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1.
Postgrad Med J ; 2020 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-32041823

RESUMEN

BACKGROUND: Residents in internal medicine programmes lack formal training in leadership, curriculum development and clinical teaching. Residency programmes created clinician-educator tracks (CETs) to formally teach residents to become effective educators and to involve them in the science of medical education. However, the curricula in these tracks are often locally developed and remain at the discretion of the individual programmes. METHODS: This survey evaluates the frequency of CETs in internal medicine residency programmes in the USA and descriptively analyses their logistical and curricular content. During the academic year 2017-2018, directors of all Accreditation Council for Graduate Medical Education (ACGME) accredited internal medicine residency programmes in the USA were invited to participate in this survey (n=420). We developed a web-based 22-question survey to assess the logistics and curricular content of CET programmes. RESULTS: A total of 150 programmes responded to the survey invitation (response rate=35.7%). Only 24% (n=36) of programmes offered a CET, the majority of which have been available for only 5 years or less. The track is most frequently offered to postgraduate year (PGY)-2 and PGY-3 residents. Only a minority of participating faculty (27.8%) have protected time to fulfil their CET role. Bedside teaching, feedback, small group teaching and curriculum development are the most commonly taught topics, and faculty mentorship and small group teaching methods are the most commonly used types of instruction. CONCLUSIONS: CETs are offered in only 24% of internal medicine residency programmes in the USA. The curricula of these tracks vary across programmes, and their success is often countered by logistic and financial challenges.

2.
Dig Dis Sci ; 2020 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-31916085

RESUMEN

AIM: In previous studies, the 5-year progression rate of gastric intestinal metaplasia to gastric adenocarcinoma has varied substantially. We investigated the incidence rate of dysplasia and gastric adenocarcinoma and the rate of progression among a cohort of patients with non-dysplastic gastric intestinal metaplasia. METHODS: This is a single-center, single-cohort retrospective study. Patients who had undergone an EGD with biopsies from 01/01/1993 to 12/31/2013 were included. The primary outcome of interest was the composite of low-grade dysplasia, high-grade dysplasia, or adenocarcinoma. Time to progression and risk factor subgroup analyses were performed. RESULTS: A total of 1628 subjects were screened, of whom 358 met the inclusion criteria. A total of 21 first-time events were recorded. The annual incidence rate of low-grade dysplasia was 2.1 (95% CI 1.3-3.5) cases per 1000 person-years, 0.5 (95% 0.2-1.3) per 1000 person-years for high-grade dysplasia, and 0.8 (95% CI 0.3-1.6) cases per 1000 person-years for gastric adenocarcinoma. The historical control group had an annual adenocarcinoma incidence rate of 0.07 per 1000 person-years. The event rate in Asians was also noted to be significantly higher between years 0-8 as compared with patients of non-Asian race, and extensive intestinal metaplasia was an independent risk factor (HR = 4.06 (95% CI 1.45-11.34), p = 0.007). CONCLUSIONS: Patients with non-dysplastic gastric intestinal metaplasia may progress to dysplasia and gastric adenocarcinoma. The incidence rate of gastric adenocarcinoma is higher than that of the historical control population (0.07 per 1000 person-years). The presence of extensive intestinal metaplasia was a risk factor for progression of disease. Triennial EGD may be warranted in patients with non-dysplastic gastric intestinal metaplasia.

3.
Headache ; 2019 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-31769041

RESUMEN

OBJECTIVE: We aimed to examine arterial stiffness and vitamin K2 status in migraine subjects by comparison to controls. BACKGROUND: Migraine is a primary headache disorder that has been associated with an increased risk of cardiovascular events. Mechanisms underlying this increased risk, however, remain unclear. Vitamin K2 deficiency emerged as a cardiovascular risk factor, but vitamin K2 status has never been explored in migraine subjects. DESIGN AND METHODS: This is a case-control, single-center, observational study that includes a cohort of subjects with migraine and their age- and sex-matched controls. Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV). Dephosphorylated-uncarboxylated matrix-Gla-protein (dp-ucMGP) was used as a marker for vitamin K2 status. A propensity-matched scoring method was used. RESULTS: A total of 146 patients (73 matched pairs) were included in this study, of whom 89% were women with a mean age of 31.9 ± 8.4 years. Compared with controls, migraine patients had statistically significantly higher mean cfPWV (7.2 ± 1.1 vs 6.4 ± 0.8 m/s, 95% confidence interval (CI) of mean difference [0.45, 1.08], P < .001), as well as higher dp-ucMGP (454.3 ± 116.7 pmol/L vs 379.8 ± 126.6 pmol/L, 95% CI of mean difference [34.63, 114.31], P < .001). Higher cfPWV was associated with higher dp-ucMGP concentrations only in the migraine with aura (MWA) group. Moreover, migraine subjects had a higher frequency of vitamin K2 deficiency (dp-ucMGP ≥ 500 pmol/L) compared to controls, but this association was not statistically significant (23/73 [31.5%] vs 16/73 [21.9%], P = .193). CONCLUSIONS: Individuals with migraine have worse indices of arterial stiffness as compared with their age- and sex-matched control subjects. This increase in arterial stiffness is associated with an increase in markers of vitamin K2 deficiency in the MWA group.

