RESUMEN
ABSTRACT: In this study, we investigated the safety and efficacy of fondaparinux sodium in postpercutaneous coronary intervention (PCI) anticoagulation therapy for patients with ST-segment elevation myocardial infarction. There are a total of 200 patients with ST segment elevation myocardial infarction underwent PCI and anticoagulation therapy. They were randomly split into experimental (n = 108) and control groups (n = 92). The experimental group received postoperative fondaparinux sodium (2.5 mg q.d), while the control group received enoxaparin (4000 IU q12 h). We did not use a loading dose for enoxaparin. Bleeding incidence and major adverse cardiovascular/cerebrovascular events were monitored during hospitalization, and at 1, 3, and 6 months postsurgery. The primary end points, including bleeding, mortality, and myocardial infarction during hospitalization, were not significantly different between the 2 groups. For secondary end points, the incidence of combined end point events at 1 month, 3 months, and 6 months after surgery in the experimental group was lower than in the control group (P < 0.05). According to Cox regression analysis, the risk of bleeding in the experimental group was significantly lower than that in the control group [hazard ratios: 0.506, 95% confidence interval (CI): 0.284-0.900] (P = 0.020). The risk of mortality in the experimental group was significantly lower than in the control group (hazard ratio: 0.188, 95% CI: 0.040-0.889) (P = 0.035). In summary, perioperative use of fondaparinux sodium during PCI in patients with STEMI in this study was associated with a lower risk of bleeding and death compared with enoxaparin use in the absence of loading dose.
Asunto(s)
Enoxaparina , Fondaparinux , Hemorragia , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Fondaparinux/uso terapéutico , Fondaparinux/efectos adversos , Fondaparinux/administración & dosificación , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Anciano , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/mortalidad , Infarto del Miocardio con Elevación del ST/diagnóstico , China/epidemiología , Resultado del Tratamiento , Hemorragia/inducido químicamente , Enoxaparina/efectos adversos , Enoxaparina/administración & dosificación , Enoxaparina/uso terapéutico , Factores de Riesgo , Factores de Tiempo , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/uso terapéutico , Estudios ProspectivosRESUMEN
BACKGROUND: Direct oral anticoagulants (DOACs) have complex dosing regimens and are often incorrectly prescribed. We evaluated a nationwide DOAC population management dashboard rollout whose purpose includes pharmacist review and correction of off-label dosing prescriptions. METHODS AND RESULTS: Using data from Veterans Health Affairs, we identified all patients prescribed DOACs for atrial fibrillation or venous thromboembolism between August 2015 and December 2019. Sites were grouped on the basis of the timing of moderate-high usage of the DOAC population management tool dashboard. Effectiveness was defined as the monthly rate of off-label DOAC prescribing and the rate of clinical adverse events (bleeding, composite of stroke or venous thromboembolism). Implementation was evaluated as the percentage of off-label DOAC prescriptions changed within 7 days. Among the 128 652 patients receiving DOAC therapy at 123 centers, between 6.9% and 8.6% had off-label DOAC prescriptions. Adoption of the DOAC population management tool dashboard before July 2018 was associated with a decline in off-label dosing prescriptions (8.7%-7.6%). Only 1 group demonstrated a significant reduction in monthly rates of bleeding following implementation. All sites experienced a reduction in the composite of venous thromboembolism or stroke following dashboard adoption. There was no difference in the implementation outcome of DOAC prescription change within 7 days in any of the adoption groups. CONCLUSIONS: Early adoption of the DOAC population management tool dashboard was associated with decreased rates of off-label DOAC dosing prescription and reduced bleeding. Following adoption of the DOAC population management tool dashboard, all sites experienced reductions in venous thromboembolism and stroke events.
