RESUMEN
Venous thromboembolism (VTE) is a common and potentially life-threatening complication in patients with cancer. Both cancer and its treatments increase the risk of developing VTE. Specific cancer types and individual patient comorbidities increase the risk of developing cancer-associated VTE, and the risk of bleeding is increased with anticoagulation therapies. The aims of this article are to summarize the latest evidence for treating cancer-associated VTE, discuss the practical considerations involved, and share best practices for VTE treatment in patients with cancer. The article pays particular attention to challenging contexts including patients with brain, lung, gastrointestinal, and genitourinary tumors and those with hematological malignancies. Furthermore, the article summarizes specific clinical scenarios that require additional treatment considerations, including extremes of body weight, nausea and gastrointestinal disturbances, compromised renal function, and anemia, and touches upon the relevance of drug-drug interactions. Historically, vitamin K antagonists and low-molecular-weight heparins (LMWHs) have been used as therapy for cancer-associated VTE. The development of direct oral anticoagulants has provided additional treatment options, which, in certain instances, offer advantages over LMWHs. There are numerous factors that need to be considered when treating cancer-associated VTE, and although various treatment guidelines are helpful, they do not reflect each unique scenario that may arise in clinical practice. This article provides a summary of the latest evidence and a practical approach for treating cancer-associated VTE.
Asunto(s)
Anticoagulantes , Neoplasias , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiología , Tromboembolia Venosa/tratamiento farmacológico , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Factores de Riesgo , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/efectos adversosRESUMEN
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.
Asunto(s)
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 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 CombinadaRESUMEN
Given the existing uncertainty regarding the effectiveness and safety of switching from low-molecular-weight heparin (LMWH) to direct oral anticoagulants (DOACs) in patients with cancer-associated venous thrombosis (CAT), we conducted a comprehensive population-based cohort study utilizing electronic health database in Hong Kong. A total of 4356 patients with CAT between 2010 and 2022 were included, with 1700 (39.0%) patients switching to DOAC treatment. Compared to continuous LMWH treatment, switching to DOACs was associated with a significantly lower risk of hospitalization due to venous thromboembolism (HR: 0.49 [95% CI = 0.35-0.68]) and all-cause mortality (HR: 0.67 [95% CI = 0.61-0.74]), with no significant difference in major bleeding (HR: 1.04 [95% CI = 0.83-1.31]) within six months. These findings provide reassurance regarding the effectiveness and safety of switching from LMWH to DOACs among patients with CAT, including vulnerable patient groups.
Asunto(s)
Anticoagulantes , Hemorragia , Heparina de Bajo-Peso-Molecular , Neoplasias , Trombosis de la Vena , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina de Bajo-Peso-Molecular/efectos adversos , Heparina de Bajo-Peso-Molecular/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Trombosis de la Vena/tratamiento farmacológico , Administración Oral , Hong Kong/epidemiología , Hemorragia/inducido químicamente , Resultado del Tratamiento , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/etiología , Estudios de Cohortes , Hospitalización/estadística & datos numéricos , Sustitución de Medicamentos , Anciano de 80 o más AñosRESUMEN
INTRODUCTION: Patients with atrial fibrillation (AF) undergoing elective procedures are at risk for Major Adverse Cardiovascular Events (MACE) and symptomatic bleeding. We aimed to identify risk factors to guide perioperative risk stratification. METHODS: We conducted a post-hoc analysis of the "Bridging Anticoagulation in Patients who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery" randomized trial. The primary outcomes were MACE and symptomatic bleeding. Our statistical approach encompassed standard univariate analysis, logistic stepwise regression, and Cox regression models. Additional interaction analyses evaluated the interplay between low-molecular-weight heparin bridge therapy and other identified risk factors. RESULTS: Among a total of 1,813 participants (mean age 71.6 ± 8.8, 73.3 % male), MACE occurred in 25 (1.4 %) individuals, with pre-procedure clopidogrel use (adjusted hazard ratio [aHR] 7.73, 95 % CI 2.63-22.72, p < 0.001) and CHA2DS2-VASc score ≥ 5 (aHR 2.89, 95 % CI 1.26-6.63, p = 0.012) identified as risk factors. Symptomatic bleeding occurred in 57 (3.1 %) individuals, with bridge therapy (aHR 1.84, 95 % CI 1.07-3.19, p = 0.029), renal disease (aHR 2.50, 95 % CI 1.34-4.67, p = 0.004), post-procedure aspirin use (aHR 2.86, 95 % CI 1.66-4.91, p < 0.001), post-procedure nonsteroidal anti-inflammatory drug use excluding aspirin (aHR 3.40, 95 % CI 1.22-9.43, p = 0.019), and major surgery (aHR 3.94, 95 % CI 2.26-6.85, p < 0.001) identified as risk factors. The interactions between risk factors and bridging therapy on MACE and symptomatic bleeding outcomes were not significant (p > 0.05). CONCLUSION: We identified predictors for MACE and symptomatic bleeding in AF patients undergoing elective procedures. These insights may help guide perioperative decisions to reduce the risk of adverse outcomes.
