Antiplatelet and Anti-Thrombotic Therapy. Ivan Anderson, MD RIHVH Cardiology

Transcription

1 Antiplatelet and Anti-Thrombotic Therapy Ivan Anderson, MD RIHVH Cardiology

2 Outline Anti-thrombotic therapy Risk stratification of stroke with atrial fibrillation DVT and PE treatment Pharmacology Anti-platelet therapy Pharmacology of PGY-12 antagonists Risk of premature discontinuation of dual anti-platelet therapy Combination of anti-thrombotic and anti-platelet therapy (the triple threat)

3 Outline Anti-thrombotic therapy Risk stratification of stroke with atrial fibrillation DVT and PE treatment Pharmacology Anti-platelet therapy Pharmacology of PGY-12 antagonists Risk of premature discontinuation of dual anti-platelet therapy Combination of anti-thrombotic and anti-platelet therapy (the triple threat)

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5 Dosing

6 Treatment Doses Deep Venous Thrombosis and Pulmonary Embolism Pradaxa: 150 mg PO BID (same) Xarelto: 15 mg PO BID x 21 days Then as per previous slide Eliquis: 10 mg PO BID x 7 days Then as per previous slide

7 Europace (2013) 15,

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9 RELY Data (Pradaxa vs Warfarin)

10 ROCKET-AF Data (Xarelto vs Warfarin)

11 ARISTOTLE Data (Eliquis vs Warfarin)

12 Package Insert Apixaban Now Removed

13 Outline Anti-thrombotic therapy Risk stratification of stroke with atrial fibrillation DVT and PE treatment Pharmacology Anti-platelet therapy Pharmacology of PGY-12 antagonists Risk of premature discontinuation of dual anti-platelet therapy Combination of anti-thrombotic and anti-platelet therapy (the triple threat)

14 Outline Anti-thrombotic therapy Risk stratification of stroke with atrial fibrillation DVT and PE treatment Pharmacology Anti-platelet therapy Pharmacology of PGY-12 antagonists Risk of premature discontinuation of dual anti-platelet therapy Combination of anti-thrombotic and anti-platelet therapy (the triple threat)

15 Acute Coronary Syndromes. Ezra A. Amsterdam et al. Circulation. 2014;130:e344-e426

16 An Activated Platelet

17 Platelet Activation

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19 Central Role of P2Y12 Receptor in Thrombus Propogation J Clin Invest Feb 1; 113(3):

20 Biotransformation and Mode of Action of Clopidogrel, Prasugrel, and Ticagrelor. Schömig A. N Engl J Med 2009;361:

21 Summary of Recommendations for Initial Antiplatelet/Anticoagulant Therapy in Patients With Definite or Likely NSTE-ACS and PCI. Ezra A. Amsterdam et al. Circulation. 2014;130:e344-e426

22 Summary of Recommendations for Initial Antiplatelet/Anticoagulant Therapy in Patients With Definite or Likely NSTE-ACS and PCI. Addition of Plavix or Ticagrelor is Class 1 Level of Evidence B for early care of Non-ST Elevation Acute Coronary Syndrome Ezra A. Amsterdam et al. Circulation. 2014;130:e344-e426

23 Cumulative Hazard Rates for the First Primary Outcome (Death from Cardiovascular Causes, Nonfatal Myocardial Infarction, or Stroke) during the 12 Months of the Study. The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. N Engl J Med 2001;345:

24 ~600% Increased Risk of Stent Thrombosis Stopping DAPT after BMS Circulation. 2007;115: (DAPT = Dual Anti-Platelet Therapy, BMS Bare Metal Stent)

25 Am J Cardiol 2006;98:

26 Stent Related Risk Factors for Instent Thrombosis Bifurcation stenting Eccentric stenosis Long stents (e.g. 26 or 30 mm) Tortuous artery

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30 STEMI After Premature Discontinuation of Anti-Platelet Therapy JACC Vol. 35, No. 5, 2000

31 A Few Notes on Effient (prasugrel) and Brilinta (ticagrelor) Effient (prasugrel): black box warning do not use if prior stroke Brilinta (ticagrelor) Often may cause dyspnea Can lead to bradyarrhythmias

32 Outline Anti-thrombotic therapy Risk stratification of stroke with atrial fibrillation DVT and PE treatment Pharmacology Anti-platelet therapy Pharmacology of PGY-12 antagonists Risk of premature discontinuation of dual anti-platelet therapy Combination of anti-thrombotic and anti-platelet therapy (the triple threat)

33 Outline Anti-thrombotic therapy Risk stratification of stroke with atrial fibrillation DVT and PE treatment Pharmacology Anti-platelet therapy Pharmacology of PGY-12 antagonists Risk of premature discontinuation of dual anti-platelet therapy Combination of anti-thrombotic and antiplatelet therapy (the triple threat)

34 WOEST Trial Randomized control trial of double versus triple therapy after PCI Double therapy: Plavix + Coumadin Triple therapy: Aspirin + Plavix + Coumadin Primary Endpoint: any bleeding Lancet 2013; 381:

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37 WOEST Trial (Death and Stent Thrombosis) Lancet 2013; 381:

38 PIONEER AF-PCI Trial Randomized control trial of anti-coagulation strategies with non-valvular A fib 2124 Patients randomized 1:1:1 to 3 groups Group 1: Xarelto 15 mg + P2Y12 inhibitor x 12 mo Group 2: Xarelto 2.5 mg + DAPT for 1, 6 or 12 mo Group 3: Coumadin + DAPT for 1, 6 or 12 mo (DAPT = Dual Anti-Platelet Therapy) Gibson CM et al. N Engl J Med 2016;375:

39 Stratification, Randomization, and Follow-up. Gibson CM et al. N Engl J Med 2016;375:

40 Cumulative Incidence of the Primary Safety End Point and a Secondary Efficacy End Point. 1 0 Endpoint: Bleeding Group 1: Xarelto 15 mg + P2Y12 inhibitor x 12 mo Group 2: Xarelto 2.5 mg + DAPT for 1, 6 or 12 mo 2 nd Endpoint: Cardiovascular Death, MI, CVA Group 3: Coumadin + DAPT for 1, 6 or 12 mo Gibson CM et al. N Engl J Med 2016;375:

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