1. MANAGEMENT OF STROKE ANTICOAGULATION Latifa Oukerraj, Jamila Zarzur Cardiologie B, CHU Ibn Sina Rabat Printemps de cardiologie Marrakech 8éme Edition

2. D ISCLOSURE S TATEMENT OF F INANCIAL I NTEREST I, Oukerraj. Latifa, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

3. C ASE 1 M R B.A HMED A 67 years old right handed presented with Acute onset of left sided weakness and inability to speak No history of: - chest pain, palpitation, dyspnoea - loss of conciousness, vomiting - Diabetes, smoke, stroke, TIA Past history Hypertension since 10 years, not on regular treatement

5. O N E XAMINATION BP – 170/100 Pulse 120/ min, Irregullar, all peripheral pulsation including carotide well felt GCS-11/15 No cardiac murmur

6. INVESTIGATIONS Hb, Platelets, GBP within normal limits Kidney and liver function tests- Normal ECG : HR = 120 c/min Atrial fibrillation (AF) Initial CT brain: an ischemic stroke affecting the cortex and subcortex of the right frontal and parietal lobes ( small size)

7. INVESTIGATIONS Transthoracic 2D Echocardiography: - spontaneous echo contrast in the left atrium and a clot in the left atrial appendage - hypertrophy and diastolic dysfunction of the left ventricle. No valvular abnormality was detected. Imaging studies of the carotid arteries and aortic arch were unremarkable

8. In addition to high blood pressure and AF, which of the following characteristics increases this patient’s risk of a recurrent ischemic stroke? A - Age under 75 B - Small size of infarct C - Presence of sludge and clot in the left atrial appendage D - Initial stroke

9. E PEDIMIOLOGY Cardioembolism accounts for 20% of ischemic strokes The more common high risk cardioembolic conditions: MS, mechanical prosthetic valve, recent MI, AF, and dilated myocardiopathy, The infarct is typically larger,the outcome is poorer: in-hospital mortality rate of cardioembolic infarction was 27.3% Cardioembolic stroke carries increased risk of hemorrhagic transformation up to 71% of cardioembolic strokes Early recurrent embolisms: 1-10% ===> 22% ( x 2 Mortality ) Cerebral Embolism Task Force Arch Neurol. 1986;43:71–84 Mac Dougall NJ et al. Expert Rev Neurother 2009;7:1103-15

10. CHADS 2 -> CHA 2 DS 2 VAS C CHADS2 RiskScore CHF1 Hypertension1 Age > 751 Diabetes1 Stroke or TIA2 CHA2DS2-VASc Risk Score CHF or LVEF < 40% 1 Hypertension1 Age > 752 Diabetes1 Stroke/TIA/ Thromboembolism 2 Vascular Disease 1 Age 65 - 741 Female1 From ESC AF Guidelines http://www.escardio.org/guidelines-surveys/esc- guidelines/GuidelinesDocuments/guidelines-afib- FT.pdf

11. B. Ahmed

12. ESTIMATING RISK OF STROKE

13. B. Ahmed

15. M R B.A HMED ’ S RISK FOR HEMORRHAGIC STROKE B.Ahmed

16. Given the patient’s risks of recurrent clot formation and intracranial bleeding, would you begin an anticoagulant therapy? A- Yes B- No

17. A NTICOAGULATION REDUCING STROKE RISK Mr B. Ahmed’s risk for stroke is about 6% /year Anticoagulation could reduce this risk by at least 2/3 compared with no anticoagulation : < 2% / year Reducing his absolute risk of stroke by at least 4% each year

18. A NTICOAGULATION AND B LEEDING RISK Mr B. Ahmed’s risk of major bleeding of 3 is about 3% to 4% per year reduced to 2%/year ( by reducing his blood pressure) Anticoagulation may x 2 this risk Absolute risk increase of 2% / year Chest. 2010;138:1093-1100

19. 3/4 of all cardioembolic strokes are fatal or disabling the benefit of anticoagulation in Mr B. Ahmed in preventing 4 strokes per year, of which 3 are fatal or disabling, per 100 patients treated, exceed the risks of anticoagulation in causing 2 major bleeds per year per 100 patients treated, many of which are not fatal or disabling.