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Fibrilación Atrial , Uso Fuera de lo Indicado , Farmacéuticos , Tromboembolia Venosa , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Estados Unidos , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/epidemiología , Femenino , Masculino , Anciano , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/epidemiología , Administración Oral , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/administración & dosificación , Pautas de la Práctica en Medicina/normas , Prescripciones de Medicamentos/estadística & datos numéricos , United States Department of Veterans AffairsRESUMEN
BACKGROUND: Direct oral anticoagulants are the standard of care for stroke prevention in eligible patients with atrial fibrillation and atrial flutter; however, bleeding remains a significant concern, limiting their use. Milvexian is an oral Factor XIa inhibitor that may offer similar anticoagulant efficacy with less bleeding risk. METHODS: LIBREXIA AF (NCT05757869) is a global phase III, randomized, double-blind, parallel-group, event-driven trial to compare milvexian with apixaban in participants with atrial fibrillation or atrial flutter. Participants are randomly assigned to milvexian 100 mg or apixaban (5 mg or 2.5 mg per label indication) twice daily. The primary efficacy objective is to evaluate if milvexian is noninferior to apixaban for the prevention of stroke and systemic embolism. The principal safety objective is to evaluate if milvexian is superior to apixaban in reducing the endpoint of International Society of Thrombosis and Hemostasis (ISTH) major bleeding events and the composite endpoint of ISTH major and clinically relevant nonmajor (CRNM) bleeding events. In total, 15,500 participants from approximately 1,000 sites in over 30 countries are planned to be enrolled. They will be followed until both 430 primary efficacy outcome events and 530 principal safety events are observed, which is estimated to take approximately 4 years. CONCLUSION: The LIBREXIA AF study will determine the efficacy and safety of the oral Factor XIa inhibitor milvexian compared with apixaban in participants with either atrial fibrillation or atrial flutter. TRIAL REGISTRATION: ClinicalTrials.gov NCT05757869.
Asunto(s)
Fibrilación Atrial , Inhibidores del Factor Xa , Pirazoles , Piridonas , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Pirazoles/uso terapéutico , Pirazoles/administración & dosificación , Piridonas/uso terapéutico , Piridonas/administración & dosificación , Piridonas/efectos adversos , Método Doble Ciego , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiología , Masculino , Femenino , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/administración & dosificación , Aleteo Atrial/complicaciones , Hemorragia/inducido químicamente , Persona de Mediana Edad , Anciano , Factor XIa/antagonistas & inhibidores , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversosRESUMEN
BACKGROUND: Following the COVID-19 pandemic, microvascular and macrovascular thrombotic problems emerged that required anticoagulants. Apixaban (RN) is a factor Xa inhibitor that treats deep vein thrombosis and the two forms of artery diseases (coronary artery disease and peripheral artery disease). MATERIALS AND METHODS: The study objective was to create fast-disintegrating Apixaban Oral Thin Films (OTF) with the help of various super disintegrants to shorten disintegration time and enhance drug release in order to assist patients who have difficulty in swallowing conventional dosage forms and increase bioavailability. OTF was created using the solvent casting method. A 22 factorial design was employed in Design-Expert® software to develop an ideal formula. RESULTS: The optimized film formula pH, drug content, disintegration time, folding endurance, and dissolution rate were estimated, and the film was subjected to a short-term stability study. The optimized formula exhibited a cumulative drug release of 93.47% in 60 sec. CONCLUSION: The drug's in vitro release pattern shows first-order kinetics and fickian diffusion was the mechanism of drug release. These findings supported that Apixaban OTFs offer a quick release of the medication from the administration site into the systemic circulation.
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Inhibidores del Factor Xa , Pirazoles , Piridonas , Piridonas/administración & dosificación , Piridonas/química , Piridonas/farmacocinética , Pirazoles/administración & dosificación , Pirazoles/farmacocinética , Pirazoles/química , Administración Oral , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/farmacocinética , Inhibidores del Factor Xa/química , Humanos , Liberación de Fármacos , SolubilidadRESUMEN
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
Therapeutic plasma exchange (TPE) is used as an effective treatment modality for a variety of autoimmune disorders. Apart from its desired effect of removing pathological blood components, it also can remove coagulation factors and drugs. Currently, there is an insufficient amount of information regarding the use of direct oral anticoagulants in this setting. In this article, we present a case report of a patient with myasthenia gravis and chronic anticoagulation with apixaban who underwent a series of TPE while continuing apixaban treatment. We observed that only 10% of daily dose was removed by the procedure and plasma levels of apixaban corresponded with expected range. TPE was not associated with shortened drug plasma half-life. We did not observe any significant alteration of apixaban pharmacokinetics during the period of TPE therapy, as well as no thrombotic or bleeding events. This case report supports the use of apixaban in patients treated by TPE, nevertheless, to firmly establish apixaban efficacy and safety profile in this clinical setting further research is needed.