Asunto(s)
Anticoagulantes , Fibrilación Atrial , Procedimientos Quirúrgicos Electivos , Hemorragia , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/cirugía , Fibrilación Atrial/epidemiología , Masculino , Femenino , Anciano , Factores de Riesgo , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Medición de Riesgo , Resultado del Tratamiento , Persona de Mediana Edad , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Procedimientos Quirúrgicos Electivos/efectos adversos , Anciano de 80 o más Años , Factores de Tiempo , Warfarina/efectos adversos , Warfarina/administración & dosificación , Esquema de Medicación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Heparina de Bajo-Peso-Molecular/efectos adversos , Heparina de Bajo-Peso-Molecular/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: The anticoagulation strategy of switching to rivaroxaban after 1 week of initial low-molecular-weight heparin (LMWH) therapy is recommended by a guideline for the treatment of acute iliofemoral deep vein thrombosis (DVT). However, the initial rivaroxaban dose in the switching strategy, as well as the effectiveness and safety of the early switching (less than 1 week) to rivaroxaban, remain inadequately substantiated. We aimed to evaluate the effectiveness and safety of early switching from LMWH to maintenance therapy of rivaroxaban (20 mg once daily) for acute iliofemoral DVT. METHODS: A retrospective cohort study was conducted using data from patients with acute iliofemoral DVT who received initial LMWH anticoagulation followed by rivaroxaban maintenance therapy. The clinical outcomes were compared between early (LMWH course ≤7 days) and routine (LMWH course >7 days) switching strategies within 3 months of initiating anticoagulation. RESULTS: 217 patients were included, 59 (27.2%) receiving early switching and 158 (72.8%) receiving routine switching. Compared with routine switching, patients with early switching had a significantly shorter hospital stay (7 days vs. 14 days, P < 0.001). The length of hospital stay was significantly positively correlated with the duration of LMWH (r = 0.762, P < 0.001). The incidences of recurrent venous thromboembolism (5.1% vs. 2.5%, P = 0.606), major bleeding (0% vs. 1.9%, P = 0.564), clinically relevant nonmajor bleeding (1.7% vs. 2.5%, P = 1.000) and all-cause mortality (6.8% vs. 2.5%, P = 0.283) were not statistically different between the 2 groups. CONCLUSIONS: Direct early switching from LMWH to maintenance therapy of rivaroxaban is effective and safe for acute iliofemoral DVT.
Asunto(s)
Esquema de Medicación , Sustitución de Medicamentos , Inhibidores del Factor Xa , Vena Femoral , Hemorragia , Heparina de Bajo-Peso-Molecular , Vena Ilíaca , Rivaroxabán , Trombosis de la Vena , Humanos , Rivaroxabán/efectos adversos , Rivaroxabán/administración & dosificación , Estudios Retrospectivos , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/mortalidad , Trombosis de la Vena/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/administración & dosificación , Factores de Tiempo , Anciano , Hemorragia/inducido químicamente , Vena Ilíaca/diagnóstico por imagen , Heparina de Bajo-Peso-Molecular/efectos adversos , Heparina de Bajo-Peso-Molecular/administración & dosificación , Factores de Riesgo , Adulto , Enfermedad Aguda , Tiempo de Internación , Recurrencia , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificaciónRESUMEN
BACKGROUND: Treating cancer-associated venous thromboembolism (CAT) with anticoagulation prevents recurrent venous thromboembolism (rVTE), but increases bleeding risk. OBJECTIVES: To compare incidence of rVTE, major bleeding, and all-cause mortality for rivaroxaban versus low molecular weight heparin (LMWH) in patients with CAT. METHODS: We developed a cohort study using Swedish national registers 2013-2019. Patients with CAT (venous thromboembolism within 6 months of cancer diagnosis) were included. Those with other indications or with high bleeding risk cancers were excluded (according to guidelines). Follow-up was from index-CAT until outcome, death, emigration, or end of study. Incidence rates (IR) per 1000 person-years with 95% confidence interval (CI) and propensity score overlap-weighted hazard ratios (HRs) for rivaroxaban versus LMWH were estimated. RESULTS: We included 283 patients on rivaroxaban and 5181 on LMWH. The IR for rVTE was 68.7 (95% CI 40.0-109.9) for rivaroxaban, compared with 91.6 (95% CI 81.9-102.0) for LMWH, with adjusted HR 0.77 (95% CI 0.43-1.35). The IR for major bleeding was 23.5 (95% CI 8.6-51.1) for rivaroxaban versus 49.2 (95% CI 42.3-56.9) for LMWH, with adjusted HR 0.62 (95% CI 0.26-1.49). The IR for all-cause mortality was 146.8 (95% CI 103.9-201.5) for rivaroxaban and 565.6 (95% CI 541.8-590.2) for LMWH with adjusted HR 0.48 (95% CI 0.34-0.67). CONCLUSIONS: Rivaroxaban performed similarly to LMWH for patients with CAT for rVTE and major bleeding. An all-cause mortality benefit was observed for rivaroxaban which potentially may be attributed to residual confounding. TRIAL REGISTRATION NUMBER: NCT05150938 (Registered 9 December 2021).
