Servicio Medicina Interna CAULE...• Pacientes con antiagregacion dual (3.873) • Aleatorizizacion...

Servicio Medicina Interna

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• Remodelamiento pulmonar, caracteristico en el Asthma.

• Implica peor evolución clínica

• Atribuido a inflamación, eosinófilos

• Datos in vitro sugieren papel de fuerzas mecánicas, y papel del broncoespasmo en remodelamiento

BACKGROUND: Servicio Medicina Interna

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• N 48 asmáticos• Aleatorizacion :

– Alergeno: Polvo de ácaros – Metacolina – Salino – Albuerol seguido de Metacolina

• Estudio basal, provocacion y 48 h despues. • Valoracion de p funcionales y biopsia bronquial por broncoscopia 4 días despues

METHODSServicio Medicina Interna

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RESULTS:

Alergeno Metacolina S. Salino (control)

Albuterol + Metacolina

Inflamacion Eosinofilos en vias aereas

Glandulas mucosas (Tinción PAS)

+ 2.17 +2.13 P=0.003 for the comparison

Colageno submucoso

+ 2.17 +1.94 P<0.001 para comparacion con 2 grupos contro


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MKI67) is a

cellular

marker for proliferation

TGF‐B: factor de crecimiento transformante beta 1 KI67: is a cellular marker for proliferation

7) is a

cellular

marker for proliferation


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• La broncoconstricción incluso sin inflamación adicional, induce remodelación de las vías aéreas de pacientes asmáticos.

• Los hallazgos tienen implicaciones para el tratamiento.

CONCLUSIONS: Servicio Medicina Interna

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Aspirin for Preventing the Recurrence of Venous Thromboembolism

• Cecilia Becattini, M.D., Ph.D., Giancarlo Agnelli, M.D., Alessandro Schenone, M.D., Sabine Eichinger, M.D., Eugenio Bucherini, M.D., Mauro Silingardi, M.D., Marina Bianchi, M.D., Marco Moia, M.D., Walter Ageno, M.D., Maria Rita Vandelli, M.D., Elvira Grandone, M.D., and Paolo Prandoni, M.D., Ph.D. for the WARFASA Investigators

• N Engl J Med 2012; 366:1959‐1967May 24, 2012


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Background

• About 20% of patients with unprovoked venous thromboembolism have a recurrence within 2 years after the withdrawal of oral anticoagulant therapy.

• Extending anticoagulation prevents recurrences but is associated with increased bleeding.

• The benefit of aspirin for the prevention of recurrent venous thromboembolism is unknown.


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Methods

• In this multicenter, investigator‐initiated, double‐blind study

• Funded by the University of Perugia and others; WARFASA • patients with first‐ever unprovoked venous

thromboembolism who had completed 6 to 18 months of oral anticoagulant treatment

• were randomly assigned to aspirin, 100 mg daily, or placebo for 2 years, with the option of extending the study treatment.

• The primary efficacy outcome:– recurrence of venous thromboembolism– major bleeding was the primary safety outcome.


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Results

Aspirina Placebo• (median study period, 24.6 months):

– Recurrencia TVP 28/205 6.6% 43/197 11.2%/ año – HR 0.58; 95% [CI], 0.36 to 0.93)

• (median treatment period of 23.9 months):– Recurrencia TVP 23 ‐ 5.9% 39 ‐ 11.0%/año– HR, 0.55; 95% CI, 0.33 to 0.92

• Hemorragias graves 1 1• Eventos adversos iguales


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Conclusions

• En pacientes con TVP espontanea la recurrencia tras suspensión de Anticoagulantes se reduce con Aspirina sin mayor incremento del riesgo hemorragico


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ANTECEDENTES

• Tto quirurgico IM según guias actuales: IM moderada severa (grade 3+) en presencia de sintomas o disfuncion ventricular

