Update on Antiplatelets and anticoagulants. Outlines. Antiplatelets and Anticoagulants 1/23/2013. Timir Paul, MD, PhD

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1 Update on Antiplatelets and anticoagulants Timir Paul, MD, PhD Antiplatelets Indications Doses Long term use (beyond 12 months) ASA and combination use of NSAIDS ASA resistance Plavix resistance Plavix and PPI Discontinuation Outlines Anticoagulants ACS and PCI Afib DVT Updated guidelines Antiplatelets and Anticoagulants Antiplatelets Aspirin P2Y12 receptor antagonists Ticlopidine Clopidogrel Prasugrel Ticagrelor Cangrelor (IV) GP IIb/IIIa Inhibitors Abciximab Eptifibatide Trofiban Anticoagulants Heparins (UFH) LMWH Enoxaparin Dalteparin Fondaparinux Direct Xa Inhibitor Rivaroxaban Epixaban Direct Thrombin inhibitor Bivalirudin Lepirudin Argatroban Dabigatran 1

2 Antiplatelets Aspirin 2011 ACCF/AHA guidelines on Aspirin P2Y12 ADP receptor antagonist 2

3 P2Y12 Receptor antagonists Prasugrel: Contraindications: Prior TIA/Stroke, hypersensitivity Precautions: Elderly (>75yrs), Weight < 60 kg CABG/surgery for 7 days Ticagrelor: Contraindications: high risk bleeding; prior hemorrhagic stroke; severe hepatic dysfunction Precautions: compliance (b.i.d. administration), drug interactions (CYP 3A4 interfering agents); regional differences (North America/ASA dose <100mg), COPD/asthma, bradyarythmia, gout syndromes, CABG/surgery (5 days) Thienopyridines 2011 ACCF/AHA guideline for PCI 3

4 2011 ACC/AHA Guidelines Postprocedural Antiplatelet Therapy 2011 ACC/AHA Guidelines Postprocedural Antiplatelet Therapy PPIs and Antiplatelets 4

5 Anticoagulants Heparins 5

6 Doses in Medical Management Doses during PCI Decision Tree 6

7 RELY Dabigatran 110 mg twice daily Equal to warfarin in stroke prevention Warfarin 1.69%/yr dabigatran (110mg) 1.53%/yr Less bleeding than warfarin Warfarin 3.36%/year dabigatran (110mg) 2.71%/yr Dabigatran 150 mg twice daily More effective than warfarin in stroke prevention Dabigatran (150mg) 1.11%/yr Equivalent bleeding to warfarin Less hemorrhagic stroke than warfarin ACC /AHA /HRS Afib Focused Update 2011 (Dabigatran) Non-inferior to warfarin in thromboembolism (Afib) Caution when CrCl < 30ml/min Increased dabigatran levels with amiodarone, verapamil Half life hours No reversal for hemorrhage Dialysis Coagulation testing??? aptt 7

8 Hanky, G., Eikelboom, J:Circulation 2011;123: Rivaroxaban Once daily As effective or better than warfarin Less hemorrhagic stroke than warfarin Similar reduction in ischemic stroke Less bleeding than warfarin No routine lab testing No reversal Half life 5-9 hours Coagulation testing: aptt Discontinuation : increased stroke? Apixaban Once or twice daily As effective or better than warfarin Less hemorrhagic stroke than warfarin Similar reduction in ischemic stroke Less bleeding than warfarin Lower overall mortality No routine lab testing No reversal Half life 8-15 hours Coagulation testing: PT, aptt 8

9 New oral anticoagulants Drug Dabigatran Rivaroxaban Apixiban (Pradaxa) (Xarelto) Mechanism Thrombin inhibitor Factor Xa inhibitor Factor Xa inhibitor of action T1/ hours 5 9 hours 12 hours Regimen 150 mg BID 20 mg QD/BID 5 mg BID Peak to trough 2 12 (QD) 3 5 Renal excretion 80% 36 45% 25 30% Dose 150 BID (CrCL >30) 20 mg daily with meal 5 mg BID (Cr =< 1.5) 75 BID (CrCL 15 30) 15 mg daily ( CrCl 15 50) 2.5 mg BID (Cr >= 1.5) Crcl < 25 Avoid use New anticoagulants Short half life less bleeding Subtherapeutic if misses one or two doses - No standard available test to asses if anticoagulated Generally safer than warfarin No antidote??? Dabigatran Cost of medication Overall cost of care Who should remain on warfarin? Patient already receiving warfarin and stable whose INR is easy to control If dabigatran, rivaroxaban, apixaban not available Cost If patient not likely to comply with twice daily dosing (Dabigatran) Chronic kidney disease (GFR < 30 ml/min) 9

10 Summary on Antiplatelets 81 mg of ASA is enough for all patients No effective RX for ASA resistance, increasing dose would not overcome resistance Take ASA 1 hour before taking NSAIDS For PVD 81 mg of ASA is enough no benefit of ASA and plavix combination If ASA allergies, plavix is an alternative Prasugrel is contraindicated for prior stroke or TIA Summary on Antiplatelets No real interaction with PPI (may avoid Omeprazole) No data for plavix beyond 12 months Clilostazol is a class I indication for LE PVD for symptom relief Prasugrel and Ticagrelor is only indicated in ACS patients Summary on Anticoagulants All patients with ACS should receive heparins or LMWH unless contraindicated For medical management heparin is for at least 48 hours and Lovenox for 8 days or during hospitalization Newer anticoagulants are safe and effective in non valvular Afib and treatment and prophylaxis of Afib Dose adjustment is required for newer anticoagulant agents and should not be used for Crcl <