4.
TH Open ; 3(2): e103-e108, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31249989

RESUMEN

Background Among medically ill patients treated with thromboprophylaxis, betrixaban was not associated with an increase in major bleeding compared with enoxaparin, but an increase in clinically relevant non-major (CRNM) bleeding was observed. The aim of this analysis is to describe the severity and clinical consequences of major and CRNM bleeding in the APEX trial. Methods The APEX trial randomized 7,513 hospitalized acutely ill medical patients to receive either enoxaparin for 6 to 14 days or betrixaban for 35 to 42 days. Subjects receiving a concomitant strong p-glycoprotein inhibitor or with creatinine clearance <30 mL/min were administered a reduced dose of study drug. Results A total of 25 (0.7%) and 21 (0.6%) major bleeds occurred in the betrixaban and enoxaparin arms, respectively ( p = NS) and a total of 91 (2.5%) and 38 (1.0%) CRNM bleeds occurred in the betrixaban and enoxaparin arm ( p < 0.001), respectively. Most major bleeds were considered moderate or severe and most CRNM bleeds were considered mild and moderate ( p = NS). One fatal major bleed occurred in each treatment arm. Rates of major or CRNM bleeds resulting in new or prolonged hospitalization (major: 44.0 vs. 28.6%; CRNM: 12.1 vs. 21.1%) or study treatment interruption or cessation (major: 72.0 vs. 71.4%; CRNM: 71.3 vs. 68.4%) were similar between treatment arms ( p = NS). Conclusions In the APEX trial, CRNM bleeds were mild or moderate in nature and had less of a clinical impact than major bleeds. The severity and clinical sequela of bleeds in the betrixaban arm were comparable to those in the enoxaparin arm. Clinical Trial Registration URL: http://www.clinicaltrials.gov .; Unique identifier: NCT01583218.

6.
Am Heart J ; 208: 81-90, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30580130

RESUMEN

BACKGROUND: CSL112 (apolipoprotein A-I [human]) is a plasma-derived apolipoprotein A-I developed for early reduction of cardiovascular risk following an acute myocardial infarction (AMI). The safety of CSL112 among AMI subjects with moderate, stage 3 chronic kidney disease (CKD) is unknown. METHODS: CSL112_2001, a multicenter, placebo-controlled, parallel-group, double-blind, randomized phase 2 trial, enrolled patients with moderate CKD within 7 days following AMI. Enrollment was stratified on the basis of estimated glomerular filtration rate and presence of diabetes requiring treatment. Patients were randomized in a 2:1 ratio to receive 4 weekly infusions of CSL112 6 g or placebo. The co-primary safety end points were renal serious adverse events (SAEs) and acute kidney injury, defined as an increase ≥26.5 µmol/L in baseline serum creatinine for more than 24 hours, during the treatment period. RESULTS: A total of 83 patients were randomized (55 CSL112 vs 28 placebo). No increase in renal SAEs was observed in the CSL112 group compared with placebo (CSL112 = 1 [1.9%], placebo = 4 [14.3%]). Similarly, no increase in acute kidney injury events was observed (CSL112 = 2 [4.0%], placebo = 4 [14.3%]). Rates of other SAEs were similar between groups. CSL112 administration resulted in increases in ApoA-I and cholesterol efflux similar to those observed in patients with AMI and normal renal function or stage 2 CKD enrolled in the ApoA-I Event Reducing in Ischemic Syndromes I trial. CONCLUSIONS: These results demonstrate the acceptable safety of the 6-g dose of CSL112 among AMI subjects with moderate stage 3 CKD and support inclusion of these patients in a phase 3 cardiovascular outcomes trial powered to assess efficacy.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Lipoproteínas HDL/efectos adversos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/tratamiento farmacológico , Insuficiencia Renal Crónica/complicaciones , Lesión Renal Aguda/sangre , Anciano , Apolipoproteína A-I/sangre , Biomarcadores/sangre , Colesterol/sangre , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular , Humanos , Análisis de Intención de Tratar , Lipoproteínas HDL/administración & dosificación , Masculino , Infarto del Miocardio/sangre , Insuficiencia Renal Crónica/sangre , Tamaño de la Muestra , Factores de Tiempo
7.
Am J Cardiol ; 123(3): 355-360, 2019 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30502047

