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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
INTRODUCTION: There is a paucity of real-world studies examining the risks of stroke/systemic embolism (SE) and major bleeding (MB) among non-valvular atrial fibrillation (NVAF) patients switching from warfarin to a direct oral anticoagulant (DOAC). This retrospective study was conducted to compare the stroke/SE and MB risks between patients switched from warfarin to apixaban, dabigatran, or rivaroxaban in real-world clinical practice. MATERIALS AND METHODS: This study used data from four United States commercial claims databases from January 1, 2012 to June 30, 2019. The study population included NVAF patients initially treated with warfarin and switched to apixaban, dabigatran, or rivaroxaban within 90 days of their warfarin prescription ending. Patients were matched 1:1 between the DOACs in each database using propensity scores and then pooled for the final analysis. Cox proportional hazards models were used to calculate the risk of stroke/SE and MB. RESULTS AND CONCLUSIONS: The final population consisted of 2,611 apixaban-dabigatran, 12,165 apixaban-rivaroxaban, and 2,672 dabigatran-rivaroxaban pairs. Apixaban vs. dabigatran was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.39-0.96) and MB (HR: 0.67; 95% CI: 0.50-0.91). Apixaban vs. rivaroxaban was associated with a similar risk of stroke/SE (HR: 0.88; 95% CI: 0.73-1.07) and a lower risk of MB (HR: 0.60; 95% CI: 0.52-0.68). There was no significant difference in either risk between dabigatran and rivaroxaban. These results provide important insights into how the risks of stroke/SE and MB for NVAF patients vary when switching from warfarin to different DOACs.
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Anticoagulantes , Fibrilación Atrial , Dabigatrán , Hemorragia , Pirazoles , Piridonas , Rivaroxabán , Accidente Cerebrovascular , Warfarina , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Warfarina/efectos adversos , Warfarina/uso terapéutico , Warfarina/administración & dosificación , Masculino , Femenino , Anciano , Estudios Retrospectivos , Estados Unidos/epidemiología , Rivaroxabán/uso terapéutico , Rivaroxabán/efectos adversos , Rivaroxabán/administración & dosificación , Dabigatrán/efectos adversos , Dabigatrán/uso terapéutico , Dabigatrán/administración & dosificación , Pirazoles/efectos adversos , Pirazoles/uso terapéutico , Pirazoles/administración & dosificación , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/epidemiología , Persona de Mediana Edad , Piridonas/efectos adversos , Piridonas/uso terapéutico , Piridonas/administración & dosificación , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Hemorragia/inducido químicamente , Administración Oral , Sustitución de Medicamentos , Embolia/prevención & control , Embolia/etiología , Embolia/epidemiología , Resultado del TratamientoRESUMEN
BACKGROUND: Real-world evidence on direct oral anticoagulant outcomes among Non-Valvular Atrial Fibrillation (NVAF) patients is limited. We aimed to evaluate stroke/systemic embolism (SE) and major bleeding (MB) risks among NVAF patients continuing or switching to different oral anticoagulants. METHODS: Using Optum's de-identified Clinformatics® Data Mart Database, we identified NVAF patients initiating apixaban or rivaroxaban between 1 January 2013 and 31 December 2021. Patients switching therapies within 30 days before or 90 days after discontinuing their initial DOAC and those who continued initial therapy were included. The index date was the switch date for switchers, while continuers were assigned a hypothetic index date. Switchers and continuers were propensity score matched based on pre-index characteristics. RESULTS: Among 167,868 apixaban and 65,888 rivaroxaban initiators, 2900 apixaban-to-rivaroxaban switchers were matched with 14,500 apixaban continuers, and 2873 rivaroxaban-to-apixaban switchers were matched with 14,365 rivaroxaban continuers. Apixaban-to-rivaroxaban switching was associated with higher stroke/SE risk (HR: 1.99, 95% CI: 1.38-2.88) and MB risk (HR:1.80, 95% CI: 1.46-2.23) than continuing apixaban. Rivaroxaban-to-apixaban switching had similar stroke/SE risk (HR: 0.74, 95% CI: 0.45-1.22) but lower MB risk (HR: 0.49, 95% CI: 0.38-0.65) than continuing rivaroxaban. CONCLUSIONS: These findings may aid physicians and patients in making informed decisions when considering a switch between apixaban and rivaroxaban.
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Isolated ectopia lentis is usually autosomal dominant and commonly due to the mutations of FBN1 gene. We report on a family with ectopia lentis. The propositus is a 6-year-old boy with bilateral superior-temporal ectopia lentis. His echocardiogram was normal and he did not meet the revised Ghent criteria for Marfan syndrome. Molecular genetic testing revealed c.1948 C>T (p.Arg650Cys) in FBN1. The mother has visual acuity of 20/20 with -4.50 right eye and -2.50 left eye. She has no evidence of ectopia lentis. DNA analysis revealed that she has the same FBN1 mutation. Seven other maternal family members also have ectopia lentis. In conclusion, we report on a case of early-onset autosomal dominant isolated ectopia lentis caused by FBN1 mutation that has previously been reported only in Marfan syndrome. The child's mother presumably represents a rare case of nonpenetrance.
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Desplazamiento del Cristalino/genética , Proteínas de Microfilamentos/genética , Mutación , Adulto , Edad de Inicio , Anciano de 80 o más Años , Niño , Preescolar , Análisis Mutacional de ADN , Desplazamiento del Cristalino/patología , Femenino , Fibrilina-1 , Fibrilinas , Expresión Génica , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Linaje , Penetrancia , FenotipoRESUMEN
Piperidine, pyrrolidine, and azetidine sulfonamides were examined as linkers in designing novel human beta(3) adrenergic receptor (beta(3)-AR) agonists. The azetidine derivative 37, and piperidine derivatives 7, 8, and 13 were found to be potent beta(3)-AR agonists and have good selectivity against beta(1)- and beta(2)-AR.
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Agonistas de Receptores Adrenérgicos beta 3 , Agonistas Adrenérgicos beta/síntesis química , Agonistas Adrenérgicos beta/farmacología , Sulfonamidas/química , Animales , Azetidinas/síntesis química , Azetidinas/farmacología , Células CHO , Cricetinae , Ciclización , Diseño de Fármacos , Humanos , Enlace de Hidrógeno , Conformación Molecular , Piperidinas/síntesis química , Piperidinas/farmacología , Pirrolidinas/síntesis química , Pirrolidinas/farmacologíaRESUMEN
The synthesis and SAR of a series of human beta3 adrenoreceptor agonists based on a template derived from a common pharmacophore coupled with 4-aminomethylpiperidine is described. Potent and selective agents were identified such as 26 that was in vitro active in CHO cells expressing human beta3-AR (EC50=49 nM, IA=1.1), and in vivo active in a transgenic mouse model.
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Agonistas de Receptores Adrenérgicos beta 3 , Agonistas Adrenérgicos beta/síntesis química , Agonistas Adrenérgicos beta/farmacología , Piperidinas/síntesis química , Piperidinas/farmacología , Animales , Células CHO , Cricetinae , Humanos , Indicadores y Reactivos , Ratones , Ratones Transgénicos , Receptores Adrenérgicos beta 3/genética , Relación Estructura-ActividadRESUMEN
The synthesis and SAR of a series of beta3 adrenoreceptor agonists based on a novel template derived from 4-aminomethylpiperidine coupled with a common pharmacophore, arylethylamine, is described. This combination led to the identification of human beta3 adrenoreceptor agonists with in vivo activity in a transgenic mouse model.