Acute management in antithrombotic-related intracerebral ... Head Stroke Pathway, Department of

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  • Acute management in antithrombotic-related

    intracerebral hemorrhage

    Stefan Engelter MD, FESO University of Basel, Switzerland

    Professor of Neurology

    Chair Rehabilitation, University Center for Medicine of Aging & Rehabilitation, Felix-Platter Hospital Basel

    Head Stroke Pathway, Department of Neurology and Stroke Center, University Hospital Basel

    10th International Congress of Internal Medicine Athens, 22nd March 2018

    Neurologie und Stroke CenterNeurorehabilitation Unit

  • Intracerebral hemorrhage related to Antithrombotics

    I. Vitamin-K-Antagonists

    II. Non-Vitamin K- or Direct orale Anticoagulants (DOAC; NOAC)

    III. Antiplatelets

    Neurorehabilitation Unit

  • Different Types

    Hemorrhagic Stroke

    Intracerebrale Hemorrhage Subarachnoidal Hemorrhage

    Subdural Hemorrhage

    Epidural Hemorrhage

    Traumatic Brain Injury

  • Frequency of intracerebral bleeds: ⇧

    4

    Béjot et al, Brain 2013

  • Causes of der intracerebral hemorrhages

    6

    ▪ Hypertensiv 35%

    ▪ Cerebrale Amyloidangiopathie (CAA) 20%

    ▪ Anticoagulation 14%

    ▪ Aneurysma, AVM, AVF,…. 5%

    ▪ Systemic diseases (liver failure, thombocytopenia,…) 5%

    ▪ Other Causes (e.g. Sinus venous thrombosis) 21%

    CAA AVM

    Stroke. 2012;43:2592-2597

  • Symposium Hirnschlagzentrum/Stroke Center USB

    «Anticoagulant treatment does not cause a bleeding;

    they can aggravate it» Kamphuisen; ESOC May 12th 2016, Barcelona

  • Symposium Hirnschlagzentrum/Stroke Center USB

    «Anticoagulant treatment does not cause a bleeding;

    it can aggravate it» Kamphuisen; ESOC May 12th 2016, Barcelona

    Neurorehabilitation Unit

  • Anticoagulants and hemorrhagic stroke: The risk in the general poulation

    Intracerebrale hemorrhage

    ❖ OR 2.82 (95% CI 2.26-3.53)

    Subarachnoidal hemorrhage

    ❖ OR 1.67 (95% CI 1.15-2.43)

    INR >3.0 ICH

    ❖ OR 7.01 (95% CI 4.10-11.9)

    Neurology 2013;81(6):566-74.

    Antithrombotic drugs and risk of hemorrhagic stroke in the general population.

  • 22. Mai 2014Symposium Hirnschlagzentrum/Stroke Center USB 10

    Hämatom Expansion ⇨ Prognosis poor HE in OAC-ICHs ⇨ 30-50%

  • Acute management in antithrombotic-related intracerebral hemorrhage

    Stroke Unit Blood

    pressure↓ Antidotes (Surgery?)Hemostatic

    Therapy

  • Death or DisabilityNeurorehabilitation Unit

  • Stroke Unit Definition

    Stroke Unit:

    ➢ A dedicated geographically clearly defined area or ward in a hospital, where

    stroke patients are admitted and

    ➢ cared for by a multi-professional team

    ✓medical,

    ✓nursing,

    ✓therapy staff

    ➢ who have specialist knowledge of cerebral function, training and skills in stroke

    care with well-defined individual tasks,

    ➢ regular interaction with other disciplines, and stroke leadership.

    ➢ This team co-ordinates care through regular (weekly), multidisciplinary meetings.

    Neurorehabilitation Unit

  • Stroke Unit – Treatment of ICH: What matters ?

    Evans Lancet 2001

    ▪ Temperature and glucose management

    ▪ Systematic screening for dysphagia

    ▪ Less complications

    ➢ Pneumonia

    ➢ Dehydration

    ▪ Early rehabilitation

    Neurorehabilitation Unit

  • Certification -> clearifies standards , .. less missunderstandings…

    This is NOT a STROKE UNIT

    We are a JOKE UNIT

  • ICH- Guidelines

    Steiner et al IJS 2014

    Acute stroke unit care reduces both death and dependency for patients

    with ICH in comparison with care on a general ward.

    Quality of evidence: High

    Strength of recommendation: Strong

    In acute ICH within 6 h of onset, intensive blood pressure reduction (systolic

    target

  • 17

    Steiner et al, Int J Stroke 2014

    Positive

    Negative

    ➢ Further research

    required

  • (Stroke. 2012;43:2539-2540.)

  • VKA-ICH ⇨ INR-Normalisation + RR⇩ in 4h

    Kuramatsu et al. JAMA 2015

    Neurorehabilitation Unit

  • VKA-intracerebral bleed– rapid INR Normalisation

    Kuramatsu et al. JAMA 2015

    Neurorehabilitation Unit

  • Intracranial bleed under VKA Fresh Frozen Plasma ⇔ Prothrombin Complex?

    Neurorehabilitation Unit

  • Hirnblutung unter VKA Fresh Frozen Plasma ⇔ Prothrombin Complex?

