Practical issues with NOACs «The Grey Zones»

Transcription

1 Practical issues with NOACs «The Grey Zones» SGK, JH Beer Dept Int Medicine Kantonsspital Baden Laboratory of Platelet Research Molecular Cardiology University of Zürich

2 Individualized Risk Assessment and Decision Making when there are no Guidelines When there are Conflicting Guidelines

3 Disclosures JH Beer Advisor, Lecture Fees or Grant Support: Astra Zeneca, Bayer, Bristol Myers Squibb / Pfizer, Inc. Boehringer Ingelheim, Daiichi Sankyo, Sanofi

4 3 Cases in the «Grey Zone» 1a) Acute ischemic stroke in afib and GI bleed (PE?) 1b) Acute ischemic stroke and afib (CHADS Vasc 6). 1c) Acute ischemic stroke and PE 1d) Hemorrhagic stroke and PE 2) Patient with afib undergoes HRT(with or without epidural): The Temporary Interruption? 3) Patient with high NOAC trough levels, CCr 50ml/min and mucocutaneous bleeding (Should we measure?) The Special Case

5 Decision Help for NOACs 6/15: A Colour Code Guide

6 1c) Acute ischemic stroke and PE (afib)

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8 Individualized Risk Assessment and Decision Making Size of the stroke: small medium large The neurologists view PE (a)symptomatic, RR, Shock, Tn? The Internists View The Cardiologists V

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11 3 Cases in the «Grey Zone» 1a) Acute ischemic stroke in afib and GI bleed (PE?) 1b) Acute ischemic stroke and afib (CHADS Vasc 6). 1c) Acute ischemic stroke and PE 1d) Hemorrhagic stroke and PE 2) Patient with afib undergoes HRT(with or without epidural) 3) Patient with high NOAC trough levels CCr 50ml/min and mucocutaneous bleeding (Should we measure?) The Special Case

12 TE: 12:365x7=0.2%?

13 TI: median 5d 3-30d after resumption of the therapy 4,692/14,236 had TI =33% (total 7,555 episodes) 9% had bridging therapy with LMWH Stroke/SE 0.3 vs 0.41% per 30d period MBleeds: 0.99 vs 0.79% per 30d period

14 Reasons for Temporary Interruption for Rivaroxaban in Rocket >50% should not have been interrupted!

15 Perioperative Management and «Normal Bleeding Risk»

16 Management of LP and Peridural Anesthesia

17 Antidote(s) Idaruzicumab (Dabigatran) ( mg iv complete reversion) Phase III with major bleeds 5g iv. Andexanet alpha (rec FXai catalytically inactive) Bolus 400mg- 800mg and infusion over 2h effective for Riva, Edoxa, Apixa) Ciraparantag (Pan-inhibitor, incl LMWH) LMW-peptide-inhibitor

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19 3 Cases in the «Grey Zone» 1a) Acute ischemic stroke in afib and GI bleed (PE?) 1b) Acute ischemic stroke and afib (CHADS Vasc 6). 1c) Acute ischemic stroke and PE 1d) Hemorrhagic stroke and PE 2) Patient with afib undergoes HRT(with or without epidural) 3) Patient with high NOAC levels, CCr 50ml/min and mucocutaneous bleeding (Should we measure? What?) The Special Case

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21 Rivaroxaban plasma concentrations in special scenarios Rivaroxaban 20 mg od: suitable for a wide range of adult patients for VTE treatment. Rivaroxaban plasma concentration predictions in extreme case scenarios with 20 mg od at steady state population modelling using data from phase II VTE treatment studies. Copied from SGAR guidelines Jan 2015, adapted from Mueck W et al. Clin Pharmacokinet 2011;50:

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23 Which Test at which Level?

24 Dabigatran Plasma Concentrations (Trough) and Clinical Outcome

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26 The New Yorker, , p. 26

27 Take Home Messages 1 Do not interrupt OAC if not necessary 2 If you interrupt, consider not to bridge 3 Individualize with risk assessments 4 4NOACs with good profiles are now available / approved which can be applied according to individual patient profiles. 5 Monitoring restricted to special situations

28 Extraslides

29 «The special case(s)» A 40 years old female with short bowel syndrome (IBD in remission), 30cm small intestine, PE A 30 year old man with short bowel syndrome, after ischemic necrosis, afib and left auricle closure, now with PE. Question(s): VKA, Apix, Dabi, Edox, Riva, LMWH, (Monitoring?)

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31 Lai A et al. Perioperative management of patients on new oral anticoagulants. Br J Surg Jun;101(7): BJS 2014

32 Lai A et al. Perioperative management of patients on new oral anticoagulants. Br J Surg Jun;101(7): BJS 2014

33 Lai A et al. Perioperative management of patients on new oral anticoagulants. Br J Surg Jun;101(7): BJS 2014

34 CHILD B CHILD A Normals

35 XIIa Vitamin-K-antagonists and new oral anticoagulants TF VIIa VII Vitamin-Kantagonist XI XIa X IX IXa Prothrombin IXa Rivaroxaban Apixaban Edoxaban Xa Thrombin VIIIa Dabigatran etexilate Fibrin Adapted from Holy, Beer Sem TH 2014 Fibrinogen

36 Clinically relevant? Below? Within? Above?

37 Antidote(s) Idaruzicumab (Dabigatran) ( mg iv komplette Reversion) Phase III bei Blutungen 5g iv. Andexanet alpha (rec FXai katalytisch inaktiv) Bolus 400mg- 800mg und Infusion über 2h wirksam für Riva, Edoxa, Apixa) Ciraparantag (Pan-Inhibitor, incl LMWH) LMW-peptid-inhibitor

38 Major Bleeds with the HAS-BLED Score as calculated from the SPORTIF Population Lip GY et al. Comparative Validation of a Novel Risk Score for Predicting Bleeding Risk in Anticoagulated Patients With Atrial Fibrillation : The HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) Score. J Am Coll Cardiol Jan 11;57(2):