RESUMEN

The PIONEER AF-PCI trial demonstrated that in atrial fibrillation patients who underwent intracoronary stenting, either rivaroxaban 15 mg daily plus P2Y12 inhibitor monotherapy (Group 1) or 2.5 mg rivaroxaban twice daily plus dual antiplatelet therapy (DAPT) (Group 2) was associated with fewer recurrent hospitalizations, primarily for bleeding and cardiovascular events, compared with standard-of-care vitamin K antagonist and DAPT (Group 3). Associated costs are unknown. This study estimates costs associated with rivaroxaban strategies compared with vitamin K antagonist and DAPT. Medication costs were estimated using wholesale acquisition costs, medication discontinuation rates, and costs of monitoring. Using a large US healthcare claims database, the mean adjusted increase in 1-year cost of care for individuals with atrial fibrillation and percutaneous coronary intervention (PCI) rehospitalized for bleeding, cardiovascular, and other events was compared with those not rehospitalized. Using adjudicated rehospitalization rates from PIONEER AF-PCI, cost differences were estimated. Rates of rehospitalization for bleeding were 6.5%, 5.4%, 10.5%, and 20.3%, 20.3%, 28.4% for cardiovascular events in Groups 1, 2, and 3. Medication and monitoring costs were $3,942, $4,115, and $1,703. One-year costs for all recurrent hospitalization costs and/or patient for the groups were $24,535, $20,205, and $29,756. One-year cost increase associated with bleeding rehospitalizations and/or patient was $4,160, $3,212, and $6,876 and was $13,264, $11,545, and $17,220 for cardiovascular rehospitalizations and/or patient. Overall estimated cost per patient was $28,476, $24,320, and $31,458. Compared with warfarin, both rivaroxaban treatment strategies had higher medication costs, but these were more than accounted for by fewer hospitalizations.


Asunto(s)
Anticoagulantes/economía , Anticoagulantes/uso terapéutico , Fibrilación Atrial/terapia , Readmisión del Paciente/economía , Anciano , Monitoreo de Drogas/economía , Quimioterapia Combinada , Femenino , Insuficiencia Cardíaca/economía , Insuficiencia Cardíaca/epidemiología , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Humanos , Relación Normalizada Internacional , Masculino , Readmisión del Paciente/estadística & datos numéricos , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/economía , Inhibidores de Agregación Plaquetaria/uso terapéutico , Rivaroxabán/economía , Rivaroxabán/uso terapéutico , Warfarina/economía , Warfarina/uso terapéutico
8.
Eur Heart J Acute Cardiovasc Care ; 8(2): 186-193, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29249166

RESUMEN

BACKGROUND:: Despite dual antiplatelet therapy, persistent thrombin generation and thrombin-mediated platelet activation account in part for the residual risk of atherothrombotic disease among patients with prior acute coronary syndrome (ACS). Inhibition of thrombin generation among high-risk ACS patients (biomarker-positive ACS) with the factor Xa inhibitor rivaroxaban may limit ongoing thrombus formation and myocardial necrosis and thereby improve clinical outcomes. OBJECTIVES AND METHODS:: ATLAS ACS 2-TIMI 51 was a double-blind, placebo-controlled clinical trial that randomized ACS patients to either rivaroxaban 2.5 mg b.i.d., rivaroxaban 5 mg b.i.d., or placebo plus standard-of-care antiplatelet therapy for a mean of 13.1 months and up to 31 months ( N=15,526). This post-hoc analysis evaluates the safety and efficacy of rivaroxaban among biomarker-positive ACS patients with and without a history of prior stroke of transient ischemic attack in the ATLAS ACS 2-TIMI 51 trial. RESULTS:: A total of 12,626 biomarker-positive ACS patients were included in this analysis. Among biomarker-positive patients without a prior history of stroke or transient ischemic attack, rivaroxaban 2.5 b.i.d. was associated with a reduction in the primary efficacy endpoint (composite of cardiovascular death, myocardial infarction, or stroke) as compared with placebo (hazard ratio=0.80, 95% confidence interval (0.68-0.94), p=0.007) at the expense of an increase in non-coronary-artery-bypass-graft-related Thrombolysis in Myocardial Infarction major bleeding (1.9% vs. 0.7%, p<0.0001), but not a significant increase in either intracranial hemorrhage (0.4% vs. 0.2%, p=0.11) or fatal bleeding (0.1% vs. 0.3%, p=0.16). CONCLUSION:: Rivaroxaban 2.5 mg b.i.d. was associated with a significant reduction in the composite of cardiovascular death, myocardial infarction, or stroke with no increase in fatal bleeding. Biomarker-positive patients with no prior history of stroke or transient ischemic attack may be a optimal target population to receive "dual pathway" therapy with rivaroxaban plus dual antiplatelet therapy for secondary prevention following ACS.