Asunto(s)
Inhibidores del Factor Xa , Intercambio Plasmático , Pirazoles , Piridonas , Humanos , Piridonas/administración & dosificación , Pirazoles/administración & dosificación , Pirazoles/farmacocinética , Intercambio Plasmático/métodos , Inhibidores del Factor Xa/administración & dosificación , Miastenia Gravis/tratamiento farmacológico , Miastenia Gravis/terapia , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Femenino , Persona de Mediana Edad , Semivida , Masculino , AncianoRESUMEN
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
Chronic kidney disease (CKD) remains a significant global health issue and is a leading cause of mortality worldwide. Patients with CKD have an increased risk of developing atrial fibrillation (AF) and venous thromboembolism (VTE). While direct oral anticoagulants (DOACs) have become a standard of care for anticoagulation (AC) in patients with AF and VTE, the appropriate use of these agents in comorbid kidney impairment warrants detailed discussion. This scientific narrative review summarizes the effectiveness and safety of apixaban use in patients with renal dysfunction by assessing the current published pharmacokinetic, interventional, observational, and guideline data. Apixaban is a highly selective, orally active, direct inhibitor of factor Xa, with well-established pharmacokinetics and consistent clinical outcomes across a broad range of patient populations, including those with kidney impairment. Overall, the scientific literature has shown that apixaban has a favorable clinical efficacy and safety profile compared with vitamin K antagonists for patients with AF or VTE and comorbid kidney impairment. These data support the approved label dosing strategy of apixaban in reducing the risk of stroke/systemic embolism in patients with nonvalvular AF and in treating VTE across all ranges of kidney function. Both clinician experience and knowledge of patient-specific factors may be required in the management of comorbid patients with advanced CKD or those requiring dialysis, as data on these patients are limited.
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Fibrilación Atrial , Inhibidores del Factor Xa , Pirazoles , Piridonas , Insuficiencia Renal Crónica , Tromboembolia Venosa , Humanos , Piridonas/farmacocinética , Piridonas/efectos adversos , Piridonas/uso terapéutico , Piridonas/administración & dosificación , Pirazoles/farmacocinética , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Pirazoles/administración & dosificación , Inhibidores del Factor Xa/farmacocinética , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Tromboembolia Venosa/tratamiento farmacológico , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/epidemiología , Estudios Observacionales como Asunto , Anticoagulantes/efectos adversos , Anticoagulantes/farmacocinética , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificaciónRESUMEN
The goal of the current study was to formulate and examine the potential of poly (lactic-co-glycolic acid) (PLGA) as carriers to facilitate the targeted administration of edoxaban tosylate monohydrate (ETM). ETM-PLGA-NPs were effectively formulated using the nanoprecipitation technique. Particle size, drug entrapment percentage, zeta potential, assessment of intestinal absorption, FT-IR, SEM, drug dissolution behavior, and histopathology investigations were used to describe ETM-PLGA-NPs. The produced NPs had a roughly spherical shape with a particle size of 99.85 d.nm, a PDI of 0.478, and a zeta potential of 38.5 mV with a maximum drug entrapment of 82.1 %. FTIR measurements showed that the drug's chemical stability remained intact after preapred into nanoparticles. In vitro drug release behavior followed the Higuchi model and revealed an early burst release of 30 % and persistent drug release of 78 % from optimized NPs for up to 120 hrs. According to in vitro data, a 1:10 ratio of ETM to PLGA provided longer-lasting ETM release and improved encapsulation efficiency. Images captured with an inverted fluorescent microscope exhibited that NPs may both greatly increase the amount of ETM accumulated in the intestinal tract and make it easier for ETM to enter the membrane beneath the cells of the intestines. The study found that using PLGA nanoparticles to encapsulate the ETM resulted in longer circulation duration (aPTT, PT, TT). In vivo investigations found that nanoparticles encapsulated had no negative impact on hematological parameters, lung, liver, or kidney tissues. All things considered, the NPs are a potential delivery method to increase the oral absorption and antithrombotic activity of ETM.
