1. HIPPOCRATIC WISDOM; “FIRST DO NO HARM” WHILE USING NOACS FOR PREVENTION OF STROKE MOHAMMED FAKHRY ABDUL MOHSEN, MD, FACC PROFESSOR OF MEDICINE COLLEGE OF MEDICINE, UOD CONSULTANT INTERNIST/CARDIOLOGIST, KING FAHD HOSPITAL OF THE UNIVERSITY. DEC 1, 2014

2. HIPPOCRATES OATH الحكيم إبوقراط It is extremely difficult Equation, do we anticoagulate or not to prevent stroke?!

3. HIPPOCRATES OATH ( قسم الحكيم إبوقراط ) This is the original version of the Hippocratic Oath: I swear by Apollo the physician, and Aesculapius the surgeon, likewise Hygeia and Panacea, and call all the gods and goddesses to witness, that I will observe and keep this underwritten oath, to the utmost of my power and judgment.ApolloAesculapiusHygeiaPanacea I will reverence my master who taught me the art. Equally with my parents, will I allow him things necessary for his support, and will consider his sons as brothers. I will teach them my art without reward or agreement; and I will impart all my acquirements, instructions, and whatever I know, to my master's children, as to my own; and likewise to all my pupils, who shall bind and tie themselves by a professional oath, but to none else. With regard to healing the sick, I will devise and order for them the best diet, according to my judgment and means; and I will take care that they suffer no hurt or damage. Nor shall any man's entreaty prevail upon me to administer poison to anyone; neither will I counsel any man to do so. Moreover, I will get no sort of medicine to any pregnant woman, with a view to destroy the child. Further, I will comport myself and use my knowledge in a godly manner. I will not cut for the stone, but will commit that affair entirely to the surgeons.cut for the stone Whatsoever house I may enter, my visit shall be for the convenience and advantage of the patient; and I will willingly refrain from doing any injury or wrong from falsehood, and (in an especial manner) from acts of an amorous nature, whatever may be the rank of those who it may be my duty to cure, whether mistress or servant, bond or free. Whatever, in the course of my practice, I may see or hear (even when not invited), whatever I may happen to obtain knowledge of, if it be not proper to repeat it, I will keep sacred and secret within my own breast. If I faithfully observe this oath, may I thrive and prosper in my fortune and profession, and live in the estimation of posterity; or on breach thereof, may the reverse be my fate! [4 ] "First do no harm" [edit] [4 ]edit It is a popular misconception that the phrase "First do no harm" (Latin: Primum non nocere) is a part of the Hippocratic oath. In fact the phrase is believed to have originated with the 19th-century surgeon Thomas InmanLatinPrimum non nocereThomas Inman

4. OBJECTIVES:  Characterize bleeding events associated with anticoagulation therapy.  Describe the safety profile of the newer anticoagulants.  Importance of individualizing therapy.  Discuss application of guideline recommendations for anticoagulants to improve the outcomes.

5. STROKES ARE DIFFERENT TYPES!  All strokes are not the same.  Stroke is a syndrome  Appropriate tools of diagnosis is extremely important !!

6. Stroke is a syndrome

14. CHADS2 SCORE  Congestive heart failure = C 1  Hypertension = H 1  Age = A 1  Diabetes = D 1  Stroke = S2 2

15. CHA 2 DS 2 – VASC SCORE  Congestive heart failure = C 1  Hypertension = H 1  Age > 75 = A 2  Diabetes = D 1  Stroke = S 2 2  Vascular disease = V 1  Age > 65 = A 1  Sex (F) = S 1

16. HAS–BLED SCORE  Hypertension = H 1  Age > 65 = A 1  Stroke = S 1  Bleeding Hx = B 1  Labile INR = L 1  Drug or Ethanol abuse = E 1 each  Abnormal Liver or = D 1 each renal function

19. CHADS 2 HAS BLED BALANCE CHA2 DS2-VASC Score HAS BLED Score NO Benefit = Harm

20. CHADS 2 HAS BLED BALANCE CHA2 DS2-VASC Score ↑ HAS BLED Score NO (Contraindicated) Great Harm

21. CHADS 2 HAS BLED BALANCE CHA2 DS2-VASC Score HAS BLED Score Benefit > > Harm

24. SECONDARY STROKE PREVENTION IN PTS WITH AF  Milestone 1: VKAs reduce stroke risk in patients with AF → RCTs  Milestone 2: VKAs in non-AF conditions → evidence based medicine.  Milestone 3: NOACs as alternative to VKAs in AF → RCTs

28. BLEEDING EVENTS IN ENGAGE-AF-TIMI 48  20,105 patients with AF and CHADS2 score ≥ 2 were included in a DB – DD clinical trial (1:1:1) testing the - primary efficacy EP (Stroke or SEE) - Primary safety EP (Major Bleeding) - G1 → Warfarin →7036 Pts compared with - G2 → High dose Edoxaban (60mg OD) → 7035 Pts - G3 → Lower dose Edoxaban (30mg OD) → 7034 Pts

35. SUMMARY 1. Compared with well-managed warfarin (TTR) 68.4%) once- daily edoxaban - Reduced bleeding (including fatal bleeding) - Reduced mortality 2. Fewer fatal bleeds and bleeding contributing to death account for ~ 50% of reduction in total mortality with edoxaban. 3. Better tolerability with edoxaban may have reduced deaths not directly related to bleeding.

36. FLEXIBLE DOSING TO AVOID ADVERSE EFFECTS?!  High- vs low-dose regimens: less ischemic events but more bleeding.  Dose modifications/reduction: - To prevent excess drug exposure in vulnerable patients.  Does it require measuring drug concentration or anticoagulant activity?!

50. HIPPOCRATES OATH الحكيم إبوقراط It is extremely difficult Equation, do we anticoagulate or not to prevent stroke in cases of nonvalvular AF?!

54. Thank You شكرا