Antiplatelets and Anticoagulants. Helen Leung, PharmD PGY1 Pharmacy Resident Memorial Hermann-Texas Medical Center

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Antiplatelets and Anticoagulants Helen Leung, PharmD PGY1 Pharmacy Resident Memorial Hermann-Texas Medical Center

Mechanism 2 http://www.medicinehack.com/2011/07/virchows-triad.html

Mechanism 3 http://drtedwilliams.net/kb/index.php?pagename=coagulation%20cascade

Classes Antiplatelets Drug (Brand) 4 Cyclooxygenase-1 Inhibitor Aspirin ADP Inhibitors/P2Y12 Inhibitors Clopidogrel (Plavix) Prasugrel (Effient) Ticagrelor (Brillinta) Cangrelor (Kengreal) Phosphodiesterase Inhibitor Dipyridamole/ASA (Aggrenox) Cilostazol (Pletal) GP IIb/IIIa Inhibitors Abciximab (ReoPro) Eptifibatide (Integrilin) Tirofiban (Aggrastat)

Classes Anticoagulants Heparin Vitamin K Antagonists Factor Xa Inhibitors Direct Thrombin Inhibitors Drug (Brand) Unfractionated heparin Enoxaparin (Lovenox) Warfarin (Coumadin) Apixaban (Eliquis) Rivaroxaban (Xarelto) Edoxaban (Savaysa) Fondaparinux (Arixtra) Dabigatran (Pradaxa) Bivalirudin (Angiomax) Argatroban 5

FDA Approved Indications Antiplatelet Stroke prophylaxis/treatment Acute coronary syndromes Anticoagulant Stroke prophylaxis Acute coronary syndromes Peripheral vascular disease Atrial fibrillation/flutter DVT prophylaxis/treatment Pulmonary embolism Heart valve replacement 6 Castaigne A, et al. Indications for Antiplatelet Medications. Rev Prat. 1999 Oct 1;49(15):1635-9. Wigle P, et al. Updated Guidelines on Outpatient Anticoagulation. Am Fam Physician. 2013 Apr 15;87(8):556-566. Antithrombotic Therapy. American Society of Hematology. 2008 Dec.

Antiplatelets

Antiplatelet ADP Inhibitors/P2Y12 Inhibitors Drugs: clopidogrel, prasugrel, ticagrelor, cangrelor (IV) Clopidogrel most commonly used 15-40% of patients are poor responders Prasugrel not impacted by reduced CYP enzyme function 8 Wallentin L. P2712 Inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use. European Heart Journal. 2009;30(16)1964-1977.

Antiplatelet Drug specific contraindications Medication Prasugrel Ticagrelor Contraindications History of stroke/tia, weight <60 kg, severe renal/hepatic impairment, age >75 History of intracranial hemorrhage, Concurrent use with aspirin >100mg daily 9 Lexicomp

Anticoagulants

Anticoagulant Heparin Unfractionated heparin low molecular weight heparin Warfarin Monitoring: titrated based on INR 11 Lexicomp

Anticoagulant Factor Xa Inhibitors Drugs: apixaban, rivaroxaban, edoxaban, fondaparinux (SQ) Renal patients: apixaban preferred Administration May crush and mix with apple sauce or water 12 Lexicomp

Anticoagulants Warfarin vs new oral anticoagulants Advantages Reversible Mechanical heart valves Disadvantages Monitoring Higher risk of major bleeding 13 Yao X, et al. Effectiveness and Safety of Dabigatran, Rivaroxaban, and Apixaban Versus Warfarin in Nonvalvular Atrial Fibrillation. JAHA. 2016.

Anticoagulant Direct Thrombin Inhibitors Drugs: dabigatran, bivalirudin (IV), argatroban (IV) Bridging to warfarin with bivalirudin or argatroban Elevates PT/INR; requires specific holding instructions and modified INR goal while bridging 14 Lexicomp

Combination Therapy Dual antiplatelet therapy (DAPT) Aspirin + ADP inhibitor PCI w/drug eluting stent Double vs triple antithrombotic therapy Anticoagulant + aspirin or ADP inhibitor Atrial fibrillation + drug eluting stent 15 Khumbani, D. Dual Antiplatelet Therapy-DAPT. JACC. 2016. Rohla M, et al. Double or triple antithrombotic combination therapy in patients who need anticoagulation and antiplatelet therapy in parallel. European Heart Journal. 2015;1:191-197.

Major Contraindications Trauma Active bleeding Intracranial hemorrhage GI bleed Bleeding disorders 16

Monitoring Signs/symptoms of bleeding or bruising Hemoglobin Platelets Drug-specific side effects Drug-specific lab tests (i.e. INR for warfarin) 17

Antiplatelets and Anticoagulants Helen Leung, PharmD PGY1 Pharmacy Resident Memorial Hermann-Texas Medical Center