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Portadores de Fármacos , Liberación de Fármacos , Nanopartículas , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Piridinas , Tiazoles , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Nanopartículas/química , Animales , Portadores de Fármacos/química , Tiazoles/farmacocinética , Tiazoles/administración & dosificación , Tiazoles/química , Piridinas/administración & dosificación , Piridinas/farmacocinética , Piridinas/química , Ratas , Masculino , Ácido Láctico/química , Absorción Intestinal/efectos de los fármacos , Ácido Poliglicólico/química , Sistemas de Liberación de Medicamentos/métodos , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/farmacocinética , Ratas Wistar , Distribución TisularAsunto(s)
Anticoagulantes , Humanos , Administración Oral , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/administración & dosificación , Hemorragia/inducido químicamente , Hemorragia/prevención & controlRESUMEN
BACKGROUND: The MAS study (Blood Advances 2024) showed that a high proportion of Italian AF patients treated with direct oral anticoagulants (DOACs) receive reduced doses. This sub-analysis of MAS data aimed to analyze the effects of reduced (appropriate or not)- or standard-dose use on DOAC activity assessed at baseline and the occurrence of thrombotic or bleeding complications during follow-up. METHODS: The MAS study design, the methods for DOAC measurement, the results, and the adverse events during follow-up, are described in detail elsewhere. RESULTS: Seven hundred AF patients (42 % of the total 1657) received a reduced dose (considered inappropriate in 140 [20 %]). They were older, more frequently women, with lower body mass index (BMI), hemoglobin levels, and creatinine clearance. They more often had cerebral or cardiovascular diseases, were taking more medications, with higher scores for thrombotic or bleeding risk. Despite the use of low doses, 133 (19.0 %) patients had high standardized C-trough DOAC levels and experienced a high proportion of bleeding events (8.3 % per year). Conversely, some patients (4.7 %) had very low levels, resulting in a high incidence of thrombotic events (6.7 % per year). No difference was detected if the reduced dose was appropriate or not. CONCLUSION: The unpredictable, highly variable inter-individual anticoagulant effect of DOACs may lead to either too low or too high anticoagulant levels, increasing the risk of thrombotic or bleeding events. This is particularly relevant for patients with high-risk conditions, such as those chosen for reduced-dose treatment. Further studies are needed to investigate this important clinical issue.
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Fibrilación Atrial , Inhibidores del Factor Xa , Humanos , Femenino , Masculino , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/sangre , Anciano , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/sangre , Administración Oral , Persona de Mediana Edad , Estudios de Seguimiento , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Italia/epidemiología , Coagulación Sanguínea/efectos de los fármacos , Coagulación Sanguínea/fisiología , Estudios ProspectivosRESUMEN
BACKGROUND: Limited real-world evidence is available comparing the safety and effectiveness of apixaban and low-molecular-weight heparins (LMWHs) for preventing recurrent venous thromboembolism (VTE) in patients with active cancer receiving anticoagulation in an extended treatment setting. This study evaluated the risk of bleeding and recurrent VTE in patients with cancer-associated VTE who were prescribed apixaban or LMWH for ≥3 months. METHODS: A US commercial claims database was used to identify adult patients with VTE and active cancer who initiated apixaban or LMWH 30 days following the first VTE diagnosis and had ≥3 months of continuous enrollment and 3 months of primary anticoagulation treatment. Patients were followed from the day after the end of primary anticoagulation treatment until the earliest of: date of disenrollment, discontinuation of index anticoagulant, switch to another anticoagulant, or end of the study period. Inverse-probability treatment weighting (IPTW) was used to balance treatment cohorts. Incidence rates (IRs) for the outcomes were calculated per 100 person-years (PY). Cox proportional hazard models were used to evaluate the adjusted risk of recurrent VTE, major bleeding (MB), and clinically relevant nonmajor bleeding (CRNMB). RESULTS: A total of 13,564 apixaban- and 2,808 LMWH-treated patients were analyzed. Post-IPTW, the treatment cohorts were balanced. Patients receiving apixaban had lower adjusted IRs for recurrent VTE (4.1 vs 9.6 per 100 PY), MB (6.3 vs 12.6), and CRNMB (26.1 vs 36.0) versus LMWH (P<.0001 for all comparisons) during the follow-up period. Patients on apixaban had a lower adjusted risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.34-0.53), MB (HR, 0.50; 95% CI, 0.41-0.61), and CRNMB (HR, 0.76; 95% CI, 0.68-0.85) versus LMWH. CONCLUSIONS: Extended anticoagulation treatment of ≥3 months with apixaban was associated with lower rates of recurrent VTE, MB, and CRNMB compared with LMWH in adults with cancer-associated VTE.