Asunto(s)
Hemorragia , Heparina de Bajo-Peso-Molecular , Neoplasias , Sistema de Registros , Rivaroxabán , Tromboembolia Venosa , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Estudios de Cohortes , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Hemorragia/inducido químicamente , Hemorragia/mortalidad , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/efectos adversos , Incidencia , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Neoplasias/mortalidad , Rivaroxabán/uso terapéutico , Rivaroxabán/efectos adversos , Suecia/epidemiología , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/mortalidad , Tromboembolia Venosa/etiologíaRESUMEN
BACKGROUND: As the elderly population continues to grow worldwide, it becomes crucial to explore safe and effective treatment options to manage venous thromboembolic disease in this vulnerable demographic group. METHODS: We carried out a retrospective cohort study (January 2017-December 2021) to analyse the efficacy and safety of bemiparin as a treatment for venous thromboembolic disease in 223 patients. We compared patients aged ≥65 years (elderly; n = 153) with patients aged less than 65 years (adults; n = 70) for a combined end point of death, recurrent thromboembolism, and major bleeding at 30 days. RESULTS: Elderly (mean age 79 ± 7.7 years) and adult patients (mean age 51.5 ± 11.6 years) received similar bemiparin doses 8470 ± 2362 International units (IU)/d versus 8754 ± 1593 IU/d, during a similar median [Interquartile range] period of 28 [9-118] versus 30 [10-90] days, respectively. At 30-day follow up a total of 24 elderly patients (15.7%), reached at least one of the end points, as compared with six adult patients (8.6%) (absolute difference 7.1%; 95% confidence interval [95% CI], -1.6 to 15.8). Recurrence of venous thromboembolic disease occurred in five elderly patients (3.3%) and in five adult patients (7.1%) (absolute difference -3.9%; 95% CI, -10.5 to 2.8). There were two episodes of major bleeding each in elderly (1.3%) and adult (2.9%) patients (absolute difference -1.6%; 95% CI, -5.8 to 2.7). CONCLUSION: Bemiparin showed a similar efficacy and safety profile in the treatment of venous thromboembolic disease in elderly and adult patients.
Asunto(s)
Hemorragia , Heparina de Bajo-Peso-Molecular , Tromboembolia Venosa , Humanos , Anciano , Masculino , Femenino , Estudios Retrospectivos , Tromboembolia Venosa/tratamiento farmacológico , Persona de Mediana Edad , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/efectos adversos , Heparina de Bajo-Peso-Molecular/administración & dosificación , Anciano de 80 o más Años , Hemorragia/tratamiento farmacológico , Factores de Edad , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Adulto , Recurrencia , Resultado del TratamientoRESUMEN
BACKGROUND: To find a new bedside method to monitor the anticoagulation effects of low-molecular-weight heparins (LMWHs) in patients with a high risk of venous thromboembolism (VTE). RESEARCH DESIGN AND METHODS: A total of 32 hospitalized patients (aged ≥60 years) who were at high risk of VTE were assigned to receive subcutaneous LMWH for 5 to 14 days. Plasma anti-factor Xa (anti-Xa) activity was conducted by a chromogenic method, and the glass bead-activated whole blood clotting time (gb-ACT) value was obtained by a Sonoclot Analyzer. RESULTS: A correlation between the gb-ACT values and the anti-Xa levels was suggested (R = 0.447, p = 0.002), and it was stronger in the older group aged 80 years above (R = 0.467, p = 0.008) and in the group of patients with an eGFR of 30 ~ 60 mL/min (R = 0.565, p = 0.005). The area under the curve (AUC) for gb-ACT by receiver operating characteristic (ROC) curve evaluation was 0.725 (p = 0.011), and the gb-ACT >282.5s provided a sensitivity of 60% and specificity of 74% for anti-Xa >0.800 IU/ml. CONCLUSIONS: The gb-ACT values detected by a Sonoclot Analyzer could act as a novel bedside method in the monitoring of LMWH anticoagulation.