Asunto(s)
Síndrome Coronario Agudo/complicaciones , Rivaroxabán/administración & dosificación , Prevención Secundaria/métodos , Terapia Trombolítica/métodos , Trombosis/prevención & control , Troponina/sangre , Administración Oral , Biomarcadores/sangre , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Quimioterapia Combinada , Inhibidores del Factor Xa/administración & dosificación , Estudios de Seguimiento , Humanos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Trombosis/sangre , Trombosis/etiología , Factores de Tiempo , Resultado del Tratamiento
9.
Am J Cardiol ; 122(11): 1896-1901, 2018 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-30340765

RESUMEN

Patients with both acute coronary syndromes (ACS) and congestive heart failure are at an increased risk of recurrent cardiovascular (CV) events attributed in part to both excess thrombin generation and impaired fibrinolysis. We hypothesized that patients with the overlap of ACS and CHF would thus derive particular benefit from antithrombotic therapy with rivaroxaban. ATLAS-ACS-2 Thrombolysis in Myocardial Infarction-51 was a double-blind, multicenter, phase 3 clinical trial that randomized patients within 7 days of an ACS event to standard of care plus either rivaroxaban 2.5 mg BID, 5 mg BID, or placebo (n = 15,526). In this post hoc subgroup analysis, subjects with a history of CHF at randomization (n = 1,694) were evaluated. Among subjects with a history of CHF, both rivaroxaban doses reduced the primary composite end point of CV death, myocardial infarction, or stroke (2.5 mg BID vs placebo: hazard ratio [HR] 0.59, 95% confidence interval [CI] (0.42, 0.81), p = 0.001; 5 mg BID vs placebo: HR 0.61, 95% CI (0.44, 0.84), p = 0.002; p interaction = 0.006). Both doses of rivaroxaban reduced CV mortality (rivaroxaban 2.5 mg BID vs placebo: 4.1% vs 9.0%, HR 0.45, 95% CI [0.27, 0.74], p = 0.002; rivaroxaban 5 mg BID vs placebo: 5.8% vs 9.0%, HR 0.62, 95% CI [0.40, 0.96], p = 0.031) as well as all-cause mortality. There was no significant increase in noncoronary artery bypass graft-related Thrombolysis in Myocardial Infarction major bleeding with either dose of rivaroxaban as compared with placebo (rivaroxaban 2.5 mg BID = 0.4% vs rivaroxaban 5 mg BID = 1.1% vs placebo = 0.5%). Rivaroxaban also did not increase either intracranial hemorrhage or fatal bleeding. In conclusion, in ACS subjects with a history of CHF, secondary prevention with rivaroxaban reduced the composite of CV death, myocardial infarction, or stroke without an increase in noncoronary artery bypass graft-related major bleeding. These findings require further prospective evaluation in an adequately powered phase 3 study.


Asunto(s)
Síndrome Coronario Agudo/prevención & control , Insuficiencia Cardíaca/complicaciones , Rivaroxabán/administración & dosificación , Prevención Secundaria/métodos , Terapia Trombolítica/métodos , Síndrome Coronario Agudo/epidemiología , Síndrome Coronario Agudo/etiología , Causas de Muerte/tendencias , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Inhibidores del Factor Xa/administración & dosificación , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Estados Unidos/epidemiología
10.
Am Heart J ; 198: 84-90, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29653652