• En IM degenerativa, tecnica de Anuloplastia con anillo y aproximación de velos mitrales creando un doble orificio

• Estandarizacion de un procedimiento mecanizado de grapaje de los velos mitrales, desde abordaje transeptal (MitraClip, Abbott Vascular)


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Tecnica de aproximar y grapar los gordes de las 2 valvas mitrales


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METHODS

• N =279 con IM moderada‐severa (grade 3+ or 4+)• Aleatorizacion en proporcion 2:1• Reparacion percutanea versus cirugia convencional

• Variable principal:– compuesto por: No mortalidad, No disfunción valvular (IM) grado +3 o +4

• Variable de seguridad:– compuesto de eventos adversos mayores a 30 dias

• Valoracion a 12 meses


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RESULTS

Reparacion Cirugia convencionalV principal 55% 73% (P=0.007). Muerte 6% 6%Cirugia mitral 20% 2%IM grade 3+ or 4+ 21% 20%Eventos adversos mayores a 30 dias:

15% 48%a 12 meses (tamaño ventricular, Clase NYHA y calidad de vida): igual


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CONCLUSIONS

Aunque la reparación percutanea fue menos efectiva para reducir la IM que la cirugia convencional, el procedimiento se asoció con mayor seguridad y mejoria clinica semejante.


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ANTECEDENTES:

• La antiagregación produce complicaciones gastrointestinales.

• IBP reducen complicaciones gastrointestinales en pacientes de alto riesgo antiagregados

• Estudios observacionales sugieres interaccion negativa entre clopidogrel e IBP

• Otros estudios observacionales no lo confirman

• Estudios ex‐vivo parecen evidenciar intreraccion negativa entre IBP, Omeprazol y clopidogrel

• Se sugiere que los polimorfismo genticos (cytochrome P‐450) puedan jugar un papel en la interaccion ibp‐clopidogrel.


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• Pacientes con antiagregacion dual (3.873)• Aleatorizizacion a recibir Omeprazol o placebo• Variable principal digestiva:

– hemorragia digestiva manifiesta u oculta, ulcera o erosiones, obstrucción o perforación

• Variable principal vascular: – combinación de muerte cardiovascular, iam no mortal, revascularización o acv.

• El estudio fue interrumpido prematuramente cuando el patrocinador retiro la financiación: (Cogentus Pharmaceuticals).

METODOSServicio Medicina Interna

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3761 se incluyeron en los análisis. Clopid+AAS+IBP + placebo

VP digestiva 180 dias:1,1% 2,9%

HR 0,34, 95% [IC]: 0,18 a 0,63, p <0,001) . H Digestiva alta

HR, 0,13; 95% CI, 0,03 a 0,56, p = 0,001).

VP vascular 4,9% 5,7% HR, 0,99, 95% CI, 0,68 a 1,44, p = 0,96)

Los subgrupos de alto riesgo no muestran una heterogeneidad significativa.Acontecimientos adversosGraves igualDiarrea mayor

RESULTADOS: Servicio Medicina Interna

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• En doble antiagregación de aspirina y clopidogrel, la gastroproteccion profilactica con omeprazol redujo la incidencia de hemorragia digestiva alta.

• No hubo interacción aparente cardiovascular entre clopidogrel y omeprazol: – the current study reveals no signal of harm from concomitant clopidogrel and PPI use.

– … pero nuestros resultados no descartan una diferencia clínicamente significativa en los eventos cardiovasculares debido al uso de un IBP.

CONCLUSIONES: Servicio Medicina Interna

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Prednisone, Azathioprine, and N‐Acetylcysteine for Pulmonary Fibrosis

• The Idiopathic Pulmonary Fibrosis Clinical Research Network

• N Engl J Med 2012; 366:1968‐1977May 24, 2012


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Background

• A combination of prednisone, azathioprine, and N‐acetylcysteine (NAC) has been widely used as a treatment for idiopathic pulmonary fibrosis.

