférica , Humanos , Enfermedad Arterial Periférica/cirugía , Fibrinolíticos/uso terapéutico , Trombosis/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Extremidad Inferior/irrigación sanguínea , Extremidad Inferior/cirugía , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Rivaroxabán/uso terapéutico , Rivaroxabán/administración & dosificaciónRESUMEN
Despite a higher safety profile compared to vitamin K antagonists, rivaroxaban therapy is still connected with multiple adverse effects, such as a high risk of bleeding. Thus, therapeutic drug monitoring (TDM) of rivaroxaban concentrations is suggested. An alternative to plasma samples can be dried blood spots (DBS), which minimize the cost of sample storage and transport. In this study, we developed a UPLC-MS/MS method for the analysis of rivaroxaban in DBS and plasma samples. Chromatographic separation was achieved on a Zorbax Eclipse Plus C18 column (2.1 × 100 mm; 3.5 µm, Agilent Technologies Inc., Santa Clara, CA, USA) with a mobile phase consisting of water and acetonitrile, both containing 0.1% formic acid. The analytes were detected using a positive ionization mode by multiple reaction monitoring. We validated the method according to ICH guidelines. The precision and accuracy were satisfactory. Extraction recovery was approximately 57% and 66% for DBS and plasma samples, respectively. A high correlation between rivaroxaban concentrations in plasma and DBS samples collected from patients was confirmed with Deming regression. The suitability of both sampling techniques for the rivaroxaban TDM was also verified by Bland-Altman plots based on DBS-predicted and observed plasma concentrations. In addition, we found a significant relationship between rivaroxaban concentrations and coagulation parameters, including prothrombin time (PT) and international normalized ratio (INR).
Asunto(s)
Pruebas con Sangre Seca , Monitoreo de Drogas , Rivaroxabán , Espectrometría de Masas en Tándem , Trombosis de la Vena , Rivaroxabán/sangre , Humanos , Espectrometría de Masas en Tándem/métodos , Pruebas con Sangre Seca/métodos , Cromatografía Líquida de Alta Presión/métodos , Trombosis de la Vena/sangre , Trombosis de la Vena/tratamiento farmacológico , Monitoreo de Drogas/métodos , Inhibidores del Factor Xa/sangre , Reproducibilidad de los Resultados , Cromatografía Líquida con Espectrometría de MasasRESUMEN
BACKGROUND: The first purpose of this study was to determine whether a measurement of the level of direct oral anticoagulants (DOACs) was possible with heparin-calibrated chromogenic anti-factor Xa activity (AXA). The second purpose of this study was to evaluate whether the antidote treatment decision level (30 or 50 ng/mL of DOAC) can be determined by unfractionated heparin (UHF)/low molecular weight heparin (LMWH)-calibrated AXA. METHODS: AXA was measured by using two reagents and dedicated analyzers (Sysmex CS-5100 analyzer and STA R Max3). Four types of calibrators were used: 1) Stago DOAC (rivaroxaban, edoxaban, and apixaban)-specific calibrator, 2) Stago LMWH calibrator, 3) Sysmex UHF calibrator, and 4) Sysmex LMWH calibrator. Regression analysis was used between assays. Receiver operating characteristic (ROC) curves were performed, and the concordance rate was calculated. RESULTS: The correlation coefficients were in the range of 0.75 - 0.91 for rivaroxaban and 0.81 - 0.94 for apixaban. The correlation coefficient between edoxaban-calibrated AXA and Sysmex LMWH/Sysmex UHF calibrator-calibrated AXA was low (r = 0.47). Overall correlation between DOAC-calibrated AXA and Stago LMWH-calibrated AXA was linear, at only low concentration in all three DOACs. The concordance rate (89.3 - 100%) is good for de-termining the antidote management level by UFH/LMWH-calibrated AXA, compared with those of DOAC-calibrated AXA in rivaroxaban and apixaban. The concordance rate ranged from 63% to 67% between Sysmex UFH/ LMWH-calibrated AXA and edoxaban-calibrated AXA. CONCLUSIONS: The findings of our study suggest limitations in calculating accurate concentrations, when using UFH/LMWH-calibrated AXA to measure DOAC. This study demonstrates that UFH/LMWH-calibrated AXA may be useful in determining the presence of DOACs at the cutoff level for the antidote treatment in rivarovaban and apixaban. However, in edoxaban, UFH/LMWH-calibrated AXA could not accurately measure the presence of DOACs at the cutoff for antidote treatment.
