Acute management in antithrombotic-related intracerebral ... · Head Stroke Pathway, Department of...
Transcript of Acute management in antithrombotic-related intracerebral ... · Head Stroke Pathway, Department of...
Acute management in antithrombotic-related
intracerebral hemorrhage
Stefan Engelter MD, FESOUniversity 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 MedicineAthens, 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: ⇧
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Béjot et al, Brain 2013
Causes of der intracerebral hemorrhages
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▪ 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 <140 mmHg)
Quality of evidence: Moderate
Strength of recommendation: Weak
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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 VKAFresh Frozen Plasma ⇔ Prothrombin Complex?
Neurorehabilitation Unit
Hirnblutung unter VKAFresh Frozen Plasma ⇔ Prothrombin Complex?
Steiner et al Lancet Neurol 2016
Intracranial bleed under VKAFresh 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;27:86-91Neurorehabilitation Unit
Specific antidotes for DOACs
Monagle S et al. Future Cardiol 2017;13(2):153-159
L.C
H.C
OM
.HC
.10.2
015.0
737
-EN
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 <75ng/mlNeurorehabilitation Unit
Tranexamic acid for IntraCerebral Haemorrhage
▪ Tranexamic acid for IntraCerebral Haemorrhage 2 – TICH 2
▪ International, RCT
▪ ICB <8h since symptom onset
▪ TXA vs. Placebo
▪ 2325 patients
▪ Subgroup with antiplatelets
▪ RESULTS: May 16th 2018
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 <12h (since onset)
▪ Primary outcome: Hematoma Expansion at 24 hrs
▪ Started 1/2017
▪ N=12 pt (March 13th)
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 <48h) within 12
hours of onset
▪ Study treatment: TICH-II regimen
▪ best medical treatment (international guidelines/SOP), may include specific
antidots for NOAC in the future ( study treatment as “add-on”)
▪ Primary Outcome: hematoma expansion on follow-up imaging at 24 hours
▪ Sample size: 109 patients, interims analysis after 70 patients
Intracerebral Hemorrhage associated with Antiplatelets
Intracerebral Hemorrhage associated with Antiplatelets
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▪ Supratentorial intracrebral ICH (<6h after symptom onset)
▪ RCT: Platelet transfusion (1-2 platelet concentrats) ⇔ standard care
▪ PROBE
▪ 97 pts with platelet transfusion ⇔ 93 pts with standard care
▪ Primary endpoint: shift in death/dependency (modified Rankin scale score at 3 M)
Platelet transfusion
HARMFUL !
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-<1.3 in 4h
➢ NOAC
✓ Optimal Management: yet to be determined
PCC: effectiveness not shown
Antidotes
currently only for Dabigatran (“Praxbind”),
clinical effectiveness unclear
Tranexamid Acid: -> “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
[email protected]; [email protected]
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 PetersPhilippe Lyrer
Blutungsrisiko unter NOAC verglichen mit VKA
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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?
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▪ First data collaborative registry data published/analyzed recently
▪ Purrucker & Veltkamp (JAMA Neurology 2015): prospective registry of 38 german
Stroke Units – 61 NOAC-ICH patients
▪ Duncan Wilson & David Werring (personal communcation): international collaborative
registry based analysis of 13 stroke centers – 97 NOAC-ICH patients
▪ Hematoma volume: 14.4ml – 23.7ml
▪ Hematoma expansion: 38%-40%
▪ Mortality: 28% - 31 %
▪ Unfarorable outcome (mRS 3-6): 65%
No evidence based
treatment option
available