RESUMEN

BACKGROUND: Approximately 15%-30% of patients in trials of medical thromboprophylaxis will have missing compression ultrasound (CUS) data. The goal of the present analysis was to perform analyses to minimize missing data. METHODS: The APEX trial randomized 7,513 acutely medically ill hospitalized patients to thromboprophylaxis with either betrixaban for 35-42 days or enoxaparin for 6-14 days. A modified intent-to-treat (mITT) analysis was performed and included all subjects administered study drug, irrespective of CUS performance, and an analysis of symptomatic events which do not require performance of a CUS (symptomatic deep vein thrombosis, nonfatal pulmonary embolism, and venous thromboembolism (VTE)-related mortality). RESULTS: In the mITT population, betrixaban significantly reduced the primary end point (which included both symptomatic and CUS events) (165 [4.4%] vs 223 [6.0%]; relative risk = 0.75; 95% CI 0.61-0.91; P = .003; absolute risk reduction [ARR] = 1.6%; number needed to treat [NNT] = 63). Betrixaban also reduced symptomatic VTE through day 42 (35 [1.28%] vs 54 [1.88%], hazard ratio [HR] = 0.65; 95% CI 0.42-0.99; P = .044; ARR = 0.6%; NNT=167) as well as through day 77 (37 [1.02%] vs 67 [1.89%]; HR= 0.55; 95% CI 0.37-0.83; P = .003; ARR = 0.87%; NNT=115) as well as the individual end point of nonfatal pulmonary embolism (9 [0.25%] vs 20 [0.55%]; HR= 0.45; 95% CI 0.21-0.99; P = .041; ARR = 0.30%; NNT=334). On an "as-treated" basis, 80 mg of betrixaban reduced VTE-related mortality through day 77 (10 [0.34%] vs. 22 [0.79%]; HR=0.46; 95% CI 0.22-0.96; P = .035; ARR = 0.45%; NNT=223). CONCLUSION: In an mITT analysis of all patients administered study drug, extended-duration betrixaban reduced the primary end point as well as symptomatic events. In an as-treated analysis, 80 mg of betrixaban reduced VTE-related death.


Asunto(s)
Anticoagulantes/uso terapéutico , Benzamidas/uso terapéutico , Hospitalización , Embolia Pulmonar/prevención & control , Piridinas/uso terapéutico , Tromboembolia Venosa/prevención & control , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Enfermedad Crítica/terapia , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Incidencia , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Masculino , Prevención Primaria/métodos , Pronóstico , Modelos de Riesgos Proporcionales , Embolia Pulmonar/epidemiología , Medición de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Tromboembolia Venosa/epidemiología
12.
Int Urol Nephrol ; 50(6): 1075-1083, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29383580

RESUMEN

Sickle cell nephropathy is a major complication of sickle cell disease. It manifests in different forms, including glomerulopathy, proteinuria, hematuria, and tubular defects, and frequently results in end-stage renal disease (ESRD). Different pathophysiologic mechanisms have been proposed to explain the development of nephropathy in SCD, where hemolysis and vascular occlusion are the main contributors in the manifestations of this disease. Markers of renal injury, such as proteinuria and tubular dysfunction, have been associated with outcomes among patients with sickle cell nephropathy and provide means for early detection of nephropathy and screening prior to progression to renal failure. In small-sized clinical trials, hydroxyurea has demonstrated to be effective in slowing the progression to ESRD. Dialysis and renal transplantation represent the last resort for patients with sickle cell nephropathy. Nevertheless, despite the availability of diagnostic and therapeutic strategies, sickle cell nephropathy remains a challenging and under-recognized complication for patients with sickle cell disease.


Asunto(s)
Anemia de Células Falciformes/complicaciones , Enfermedades Renales/fisiopatología , Enfermedades Renales/terapia , Glomérulos Renales/fisiopatología , Túbulos Renales/fisiopatología , Analgésicos/uso terapéutico , Biomarcadores/sangre , Biomarcadores/orina , Tasa de Filtración Glomerular , Hematuria/etiología , Humanos , Hidroxiurea/uso terapéutico , Enfermedades Renales/diagnóstico , Enfermedades Renales/etiología , Fallo Renal Crónico/etiología , Inhibidores de la Síntesis del Ácido Nucleico/uso terapéutico , Terapia de Reemplazo Renal
13.
Prog Cardiovasc Dis ; 60(4-5): 524-530, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29397950

RESUMEN

Dual antiplatelet therapy (DAPT) has been the cornerstone of antithrombotic management for patients undergoing percutaneous coronary intervention (PCI). However, approximately 10% of these patients have concomitant atrial fibrillation (AF) and require chronic oral anticoagulant (OAC) in addition to DAPT. This traditional "triple therapy" has been associated with a three to four-fold increased risk of bleeding. The safety of non-vitamin K OAC (NOAC)-based strategies, using a NOAC plus a P2Y12 inhibitor, has been compared to vitamin K antagonist (VKA)-based triple therapy in the PIONEER AF-PCI and REDUAL PCI randomized trials, both of which have demonstrated that NOAC-based strategies are safer and provide an attractive alternative to VKA-based triple therapy among AF patients who undergo PCI. This article reviews the rationale, evidence, and recent evaluation of triple antithrombotic therapy among AF patients undergoing PCI.