Asunto(s)
Anticoagulantes , Monitoreo de Drogas , Inhibidores del Factor Xa , Heparina de Bajo-Peso-Molecular , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/prevención & control , Anciano , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Femenino , Masculino , Anciano de 80 o más Años , Persona de Mediana Edad , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina de Bajo-Peso-Molecular/efectos adversos , Monitoreo de Drogas/métodos , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/efectos adversos , Factores de Edad , Tiempo de Coagulación de la Sangre TotalRESUMEN
BACKGROUND: Optimal first-trimester anticoagulation is still challenging in pregnant women with mechanical heart valves (MHVs) requiring high-dose warfarin. This multicenter prospective study aims to determine the optimal anticoagulation regimens for pregnant patients with MHVs. METHODS: All women were allocated to one of three treatment options during first trimester including lone low-molecular-weight heparin (LMWH), combination of LMWH + 2.5 mg warfarin, and LMWH+4 mg warfarin. Primary maternal outcome included a combination of death, thromboembolism, severe bleeding, and need for treatment of mechanical valve thrombosis (MVT). Any fetal loss was determined as primary fetal outcome. RESULTS: The study included 78 pregnancies in 65 women with MHVs. Primary maternal outcome rate was 44%, 12.5%, 3.5%, respectively. The rates of primary maternal outcome (44 vs 3.5%, P < .001), obstructive MVT (16 vs 0%, P = .04), MVT requiring treatment (28 vs 0%, P = .003), and cerebral embolism (24 vs 3.4%, P = .041) were found to be significantly higher in lone LMWH group compared to LMWH + 4 mg warfarin group. Moreover, the rates of primary maternal outcome (12.5 vs 44%, P = .015) and treatment for MHV thrombus (4.2 vs 28%, P = .049) were significantly lower in LMWH + 2.5 mg warfarin group compared to lone LMWH group. The incidences of fetal loss were 8 (32%) in the lone LMWH group, 8 (33.3%) in LMWH + 2.5 mg warfarin group, and 11 (37.9%) in LMWH + 4 mg warfarin group (P = .890 for 3-group).Warfarin related-embryopathy was not observed in any case. CONCLUSIONS: The combined anticoagulation strategy of LMWH plus low-dose warfarin during the first trimester of pregnancy may result in less maternal complications with comparable fetal outcomes in patients with MHVs. CONDENSED ABSTRACT: Low-molecular-weight heparin (LMWH) is thought to be safer for the fetus, however it is suspected to be less protective for the mother. To solve this dilemma, the authors suggested a novel anticoagulation strategy in pregnant women with prosthetic valves. Seventy-eight pregnancies of 65 women (median age 32 [27-35] years) were included in the study. A combination of LMWH and a reduced dose warfarin were associated with low rates of thrombus-related complications in pregnant patients with mechanical heart valves.
Asunto(s)
Anticoagulantes , Prótesis Valvulares Cardíacas , Heparina de Bajo-Peso-Molecular , Complicaciones Cardiovasculares del Embarazo , Warfarina , Humanos , Femenino , Embarazo , Anticoagulantes/administración & dosificación , Adulto , Warfarina/administración & dosificación , Warfarina/efectos adversos , Complicaciones Cardiovasculares del Embarazo/tratamiento farmacológico , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/efectos adversos , Estudios Prospectivos , Prótesis Valvulares Cardíacas/efectos adversos , Quimioterapia Combinada , Resultado del Embarazo , Primer Trimestre del Embarazo , Tromboembolia/prevención & control , Tromboembolia/etiología , Tromboembolia/epidemiología , Trombosis/prevención & control , Trombosis/etiologíaRESUMEN
PURPOSE: Guidelines recommend low-molecular-weight heparins (LMWHs) for patients with cancer-associated thrombosis. However, until recently, only dalteparin and tinzaparin were approved in the European Economic Area (EEA) for these patients. This study compares the benefit-risk profile of enoxaparin with dalteparin and tinzaparin for the extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrence in adult patients with active cancer. METHODS: A semi-quantitative structured benefit-risk assessment was conducted for the label-extension application of enoxaparin based on the benefit-risk action team descriptive framework: define decision context; determine key benefit and risk outcomes; identify data sources; extract data; interpret results. RESULTS: The key benefits were defined as reduced all-cause mortality and venous thromboembolism (VTE) recurrence (including symptomatic DVT, fatal PE or non-fatal PE); the key risks were major and non-major bleeding of clinical significance, and heparin-induced thrombocytopenia (HIT). Enoxaparin demonstrated comparable effects for the reduction of VTE recurrence and all-cause mortality versus other EEA-approved LMWHs (dalteparin, tinzaparin). There was no evidence of a significant difference between enoxaparin and the comparator groups with regard to incidence of major and non-major bleeding. The data on HIT were too limited to assess the difference between the two groups. CONCLUSIONS: The assessment demonstrated a favourable benefit-risk profile for enoxaparin similar to that of other EEA-approved LMWHs for the treatment of DVT and PE and the prevention of recurrence in patients with active cancer and thus supported the label-extension approval.
