OAC and NOAC with or without platelet inhibition

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1 Zürich Preoperative antithrombotic management OAC and NOAC with or without platelet inhibition Miodrag Filipovic Anästhesiologie & Intensivmedizin

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4 Case 1 76 yr old male patient Hypertensive heart disease Atrial fibrillation Dyspnoe NYHA II, no angina History of stroke (good recovery) Peripheral arterial disease Impaired renal function (creatinine 140 mmol/l clearance 45 ml/min) Medication: Bisoprolol (Concor ) Atorvastatin (Sortis ) Dabigatran (Pradaxa ) Scheduled for sigma resection

5 Considerations 1. Risk and harmfulness of bleeding Procudure under ungoing antithrombotic/antiplatelet medication? 2. Risk of a thromboemblic event 3. Urgency of the procedure 4. Special circumstances Pregnancy Renal function History of heparin-induced thrombocytopenia (HIT)...

6 Case 1 76 yr old male patient Hypertensive heart disease Atrial fibrillation Dyspnoe NYHA II, no angina History of stroke (good recovery) Peripheral arterial disease Impaired renal function (creatinine 140 mmol/l clearance 45 ml/min) Medication: Bisoprolol (Concor ) Atorvastatin (Sortis ) Dabigatran (Pradaxa ) Scheduled for sigma resection 1. Risk and harmfulness of bleeding Procudure under ungoing antithrombotic/antiplatelet medication? 2. Risk of a thromboemblic event 3. Urgency of the procedure 4. Special circumstances Pregnancy Renal function History of HIT...

7 Thromboembolic Risk Lip GY et al. Chest. 2010;137: Σ=6

8 Thromboembolic Risk Friberg L, et al. J Am Coll Cardiol 2015;65:225-32

9 Camm AJ, et al Eur Heart J 2012;33:

10 Camm AJ, et al Eur Heart J 2012;33:

11 DOAC Efficacy and safety Ruff CT, et al. Lancet 2014; 383:955-62

12 DOAC Efficacy and safety Hemorrhagic stroke Ruff CT, et al. Lancet 2014; 383:955-62

13 Fibrinogen Fibrin Prothrombin Thrombin Ca 2+ + Va + Xa Activated platelet VIIa + TF X Activated platelet VIIIa +Ca 2+ +IXa XIa XIIa Filipovic M, Schnider T. F1000 Med Rep 2010; 2:pii:37

14 Thrombin Inhibitors Fibrinogen Fibrin Prothrombin Thrombin FXa Inhibitors Ca 2+ + Va + Xa Activated platelet Activated platelet VIIIa +Ca 2+ +IXa X VIIa + TF XIa XIIa Filipovic M, Schnider T. F1000 Med Rep 2010; 2:pii:37

15 Thrombin Inhibitors Lepirudin (Refludan ) [i.v.] Bivalirudin (Angiox ) [i.v.] Argatroban (Argatra ) [i.v.] Dabigatran (Pradaxa ) [p.o.] Fibrinogen Fibrin Prothrombin FXa Inhibitors Ca 2+ + Va + Xa Danaparoid (Orgaran ) [i.v./s.c.] Rivaroxaban (Xarelto ) [p.o.] Apixaban (Eliquis ) [p.o.] Edoxaban [p.o.] VIIa + Betrixaban [p.o.] TF Thrombin X Activated platelet VIIIa +Ca 2+ +IXa XIa XIIa Filipovic M, Schnider T. F1000 Med Rep 2010; 2:pii:37

16 DOAC Indications (CH, May 2015) VTE- Prophylaxis Venous thromboembolism Treatment Atrial Fibrillation Rivaroxaban (Xarelto ) Apixaban (Eliquis ) Rivaroxaban (Xarelto ) Apixaban (Eliquis ) Edoxaban (Lixiana ) Dabigatran (Pradaxa ) (after initial Heparin/LMWH) Rivaroxaban (Xarelto ) Apixaban (Eliquis ) Edoxaban (Lixiana ) Dabigatran (Pradaxa )

17 Direct ( new ) oral anticoagulans Dabigatran Rivaroxaban Edoxaban Apixaban Target IIa Xa Xa Xa Half Life [h] Renal Elimination 80% 60% (30% unchanged) 50% 25% Monitoring (Specific) Thrombin time Anti-Xa-Activity (spec. calibrator) Anti-Xa-Activity (spec. calibrator) Anti-Xa-Activity (spec. calibrator) Reversibility Unspecific Unspecific Unspecific Unspecific Galanis T, et al. J Thromb Haemost 2011; 31: (mod.)

