OAC and NOAC with or without platelet inhibition



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Zürich 11.06.2015 Preoperative antithrombotic management OAC and NOAC with or without platelet inhibition Miodrag Filipovic miodrag.filipovic@kssg.ch Anästhesiologie & Intensivmedizin

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

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)...

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...

Thromboembolic Risk Lip GY et al. Chest. 2010;137:263-72 Σ=6

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

Camm AJ, et al Eur Heart J 2012;33: 2719-47

Camm AJ, et al Eur Heart J 2012;33: 2719-47

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

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

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

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

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

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 )

Direct ( new ) oral anticoagulans Dabigatran Rivaroxaban Edoxaban Apixaban Target IIa Xa Xa Xa Half Life [h] 12 17 7 11 20 25 12 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: 310-20 (mod.)

Dabigatran: renal function Weitz JI, et al. Circulation. 2012;126:2428-32

www.kardiologie.kssg.ch/home/aerzte_fachpersonen/ thromboseprophylaxe-und-periinterventionelle-antithrombotische-t.html

DOACs Bridging?... Heparin bridging did not reduce cardiovascular events, but led to significantly higher rates of major bleeding complications (2.7% ( 95% CI 1.1-5.5) vs. 0.5% ( 0.1-1.4); P = 0.010). Beyer-Westendorf J, et al. Eur Heart J 2014; 35: 1888-1896

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

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

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

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

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

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

DOACs Activity to measure? Cuker A, et al. J Am Coll Cardiol 2014;64:1128-39

DOACs Activity coagulation tests Cuker A, et al. J Am Coll Cardiol 2014;64:1128-39

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

Atrial fibrillation and PCI Lip GY, et al Eur Heart J 2014;33: 2719-47

Atrial fibrillation and PCI Lip GY, et al Eur Heart J 2014;33: 2719-47

Atrial fibrillation and PCI Stroke risk Bleeding risk Clinical setting Antithrombotic therapy Lip GY, et al Eur Heart J 2014;33: 2719-47

Atrial fibrillation and ACS Lip GY, et al Eur Heart J 2014;33: 2719-47

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...

adaptiert von ACCP Guidelines

OAK: Bridging? Steinberg BA, et al. Circulation. 2015; 131: 488-494

Bridging? Steinberg BA, et al. Circulation. 2015; 131: 488-494

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

Platelet Inhibition? Windecker S, et al. Eur Heart J 2014; 35:2541-619

Guidelines: Aspirin (Europe) Kristensen SD, et al. Eur Heart J. 2014; 35: 2383-2431

Management of bleeding

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

miodrag.filipovic@kssg.ch

miodrag.filipovic@kssg.ch