Asunto(s)
Dalteparina , Enoxaparina , Heparina de Bajo-Peso-Molecular , Neoplasias , Embolia Pulmonar , Tinzaparina , Trombosis de la Vena , Humanos , Enoxaparina/administración & dosificación , Enoxaparina/efectos adversos , Enoxaparina/uso terapéutico , Embolia Pulmonar/prevención & control , Embolia Pulmonar/tratamiento farmacológico , Trombosis de la Vena/prevención & control , Trombosis de la Vena/tratamiento farmacológico , Medición de Riesgo , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Dalteparina/administración & dosificación , Dalteparina/efectos adversos , Dalteparina/uso terapéutico , Tinzaparina/administración & dosificación , Tinzaparina/uso terapéutico , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina de Bajo-Peso-Molecular/efectos adversos , Heparina de Bajo-Peso-Molecular/uso terapéutico , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Prevención Secundaria/métodos , Hemorragia/inducido químicamente , AdultoRESUMEN
BACKGROUND: Little is known about the safety and efficacy of discontinuing antiplatelet therapy via LMWH bridging therapy in elderly patients with coronary stents implanted for > 12 months undergoing non-cardiac surgery. This randomized trial was designed to compare the clinical benefits and risks of antiplatelet drug discontinuation via LMWH bridging therapy. METHODS: Patients were randomized 1:1 to receive subcutaneous injections of either dalteparin sodium or placebo. The primary efficacy endpoint was cardiac or cerebrovascular events. The primary safety endpoint was major bleeding. RESULTS: Among 2476 randomized patients, the variables (sex, age, body mass index, comorbidities, medications, and procedural characteristics) and percutaneous coronary intervention information were not significantly different between the bridging and non-bridging groups. During the follow-up period, the rate of the combined endpoint in the bridging group was significantly lower than in the non-bridging group (5.79% vs. 8.42%, p = 0.012). The incidence of myocardial injury in the bridging group was significantly lower than in the non-bridging group (3.14% vs. 5.19%, p = 0.011). Deep vein thrombosis occurred more frequently in the non-bridging group (1.21% vs. 0.4%, p = 0.024), and there was a trend toward a higher rate of pulmonary embolism (0.32% vs. 0.08%, p = 0.177). There was no significant difference between the groups in the rates of acute myocardial infarction (0.81% vs. 1.38%), cardiac death (0.24% vs. 0.41%), stroke (0.16% vs. 0.24%), or major bleeding (1.22% vs. 1.45%). Multivariable analysis showed that LMWH bridging, creatinine clearance < 30 mL/min, preoperative hemoglobin < 10 g/dL, and diabetes mellitus were independent predictors of ischemic events. LMWH bridging and a preoperative platelet count of < 70 × 109/L were independent predictors of minor bleeding events. CONCLUSIONS: This study showed the safety and efficacy of perioperative LMWH bridging therapy in elderly patients with coronary stents implanted > 12 months undergoing non-cardiac surgery. An alternative approach might be the use of bridging therapy with half-dose LMWH. TRIAL REGISTRATION: ISRCTN65203415.
