NOACs: PERI-OPERATIEVE AANDACHTSPUNTEN: EEN UPDATE. prof. dr. Erik Vandermeulen Anesthesiologie UZ Leuven

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1 NOACs: PERI-OPERATIEVE AANDACHTSPUNTEN: EEN UPDATE prf. dr. Erik Vandermeulen Anesthesilgie UZ Leuven

2 Mgelijke belangenverstrengeling Geen

3 New Oral Anticagulants (NOACs) ORAL TTP889 Rivarxaban Apixaban LY YM150 DU-176b (Edxaban) (PRT Ximelagatran Dabigatran X Fibringen TF/VIIa IXa VIIIa Va Xa II IIa IX Fibrin Mdified frm Weitz JL and Bates SM. J Thrmb Haemst 2005; 3: AT PARENTERAL TFPI (tifacgin) APC (drtrecgin alfa) stm (ART-123) TB-402 Fndaparinux Idraparinux DX-9065a Otamixaban

4 Rivarxaban (Xarelt ) Direct-acting, ral, selective, cmpetitive factr Xa (fxa) inhibitr t1/2=7-11 h, Tmax=1-2 h 10 mg q.d., started 6-8 h pstperatively in prphylaxis 10 mg b.i.d. in high dse Mnitring nt necessary High bilgic availability (80-90%) Dual mechanism f eliminatin 33% renal excretin (unchanged drug) 66% hepatic metablism 50% renal excretin 50% biliary excretin Dse reductin may be necessary if CrCl ml/min Fixed dse, independent frm Age, sex, bdy weight,

5 Apixaban (Eliquis ) Direct-acting, ral, selective, cmpetitive fxa inhibitr t1/2=11-15 h, Tmax=1-2 h 2.5 mg q.d. PO, started h pstperatively in prphylaxis 5 mg b.i.d. in high dse Mnitring nt necessary Bilgical availability 66% Eliminatin nly minimally influenced by renal functin (25%) Dse reductin may be necessary if serum creatinine 1.5 mg/dl, age 80 y r bdy weight 60 kg

6 Edxaban (Lixiana ) Direct-acting, ral, selective, cmpetitive fxa inhibitr t1/2= 6-11 h, Tmax=1-2 h Nt released yet, hence n exact dsing infrmatin available yet 30 mg q.d. PO?, started 6-8 h pstperatively in prphylaxis? mg q.d. in high dse? Mnitring nt necessary Bilgical availability 45-60% Eliminatin nly minimally influenced by renal functin (35%)

7 Dabigatran (Pradaxa ) Oral, direct acting thrmbin inhibitr t1/2=12-17 u, Tmax=2-4 u mg q.d., started 1-4 h pstperatively in prphylaxis mg b.i.d. in high dse Bilgical availability 6-7% (phdependent) Mnitring nt necessary Dsing dependent n kidney functin Dse reductin if CrCl ml/min, age 75 y, bdy weight 50 kg r a high risk f bleeding

8 Rivarxaban Mnitring f Effect Kubitza D et al. Eur J Clin Pharmacl 2005; 61,

9 Rivarxaban Mnitring f Effect Duxfils J et al. Thrmbsis Research 2012; 130 (Suppl 2),

10 Rivarxaban Mnitring f Effect Nrmal prthrmbin time in the presence f therapeutic levels f rivarxaban The baseline PT fr this patient was clse t the lwer limit f the nrmal range s the prlngatin ver baseline caused by the drug was nt sufficient t extend the PT abve the upper limit f the nrmal range. A nrmal PT des nt always exclude therapeutic anticagulatin. It serves as a cautin against reliance n the PT in the assessment f cagulatin intensity f patients n rivarxaban. Van Veen JJ et al. BJH 2013; 160,

11 Rivarxaban Mnitring f Effect N data available that assciate PT changes with bleeding risk N data available suggesting that PT is a valid marker fr the anticagulant efficacy In emergency situatins in patients n rivarxaban, a prlnged PT therefre may at mst suggest the recent intake f the drug: it wuld suggest the likely intake f rivarxaban in the last 7 hurs. Cnversely, a nn-delayed PT will nly suggest that rivarxaban was likely taken mre than apprximately 7 hurs ag. The planning f an urgent surgical/invasive prcedure based n the results f the PT/aPTT (as fr VKAs and unfractinated heparin) is nt a validated strategy and cannt be recmmended at the current time A mre specific test and sensitive fxa assay shuld be used t cnfirm the plasma cncentratin f rivarxaban

12 Rivarxaban Mnitring f Effect Duxfils J et al. Thrmbsis Research 2012; 130 (Suppl 2),

13 Apixaban Mnitring f Effect Duxfils J et al. Thrmbsis Haemstasis 2013; 110,

14 Apixaban Mnitring f Effect Barrett YC et al. Thrmbsis Haemstasis 2010; 104,

15 Apixaban Mnitring f Effect Duxfils J et al. Thrmbsis Haemstasis 2013; 110,

16 Dabigatran Mnitring f Effect aptt Gives nly apprximate indicatin f the anticagulatin intensity Is useful t determine an excess f anticagulant activity in patients wh are bleeding r at risk f bleeding Limited sensitivity and nt suitable fr precise quantificatin f the anticagulant effect, especially at high plasma cncentratins f dabigatran. Duxfils J et al. Thrmb Haemst 2012; 107,