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Heparina de Bajo-Peso-Molecular , Neoplasias , Pirazoles , Piridonas , Tromboembolia Venosa , Humanos , Piridonas/uso terapéutico , Piridonas/efectos adversos , Piridonas/administración & dosificación , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Pirazoles/administración & dosificación , Tromboembolia Venosa/etiología , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/prevención & control , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Femenino , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/efectos adversos , Heparina de Bajo-Peso-Molecular/administración & dosificación , Masculino , Persona de Mediana Edad , Anciano , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Hemorragia/inducido químicamente , Hemorragia/etiología , Resultado del Tratamiento , Adulto , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/administración & dosificaciónRESUMEN
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: Stroke prevention guidance for patients with atrial fibrillation (AF) uses evidence generated from randomised controlled trials (RCTs). However, applicability to patient groups excluded from trials remains unknown. Real-world patient data provide an opportunity to evaluate outcomes in a trial analogous population of direct oral anticoagulants (DOACs) users and in patients otherwise excluded from RCTs; however, there remains uncertainty on the validity of methods and suitability of the data. Successful reference trial emulation can support the generation of evidence around treatment effects in groups excluded or underrepresented in trials. We used linked United Kingdom primary care data to investigate whether we could emulate the pivotal ARISTOTLE trial (apixaban versus warfarin) and extend the analysis to investigate the impact of warfarin time in therapeutic range (TTR) on results. METHODS AND FINDINGS: Patients with AF in the UK Clinical Practice Research Datalink (CPRD Aurum) prescribed apixaban or warfarin from 1 January 2013 to 31 July 2019 were selected. ARISTOTLE eligibility criteria were applied to this population and matched to the RCT apixaban arm on baseline characteristics creating a trial-analogous apixaban cohort; this was propensity-score matched to warfarin users in the CPRD Aurum. ARISTOTLE outcomes were assessed using Cox proportional hazards regression stratified by prior warfarin exposure status during 2.5 years of patient follow-up and results benchmarked against the trial results before treatment effectiveness was further evaluated based on (warfarin) TTR. The dataset comprised 8,734 apixaban users and propensity-score matched 8,734 warfarin users. Results [hazard ratio (95% confidence interval)] confirmed apixaban noninferiority for stroke or systemic embolism (SE) [CPRD 0.98 (0.82,1.19) versus trial 0.79 (0.66,0.95)] and death from any cause [CPRD 1.03 (0.93,1.14) versus trial 0.89 (0.80,0.998)] but did not indicate apixaban superiority. Absolute event rates for stroke/SE were similar for apixaban in CPRD Aurum and ARISTOTLE (1.27%/year), whereas a lower event rate was observed for warfarin (CPRD Aurum 1.29%/year, ARISTOTLE 1.60%/year). Analysis by TTR suggested similar effectiveness of apixaban compared with poorly controlled warfarin (TTR < 0.75) for stroke/SE [0.91 (0.73, 1.14)], all-cause death [0.94 (0.84, 1.06)], and superiority for major bleeding [0.74 (0.63, 0.86)]. However, when compared with well-controlled warfarin (TTR ≥ 0.75), apixaban was associated with an increased hazard for all-cause death [1.20 (1.04, 1.37)], and there was no significant benefit for major bleeding [1.08 (0.90, 1.30)]. The main limitation of the study's methodology are the risk of residual confounding, channelling bias and attrition bias in the warfarin arm, and selection bias and misclassification in the analysis by TTR. CONCLUSIONS: Analysis of noninterventional data generated results demonstrating noninferiority of apixaban versus warfarin consistent with prespecified benchmarking criteria. Unlike in ARISTOTLE, superiority of apixaban versus warfarin was not seen, possible due to the lower proportion of Asian patients and higher proportion of patients with well-controlled warfarin compared to ARISTOTLE. This methodological template can be used to investigate treatment effects of oral anticoagulants in patient groups excluded from or underrepresented in trials and provides a framework that can be adapted to investigate treatment effects for other conditions.