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Stents , Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/efectos adversos , Dalteparina/administración & dosificación , Dalteparina/uso terapéutico , Dalteparina/efectos adversos , Resultado del Tratamiento , Procedimientos Quirúrgicos Operativos/efectos adversos , Hemorragia/inducido químicamente , Placebos/administración & dosificación , Atención Perioperativa/métodosRESUMEN
OBJECTIVES: To evaluate the effectiveness and safety of rivaroxaban anticoagulation in COVID-19 patients. METHODS: PubMed, Embase, Cochrane Library electronic databases, and ClinicalTrials.gov were searched to identify all relevant randomized controlled trial studies from December 2019 to July 2023. RESULTS: A total of 6 randomized controlled trials, which included a total of 3323 patients, were considered for evaluation. Overall, short-term all-cause mortality and hospitalization rates were not significantly different between the rivaroxaban and control groups. Thrombotic events were significantly reduced in the rivaroxaban prophylaxis group compared to the placebo control group. However, the reduction in thrombotic events was not significantly different between rivaroxaban therapy and heparin or low-molecular-weight heparin (LMWH). Rivaroxaban prophylaxis and the therapeutic dose may be associated with a higher rate of overall bleeding rate, but major bleeding rates did not differ substantially. CONCLUSION: Rivaroxaban may reduce thrombotic events in COVID-19 patients, but it does not appear to have an advantage over heparin or LMWH, and it may increase the risk of bleeding.INPLASY Reg. No.: INPLASY 202370097.
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Anticoagulantes , Tratamiento Farmacológico de COVID-19 , COVID-19 , Hemorragia , Ensayos Clínicos Controlados Aleatorios como Asunto , Rivaroxabán , Humanos , Rivaroxabán/uso terapéutico , Rivaroxabán/efectos adversos , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , COVID-19/complicaciones , Hemorragia/inducido químicamente , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Trombosis/prevención & control , Trombosis/etiología , Resultado del Tratamiento , Heparina/uso terapéutico , Heparina/efectos adversos , SARS-CoV-2RESUMEN
BACKGROUND: Acute pulmonary embolism (PE) is a life-threatening situation in cancer patients. In this situation, anticoagulant therapy is complex to administer due to the risk of bleeding. Only few studies have been conducted when these patients are admitted to the intensive care unit (ICU). The aim of this study was to assess the association between anticoagulation strategies as well as other factors with 90-day mortality in patients with cancer and PE admitted to ICU. Major bleeding was also evaluated according to the type of anticoagulation. METHODS: Retrospective study carried out in 4 ICUs in France over a 12-year period (2009-2021). All patients with cancer and PE were included. An overlap propensity score weighting analysis was performed in the subgroup of patients treated with either unfractionated heparins (UFH) alone or low-molecular-weight heparins (LMWH) alone on 90-day mortality and major bleeding. RESULTS: A total of 218 consecutive cancer patients admitted to ICU and presenting PE were included. The 90-day mortality rate was 42 % for the global cohort. After propensity score analysis in the subgroup of patients treated with either "UFH alone" (n = 80) or "LMWH alone" (n = 71), the 90-day mortality was similar in patients treated with UFH alone (42.6 %) vs LMWH alone (39.9 %): OR = 1.124, CI 95 % [0.571-2.214], p = 0.750. There was a significant increased toward major bleeding rates in the "UFH alone" group (25.5 %) as compared to "LMWH alone" group (11.5 %), p = 0.04. CONCLUSION: In 218 patients admitted to ICU and presenting PE, the 90-day mortality rate was 42 %. Treatment with UFH alone was associated with a mortality comparable to treatment with LMWH alone but it appeared to be more prone to major bleeding.
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Anticoagulantes , Unidades de Cuidados Intensivos , Neoplasias , Embolia Pulmonar , Humanos , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Estudios Retrospectivos , Masculino , Embolia Pulmonar/mortalidad , Embolia Pulmonar/tratamiento farmacológico , Femenino , Neoplasias/complicaciones , Neoplasias/mortalidad , Neoplasias/tratamiento farmacológico , Anciano , Factores de Riesgo , Persona de Mediana Edad , Hemorragia/mortalidad , Hemorragia/inducido químicamente , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina de Bajo-Peso-Molecular/efectos adversos , Enfermedad Aguda , Heparina/uso terapéutico , Heparina/efectos adversos , Francia/epidemiologíaRESUMEN
INTRODUCTION: Hematomas are a rare cause of intestinal obstruction. Subcutaneous heparin can bring about direct punctures on small bowel loops, potentially leading to traumatic hematoma and intestinal obstruction. CASE REPORTS: We present three cases of pediatric patients with clinical signs of intestinal obstruction treated with subcutaneous heparin. Two cases had increased acute-phase reactants and radiological signs of intestinal suffering, so surgical treatment was decided upon, with intramural hematoma emerging as an intraoperative finding. The third case was conservatively managed with anticoagulant discontinuation and gut rest, since the patient had an adequate general condition and no findings compatible with ischemia or necrosis were noted in the complementary tests. DISCUSSION: The administration of subcutaneous heparin may cause intestinal wall hematomas due to its anticoagulating effect and to the risk of inadvertent punctures on small bowel loops.