Asunto(s)
Inhibidores del Factor Xa , Heparina , Pirazoles , Piridinas , Piridonas , Rivaroxabán , Tiazoles , Piridonas/análisis , Humanos , Pirazoles/análisis , Rivaroxabán/sangre , Rivaroxabán/análisis , Inhibidores del Factor Xa/farmacología , Calibración , Heparina/análisis , Anticoagulantes/farmacología , Anticoagulantes/análisis , Curva ROC , Reproducibilidad de los Resultados , Pruebas de Coagulación Sanguínea/métodos , Pruebas de Coagulación Sanguínea/instrumentación , Pruebas de Coagulación Sanguínea/normas , Monitoreo de Drogas/métodos , Monitoreo de Drogas/instrumentaciónRESUMEN
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.
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Anticoagulantes , Fibrilación Atrial , Coagulación Sanguínea , Dabigatrán , Rivaroxabán , Warfarina , Humanos , Dabigatrán/efectos adversos , Dabigatrán/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Rivaroxabán/efectos adversos , Rivaroxabán/uso terapéutico , Masculino , Femenino , Anciano , Estudios Retrospectivos , Warfarina/efectos adversos , Warfarina/uso terapéutico , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Coagulación Sanguínea/efectos de los fármacos , Resultado del Tratamiento , Anciano de 80 o más Años , Antitrombinas/efectos adversos , Antitrombinas/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/epidemiologíaRESUMEN
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.
Asunto(s)
Anticoagulantes , Menorragia , Calidad de Vida , Humanos , Femenino , Menorragia/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Adulto , Estudios Prospectivos , Persona de Mediana Edad , Incidencia , Warfarina/uso terapéutico , Warfarina/efectos adversos , Administración Oral , Rivaroxabán/uso terapéutico , Rivaroxabán/efectos adversos , Rivaroxabán/administración & dosificación , Sudáfrica , Factores de RiesgoRESUMEN
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.
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Anticoagulantes , Inflamación , Receptores Proteinasa-Activados , Transducción de Señal , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Anticoagulantes/uso terapéutico , Anticoagulantes/farmacología , Anticoagulantes/administración & dosificación , Receptores Proteinasa-Activados/metabolismo , Transducción de Señal/efectos de los fármacos , Administración Oral , Animales , Rivaroxabán/uso terapéutico , Rivaroxabán/farmacología , Rivaroxabán/administración & dosificación , Piridonas/farmacología , Piridonas/uso terapéutico , Piridonas/administración & dosificaciónRESUMEN
ABSTRACT: The dual pathway inhibition (DPI) with low-dose rivaroxaban and aspirin in patients with stable atherosclerotic vascular disease reduces the occurrence of cardiovascular events, with no significant increase of intracranial or other critical organ bleedings. Our observational study aimed to describe the clinical performance, adherence, and persistence of DPI therapy among a real-world setting of patients with an established diagnosis of coronary artery (CAD) and/or peripheral artery disease (PAD). We prospectively included all consecutive patients with an established diagnosis of CAD and/or PAD treated with aspirin (ASA) 100 mg once daily and rivaroxaban 2.5 mg twice daily. Clinical evaluation was performed at baseline, before starting treatment, at 1 month, and every 6 months after the study drug administration. A total of 202 consecutive patients (mean age 66 ± 10 years; male 80%) eligible to DPI therapy were included. During a mean follow-up of 664 ± 177 days, the incidence rate of major bleedings and of major adverse cardiovascular events was 0.8 and 1.1 per 100 patients/year, respectively. The adherence to pharmacological treatment was 99%. Additionally, 13.4% of patients suspended the DPI therapy during the follow-up. Minor bleedings resulted the most common cause of both temporary and permanent DPI therapy discontinuation. This observational study supports the safety of DPI with low-dose rivaroxaban and aspirin among patients with CAD and PAD in a real-world setting, showing high persistence and maximum adherence to medical treatment.
Asunto(s)
Aspirina , Enfermedad de la Arteria Coronaria , Inhibidores del Factor Xa , Hemorragia , Cumplimiento de la Medicación , Enfermedad Arterial Periférica , Inhibidores de Agregación Plaquetaria , Rivaroxabán , Humanos , Rivaroxabán/efectos adversos , Rivaroxabán/administración & dosificación , Aspirina/efectos adversos , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Masculino , Anciano , Femenino , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/administración & dosificación , Enfermedad Arterial Periférica/tratamiento farmacológico , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/epidemiología , Estudios Prospectivos , Persona de Mediana Edad , Hemorragia/inducido químicamente , Resultado del Tratamiento , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Factores de Tiempo , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/diagnóstico , Factores de RiesgoRESUMEN
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.