• The safety and efficacy of this three‐drug regimen is unknown.

• A survey of pulmonologists showed that almost 50% used a regimen of either two drugs (azathioprine plus prednisone) or three drugs (azathioprine, prednisone, and N‐acetylcysteine [NAC]) when therapy was offered to their patients with mild idiopathic pulmonary fibrosis.


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High‐Dose Acetylcysteine in Idiopathic Pulmonary Fibrosis

• Maurits Demedts, M.D., Juergen Behr, M.D., Roland Buhl, M.D., Ulrich Costabel, M.D., P.N., Richard Dekhuijzen, M.D., Henk M. Jansen, M.D., William MacNee, M.D., Michiel Thomeer, M.D., Benoit Wallaert, M.D., François Laurent, M.D., Andrew G. Nicholson, M.D., Eric K. Verbeken, M.D., Johny Verschakelen, M.D., Christopher D.R. Flower, M.D., Frédérique Capron, M.D., Stefano Petruzzelli, M.D., Paul De Vuyst, M.D., Jules M.M. van den Bosch, M.D., Eulogio Rodriguez‐Becerra, M.D., Giuseppina Corvasce, Ph.D., Ida Lankhorst, M.D., Marco Sardina, M.D., and Mauro Montanari, Ph.D. for the IFIGENIA Study Group

• N Engl J Med 2005; 353:2229‐2242November 24, 2005


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RESULTADOS

P+Aza P+Aza+Acetilcisteina 600 mg/8 h• N 90 92• neumonia intersticial usual 75 80• completan el tratamiento 75% 68%• Diferencia CVF ‐190 ‐60

0.18 liter (IC 95% 0.03 to 0.32) , • Diferencia relativa CVF 9% (P=0.02)• Diferencia DLCO comienzo‐final del tratamiento

‐60 ‐11 0.75 mmol/min/Kp(CI 95% 0.27 to 1.23)

• Diferencia relativa DLCO 24 percent, (P=0.003). • Mortalidad 11% 9% (P=0.69)

• No diferencias en efectos adverso salvo mayor mielodepresión con acetilcisteina (P=0.03).


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Methods• randomized, double‐blind, placebo‐controlled trial

• patients with idiopathic pulmonary fibrosis who had mild‐to‐moderate lung‐function impairment

– ages of 35 and 85 years– [FVC] of ≥50% – DLCO ≥30% of the predicted value)

• three groups in a 1:1:1 ratio:– Combination therapy

• prednisone, 0.5 mg per kilogram of ideal body weight and was tapered to 0.15 mg per kilogram during a period of 25 weeks.

• azathioprine, (maximum, 150 mg per day) was based on the patient's ideal weight

• NAC 600 mg orally three times a day

– NAC alone

– placebo

• The primary outcome was the change in longitudinal measurements of forced vital capacity during a 60‐week treatment period.


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Results

Tratamiento combinacion NAC PlaceboN 77 78

When approximately 50% of data had been collected a planned interim analysis revealed that patients in the combination‐therapy group, as compared with the placebo group, had increased rate of death (8 vs. 1, P=0.01)increased rate hospitalization (23 vs. 7, P<0.001).

These observations, coupled with no evidence of physiological or clinical benefit for combination therapy, prompted the independent data and safety monitoring board to recommend termination of the combination‐therapy group at a mean follow‐up of 32 weeks.

(Data from the ongoing comparison of the NAC‐only group and the placebo group are not reported here).


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Conclusions

• Increased risks of death and hospitalization were observed in patients with idiopathic pulmonary fibrosis who were treated with a combination of prednisone, azathioprine, and NAC, as compared with placebo.

• These findings provide evidence against the use of this combination in such patients.


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BackgroundRivaroxaban a dosis fija ha sido eficaz en el tratamiento de TVP.