Asunto(s)
Anticoagulantes , Fibrilación Atrial/tratamiento farmacológico , Enfermedad Coronaria/cirugía , Intervención Coronaria Percutánea , Ajuste de Riesgo/métodos , Anticoagulantes/clasificación , Anticoagulantes/farmacología , Fibrilación Atrial/complicaciones , Enfermedad Coronaria/complicaciones , Quimioterapia Combinada/métodos , Humanos , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos
14.
J Thromb Thrombolysis ; 45(1): 1-8, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29188425

RESUMEN

Hospitalized acute medically ill patients with a history of venous thromboembolism (VTE) are at increased risk for recurrent VTE. We characterized the efficacy and safety of betrixaban for prevention of recurrent VTE in these high risk patients. The APEX trial randomized 7513 acutely ill hospitalized medical patients at risk for developing VTE to receive either betrixaban for 35-42 days or enoxaparin for 10 ± 4 days to prevent VTE. This exploratory post-hoc analysis assessed the efficacy and safety of betrixaban versus enoxaparin among subjects with and without prior VTE. Time-to-multiple symptomatic VTE events was also calculated. Approximately 8% of subjects in both arms had prior VTE, which was associated with a fourfold increase in adjusted risk of VTE [MV OR 4.03, 95% CI 3.06-5.30, p < 0.001]. Betrixaban reduced VTE compared with enoxaparin among subjects with prior VTE [32 (10.4%) vs. 55 (18.9%), RR 0.57, 95% CI 0.38-0.86, p = 0.006, ARR 8.5%, NNT 12] and without prior VTE [133 (3.9%) vs. 168 (4.9%), RR 0.79, 95% CI 0.64-0.99, p = 0.042, ARR 1.0%, NNT 100] (interaction p > 0.05). Additionally, four subjects in the enoxaparin arm and one subject in the betrixaban arm experienced a recurrent VTE. Compared with enoxaparin, betrixaban use was associated with reduction of recurrent VTE events through the active treatment period [36 vs. 57, HR 0.63, 95% CI 0.41-0.97, p = 0.045] and through the end of study [38 vs. 71, HR 0.54, 95% CI 0.36-0.81, p = 0.004]. Prior VTE is associated with a fourfold increase in the risk of VTE among hospitalized medically ill patients. Only 12 such patients would need to be treated with betrixaban versus enoxaparin to prevent an additional VTE endpoint. Betrixaban reduced not only the first but also all recurrent VTE events in a time-to-any-event analysis. TRIAL REGISTRATION: http://www.clinicaltrials.gov , Unique identifier: NCT01583218.


Asunto(s)
Benzamidas/uso terapéutico , Piridinas/uso terapéutico , Tromboembolia Venosa/prevención & control , Adulto , Anciano , Benzamidas/administración & dosificación , Enoxaparina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piridinas/administración & dosificación , Recurrencia , Prevención Secundaria/métodos , Resultado del Tratamiento , Tromboembolia Venosa/tratamiento farmacológico
15.
TH Open ; 2(1): e16-e24, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31249924

RESUMEN

Background Elevated D-dimer concentrations are associated with an increased risk of venous thromboembolism (VTE). However, they may also provide prognostic value. The present analysis sought to study the association of D-dimer levels with VTE event rates and the efficacy of betrixaban versus enoxaparin in the APEX trial. Methods Hospitalized acutely medically ill subjects ( n = 7,513) were randomized in a double-dummy double-blind fashion to either extended-duration oral betrixaban (80 mg once daily for 35-42 days) or standard dose subcutaneous enoxaparin (40 mg once daily for 10 ± 4 days) for venous thromboprophylaxis. D-dimer was assessed using a central core laboratory measurement. Results For every 0.25 µg/mL increase in D-dimer concentration, there was a 2% increase in the relative risk of experiencing the primary efficacy endpoint (asymptomatic deep vein thrombosis [DVT], symptomatic DVT, nonfatal pulmonary embolism, or VTE-related death) in both the betrixaban ( p < 0.001) and enoxaparin ( p < 0.001) treatment arms. Among D-dimer-positive (≥ 2 × upper limit of normal; corresponding to ≥ 1.00 µg/mL) subjects, extended-duration betrixaban reduced the risk of experiencing the primary efficacy outcome (5.4% [ n = 124] vs. 7.6% [ n = 170]; odds ratio = 0.69; 95% confidence interval: 0.55-0.88; absolute risk reduction = 2.2%, number needed to treat = 46, p = 0.003). There was no interaction between D-dimer and the treatment effect ( p int = 0.53). Conclusion Extended-duration betrixaban was superior to standard-duration enoxaparin, irrespective of D-dimer level at baseline. To prevent one VTE event, 46 D-dimer-positive patients would need to be treated with betrixaban.

