Anticoagulacion oral

1,531 views

Published on

Published in: Health & Medicine, Business
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
1,531
On SlideShare
0
From Embeds
0
Number of Embeds
85
Actions
Shares
0
Downloads
0
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide

Anticoagulacion oral

  1. 1. Anticoagulacion oral DABIGATRAN
  2. 2. DABIGATRAN
  3. 3. DABIGATRAN <ul><li>Hasta la fecha, los anticoagulantes más desarrollados (con estudios fase III) son dabigatran, rivaroxaban y apixaban. </li></ul><ul><li>Dabigatran es un inhibidor directo de la trombina y está aprobado para la prevención de la enfermedad trombo-embólica venosa después de cirugía ortopédica. </li></ul><ul><li>Rivaroxaban también está aprobado para la prevención de la enfermedad trombo-embólica venosa después de cirugía ortopédica. En FA, el estudio ROCKET demostró superioridad en la prevención de ictus y embolia sistémica respecto a warfarina con el mismo riesgo de sangrado, aunque los resultados conocidos hasta ahora son por protocolo y no por intención de tratar (resultados no publicados) </li></ul><ul><li>Apixaban también es un inhibidor directo del factor Xa. No se ha probado su utilidad para la prevención del ictus en FA respecto a la warfarina, aunque sí respecto al AAS en pacientes a los que no se consideró adecuado anticoagular con AVK. </li></ul>
  4. 4. DABIGATRAN <ul><li>Es inhibidor de la trombina </li></ul><ul><li>RE-LY : se eligieron pacientes con al menos dos registros de ECG en FA en los ultimos 6 meses con FA de al menos 30seg de duración. Además debian de tener al menos un factor de riesgo mayor, o ser mayor de 65años y tener un factor de riesgo menor para embolismo cardiaco. </li></ul><ul><li>Se randomizaron a dabigatran 110mg dos veces al dia, 150mg dos veces al dia, y warfarina (INR 2-3). </li></ul>
  5. 5. DABIGATRAN <ul><li>End point primario : demostrar la no inferioridad del producto mediante la aparición de ictus (isquémico o hemorrágico) o de embolismo sistémico. </li></ul><ul><li>End point secundario : todos los ictus, embolismo sistémico, y muerte, y un compuesto de ictus, embolismo sistemico y pulmonar, infarto agudo de miocardioy muerte vascular incluyendo hemorragia. </li></ul>
  6. 6. DABIGATRAN <ul><li>No contempló la administración conjunta de otros antiagregantes o anticoagulantes. </li></ul><ul><li>Los inhibidores de la Glicoproteina P interactúan con el dabigatran por lo que no se dio quinidina conjuntamente, aunque si verapamilo y amiodarona. </li></ul><ul><li>En caso de cirugía se interrumpió la toma de dabigatran 24h antes. </li></ul><ul><li>No se discontinuó para cardioversión. </li></ul>
  7. 7. DABIGATRAN 4.13%/año 0.38%/año 3.36%/año 1.69%/año WARFARINA 3.64%/año 0.1%/año 3.11%/año 1.11%/año P<0.001 DABIGATRAN 150 3.75%/año 0.12%/año 2.71%/año 1.53%/año DABIGATRAN 110 Mortalidad Ictus hemorrágico Sangrado mayor EFICACIA PRIMARIA (no inferioridad) FARMACO
  8. 8. DABIGATRAN <ul><li>En pacientes con FA no valvular , el estudio RE-LY demostró que a una dosis de 150 mg/12h, el dabigatran era más efectivo en la prevención de ictus y embolia sistémica que la warfarina, y que a una dosis de 110 mg/12h era más seguro (menos hemorragias graves). Ello ha motivado su aceptación en muchos países, entre ellos EEUU (octubre 2010) y Canadá. Sin embargo la FDA no lo ha aprobado para la prevención y ni tratamiento del tromboemlismo venoso. </li></ul><ul><li>No existe un método perfecto para la monitorización de estos fármacos para las situaciones concretas que lo exijan (hemorragia, cirugía, punciones). El test Hemoclot ® para el dabigatran ya está comercializado, aunque todavía no se conocen los valores a los cuáles se puede asegurar una hemostasia correcta. </li></ul><ul><li>No existe antídoto para ninguno de estos tres fármacos. En caso de hemorragia, debe suspenderse el fármaco y adoptar medidas generales. En casos graves puede probarse la administración de factor VIIa o de complejo protrombínico. </li></ul>
  9. 9. DABIGATRAN <ul><li>American Society of Hematology (june 2011) </li></ul><ul><li>Ask the hematologist </li></ul><ul><li>Stephan Moll, MD </li></ul><ul><li>Associate Professor, Hemophilia and Thrombosis Center, University of North Carolina School of Medicine, Department of Medicine, Division of Hematology-Oncology, Chapel Hill, NC   </li></ul><ul><li>In patients tolerating warfarin well and having stable INRs I would not yet consider a switch to dabigatran. </li></ul><ul><li>It is a relatively new drug, and even though it has been used in a large number of patients (more than 20,000 in the phase III VTE2 and atrial fibrillation3 trials). </li></ul><ul><li>I would like to see more real-life experience with the drug, more published data in the peer-reviewed literature on optimal management of major bleeding complications, and a comprehensive FDA review of the VTE trial data during the approval process for the VTE indication. </li></ul>
