Complicaciones comunes de la fibrilacion atrial y su prevencion

1. PREVENCION DE COMPLICACIONES
EN FIBRILACION ATRIAL NO
VALVULAR
Dr. Daniel Meneses
Cardiólogo Intervencionista
© Daniel Meneses, 2014

2. http://www.pinterest.com/

3. 5 millones de pacientes actualmente
Para el 2050 serán 12-16 millones
FA es la arritmia mas común.
En el 2010 se diagnosticaron 1.2 millones de casos
FA contribuye a mas de 80 000 muertes anuales
El riesgo de por vida de desarrollarla en mayores de 40
años es de 1:4
En el mundo hay 600 millones de casos
26 Billones de dólares anuales son sus costos
Se ha caracterizado como una nueva epidemia
Gonzalez, A. (July 07, 2011). Atrial fibrillation is emerging as the new epidemic.
Cardiac Rhythm News. Retrieved August 23, 2011,

22. Dynamic interactions between atrial and ventricular function during atrial fibrillation (AF).
Iwasaki Y et al. Circulation. 2011;124:2264-2274
Copyright © American Heart Association, Inc. All rights reserved.

24. 1. RESERVORIO DE PRESION PARA MANTENER LA PRESION DEL ATRIO IZQUIERDO
2. ORGANO SENSOR DE PRESION. 30% DE LA PRODUCCION DE PEPTIDO ATRIAL NATRIURETICO
3. RESERVORIO DINAMICO DE SANGRE EN EL CICLO ATRIAL
4. CONTRACCION ACTIVA MEJORA EL LLENADO ATRIAL Y LA SISTOLE VENTRICULAR

26. MECANISMOS DE LA FIBRILACION ATRIAL
Iwasaki Y et al. Circulation. 2011;124:2264-2274
Copyright © American Heart Association, Inc. All rights reserved.

27. Abnormalities of refractoriness (A) and conduction velocity (B) are the major determinants of
atrial fibrillation (AF) reentry substrates.
Iwasaki Y et al. Circulation. 2011;124:2264-2274
Copyright © American Heart Association, Inc. All rights reserved.

28. Conceptual models of reentry and implications for atrial fibrillation (AF).
Iwasaki Y et al. Circulation. 2011;124:2264-2274
Copyright © American Heart Association, Inc. All rights reserved.

29. Types of atrial fibrillation (AF)–promoting remodeling.
Iwasaki Y et al. Circulation. 2011;124:2264-2274
Copyright © American Heart Association, Inc. All rights reserved.

30. 1. RECURRENCIA PRECOZ DESPUES DE LA CARDIOVERSION
2. RESISTENCIA PROGRESIVA A LOS MEDICAMENTOS
3. PROGRESION DE FIBRILACION ATRIAL PAROXISTICA A FORMAS PERSISTENTES
1. FIBROSIS LLEVA A RIGIDEZ ATRIAL Y A PERPETUACION DE LA FIBRILACION ATRIAL
2. DILATACION ATRIAL
3. REDUCCION DE LA FUNCION SISTOLICA DEL VENTRICULO IZQUIERDO

31. Mechanisms underlying atrial fibrillation (AF)–related thromboembolism. vWF indicates von
Willebrand factor; NOS, nitric oxide synthase; TF, tissue factor; TFPI, tissue factor pathway
inhibitor; TM, thrombomodulin; TNFα, tumor necrosis factor-α; VEGF, vascular endothelial
growth factor; TGF-β1, transforming growth factor-β1; F1+2, prothrombin fragment 1+2; TAT,
thrombin/antithrombin complex; tPA-Ag, tissue-type plasminogen activator–antigen; tPA-PAI,
tissue-type plasminogen activator/plasminogen activator inhibitor; and β-TG, β-
thromboglobulin.
Iwasaki Y et al. Circulation. 2011;124:2264-2274
Copyright © American Heart Association, Inc. All rights reserved.

