anticoagulación e insuficiencia renal - grupoaran.com
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Anticoagulación e insuficiencia renal
Dr. Pere Domènech Santasusana Jefe de Sección de la Unidad de Trombosis y Hemostasia. Hospital Universitario de Bellvitge
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Conclusiones: En pacientes con fibrilación auricular no valvular, especialmente con insuficiencia renal y en ancianos, las ecuaciones de FGe tienden a sobreestimar la función renal respecto a CG y, por ello, a recomendar una sobredosificación de los ACOD
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Mean creatinine clearance by age cut-off
Cook. Journal of Thrombosis and Haemostasis, 5: 937–941
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RIETE: Cumulative incidence of adverse events in 579 PE patients with CrCl <30 ml/min
Falga. Thromb Haemost 2007; 98: 771
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RIETE: Cumulative incidence of adverse events in 458 DVT patients with CrCl <30 ml/min
Falga.Thromb Haemost 2007; 98: 771
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Trujillo-Santos. The American Journal of Medicine (2013) 126, 425-434
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CONCLUSIONS: In comparison with low-molecular-weight heparin, initial therapy with unfractionated heparin was associated with a higher mortality and higher rate of fatal pulmonary embolism in patients with creatinine clearance levels 60 mL/min or 30 mL/min, but not in those with levels between 30 and 60 mL/min.
Trujillo-Santos. The American Journal of Medicine (2013) 126, 425-434
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Profilaxis Tratamiento
Cl Cr <30 ml/min Cl Cr 30-50 ml/min Cl Cr <30 ml/min Cl Cr 30-50 ml/min
bemiparina 2500UI/d Sin cambios ajustar la dosis al 75%
Sin cambios
dalteparina n.d. n.d. control anti-Xa control anti-Xa
enoxaparina 20 mg cada 24 h Sin cambios 1 mg/kg al día Sin cambios
nadroparina Reducir 25-33% Reducir 25-33% contraindicado Reducir 25-33%
tinzaparina n.d. n.d. No se acumula > 20ml/min
Sin cambios
n.d.= no disponible
Recomendaciones de dosificación de las HBPM según la función renal
En pacientes con insuficiencia renal grave en los que se usen HBPM, las fichas técnicas sugieren considerar la determinación de actividad anti-Xa en el pico máximo para reajustar dosis, además del seguimiento clínico cuidadoso
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Indicación Dosis subcutánea
Profilaxis TEV FG >50 ml/min: 2.5mg /24h FG 20-50 ml/min: 1.5 mg /24h Contraindicado si FG<20 ml/min
Tratamiento del TEV 50-100 kg: 7.5mg /24h <50 kg: 5 mg/24h >100 kg: 10mg /24h (7.5 mg/h si FG 30-50 ml/min) Contraindicado si FG<30 ml/min
Tratamiento del SCA 2.5mg /24h Contraindicado si FG <20 ml/min
Fondaparinux
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• Administración iv • Vida media 45 min • No se elimina por la orina
– Puede administrarse a la misma dosis en pacientes con IR severa
• Metabolismo hepático CYP 3A4/5 dependiente – Precaución en la insuficiencia hepática
• Debe ajustarse a un TTPa 1.5-3 • No posee antídoto
Argatroban
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Proportion of patients in different time-in-therapeutic ranges (TTR) across worsening eGFR strata. eGFR indicates estimated glomerular filtration rate.
Szummer. J Am Heart Assoc. 2017;6:e004925.
Conclusion- Severe chronic kidney disease (eGFR 75%) is associated with lower risk of adverse events, independently of underlying renal function.
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Limdi.J Am Soc Nephrol 2009;20:912–21 Elliott. Am J Kidney Dis 2007;50:433–40
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Características anticoagulantes orales de acción directa
Dabigatran Pradaxa®
Rivaroxabán Xarelto®
Apixabán Eliquis®
Edoxabán Lixiana®
Objetivo IIa (trombina) Xa Xa Xa
Biodisponibilidad, % 3–7 80 50 62
Horas para la Cmax 1–3 2–4 3–4 1–2
Semivida, horas 12–17 5–13 12 8–10
Aclaramiento renal, % 80 33 27 50
Transportadores gp-P gp-P gp-P gp-P
Metabolismo CYP % Ninguno 32% <32% <4%
Unión a proteínas, % 35 92–95 87 40–59
Régimen de dosis BID QD BID QD
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Chan 2016. JACC 67:2888
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Heidbuchel et al. Europace. 2015;17:1467-507
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Liesenfeld i col. J Thromb Haemost 2011; ;9:2168-75.
Dabigatran: Dependencia de las concentraciones plasmáticas mínimas, en el estado estacionario, del aclaramiento de creatinina después de una dosis de 110 i 150 mg bid.
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Dabigatran: Perfiles de simulación de la concentración plasmática mediana en función del tiempo en el estado estacionario de 150 mg bid en varios subgrupos de pacientes
Liesenfeld y col. J Thromb Haemost 2011;
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Rely rial Probability of Major Bleeding Event and Ischemic Stroke/SEE Versus Trough
Plasma Concentration of Dabigatran
Reilly. JACC 2014; 63:321–8
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ENGAGE AF-TIMI 48 trial. Probability of clinical outcomes versus edoxaban concentration
Ruff. Lancet 2015; 385: 2288–95
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Sensibilidad y linealidad de los tests de laboratorio para las concentraciones alrededor de las esperadas en terapéutica para dabigatran, rivaroxaban y apixaban
Cuker. JACC 2014; 64:1128
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Only apixaban has been recently approved in US for the use in patients with end-stage renal dysfunction on hemodialysis (the recommended dose of 5 mg twice daily should be halved in patients with body weight of ≤60 kg and or age ≥ 80 years).
Dosing recommendations in the US based on kidney function measured by creatinine clearance
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Dosing of DOACs for VTE treatment
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Última toma del AOD antes de la cirugía electiva
Heidbuchel for the European Heart Rhythm Association. Europace 2015
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Raccah. CHEST 2016; 149(6):1516-1524
A meta-analysis: Comparison of hemorrhagic stroke risk in patients with renal failure receiving DOACs vs VKAs in AF
eCrCl < 50 mL/min.
eCrCl 50 to 80 mL/min
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Major bleeding
Primary efficacy outcome (Stroke/Systemic embolism)
All-cause mortality
Hohnloser. European Heart Journal (2012) 33, 2821–2830
Aristotle: Effect of apixaban vs. warfarin for outcomes of stroke or systemic embolism, mortality, and major bleed according to renal function estimated with the Cockcroft–Gault
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Primary efficacy
Major bleeding
Prins et al. Thrombosis Journal 2013, 11:21
Pooled analysis of the EINSTEIN-DVT and PE randomized studies
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Subgroup analyses of the landmark randomized phase III trials of NOACs vs. warfarin for stroke prevention in patients with non-valvular AF and mild to moderate CKD.
Potpara. Curr Med Chem. 2016;23(19):2055-69
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Heidbuchel et al. Europace. 2015;17:1467-507
Management of bleeding in patients taking NOACs. Possible therapeutic measures in case of minor or severe bleeding in patients on NOAC therapy
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Esto es todo