    Steiner et al Lancet Neurol 2016

    Intracranial bleed under VKA Fresh Frozen Plasma ⇔ Prothrombin Complex?

    Neurorehabilitation Unit

  • Alberts. Lancet Neurology 2012:1066

    Non-VKA oral Anticoagulants (NOAC)

    Direct oral Anticoagulants (DOACS)

  • ICH during Warfarin vs NOAC therapy

    Takahashi H et al. Am J Cardiol 2016;118:222-225

  • NOAC-associated ICH ↔ VKA-associated ICH 90-day mortality

    Wilson D et al. Neurology 2017;88:1-8

    Poor outcome

    65% (mRS 3-5)

  • Neurorehabilitation Unit

  • Neurorehabilitation Unit

  • Pharmacokinetic and reversal of DOACs

    Abo-Salem E, Becker RC. Curr Opin Pharmacol 2016;27:86-91 Neurorehabilitation Unit

  • Specific antidotes for DOACs

    Monagle S et al. Future Cardiol 2017;13(2):153-159

  • L .C

    H .C

    O M

    .H C

    .1 0 .2

    0 1 5 .0

    7 3 7

    -E N

    Idarucizumab – Antidote -> Dabigatran

    ▪ Group A: patients who had serious bleeding (n=51) ▪ Hemostasis was restored at a median of 11.4 hours

    ▪ Group B: patients who required an urgent procedure (n=39)

    ▪ No control group

    ▪ Primary endpoint: hemostatic normalization: 100%

    ▪ Thromboembolic complications: 6.3%; Mortality 18.8%

    Pollack CV. N Engl J Med 2015 and 2017

    approved 10/2015

    (3500 USD)

    Neurorehabilitation Unit

  • Kermer et al Int J Stroke 2017

    - Retrospective

    - Case series

    - 12 Pats with intracranial bleed under Dabigatran treated with Idarucizumab

     only 2/12 with Hämatoma Expansion

     only 1/12 died

    Neurorehabilitation Unit

  • Connolly et al NEJM 2016

    single arm: No control group

    Primary endpoint: hemostatic normalization

    Thromboembolic complications: 18%

    Mortality 15%

    Neurorehabilitation Unit

  • 89%

    93%

    CAVE: 20/67 Patients excluded due to plasmalevel

  • Tranexamic acid for IntraCerebral Haemorrhage

    ▪ Tranexamic acid for IntraCerebral Haemorrhage 2 – TICH 2

    ▪ International, RCT

    ▪ ICB

  • Tranexamic acid in NOAC –ICH -> TICH-NOAC

    ▪ Tranexamic acid for IntraCerebral Haemorrhage associated with

    NOAC – TICH-NOAC ▪ Swiss, randomised, placebo-controlled, proof of concept study

    ▪ ICB

  • TICH-NOAC

    ▪ Design: Randomized, placebo-controlled multi-center trial

    ▪ Coordinating Center: Basel, Co-PIs Stefan Engelter and Philippe Lyrer

    ▪ Patients: ICH while under treatment with a NOAC (last intake

  • Intracerebral Hemorrhage associated with Antiplatelets

  • Intracerebral Hemorrhage associated with Antiplatelets

  • 68

    ▪ Supratentorial intracrebral ICH (

  • Surgery

    Mendelow et al, Lancet 2013

  • Acute management in antithrombotic-related intracerebral haemorrhage

    Take home messages

    ➢ STROKE UNIT THERAPY: EFFECTIVE

    ➢ EARLY Blood pressure lowering useful (target?)

    ➢ Vitamin-K-Antagonists

    ✓ Vitamine K, PCC, blood pressure↓ (TRAGET 160?); INR- “TICH-NOAC”-Study ongoing

     Blood pressure lowering: promising

    ➢Antiplatelet-related ICH ❖ NO platelet transfusion (harmful)

    ❖ Tranexamid Acid?

    ➢ TICH-2- Results: -> 16th May 2018 (subgroup antiplatelets)

  • Thank you for your attention

    stefan.engelter@usb.ch; stefan.engelter@fps.ch

    David Seiffge, Christopher Traenka, Alexandros Polymeris, Sebastian Thilemann, Lisa Hert, Mandy Müller, Urs Fisch, Mirjam Rhyner, Marina Maurer, Suzana Eble, Leo Bonati, Gian Marco De Marchis, Henrik Gensicke, Nils Peters Philippe Lyrer

  • Blutungsrisiko unter NOAC verglichen mit VKA

    75

    Courtesy P. Michel, CHUV

    modified from: Connolly et al, NEJM 2009; Granger et al NEJM 2011; Patel et al, NEJM 2011; Giugliano et al NEJM 2013

    0%

    -50%

    -75%

    Dabigatran

    150mg 110mg

    Riva-

    roxaban

    Apixaban Edoxaban

    60mg 30mg

    Significant in all NOACs

    - 69%- 60% - 58% - 53%- 33% - 70%

    -25%

  • What do we know about NOAC-ICH?

    76

    ▪ First data collaborative registry data published/analyzed recently

    ▪ Purrucker & Veltkamp (JAMA Neurology 2015): prospective registry of 38 german

    Stroke U