16.
J Thromb Thrombolysis ; 44(4): 457-465, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28905172

RESUMEN

BACKGROUND: Among patients hospitalized with acute heart failure (HF), the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in short-term stroke prediction remains unclear. METHODS: In the APEX trial, 7513 patients hospitalized for an acute medical illness were randomized to receive either extended-duration betrixaban (80 mg once daily for 35-42 days) or standard-of-care enoxaparin (40 mg once daily for 10 ± 4 days) for venous thromboprophylaxis. Baseline NT-proBNP concentrations were obtained in 3261 patients admitted for HF. Stroke events were adjudicated by an independent clinical events committee blinded to thromboprophylaxis allocation. The association of NT-proBNP level and other risk factors and biomarkers with stroke was assessed at 77 days after randomization. RESULTS: In univariate analysis, the risk of stroke at 77 days was associated with baseline NT-proBNP (HR 3.63 [95% CI 1.47-8.99]; P = 0.005), D-dimer (HR 2.73 [95% CI 1.03-7.20]; P = 0.043), and hsCRP (HR 3.03 [95% CI 1.36-6.75]; P = 0.007). In multivariable analysis adjusting for hsCRP and thromboprophylaxis, NT-proBNP was associated with the risk of stroke (adjusted HR 3.64 [95% CI 1.35-9.83]; P = 0.011). The interaction of NT-proBNP with the treatment effect was not significant (Pint = 0.30). CONCLUSIONS: Baseline NT-proBNP concentration was associated with short-term stroke among patients hospitalized with acute HF. Stroke risk assessment models should consider incorporation of NT-proBNP measurement.


Asunto(s)
Benzamidas/administración & dosificación , Enoxaparina/administración & dosificación , Insuficiencia Cardíaca/complicaciones , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Piridinas/administración & dosificación , Accidente Cerebrovascular/diagnóstico , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Femenino , Insuficiencia Cardíaca/tratamiento farmacológico , Hospitalización , Humanos , Masculino , Medición de Riesgo , Trombosis de la Vena
17.
J Am Heart Assoc ; 6(7)2017 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-28698258

RESUMEN

BACKGROUND: Extended-duration betrixaban showed a significant reduction in venous thromboembolism in the APEX trial (Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study). Given the variable clinical impact of different efficacy and safety events, one approach to assess net clinical outcomes is to include only those events that are either fatal or cause irreversible harm. METHODS AND RESULTS: This was a post hoc analysis of the APEX trial-a multicenter, double-blind, randomized controlled trial comparing extended-duration betrixaban versus standard-of-care enoxaparin. A composite of all fatal or irreversible safety (fatal bleeding or intracranial hemorrhage) and efficacy events (cardiopulmonary death, myocardial infarction, pulmonary embolism, and ischemic stroke) was evaluated in a time-to-first event analysis. In patients with positive D-dimer results, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.80% versus 3.54%; hazard ratio, 0.73; absolute risk reduction, 1.26%; number needed to treat, 79 [P=0.033]) and at study end at 77 days (6.27% versus 4.36%; hazard ratio, 0.70; absolute risk reduction, 1.91%; number needed to treat, 52 [P=0.005]) versus enoxaparin. In all patients, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.08% versus 2.90%; hazard ratio, 0.71; absolute risk reduction, 1.18%; number needed to treat, 86 [P=0.006]) and 77 days (5.17% versus 3.64%; hazard ratio, 0.70; absolute risk reduction, 1.53%; number needed to treat, 65 [P=0.002]). CONCLUSIONS: Among hospitalized medically ill patients, extended-duration betrixaban demonstrated an ≈30% reduction in fatal or irreversible ischemic or bleeding events compared with standard-duration enoxaparin. A total of 65 patients would require treatment with betrixaban to prevent 1 fatal or irreversible event versus enoxaparin. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01583218.


