1. Stroke in the era of NOACs George Ntaios MD, MSc (Stroke Medicine), PhD University of Thessaly, Greece Oslo 11/12/2015

2. Disclosures Scholarships: European Stroke Organization; Hellenic Society of Atherosclerosis. Honoraria: Medtronic; Quintiles; Boehringer-Ingelheim. Speaker fees: Sanofi; Boehringer-Ingelheim; Galenica; Elpen; Bayer Support to attend conferences: Bayer; Sanofi-Aventis; Pfizer; Lundbeck; Boehringer- Ingelheim; Galenica; Elpen; BMS Participation in trials: – NAVIGATE-ESUS / National Coordinator (Greece) – GLORIA-AF / Sub-investigator (Larissa). – FOURIER / Principal investigator (Larissa). – PRECIOUS / National Coordinator (Greece). – ENOS / National Coordinator (Greece). – EBBINGHAUS / Principal Investigator (Larissa). – BIOSIGNAL / Principal Investigator (Larissa). – PREVISE / Principal investigator (Larissa).

3. Hercules and Lernaean Hydra by Lorenzo Matialli, Habsburg Palace, Vienna

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

7. 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

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

9. NOACs could be the answer? Ntaios et al. Stroke 2012

10. Intracranial haemorrhage while on anticoagulants

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

12. Ntaios et al. Int J Stroke. 2015;Suppl A100:128-35

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

15. NOACs could be the answer? Ntaios et al. Stroke 2012

16. Ntaios & Lip. Curr Opin Neurol 2015

17. Our patient (… and his grand-grand-son) 81yrs Fully independent at 3months Hypertensive, Non-smoker, non-diabetic LDL: 104mg/dl LA diameter: 42mm Triplex: - 24hrs ECG: -

18. Hart et al. Lancet Neurol 2014; 13: 429–38 ESUS: Embolic Strokes of Undetermined Source

19. ESUS: diagnostic criteria Stroke detected by CT or MRI that is not lacunar. Absence of extracranial or intracranial atherosclerosis causing >50% luminal stenosis in arteries supplying the area of ischemia. No major-risk cardioembolic source of embolism ( permanent or paroxysmal AF, sustained atrial flutter, intracardiac thrombus, prosthetic cardiac valve, atrial myxoma or other cardiac tumours, mitral stenosis, recent (<4 weeks) MI, LVEF<30%, valvular vegetations, or infective endocarditis ). No other specific cause of stroke identified. Hart et al. Lancet Neurol 2014; 13: 429–38

20. ESUS: potential causes Hart et al. Lancet Neurol 2014; 13: 429–38

21. ESUS: Embolic Strokes of Undetermined Source

22. ESUS in the Athens Stroke Registry

23. Ntaios et al. Stroke 2015; 46:176-81

24. ESUS: stroke severity Ntaios et al. Stroke 2015; 46:176-81

25. ESUS: 5-yrs functional outcome Ntaios et al. Stroke 2015; 46:2087-93

26. ESUS: 5-yrs stroke recurrence Ntaios et al. Stroke 2015; 46:2087-93

27. So, how to treat my ESUS patient? Furie et al. Stroke 2011;42:227-76 Approach 1

28. So, how to treat my ESUS patient? Approach 2

29. So, how to treat my ESUS patient? Approach 3

30. RESPECT - ESUS Dabigatran 110/150 1x2 Aspirin 100mg 1x1 R

31. NAVIGATE - ESUS Rivaroxaban 15mg 1x1 Aspirin 100mg 1x1 R

32. ATTICUS Apixaban Aspirin 100mg 1x1 R

33. -Everybody gets happy! -Almost half stroke patients get an anticoagulant!

34. Stroke is a syndrome, not a disease.

36. Neither a “general” neurologist nor a “general” physician is truly qualified to care for all aspects of stroke, without special training. We are attracted to the concept of “strokology” as a discipline with specific accreditation.

37. NOACs, stroke & the future UNTREATED ON WARFARIN ON A NOAC 23 INR LowNormalHigh ISHS IS HS Courtesy of Dr. Pinachyan

38. Take-home messages NOACs are here to stay, to raise new questions & provide answers to unmet needs. ESUS: potetial new indication for NOACs. Stroke Medicine is rapidly changing (…and so should we)!