Αντιπηκτική κ Αντιθρομβωτική Αγωγή (από την πλευρά του καρδιολόγου) Σταύρος Γαβριηλίδης Ομότιμος Καθηγητής Α.Π.Θ.

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1 Αντιπηκτική κ Αντιθρομβωτική Αγωγή (από την πλευρά του καρδιολόγου) Σταύρος Γαβριηλίδης Ομότιμος Καθηγητής Α.Π.Θ. ΠΡΠ 16/10/2013

2 Κλινικές επιπτώσεις της θρόμβωσης Τα θρομβοεμβολικά επεισόδεια ευθύνονται για περισσότερους από εισαγωγές σε νοσοκομείο το χρλονο στις ΗΠΑ Η πνευμονική εμβολή προκαλεί ή συμβάλει στον θάνατο στο 12% των νοσηλευομένων και εθύνεται για έως θανάτους τον χρόνο στις ΗΠΑ.

3 Virchow s Triad

4 Κλινική Σημασία της Θρόμβωσης 1. Απόφραξη αρτηριών και φλεβών Ισχαιμία ή νέκρωση των αρδευομένων περιοχών 2. Εμβολή

5 Θεραπευτική χορήγηση αντιπηκτικών Κολπική μαρμαρυγή Έμφραγμα του μυοκαρδίου Πνευμονική εμβολή Θρόμβωση των εν τω βάθει φλεβών Φλεβική φλεμβοθρόμβωση Καρδιακή ανεπάρκεια Βαλβιδοπάθειες Προσθετικές καρδιακές βαλβίδες Εγκεφαλικό επισόδειο, Γενετικές ή επίκτητες εκδηλώσεις υπερπηκτικότητας

6 Θεραπευτική χορήγηση αντιπηκτικών 1.1 Coumarins (vitamin K antagonists) 1.2 Heparin and derivative substances Low molecular weight heparin Synthetic pentasaccharide inhibitors of factor Xa (Fondaparinux ) 1.3 Direct factor Xa inhibitors (Αpixaban, Rivaroxaban) 1.4 Direct thrombin inhibitors (Dabigatran (Pradaxa)

7 Loading Dose then Maintenance Dose Daily Dose Maintenance Dose Only Daily Dose

8 1) Delayed onset/offset 2) Unpredictable dose response 3) Narrow therapeutic index 4) Drug-drug, drug-food interactions 5) Problematic monitoring 6) High bleeding rate 7) Slow reversibility

9 Αναστροφή της δράσης της warfarin Plasma Rapid but short-lasting Vitamin K Not rapid, but lasts 1-2 weeks. Do not use if wishing to restart warfarin within next week.

10 Dabigatran Oral direct thrombin inhibitor Twice daily dosing Renal clearance Rivaroxaban Direct factor Xa inhibitor Once daily (maintenance), twice daily (loading) Renal clearance Apixaban Direct factor Xa inhibitor Twice daily dosing Hepatic clearance Edoxaban Direct factor Xa inhibitor Once daily dosing Hepatic clearance Circulation 2010;121:1523

11 Features Warfarin New Agents Onset Slow Rapid Dosing Variable Fixed Food effect Yes No Drug interactions Many Few Monitoring Yes No Half-life Long Short Antidote Yes No

12 Despite continued use of warfarin, NOACs are considered by many professional medical organizations to be the best option for anticoagulation of SPAF patients: ESC 2012 AF Update Guidelines ACCP 2012 Guidelines Canadian AF Guidelines

13 No antidote when bleeding No antidote for urgent procedures Lack standard measurement Dependence on renal function Best treatment is prevention Warfarin has no great antidote Time is a great antidote RELY analysis 2012 shows no increase in bleeding in this setting Do not need one Time since last dose is helpful Rivaroxaban, apixaban modest renal effect Cost Highly cost effective in analyses No head-to-head comparisons of new agents

14 ANTIPLATELET THERAPY Aspirin: Primary prevention of MI in high risk persons Secondary prevention of MI,TIA & stroke Clopidogrel: for persons who can t take aspirin Aspirin+clopidogrel: Acute coronary syndromes

15 ANTIPLATELET DRUGS Aspirin Clopidogrel Abciximab Prasurgrel Ticagrelor

16 GLYCOPROTEIN IIb/IIIa RECEPTOR ANTAGONISTS ABCIXIMAB Integrelin Others USE: Acute coronary syndromes

17 Κολπική Μαρμαρυγή

18 Paroxysmal Self-Terminating Persistent Lasts > 7 Days Permanent Cardioversion Failed or Not Attempted Normal Sinus Rhythm Atrial Fibrillation Paroxysmal AF is as likely to cause stroke as persistent or permanent AF

19 Warfarin better Control better AFASAK SPAF RRR of stroke: 62% BAATAF CAFA SPINAF EAFT RRR All-cause mortality: 26% Aggregate 100% 50% 0-50% -100% RRR, relative risk reduction. Hart RG, et al. Ann Intern Med. 1999;131:

20 Διαγνωστική Αξιολογηση 1. Στους περισσότερους αρρώστους με ΚΜ διάρκειας < 48 h μπορεί να γίνει ανάταξη μετα χορήγηση ηπαρίνης χαμηλού μοριακού βάρους (LMWH) χωρίς τον κίνδυνο ΑΕΕ. 2. Εάν η διάρκεια της ΚΜ είναι > 48 h ή υπάρχει αμφιβολία για την διάρκειά της, πριν την ανάταξη μπορεί να χρειασθεί Διοισοφάγειο ΗΧΩ για να αποκλειστεί η ύπαρξη ενδοκαρδιακού θρόμβου Στους περισσότερους αρρώστους με οξεία (πρόσφατη) ΚΜ απαιτείται αντιπηκτική αγωγή εκτός αν είναι χαμηλού κινδύνου για ΑΕΕ και δεν είναι απαραίτητη η καρδιοανάταξη (τερματισμός της ΚΜ εντός 24-48h)

21 Score (points) Prevalence (%)* Congestive Heart failure 1 32 Hypertension 1 65 Age > 75 years 1 28 Diabetes mellitus 1 18 Stroke or TIA 2 10 Moderate-High risk > Low risk VanWalraven C, et al. Arch Intern Med 2003; 163:936. * Nieuwlaat R, et al. (EuroHeart survey) Eur Heart J 2006 (E-published).