Asunto(s)
Anticoagulantes/efectos adversos , Benzamidas/efectos adversos , Enfermedades Cardiovasculares/etiología , Enoxaparina/efectos adversos , Inhibidores del Factor Xa/efectos adversos , Hemorragia/inducido químicamente , Piridinas/efectos adversos , Tromboembolia Venosa/prevención & control , Enfermedad Aguda , Adulto , Anciano , Anticoagulantes/administración & dosificación , Benzamidas/administración & dosificación , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/mortalidad , Método Doble Ciego , Enoxaparina/administración & dosificación , Inhibidores del Factor Xa/administración & dosificación , Femenino , Hemorragia/diagnóstico , Hemorragia/mortalidad , Humanos , Pacientes Internos , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/mortalidad , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Piridinas/administración & dosificación , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Tromboembolia Venosa/complicaciones , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/mortalidad
18.
J Am Soc Hypertens ; 11(9): 589-597, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28756183

RESUMEN

Subclinical vitamin K deficiency is prevalent among renal transplant recipients and is associated with an increased risk of cardiovascular disease. However, the association between vitamin K supplementation and improvement of arterial stiffness has not been explored in the renal transplant population. The KING trial (vitamin K2 In reNal Graft) is a single-arm study that evaluated the association between the change in vitamin K status and indices of arterial stiffness following 8 weeks of menaquinone-7 (vitamin K2) supplementation (360 µg once daily) among renal transplant recipients (n = 60). Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV). Subclinical vitamin K deficiency was defined as plasma concentration of dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP) >500 pmol/L.At baseline, 53.3% of the study subjects had subclinical vitamin K deficiency. Supplementation was associated with a 14.2% reduction in mean cfPWV at 8 weeks (cfPWV pre-vitamin K2 = 9.8 ± 2.2 m/s vs. cfPWV post-vitamin K2 = 8.4 ± 1.5 m/s; P < .001). Mean dp-ucMGP concentrations were also significantly reduced by 55.1% following menaquinone-7 supplementation with a reduction in the prevalence of subclinical deficiency by 40% (P = .001). When controlled for age, durations of hemodialysis and transplantation, and the change in 24-hour mean arterial pressure, the improvement in arterial stiffness was independently associated with the reduction in dp-ucMGP concentration (P = .014).Among renal transplant recipients with stable graft function, vitamin K2 supplementation was associated with improvement in subclinical vitamin K deficiency and arterial stiffness. (Clinicaltrials.gov: NCT02517580).


Asunto(s)
Fallo Renal Crónico/terapia , Trasplante de Riñón , Rigidez Vascular/efectos de los fármacos , Vitamina K 2/uso terapéutico , Deficiencia de Vitamina K/tratamiento farmacológico , Vitaminas/uso terapéutico , Adulto , Biomarcadores/sangre , Proteínas de Unión al Calcio/sangre , Suplementos Dietéticos , Proteínas de la Matriz Extracelular/sangre , Femenino , Humanos , Fallo Renal Crónico/sangre , Masculino , Persona de Mediana Edad , Proyectos Piloto , Prevalencia , Estudios Prospectivos , Análisis de la Onda del Pulso , Diálisis Renal , Resultado del Tratamiento , Calcificación Vascular/sangre , Calcificación Vascular/tratamiento farmacológico , Calcificación Vascular/epidemiología , Vitamina K/sangre , Deficiencia de Vitamina K/sangre , Deficiencia de Vitamina K/epidemiología
20.
Biomed Res Int ; 2017: 2543262, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28299320

RESUMEN

Background. Prior studies have demonstrated that conventional and emerging CV risk factors are associated with worsening arterial stiffness among end-stage renal disease (ESRD) patients on hemodialysis. The present cross-sectional study evaluates the association between the etiology of ESRD and arterial stiffness among a cohort of hemodialysis patients. Methods. Etiology of ESRD was identified from patients' medical records and classified as either vascular renal disease, diabetic nephropathy, nondiabetic glomerulopathy, tubular interstitial nephropathy, hereditary nephropathy, or ESRD of unconfirmed etiology. Results. A total of 82 subjects were enrolled. cfPWV was independently associated with the composite of either diabetic nephropathy or vascular renal disease (p = 0.022), pulse pressure (p = 0.001), and a history of CV events (p = 0.025), but not history of hypertension or diabetes mellitus alone. The median cfPWVs in diabetic nephropathy and vascular renal disease were comparable and significantly higher than median cfPWVs in other etiologies of ESRD. Conclusion. The study suggests that the etiology of ESRD is independently associated with arterial stiffness among hemodialysis patients. Furthermore, arterial stiffness was higher among patients who developed renal sequelae of either diabetes mellitus or hypertension as compared with those who have a history of either diabetes mellitus or hypertension alone.


Asunto(s)
Enfermedades Cardiovasculares/complicaciones , Nefropatías Diabéticas/complicaciones , Fallo Renal Crónico/etiología , Diálisis Renal , Enfermedades Vasculares/complicaciones , Rigidez Vascular , Adulto , Anciano , Presión Sanguínea , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Hipertensión/complicaciones , Masculino , Registros Médicos , Persona de Mediana Edad , Factores de Riesgo
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