  10. 10. DABIGATRAN <ul><li>Management of Major Bleeding   </li></ul><ul><li>One major reason for me not to prescribe dabigatran more frequently off label in VTE patients is that neither a reversal agent nor an established evidence-based strategy exist for management of major bleeding. In patients on warfarin who have a major bleed, established treatment options include vitamin K, fresh frozen plasma (FFP), prothrombin complex concentrates (PCCs), and recombinant factor VIIa, depending on the degree of bleeding. </li></ul><ul><li>For bleeding on dabigatran, suggested management strategies are based on ex vivo plasma mixing studies, rat-tail bleeding models, or limited studies on healthy volunteers, and are mostly published only in abstract form. I am not aware of any peer-reviewed, full-length, patient-data-based publications on management of major bleeding in patients on dabigatran. </li></ul><ul><li>Major bleeding occurred at rates of one in 32 patients and one in 63 patients in the atrial fibrillation2 and VTE trial3, respectively. </li></ul><ul><li>It would be helpful to have data from these trials reporting how major bleeding was managed and what the clinical outcomes were, so that clinicians would have at least some clinical data to go by in their decisions about how to manage such patients. </li></ul>
  11. 11. DABIGATRAN <ul><li>Management of Major Bleeding   </li></ul><ul><li>In the event of bleeding in patients on dabigatran, management strategies should be individualized according to the severity and location of the bleed. </li></ul><ul><li>Dabigatran is predominantly (80%) cleared by the kidney. It has a plasma half-life of 13 hours (range 11-22 hours) in individuals with normal renal function (creatinine clearance greater than 80 mL/min). This increases to 18 hours (range 13-23 hours) and 27 hours (range 22-35 hours) in patients with creatinine clearances of 30-50 mL/min and less than 30 mL/min,5 highlighting the need to maintain good renal output and consider hemodialysis in cases of major and life-threatening bleeding. </li></ul><ul><li>Supportive measures, such as mechanical compression, surgical intervention, and fluid replacement, should of course be employed. Beyond that, treatment options include activated charcoal to prevent absorption of residual drug if the last drug intake was within two to four hours; PCCs with or without additional FFP; activated PCCs; recombinant factor VIIa; or antifibrinolytic drugs (aminocaproic acid or tranexamic acid). </li></ul><ul><li>As major bleeding is likely to occur in some patients taking dabigatran, emergency departments and hematologists may want to proactively establish a management strategy for their institutions. To assist in the development of these approaches, I have provided suggestions for drug selection and dosing through Clot Connect , the educational resource of the University of North Carolina Blood Clot Education Outreach Program. http://clotconnectmd.wordpress.com/2010/12/06/pradaxa-management-of-major-bleeding/  </li></ul>
  12. 12. DABIGATRAN <ul><li>http://clotconnectmd.wordpress.com/2010/12/06/pradaxa-management-of-major-bleeding/ </li></ul><ul><li>Charcoal to prevent residual drug in the stomach to be absorbed. </li></ul><ul><li>Consider hemodialysis . </li></ul><ul><li>Recombinant factor VIIa (NovoSeven; 90 mcg/kg x1). It is important to realize that it is not clear (a) whether recombinant factor VIIa is effective in this situation and (b) what VIIa dose might be appropriate. In addition, rVIIa is prothrombotic, and that needs to be kept in mind when considering use of the drug. </li></ul><ul><li>I would consider fibrinolytic drugs (Amicar or tranexamic acid) as adjuncts. </li></ul><ul><li>One could consider FEIBA ® (activated prothrombin complex concentrate). But I would worry some about its prothrombotic effect, if the patient had had a recent thrombotic event or was quite hypercoagulable by history. </li></ul><ul><li>Based on reference 3, I would NOT give Prothrombin complex concentrate (PCC; in the U.S.: Bebulin® or Profilnine®. </li></ul><ul><li>I would NOT give FFP (Fresh Frozen Plasma). </li></ul>
  13. 13. DABIGATRAN SANGRADO LIGERO MODERADO SEVERO RIESGO VITAL NO DAR 1-2 DOSIS SUSPENDER TRANSITORIAMENTE MEDIDAS LOCALES CONTROL EN ZONA DE SANGRADO SOPORTE: FLUIDOS SANGRE MONITORIZACION HEMODIALISIS FVIIa PCC

×