George Ntaios University of Thessaly, Larissa DOACs and real-world data: What have we learned that the RCTs have not told us? Acute Stroke

Disclosures Scholarships: European Stroke Organization; Hellenic Society of Atherosclerosis. Honoraria: Medtronic; Quintiles; CHUV; Belgian Stroke Council; Boehringer-Ingelheim. Speaker fees: Sanofi; Boehringer-Ingelheim; Galenica; Elpen; Bayer; Winmedica Support to attend conferences: Bayer; Sanofi-Aventis; Pfizer; Lundbeck; Boehringer- Ingelheim; Galenica; Elpen; Bristol Myers Squibb. Participation in trials: – NAVIGATE-ESUS / Steering Committee member, National Coordinator (Greece) & Principal Investigator (Larissa) – PRECIOUS / National Coordinator (Greece) & Executive Committee member. – ENOS / National Coordinator (Greece). – FOURIER / Principal investigator (Larissa). – GLORIA-AF / Sub-investigator (Larissa). – EBBINGHAUS / Principal Investigator (Larissa). – BIOSIGNAL / Principal Investigator (Larissa). – PREVISE / Principal investigator (Larissa). – RECOVERY / Principal investigator (Larissa)

Ischemic stroke in anticoagulated patient

Ηλικία 80 >4.5 ώρες από την έναρξη του ΑΕΕ Άγνωστη ώρα έναρξης του ΑΕΕ NIHSS 25 Ραγδαία κλινική βελτίωση Ενδοκράνιoς αιμορραγία (CT ή MRI) Υπόπυκνη περιοχή >30% της κατανομής της μέσης εγκεφαλικής Πρόσφατο ΑΕΕ (<3 μήνες) Ιστορικό ΑΕΕ και συνύπαρξη ΣΔ Βαριά συννοσηρότητα Αιμορραγική διάθεση Βαριά ηπατοπάθεια Προηγούμενο αιμορραγικό ΑΕΕ Υποψία υπαραχνοειδούς αιμορραγίας ΑΠ >185/110 παρά τη χορήγηση IV ανθυπερτασικών Αιμοπετάλια <100,000/mm 3 Λήψη LMWH ή per os αντιπηκτικών (INR >1.5, aPTT >33sec) Υποψία διαχωριστικού ανευρύσματος αορτής Ένδο ‐ ή περικαρδίτιδα, παγκρεατίτιδα Πρόσφατο (<3 μήνες) χειρουργείο/αιμορραγία πεπτικού ή ουροποιητικού Σάκχαρο 400mg/dl Ενδοκράνιος όγκος ή ανεύρυσμα Επιληπτική κρίση κατά το ΑΕΕ Πρόσφατη (<10 ημ.) ανάνηψη/παρακέντηση αρτηρίας ή οσφυονωτιαία

Ischemic stroke in VKA-anticoagulated patient

INR: 1.6

Ischemic stroke in VKA-anticoagulated patient Λήψη LMWH ή per os αντιπηκτικών (INR >1.5, aPTT >33sec)

Ischemic stroke in NOAC-anticoagulated patient European Cardiology Review 2015;10:76–8

Idarucizumab: an antidote for dabigatran ThrombinDabigatranIdarucizumab

Idarucizumab: an antidote for dabigatran

–2 Time after end of infusion (hours) dTT (s)

Andexanet: an antidote for Xa inhibitors Siegal et al. NEJM2015

Andexanet: an antidote for Xa inhibitors

Siegal et al. NEJM2016

Ciraparantag: an antidote for … all Ansell et al. NEJM2014

Ciraparantag: an antidote for … all Ansell et al. NEJM2014

Step 1: Run Step 2: Antidote Step 3: CT scan Step 4: rTPA Ischemic stroke in NOAC-anticoagulated patient

Acute endovascular treatment - thrombectomy

Anticoagulation after AF-stroke: how soon (or late?)

Ntaios & Michel. Cerebrovasc Dis 2011

Anticoagulation after AF-stroke: how soon (or late?) Reasons to start early Low NIHSS Small/no brain infarction on MRI High recurrence risk e.g. thrombus on echo No haemorrhagic transformation Patient is clinically stable Young patient Blood pressure is controlled Reasons to wait High NIHSS Large/moderate brain infarction Haemorrhagic transformation Neurologically unstable Elderly patient Uncontrolled hypertension

The rule TIA  1 day Small infarct  3 days Moderate infarct  6 days Large infarct  12 days

NOACs could be the answer? Ruff et al. Lancet 2013

Restart OAC after AF/OAC-related ICH ?

ESO ICH Guidelines Steiner et al. Int J Stroke. 2014

Restart OAC after AF/OAC-related ICH Nielsen et al. Circulation 2015

Restart OAC after AF/OAC-related ICH Nielsen et al. Circulation 2015

Restart OAC after AF/OAC-related ICH Nielsen et al. Circulation 2015

Forget guidelines: we need to individualize

Bleeding vs. thromboembolic risk

Prognostic scores? HAS-BLED CHA2DS2-VASC2 CHADS2

Well, sorry….

Cerebral microbleeds

Cerebral microbleeds & ICH risk Charidimou et al. Stroke 2013

Cerebral microbleeds & ischemic stroke risk Charidimou et al. Stroke 2013

Forget guidelines: we need to individualize

NOAC vs. VKA: Intracranial haemorrhage Ruff et al. Lancet 2013

LAA occlusion? Holmes et al. JACC 2015

Talk & listen to your patients

Take-home messages Stroke in anticoagulated patient? Restart antithrombotics after ICH? How soon OAC after IS?