20. Given the patient’s risks of recurrent clot formation and intracranial bleeding, when would you begin anticoagulant therapy? A - Immediately B - In 1 week C - In 2 weeks D - In 1 month

22. M. Paciaroni Stroke 2007

23. Results RECURRENT ISCHEMIC STROKE CEREBRAL SYMPTOMATIC BLEEDING 3% VS 4.9% OR 0.68 (0.44-1.06) P=0.09 2.5% VS 0.7% OR 2.89 (1.19-7.01) P=0.02 M. Paciaroni Stroke 2007

24. R ECOMMANDATIONS Anticoagulation in Acute Stroke Guidelines for the Early Management of Patients With Acute Ischemic Stroke Stroke 2013;44

25. Since Mr B.Ahmed has a moderate risk of hemorrhagic transformation of the fresh brain infarct in the first 2 weeks -- particularly, in the first 5 days or so -- it is probably advisable to practice according to the guidelines in this case

26. W HAT IF ?

28. RECOMMANDATIONS!!! Anticoagultion in Acute Stroke ESOAHA/ASA TIA OR Minor Stroke Immediately < 2 weeks Large Brain Infarct Size OR no controled Hypertension > 4 weeks« Further delays »

29. Blood tests indicate that the patient has normal kidney and liver function. Given that anticoagulant therapy is to begin in 2 weeks, what anticoagulant regimen would you select? A- Begin heparin in 2 weeks, then transition to warfarin B- Begin heparin in 2 weeks, then transition to a novel anticoagulant C- Begin warfarin after 2 weeks D- Begin a novel agent after 2 weeks

30. W ARFARIN THERAPY InconvénientsAvantages Fenêtre thérapeutique étroite Nécessité de surveillance par INR Pas d’influence de la fonction rénale Variation individuelleAntidote Interactions : alimentsCout Interactions : médicaments Nécessité « bridging »

31. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: Circulation 2008; 113, 409–449

32. N OVEL O RAL A NTICOAGULANTS

34. N OACS IN STROKE PREVENTION NON VALVULAR Afib associated to 1 or more  History of stroke or TAI or systemic embolism  FEVG≤40%  NYHA ≥ 2/4  Age ≥ 75 years  Age ≥ 65 years associated to : diabetis, coronary diseases or Hypertension Labile INRs with Warfarin

35. N OACS IN STROKE PREVENTION  Xarelto* (Rivaroxaban) 15 et 20 mg daily ( CrCl 15-50 mL/min)  Pradaxa* (Dabigatran) 75 et 150 mg twice daily ( CrCl 15-30 mL/min)  Eliquis* (Apixaban) 2.5 et 5 mg twice daily (age ≥ 80 years, weight ≤ 60 kg, or serum creatinine ≥ 1.5 mg/dL)

36. Blood tests indicate that the patient has normal kidney and liver function. Given that anticoagulant therapy is to begin in 2 weeks, what anticoagulant regimen would you select? A- Begin heparin in 2 weeks, then transition to warfarin B- Begin heparin in 2 weeks, then transition to a novel anticoagulant C- Begin warfarin after 2 weeks D- Begin a novel agent after 2 weeks

37. T AKE H OME M ESSAGE

38. 2 immediate concerns after an ischemic stroke caused by cardiogenic cerebral embolism: Risk of ischemic stroke recurrence and Risk for hemorrhagic stroke due to hemorrhagic transformation of the fresh brain infarct or subsequent spontaneous The clinical predictors are used in the CHADS 2 and CHA 2 DS 2 - VASc stroke prediction indices; Predictors of intracranial bleeding: large infarct size, increasing age, hypertension, stroke attributable to cardiogenic embolism, low platelet count; and high blood glucose; Although the timing of initiation of anticoagulation therapy after acute stroke is controversial, it is current practice in most patients to delay therapy until 2 weeks after a stroke because the risk of intracranial bleeding is greatest during the first 2 weeks; and Anticoagulant therapy may be initiated with heparin and then transitioned to warfarin or one of the novel agents or started directly with an oral agent

39. Thank you