18 Dabigatran: renal function Weitz JI, et al. Circulation. 2012;126:

19 thromboseprophylaxe-und-periinterventionelle-antithrombotische-t.html

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21 DOACs Bridging?... Heparin bridging did not reduce cardiovascular events, but led to significantly higher rates of major bleeding complications (2.7% ( 95% CI ) vs. 0.5% ( ); P = 0.010). Beyer-Westendorf J, et al. Eur Heart J 2014; 35:

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23 Case 1 76 yr old male patient Hypertensive heart disease Atrial fibrillation Dyspnoe NYHA II, no angina History of stroke (good recovery) Peripheral arterial disease Impaired renal function (creatinine 140 mmol/l clearance 45 ml/min) Medication: Bisoprolol (Concor ) Atorvastatin (Sortis ) Dabigatran (Pradaxa ) Scheduled for sigma resection

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25 DOACs bleeding Heidbuchel H, et al. Europace. 2013;15(5):625-51

26 DOACs bleeding Heidbuchel H, et al. Europace. 2013;15(5):625-51

27 DOACs bleeding Tranexamic acid Heidbuchel H, et al. Europace. 2013;15(5):625-51

28 DOACs bleeding Reilly PA, et al. J Am Coll Cardiol 2014; 63:321-8

29 DOACs bleeding Reilly PA, et al. J Am Coll Cardiol 2014; 63:321-8

30 DOACs Activity to measure? Cuker A, et al. J Am Coll Cardiol 2014;64:

31 DOACs Activity coagulation tests Cuker A, et al. J Am Coll Cardiol 2014;64:

32 Case 2 68 yr old female patient Coronary artery and hypertensive heart disease STEMI 15 months ago PCI: RCx DES Atrial fibrillation: CHA 2 DS 2 Vasc = 7 Dyspnoe NYHA II, no angina History of stroke (good recovery) Diabetes mellitus Medication: Bisoprolol (Concor ) Atorvastatin (Sortis ) Phenprocoumon (Marcoumar ) Aspirin stopped 6 months after ACS Clopidogrel (Plavix ) stopped 12 months after ACS Scheduled for resection of lung cancer

33 Atrial fibrillation and PCI Lip GY, et al Eur Heart J 2014;33:

34 Atrial fibrillation and PCI Lip GY, et al Eur Heart J 2014;33:

35 Atrial fibrillation and PCI Stroke risk Bleeding risk Clinical setting Antithrombotic therapy Lip GY, et al Eur Heart J 2014;33:

36 Atrial fibrillation and ACS Lip GY, et al Eur Heart J 2014;33:

37 Case 2 68 yr old female patient Coronary artery and hypertensive heart disease STEMI 15 months ago PCI: RCx DES Atrial fibrillation: CHA 2 DS 2 Vasc = 7 Dyspnoe NYHA II, no angina History of stroke (good recovery) Diabetes mellitus Medication: Bisoprolol (Concor ) Atorvastatin (Sortis ) Phenprocoumon (Marcoumar ) Aspirin stopped 6 months after ACS Clopidogrel (Plavix ) stopped 12 months after ACS Scheduled for resection of lung cancer 1. Risk and harmfulness of bleeding Procudure under ungoing antithrombotic/antiplatelet medication? 2. Risk of a thromboemblic event 3. Urgency of the procedure 4. Special circumstances Pregnancy History of HIT II...

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39 adaptiert von ACCP Guidelines

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41 OAK: Bridging? Steinberg BA, et al. Circulation. 2015; 131:

42 Bridging? Steinberg BA, et al. Circulation. 2015; 131:

43 Case 2 68 yr old female patient Coronary artery and hypertensive heart disease STEMI 15 months ago PCI: RCx DES Atrial fibrillation: CHA 2 DS 2 Vasc = 7 Dyspnoe NYHA II, no angina History of stroke (good recovery) Diabetes mellitus Medication: Bisoprolol (Concor ), Amiodarne (Cordarone ) Atorvastatin (Sortis ) Phenprocoumon (Marcoumar ) Aspirin stopped 6 months after ACS Clopidogrel (Plavix ) stopped 12 months after ACS Scheduled for resection of lung cancer

44 Platelet Inhibition? Windecker S, et al. Eur Heart J 2014; 35:

45 Guidelines: Aspirin (Europe) Kristensen SD, et al. Eur Heart J. 2014; 35:

46 Management of bleeding

47 (n) (%) VKA Reversal: FFP vs. PCC Hickey M, et al. Circulation 2013;128:360-4

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