39. January, CT et al.
2014 AHA/ACC/HRS Atrial Fibrillation Guideline

41. ANTICUAGULANTES ORALES
– Inhibidores directos de Trombina:
• Ximelagatran (retirado: SPORTIF III + V
• Dabigatran: RE-LY
– Inhibidores directos del factor Xa
• Apixaban: AVERROES y ARISTOTLE
• Edoxaban: ENGAGE AF-TIMI 48 (en curso)
• Rivaroxaban: ROCKET AF

46. RE-LY
Dabigatran vs warfarina
• Evaluar la seguridad y eficacia de Dabigatran
comparado con Warfarina en pacientes con
fibrilacion atrial no valvula para prevencion de
ictus o embolismo sistemico

47. RE-LY
Dabigatran vs warfarin – Study design
Randomized, phase III, open label, non-inferiority study
Non-valvular
AF plus
at least 1
additional
risk factor*
N=18,113
• Primary efficacy: composite of all-cause stroke or
systemic embolism
• Major safety: major bleeding
• Excludes: patients with severe renal impairment
(CrCl ≤30 ml/min)
Connolly SJ et al. N Engl J Med 2009;361:1139−1151
Dabigatran 110 mg bid
Dabigatran 150 mg bid
Open-label warfarin
(target INR range 2–3)
R
Follow-up
End of
treatment
*Previous stroke or TIA , NYHA ≥Class II HF, LVEF <40%, age ≥75 years, age ≥65 with either a history of
coronary artery disease, hypertension or diabetes mellitus

50. RE-LY:Dabigatran vs warfarina:
Conclusiones
En los pacientes con FA:
Dabigatran 110 mg bid se asocio con:
Tasa de Ictus/embolismo sitemico similar a warfarina
Una menor tasa de sangrado mayor
Dabigatran 150 mg bid se asocio con:
Una tasa de ictus/embolismo sistemico menor que
Warfarina
Una tasa similar de sangrado mayor

51. Dabigatran Association with higher Risk
of Acute coronary events:
– “The robust finding that dabigatran is associated with
increased rates of MI is alarming and emphasizes the
need for continued critical appraisal of new drugs
after phase 3 trials…….”
– “New drugs have dangers that may become apparent
long after clinical trials have given way to ….daily
clinical drug use.”
The authors clearly see an alarming signal for an increased rate of MI with
dabigatran which is also recognized by the annotator and the editor. However,
there is also some general concern expressed with regard to the unreflected
use of new drugs. Hence, our communication on ‘Xarelto’ must ensure that
we differentiate by data and by market behaviour from these dabigatran
related issues.
Uchino K et al. Arch Intern Med. 2012 Mar 12;172(5):397-402

54. Comprehensive Late-stage
Development Programme
Area Study Facts Indication Status
Acute
Indications
12,729 patients vs.
standard therapy
(enoxaparin)
Launched in
>85 countries
8,101 patients vs.
standard therapy
(enoxaparin)
Completed
Chronic
Indications
4,832 patients vs.
standard therapy
(enoxaparin &
warfarin)
Completed
14,264 patients vs.
standard therapy
(warfarin)
Completed
15,526 patients in
addition to
standard therapy
VTE prevention after orthopedic surgery
VTE prevention in medically ill patients
VTE treatment and secondary prevention
Stroke prevention in atrial fibrillation
Secondary prevention ACS Completed

57. ROCKET AF
Rivaroxaban vs warfarin – Conclusiones
• Based on the prespecified primary efficacy outcome:
– A once-daily fixed-dose regimen of rivaroxaban was non-inferior to warfarin for
prevention of stroke or non-CNS systemic embolism
– Rivaroxaban was superior to warfarin while patients were taking study drug
– A sensitivity analysis in the ITT population that followed all patients in the trial until
completion showed a benefit for rivaroxaban, but did not reach superiority
• Safety:
– Similar overall incidence of bleeding and adverse events
– Increase in gastrointestinal bleeds but fewer intracranial haemorrhages and less fatal
bleeding with rivaroxaban
• Implication:
– Rivaroxaban, administered once daily, has demonstrated non-inferiority to warfarin in
the prevention of stroke or systemic embolism, with similar overall bleeding and fewer
intracranial haemorrhages and fatal bleeds
Patel MR et al. N Engl J Med 2011;365:883–891