Asunto(s)
Anticoagulantes , Fibrilación Atrial , Pirazoles , Piridonas , Accidente Cerebrovascular , Warfarina , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Warfarina/uso terapéutico , Warfarina/efectos adversos , Warfarina/administración & dosificación , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiología , Reino Unido/epidemiología , Femenino , Anciano , Masculino , Piridonas/uso terapéutico , Piridonas/administración & dosificación , Piridonas/efectos adversos , Pirazoles/uso terapéutico , Pirazoles/administración & dosificación , Administración Oral , Anciano de 80 o más Años , Persona de Mediana Edad , Resultado del Tratamiento , Hemorragia/inducido químicamente , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/administración & dosificaciónRESUMEN
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.
Asunto(s)
Aspirina , Quimioterapia Combinada , Inhibidores del Factor Xa , Extremidad Inferior , Enfermedad Arterial Periférica , Rivaroxabán , Humanos , Rivaroxabán/administración & dosificación , Rivaroxabán/uso terapéutico , Femenino , Masculino , Anciano , Enfermedad Arterial Periférica/cirugía , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Extremidad Inferior/irrigación sanguínea , Extremidad Inferior/cirugía , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Método Doble Ciego , Anciano de 80 o más Años , Procedimientos Quirúrgicos Vasculares , Persona de Mediana EdadRESUMEN
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.
Asunto(s)
Anticoagulantes , Fibrilación Atrial , Inhibidores del Factor Xa , Accidente Cerebrovascular Isquémico , Warfarina , Humanos , Warfarina/uso terapéutico , Warfarina/efectos adversos , Accidente Cerebrovascular Isquémico/prevención & control , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/diagnóstico , Masculino , Femenino , Anciano , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/mortalidad , Pronóstico , Administración Oral , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/administración & dosificación , Persona de Mediana Edad , Anciano de 80 o más Años , Piridonas/efectos adversos , Piridonas/uso terapéutico , Piridonas/administración & dosificación , Estudios Retrospectivos , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Dabigatrán/uso terapéutico , Dabigatrán/efectos adversos , Dabigatrán/administración & dosificación , Rivaroxabán/uso terapéutico , Rivaroxabán/efectos adversos , Rivaroxabán/administración & dosificación , Factores de Riesgo , Medición de Riesgo , Taiwán/epidemiología , Piridinas , TiazolesRESUMEN
BACKGROUND: New-onset postoperative atrial fibrillation (POAF) is a common complication after coronary artery bypass grafting (CABG) surgery, increasing the risk of embolism and stroke. There is a lack of information on the use of anticoagulants in this context. The choice between Warfarin and Direct oral anticoagulants (DOACs) also is not well-established. This randomized study aimed to compare the feasibility and safety of Warfarin and Rivaroxaban in preventing thrombotic events in POAF patients after isolated CABG. METHODS: A total of 66 patients were randomized parallelly with 1:1 allocation to receive either Rivaroxaban (n = 34) or Warfarin (n = 32). Major bleeding events within 30 days after discharge were the primary outcome. Secondary outcomes included minor bleeding events and thrombotic episodes. Clinical characteristics, medication regimens, and left atrial diameter were assessed. Statistical analyses were performed using appropriate tests. RESULTS: No thrombotic episodes were observed in either treatment arm. No major bleeding events occurred in either group. Four minor bleeding events were reported, with no significant difference between the treatment groups (P = 0.6). Patients with atrial fibrillation had significantly larger left atrial diameters compared to those with normal sinus rhythm (40.5 vs. 37.8 mm, P = 0.01). CONCLUSIONS: This pilot study suggests that Warfarin and Rivaroxaban are both safe and effective for preventing thrombotic episodes in POAF patients after isolated CABG. No significant differences in major bleeding events were observed between the two anticoagulants. These findings may support the preference for DOACs like Rivaroxaban due to their convenience and easier maintenance. TRIAL REGISTRATION: Number IRCT20200304046696N1, Date 18/03/2020 https//irct.behdasht.gov.ir/ .