Se pretende valorar la eficacia en el TEP


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Metodos: ECA, abierto, conducido por eventos y de no inferioridad

Variable principal: recurrencia de TEPVariable de seguridad: hemorragia mayor o clínicamente relevante

N= 4832 pacientes con TEP agudo sintomático con o sin TVP


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ResultsRivaroxaban Standard

V principal 50 (2.1%) 44 (1.8%) (noninferiority margin, 2.0; P=0.003)

HR 1.12; 95% [CI], 0.75 to 1.68).

Variable seguridad 10.3% 11.4% HR, 0.90; 95% CI, 0.76 to 1.07; P=0.23).

Hemorragia mayor 26 pac (1.1%) 52 pac (2.2%) HR 0.49; 95% CI, 0.31 to 0.79; P=0.003).

Otros eventos adversos iguales


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Conclusions

Rivaroxaban durante el tratamiento agudo del TEP no fue inferior al tratamiento estándar.

A largo plazo y tiene la ventaja potencial de ofrecer un mejor el perfil riesgo (hemorragias).


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Association of Coffee Drinking with Total and Cause‐Specific Mortality

• Neal D. Freedman, Ph.D., Yikyung Park, Sc.D., Christian C. Abnet, Ph.D., Albert R. Hollenbeck, Ph.D., and Rashmi Sinha, Ph.D.

• N Engl J Med 2012; 366:1891‐1904May 17, 2012


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Background

• Coffee is one of the most widely consumed beverages, but the association between coffee consumption and the risk of death remains unclear.


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Methods

• E. Cohortes: National Institutes of Health–AARP Diet and Health Study• Association Coffee consumption with mortality • 229,119 men and 173,141 women• 50 to 71 years of age at baseline. • coffee drinking was assessed once at baseline.• Participants with cancer, heart disease, and stroke were excluded.

• Study duration: 13 years


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Results• 5,148,760 person‐years of follow‐up between 1995 and 2008,

• MORTALITY: 33,731 men and 18,784 women died.

• In age‐adjusted models, the risk of death was increased among coffee drinkers

• after adjustment for tobacco‐smoking status and other potential confounders:VARONES– < 1 cup per day. HR: 0.99 (95% [CI], 0.95 to 1.04) – 1 cup HR 0.94 (95% CI, 0.90 to 0.99)– 2 or 3 cups, HR 0.90 (95% CI, 0.86 to 0.93)– 4 or 5 cups, HR 0.88 (95% CI, 0.84 to 0.93) (P<0.001 for trend)– 6 or more cups of coffee per day HR 0.90 (95% CI, 0.85 to 0.96)

MUJERES– <1 HR 1.01 (95% CI, 0.96 to 1.07), – 1 HR 0.95 (95% CI, 0.90 to 1.01), – 2‐3 HR 0.87 (95% CI, 0.83 to 0.92), (P<0.001 for trend). – 4‐5 HR 0.84 (95% CI, 0.79 to 0.90),– >= 6 HR and 0.85 (95% CI, 0.78 to 0.93)

• Inverse associations were observed for deaths due to heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections, but not for deaths due to cancer.

• Results were similar in subgroups, including persons who had never smoked and persons who reported very good to excellent health at baseline.


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Asociacion con enfermedad


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Asociacion con otras variablesServicio Medicina Interna

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Conclusions

• In this large prospective study, coffee consumption was inversely associated with total and cause‐specific mortality: – Men who drank 2 to 3 cups of coffee daily had a 10% decrease in their

risk for death during the 13 years of the study. – Women who drank 2 to 3 cups of coffee daily had a 13% decrease

• Whether this was a causal or associational finding cannot be determined from our data.

Limitaciones: Determinaciondel habito uns aola vez al comienzo del estudioNo datos sobre forma de preparacion del cafe , pero valido tambien para el

descafeinado


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Servicio Medicina Interna CAULE...• Pacientes con antiagregacion dual (3.873) • Aleatorizizacion...

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