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Artroplastia de Reemplazo de Rodilla , Teorema de Bayes , Metaanálisis en Red , Tromboembolia Venosa , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/etiología , Rivaroxabán/uso terapéutico , Rivaroxabán/administración & dosificación , Piridonas/administración & dosificación , Piridonas/uso terapéutico , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Dabigatrán/uso terapéutico , Dabigatrán/administración & dosificación , Pirazoles/uso terapéutico , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Embolia Pulmonar/prevención & control , Embolia Pulmonar/etiología , Enoxaparina/administración & dosificación , Enoxaparina/uso terapéutico , Hemorragia/inducido químicamente , Femenino , Fondaparinux/uso terapéutico , Piridinas , TiazolesRESUMEN
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.
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Anticoagulantes , Inhibidores de Agregación Plaquetaria , Humanos , Anticoagulantes/uso terapéutico , Femenino , Masculino , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Persona de Mediana Edad , Tiempo de Sangría , Hemorragia Bucal/prevención & control , Hemorragia Bucal/etiología , Anciano , Adulto , Higiene Bucal , Dabigatrán/uso terapéutico , Dabigatrán/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Warfarina/uso terapéutico , Warfarina/efectos adversos , Clopidogrel/uso terapéutico , Clopidogrel/efectos adversos , Pirazoles/uso terapéutico , Aspirina/efectos adversos , Aspirina/uso terapéutico , Rivaroxabán/uso terapéutico , Rivaroxabán/efectos adversosRESUMEN
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.
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Anticoagulantes , Fibrilación Atrial , Embolia , Hemorragia , Pirazoles , Piridonas , Insuficiencia Renal Crónica , Rivaroxabán , Accidente Cerebrovascular , Warfarina , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/mortalidad , Femenino , Masculino , Anciano , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/mortalidad , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidad , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Warfarina/efectos adversos , Warfarina/uso terapéutico , Rivaroxabán/efectos adversos , Rivaroxabán/uso terapéutico , Rivaroxabán/administración & dosificación , Embolia/prevención & control , Embolia/epidemiología , Embolia/etiología , Pirazoles/efectos adversos , Pirazoles/uso terapéutico , Piridonas/efectos adversos , Piridonas/uso terapéutico , Piridonas/administración & dosificación , Administración Oral , Medición de Riesgo , Anciano de 80 o más Años , Factores de Riesgo , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Incidencia , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/administración & dosificaciónRESUMEN
AIM: To evaluate the prognostic value of GDF-15 in relation the development of bleeding and events in stable CAD patients, receiving combined antithrombotic therapy. MATERIALS AND METHODS: The data was obtained from the prospective registry REGATA, 343 CAD patients (249 males), median age 68 [IQR 62; 75] years) were enrolled. Patients with sinus rhythm and concomitant PAD received acetylsalicylic acid in combination with rivaroxaban 2.5 mg bid (31.8%) or clopidogrel (24.8%). Other 43.4% with concomitant atrial fibrillation (AF) received direct oral anticoagulants in combination with antiplatelet therapy after elective percutaneous coronary interventions. Median follow-up was 12 months [IQR 9.0; 18.0]. The safety end point was major and clinically relevant bleedings (type 2-5) according to the BARC classification. Plasma samples for GDF-15 identification were taken at the inclusion and analyzed using ELISA assay. RESULTS: Frequency of BARC 2-5 bleedings was 16% (BARC 2 - 46; BARC 3 - 9; BARC 4-5 - 0), median GDF-15 level was 1185.0 pg/ml [850.0; 1680.0]. In patients with AF and concomitant MFA, the level of GDF-15 was significantly higher than in the subgroups of patients with only AF or MFA (p=0.0022). According to the quintile analysis, GDF-15 values in the top three quintiles of distribution (cut-off value >943 pg/ml) were associated with higher frequency of bleeding events: 23.2% versus 5.1%; p=0.0001. The multivariable logistic regression model demonstrated that bleeding events were independently associated with GDF-15 level>943 pg/ml (OR 2.65, 95% CI 1.11-6.30; p=0.0275), AF (OR 2.61, 95% CI 1.41-4.83; p=0.0023) and chronic kidney disease (OR 1.92, 95% CI 1.03-3.60; p=0.0401). Clinical factors determining the risk of bleeding events also determined a GDF-15 elevation. CONCLUSION: Assessment of GDF-15 level may improve bleeding risk stratification in CAD patients with concomitant AF and/or PAD receiving combined antithrombotic therapy.