Asunto(s)
Anticoagulantes , Fibrilación Atrial , Puente de Arteria Coronaria , Inhibidores del Factor Xa , Hemorragia , Rivaroxabán , Warfarina , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/etiología , Fibrilación Atrial/prevención & control , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/fisiopatología , Proyectos Piloto , Masculino , Puente de Arteria Coronaria/efectos adversos , Femenino , Anciano , Persona de Mediana Edad , Rivaroxabán/efectos adversos , Rivaroxabán/administración & dosificación , Resultado del Tratamiento , Warfarina/efectos adversos , Warfarina/administración & dosificación , Warfarina/uso terapéutico , Factores de Tiempo , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/administración & dosificación , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Hemorragia/inducido químicamente , Estudios de Factibilidad , Factores de Riesgo , Enfermedad de la Arteria Coronaria/cirugíaRESUMEN
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.
Asunto(s)
Anticoagulantes , Heparina de Bajo-Peso-Molecular , Cirrosis Hepática , Vena Porta , Rivaroxabán , Trombosis de la Vena , Warfarina , Humanos , Proyectos Piloto , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Masculino , Rivaroxabán/administración & dosificación , Rivaroxabán/efectos adversos , Rivaroxabán/uso terapéutico , Vena Porta/diagnóstico por imagen , Femenino , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/diagnóstico por imagen , Persona de Mediana Edad , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Warfarina/administración & dosificación , Warfarina/efectos adversos , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/efectos adversos , Administración Oral , Resultado del Tratamiento , Anciano , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/uso terapéutico , Adulto , Inyecciones Subcutáneas , Tomografía Computarizada por Rayos X , Quimioterapia CombinadaAsunto(s)
Anticoagulantes , Hemorragia Gastrointestinal , Neoplasias Gastrointestinales , Humanos , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/complicaciones , Hemorragia Gastrointestinal/inducido químicamente , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Administración Oral , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/administración & dosificaciónRESUMEN
Importance: Direct-acting oral anticoagulants (DOACs) are commonly prescribed with antiseizure medications (ASMs) due to concurrency of and the association between atrial fibrillation (AF) and epilepsy. However, enzyme-inducing (EI) ASMs may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk. Objective: To assess the rates of thromboembolic and major bleeding events in adults with AF and epilepsy dispensed DOACs and EI ASMs vs DOACs with non-EI ASMs. Design, Setting, and Participants: This active-comparator, new-user cohort study included US health care data from the Clinformatics Data Mart database from October 2010 to September 2021 for a nationally representative population of adults with AF and epilepsy. Exposure: Evaluations included episodes of contiguous coadministration of DOACs for AF with EI ASMs (exposed) or non-EI ASMs (referent) for epilepsy. Main Outcomes and Measures: Thromboembolic events (primary outcome) and major bleeding events (secondary outcome) were identified based on a series of validated, diagnosis-based coding algorithms. Data-adaptive, high-dimensional propensity score matching was used to control for observed confounders and proxies for unobserved confounders. Adjusted hazard ratios (AHRs) were estimated using Cox proportional hazards regression models with robust variance estimators to account for clustering within matched pairs. Results: This study included 14â¯078 episodes (median age, 74 [IQR, 67-81]; 52.4% female) and 14â¯158 episodes (median age, 74 [IQR, 67-81]; 52.4% female) of incident DOAC and ASM use that met eligibility criteria for assessment of thromboembolic and major bleeding outcomes, respectively. Incidence was 88.5 per 1000 person-years for thromboembolic events and 68.3 per 1000 person-years for bleeding events. Compared with use of non-EI ASMs, use of EI ASMs with DOACs was not associated with a difference in risk of thromboembolic events (AHR, 1.10; 95% CI, 0.82-1.46) but was associated with a reduction in risk of major bleeding events (AHR, 0.63; 95% CI, 0.44-0.89). Conclusions and Relevance: In this cohort study, EI ASMs were not associated with alteration in DOAC efficacy. Further research is needed on the reduction in bleeding risk associated with EI ASMs, as this may suggest that pharmacokinetic interactions are associated with lowering DOAC levels without negating therapeutic effects.