INTRODUCCION: Los hematomas son una causa poco frecuente de obstrucción intestinal. La heparina subcutánea tiene riesgo de producir la punción directa de un asa intestinal, provocando un hematoma traumático que genere una obstrucción intestinal. CASOS CLINICOS: Se describen tres casos de pacientes pediátricos con clínica de obstrucción intestinal en tratamiento con heparina subcutánea. Dos casos presentaron elevación de reactantes de fase aguda y signos radiológicos de sufrimiento intestinal por lo que se optó por tratamiento quirúrgico, con el hallazgo intraoperatorio de hematoma intramural. El tercer caso fue manejado de manera conservadora con supresión de la anticoagulación y reposo intestinal, dado el adecuado estado general y ausencia de hallazgos compatibles con isquemia o necrosis en las pruebas complementarias. COMENTARIOS: La administración de heparina subcutánea puede provocar la aparición de hematomas de pared intestinal, tanto por su efecto anticoagulante, como por el riesgo de punción inadvertida de un asa intestinal.
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Heparina de Bajo-Peso-Molecular , Obstrucción Intestinal , Humanos , Niño , Heparina de Bajo-Peso-Molecular/efectos adversos , Anticoagulantes/efectos adversos , Obstrucción Intestinal/inducido químicamente , Obstrucción Intestinal/cirugía , Hematoma/inducido químicamente , Hematoma/complicaciones , Hematoma/cirugía , Hemorragia Gastrointestinal/cirugía , Heparina/efectos adversosRESUMEN
OBJECTIVE: To assess women's experiences with skin-related side effects following subcutaneous low molecular weight heparin (LMWH) injections after a cesarean section, and to analyze their impact on treatment adherence. METHOD: A questionnaire was developed in collaboration with Cesarine, a patients' association, to explore various aspects of LMWH administration, including prevention methods, cutaneous side effects, treatment compliance, perceived constraints, apprehension, and understanding of treatment benefits. Additionally, women's opinions on an alternative oral administration approach were solicited, taking into consideration breastfeeding contraindication. The questionnaire was on the Facebook® page and blog of the association. RESULTS: One hundred and sixty-four women participated in the survey. Among them, 139 women (84.8%) reported bruising, while 117 (71.3%) reported pruritus, erythema, or nodules at the injection site. Treatment discontinuation was observed in 36 cases (22%), decided mostly by the women themselves (77.8%). The main reasons cited for discontinuation were discomfort during injection (71.4%), skin reactions (31.4%), and a perceived lack of effectiveness (54.3%). Furthermore, 88 women (53.7%) wanted to quit the treatment prematurely, citing similar reasons. Thirty-three women (20.1%) reported oversights. For most women, the treatment was perceived as burdensome and caused apprehension. An alternative oral administration method was of interest to 131 women (79.9%). However, only 28 (17.8%) would have accepted if the medication was incompatible with breastfeeding. CONCLUSION: Cutaneous side effects of LMWH injections, as well as injection process itself, have a negative impact on adherence in the postpartum period following a c-section. These findings highlight the need to explore alternative to improve women's compliance and comfort.
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Anticoagulantes , Cesárea , Heparina de Bajo-Peso-Molecular , Humanos , Femenino , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina de Bajo-Peso-Molecular/efectos adversos , Adulto , Encuestas y Cuestionarios , Inyecciones Subcutáneas , Embarazo , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Lactancia Materna , Cumplimiento de la Medicación/estadística & datos numéricosRESUMEN
OBJECTIVE: Azvudine is an effective treatment for patients infected with common COVID-19. However, physicians have reported a series of adverse reactions, including multiple cases of liver injury, caused by azvudine in clinical practice. This study assessed the incidence, clinical features, and associated risk factors of liver injury induced by azvudine in real-world settings, offering guidance for safe clinical use. MATERIALS AND METHODS: This study utilized the Chinese Hospital Pharmacovigilance System (CHPS) to retrospectively analyze the treatment of COVID-19 patients with azvudine at Changsha Central Hospital from December 19, 2022, to June 6, 2023. A case-control study was conducted to analyze the occurrence of azvudine-induced liver injury in COVID-19 patients who triggered a CHPS alert compared to normal COVID-19 patients. RESULTS: Among the total of 2,141 COVID-19 patients, 31 (1.45%) developed azvudine-induced liver injury, which is classified as an occasional adverse reaction. Liver injury was observed in 93.55% of patients between days 4 and 12 of the azvudine treatment, with elevated transaminases as the primary clinical manifestation. Univariate and binary logistic regression analyses indicated that low albumin levels and co-administration of low-molecular-weight heparin were statistically significant risk factors (p < 0.05). CONCLUSION: This study represents the first investigation of azvudine-induced liver injury and high-risk patients using the CHPS. The findings provide valuable insights to promote the safety of anti-COVID-19 drugs, serving as an important reference for future drug safety measures.