17 Dabigatran Mnitring f Effect ECT PT Ecarin cltting Time (ECT) ECT prvides a direct measure f the activity f direct thrmbin inhibitrs PT/INR Unreliable in patients n dabigatran Duxfils J et al. Thrmb Haemst 2012; 107,

18 Dabigatran Mnitring f Effect HTI Thrmbin Time (TT) and Hemclt Thrmbin Inhibitr (HTI) Nrmal TT measurement indicates n clinically relevant anticagulant effect f dabigatran Thrmbin Time (TT) t sensitive when cncentratins > 25 ng/ml A calibrated diluted thrmbin time (dtt) with dabigatran standards t calculate the dabigatran plasma cncentratin is necessary Linear relatinship between dabigatran cncentratin and the dtt (HTI), which is therefre suitable fr the precise quantitative assessment f dabigatran cncentratins Duxfils J et al. Thrmb Haemst 2012; 107,

19 NOACs Elective prcedures Minimal bleeding risk Minr dental wrk Minr dermatlgical prcedures Cataract surgery Diagnstic endscpy (n bipsy) Crnargraphy/PCI via radial artery Pacemaker r ICD replacement Lw bleeding risk Endscpy with bipsy Phleblgical prcedures Angigraphy Implantatin f pacemaker r ICD EFO r RFCA High bleeding risk Cardiac surgery Intracranial r spinal surgery Neuraxial anesthesia/spinal puncture Thracic and majr abdminal surgery Vascular surgery Jint replacement surgery Majr nclgical surgery Urlgical surgery Resectin f cln plyps (>2 cm Ø at base) Bipsy f prstate, kidney r liver Endscpic sfinctertmy

20 Selective fxa inhibitrs - Elective prcedure Renal functin (CrCl ml/min) Minimal prcedure/bleeding risk Stp rivarxaban r apixaban befre an elective prcedure Prcedure and/r patient with lw bleeding risk Prcedure and/r patient with high bleeding risk h 24 h 48 h h 48 h 48 h NO bridging therapy with LMWH is required Resume rivarxaban r apixaban after an elective prcedure Minimal prcedure/bleeding risk >8 h (if hemstasis cmplete) Prcedure and/r patient with lw bleeding risk h (if hemstasis cmplete/n re-interventin) Prcedure and/r patient with high bleeding risk h (if hemstasis cmplete/ n re-interventin) If deemed necessary a LMWH can be used instead t bridge the immediate pstperative perid

21 Direct thrmbin inhibitrs - Elective prcedure Renal functin (CrCl ml/min) Minimal prcedure/bleeding risk Stp dabigatran befre an elective prcedure Prcedure and/r patient with lw bleeding risk Prcedure and/r patient with high bleeding risk h 24 h 48 h h 48 h 96 h NO bridging therapy with LMWH is required Resume dabigatran after an elective prcedure Minimal prcedure/bleeding risk >8 h (if hemstasis cmplete) Prcedure and/r patient with lw bleeding risk h (if hemstasis cmplete/n re-interventin) Prcedure and/r patient with high bleeding risk h (if hemstasis cmplete/ n re-interventin) If deemed necessary a LMWH can be used instead t bridge the immediate pstperative perid

22 NOACs Pst-prcedure plicy 6-8 h pst-prcedure: Start LMWH in a prphylactic dse (max. 50 IU axa/kg q.d.) 24 h pst-prcedure: Dse f LMWH may be increased t an intermediate dse (max. 100 IU axa/kg q.d.) Only if intermediate high thrmbtic risk AND in absence f a neuraxial catheter (i.e. Patient-cntrlled epidural analgesia) h pst-prcedure: Dse f LMWH may be increased t a therapeutic dse (max. 150 IU axa/kg q.d. t 100 IU axa/kg b.i.d.) Only if high thrmbtic risk AND in absence f a neuraxial catheter (Patient-cntrlled epidural analgesia)

23 NOACs Restarting pst-prcedure Minimal prcedure and/r bleeding risk >8 h pst-prcedure Prcedure and/r patient with lw/high bleeding risk h pst-prcedure If hemstasis cmplete N re-interventin anticipated First dse t be administered at the time the next dse f LMWH was planned

24 NOACs - Summary Dabigatran (Pradaxa ) Rivarxaban (Xarelt ) Apixaban (Eliquis ) Edxban (Lixiana ) Site f actin Thrmbin Factr Xa Factr Xa Factr Xa Mechanism Direct inhibitin Direct inhibitin Direct inhibitin Direct inhibitin Tmax 2-4 h 2-4 h 3-4 h 1-2 h t 1/ h 7-13 h 8-15 h 6-11 Eliminatin Renal 80% Biliary 20% Mnitring dtt (HTI ), aptt, ECT Renal 66% Biliary 33% PT (nly if INR 1.0), specific axa-assay Renal 25% Biliary 75% specific axa-assay Mainly renal PT? specific axa-assay Reversal PCC, apcc? PCC, apcc? PCC, apcc? PCC?, apcc? Hemdialysis Yes N N? Elective surgery Stp h Stp 48 h Stp 48 h Stp h? Neuraxial blck N N N N