Asunto(s)
Factor 15 de Diferenciación de Crecimiento , Hemorragia , Sistema de Registros , Humanos , Masculino , Femenino , Anciano , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Hemorragia/etiología , Persona de Mediana Edad , Factor 15 de Diferenciación de Crecimiento/sangre , Estudios Prospectivos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/sangre , Quimioterapia Combinada , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Aspirina/administración & dosificación , Aspirina/efectos adversos , Clopidogrel/administración & dosificación , Clopidogrel/efectos adversos , Pronóstico , Federación de Rusia/epidemiología , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Rivaroxabán/administración & dosificación , Rivaroxabán/efectos adversos , Intervención Coronaria Percutánea/métodos , Intervención Coronaria Percutánea/efectos adversosRESUMEN
Importance: Direct oral anticoagulants (DOACs), comprising apixaban, rivaroxaban, edoxaban, and dabigatran, are commonly used medications to treat patients with atrial fibrillation and venous thromboembolism. Decisions about how to manage DOACs in patients undergoing a surgical or nonsurgical procedure are important to decrease the risks of bleeding and thromboembolism. Observations: For elective surgical or nonsurgical procedures, a standardized approach to perioperative DOAC management involves classifying the risk of procedure-related bleeding as minimal (eg, minor dental or skin procedures), low to moderate (eg, cholecystectomy, inguinal hernia repair), or high risk (eg, major cancer or joint replacement procedures). For patients undergoing minimal bleeding risk procedures, DOACs may be continued, or if there is concern about excessive bleeding, DOACs may be discontinued on the day of the procedure. Patients undergoing a low to moderate bleeding risk procedure should typically discontinue DOACs 1 day before the operation and restart DOACs 1 day after. Patients undergoing a high bleeding risk procedure should stop DOACs 2 days prior to the operation and restart DOACs 2 days after. With this perioperative DOAC management strategy, rates of thromboembolism (0.2%-0.4%) and major bleeding (1%-2%) are low and delays or cancellations of surgical and nonsurgical procedures are infrequent. Patients taking DOACs who need emergent (<6 hours after presentation) or urgent surgical procedures (6-24 hours after presentation) experience bleeding rates up to 23% and thromboembolism as high as 11%. Laboratory testing to measure preoperative DOAC levels may be useful to determine whether patients should receive a DOAC reversal agent (eg, prothrombin complex concentrates, idarucizumab, or andexanet-α) prior to an emergent or urgent procedure. Conclusions and Relevance: When patients who are taking a DOAC require an elective surgical or nonsurgical procedure, standardized management protocols can be applied that do not require testing DOAC levels or heparin bridging. When patients taking a DOAC require an emergent, urgent, or semiurgent surgical procedure, anticoagulant reversal agents may be appropriate when DOAC levels are elevated or not available.
Asunto(s)
Anticoagulantes , Reversión de la Anticoagulación , Pérdida de Sangre Quirúrgica , Atención Perioperativa , Hemorragia Posoperatoria , Humanos , Administración Oral , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Anticoagulantes/sangre , Fibrilación Atrial/tratamiento farmacológico , Atención Perioperativa/métodos , Piridinas/administración & dosificación , Piridinas/efectos adversos , Piridinas/sangre , Rivaroxabán/administración & dosificación , Rivaroxabán/efectos adversos , Rivaroxabán/sangre , Tromboembolia Venosa/tratamiento farmacológico , Dabigatrán/administración & dosificación , Dabigatrán/efectos adversos , Dabigatrán/sangre , Tiazoles/administración & dosificación , Tiazoles/efectos adversos , Tiazoles/sangre , Pérdida de Sangre Quirúrgica/prevención & control , Hemorragia Posoperatoria/inducido químicamente , Hemorragia Posoperatoria/epidemiología , Hemorragia Posoperatoria/prevención & control , Procedimientos Quirúrgicos Electivos/efectos adversos , Reversión de la Anticoagulación/métodosRESUMEN
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.).
Asunto(s)
Aspirina , Inhibidores del Factor Xa , Claudicación Intermitente , Enfermedad Arterial Periférica , Rivaroxabán , Humanos , Rivaroxabán/uso terapéutico , Rivaroxabán/administración & dosificación , Rivaroxabán/efectos adversos , Claudicación Intermitente/tratamiento farmacológico , Femenino , Masculino , Anciano , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Aspirina/efectos adversos , Persona de Mediana Edad , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/farmacología , Enfermedad Arterial Periférica/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Quimioterapia Combinada , Resultado del Tratamiento , Hemorragia/inducido químicamenteRESUMEN
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.