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Azidas , COVID-19 , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Desoxicitidina/análogos & derivados , Humanos , Heparina de Bajo-Peso-Molecular/efectos adversos , Farmacovigilancia , Estudios Retrospectivos , Estudios de Casos y Controles , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/tratamiento farmacológico , Estudios Prospectivos , Factores de Riesgo , AlbúminasRESUMEN
Current guidelines suggest a 3-month anticoagulant treatment course for isolated distal deep vein thrombosis (IDDVT), but shorter durations of treatment are frequently prescribed in clinical practice. We investigated whether a 6-week treatment with low-molecular-weight heparin (LMWH) at intermediate dosage can be an effective and safe alternative to vitamin K antagonists (VKA) in patients with IDDVT (non-inferiority trial). In a multicenter, open-label, randomized trial, 260 outpatients with symptomatic IDDVT were randomly assigned to receive either LMWH followed by VKA for 12 weeks or LMWH 1 mg/kg subcutaneously twice a day for 2 weeks followed by 1 mg/kg subcutaneously once a day for 4 weeks. The follow-up was 6 months and the primary endpoint was the composite measure of recurrent venous thromboembolism (VTE) defined as: recurrence or extension of IDDVT, proximal DVT, and pulmonary embolism (PE). The study was stopped prematurely due to slow recruiting rates. The primary efficacy outcome occurred in 14 patients receiving LMWH (10.8%) and in five patients receiving VKA (3.8%); risk difference was 0.069 (95% CI: 0.006-0.132), hazard ratio 2.8 (95% CI: 1.04-7.55). There was one PE in the VKA group and one proximal DVT in the LMWH group. IDDVT recurrence was 10.0% in the LMWH group versus 3.1% in the VKA group (p = .024). Two patients had clinically relevant bleedings (1.6%) in the LMWH group versus one (0.8%) in VKA group (p = .56). In conclusion, VKA for 12 weeks seems superior to LMWH for 6 weeks in reducing the risk of VTE recurrences in our cohort of outpatients with IDDVT.
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Isquemia Mesentérica , Embolia Pulmonar , Tromboembolia Venosa , Trombosis de la Vena , Humanos , Heparina de Bajo-Peso-Molecular/efectos adversos , Warfarina/efectos adversos , Tromboembolia Venosa/tratamiento farmacológico , Estudios Prospectivos , Trombosis de la Vena/tratamiento farmacológico , Anticoagulantes/efectos adversos , Embolia Pulmonar/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , RecurrenciaRESUMEN
BACKGROUND: Direct oral anticoagulants (DOACs) used as an alternative to low-molecular-weight heparin (LMWH) for thromboprophylaxis after cancer surgery for venous thromboembolic events (VTE) remains unclear. This study aimed to investigate the efficacy and safety of DOACs versus LMWH in these patients. MATERIALS AND METHODS: A search of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science was carried out and included all randomized controlled trials (RCTs) and observational studies that directly compared DOACs with LMWH for thromboprophylaxis in patients after cancer surgery through July 25, 2023. The primary efficacy and safety outcomes were VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB) within 30 days of surgery. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) tool for RCTs and ROBINS-I tool for non-randomized studies. This study was registered in PROSPERO (CRD42023445386). RESULTS: We retrieved 5149articles, selected 27 for eligibility, and included 10 studies (three RCTs and seven observational studies) encompassing 3054 patients who underwent postoperative thromboprophylaxis with DOACs (41%) or LMWH (59%). Compared to LMWH thromboprophylaxis, DOACs had a comparable risk of VTE (RR:0.69[95% CI:0.46-1.02], I2 = 0%), major bleeding (RR:1.55 [95% CI:0.82-2.93], I2 = 2%), and CRNMB (RR, 0.89 [95% CI, 0.4-1.98], I2 = 31%) during the 30-day postoperative period. Subgroup analysis of VTE and major bleeding suggested no differences according to study type, extended thromboprophylaxis, tumor types, or different types of DOAC. CONCLUSION: DOACs are potentially effective alternatives to LMWH for thromboprophylaxis in patients undergoing cancer surgery, without increasing the risk of major bleeding events.