22 Weight (points) Congestive heart failure or LVEF < 35% 1 Hypertension 1 Age > 75 years 2 Diabetes mellitus 1 Stroke/TIA/systemic embolism 2 Vascular Disease (MI/PAD/Aortic plaque) 1 Age years 1 Sex category (female) 1 Moderate-High risk > 2 Low risk 0-1 Lip GYH, Halperin JL. Am J Med 2010; 123: 484.

23 Assess Thromboembolic Risk (CHADS 2 ) CHADS 2 = 0 CHADS 2 = 1 CHADS 2 > 2 Increasing stroke risk No antithrombotic ASA OAC* OAC* OAC No additional risk factors of stroke Either female sex or vascular disease Age > 65 y or combination of female sex and vascular disease *Aspirin is a reasonable alternative in some as indicated by risk/benefit

24 Choice of anticoagulant.

25 Approved agents for the prevention of stroke in patients with AF VKA Dabigatran Drug Target Dose/regimen Supporting data Multiple coagulation factors Thrombin E.g. warfarin Initial dose: typically 10 mg od for 2 days Maintenance dose: typically 3 9 mg od () 110 mg bid 150 mg bid RE-LY Newly identified events in RE-LY Rivaroxaban Factor Xa 20 mg od 15 mg od for patients with moderate renal impairment ROCKET AF 390 Apixaban Factor Xa 5 mg bid 2.5 mg bid for patients with 2 of the following criteria: age 80 years; body weight 60 kg; serum creatinine 1.5 mg/dl ARISTOTLE 391 AVERROES 392

26 Έμφραγμα του μυοκαρδίου

27

28 Anti-coagulation Indication post MI: LV thrombus or aneurysm LVEF < 30% CHF History of thrombo-embolism Chronic atrial fibrillation-continue indefinitely

29 Figure 1 Source: Canadian Journal of Cardiology (DOI: /j.cjca ) Copyright Canadian Cardiovascular Society Terms and Conditions

30 Figure 2 Source: Canadian Journal of Cardiology (DOI: /j.cjca ) Copyright Canadian Cardiovascular Society Terms and Conditions

31 Figure 3 Source: Canadian Journal of Cardiology (DOI: /j.cjca ) Copyright Canadian Cardiovascular Society Terms and Conditions

32 Figure 4 Source: Canadian Journal of Cardiology (DOI: /j.cjca ) Copyright Canadian Cardiovascular Society Terms and Conditions

33 Πνευμονική Εμβολή

34 Therapeutic strategies High-risk pulmonary embolism Intravenous unfractionated heparin should be the preferred Non-high-risk pulmonary embolism LMWH or fondaparinux, given subcutaneously is the treatment of choice.

35 Ιndications and targets Anticoagulation recommendations Indication Pulmonary embolus. Proximal deep vein thrombosis (DVT). Which anticoagulant to use and the international normalised ratio (INR) Warfarin (3.5 for pulmonary embolus sustained whilst already on warfarin with INR above 2). Duration At least 3 months if risk factors are temporary, but at least 6 months if they are permanent or cause unknown. Prophylaxis of venous thromboembolism Warfarin not indicated. Dabigatran etexilate and rivaroxaban are both licensed for use in adults after total hip replacement or total knee replacement surgery Dabigatran - continued for 10 days Rivaroxaban - continue for 5 weeks

36 Βαλβιδοπάθειες Προσθετικές βαλβίδες

37 Bioprosthetic Valves

38 Mechanical Prosthetic Valves Starr-Edwards Ball-in-Cage Valve Bjork-Shiley Single Tilting Disk Valve

39 Replacement Valves Medtronic-Hall Valve Tilting Disk St. Jude Valve Bi-leaflet Tilting Disk

40 Bonow et al, JACC 2008;52:e1-e142. Antithrombotic Therapies for VHD I IIa IIb III AVR, mechanical bileaflet (or Medtronic Hall) and no risk factors INR target AVR, mechanical bileaflet (or Medtronic Hall) with risk factors INR target AVR, Starr-Edwards or other disc valve and no risk factors INR target * Risk factors include atrial fibrillation, previous thromboembolism, LV dysfunction, hypercoagulable condition

41 Bonow et al, JACC 2008;52:e1-e142. Antithrombotic Therapies for VHD I IIa IIb III MV, mechanical valve INR target AVR, biological valve with risk factors INR MV, biological valve with risk factors INR

42 Bonow et al, JACC 2008;52:e1-e142. Antithrombotic Therapies for VHD I IIa IIb III AVR or MV, unable to take warfarin ASA mg daily Any mechanical heart valve ASA mg daily Biological valve with risk factors ASA mg daily I IIa IIb III AVR or MV, biological valve and no risk factors ASA mg daily

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