Antiplatelet Therapy

Aka: Antiplatelet Therapy, Clopidogrel, Plavix, Thienopyridine, Thiophene, Prasugrel, Effient, Brilinta, Ticagrelor

1. See Also
   1. Antiplatelet Therapy for Vascular Disease
2. Mechanism: Thienopyridine Class
   1. Blocks Platelet ADP
   2. Inhibits platelet aggregation
3. Indications
   1. Cerebrovascular Accident Prevention
   2. Coronary Artery Disease Prevention (especially if Aspirin Allergy)
   3. Post-ST Elevation MI (with or without reperfusion)
4. Preparations
   1. Clopidogrel (Plavix)
      1. Plavix will be generic as of May 2012
      2. Less GI Bleeding than Aspirin or Prasugrel
         1. Option if GI Bleeding occurs with Aspirin
         2. Switch to Plavix does not prevent recurrent GI Bleed
            1. GI Bleed occurs in 8% of those switched to Plavix
            2. Consider adding PPI to Aspirin instead of Plavix
   2. Prasugrel (Effient)
      1. More effective than Plavix in cardiovascular event reduction
      2. Higher risk of bleeding than Plavix in age >75 years, weight <60 kg, CVA history
      3. Avoid in prior Cerebrovascular Accident (CVA) or Transient Ischemic Attack (TIA)
      4. Typically initiated in the catheter lab
         1. Do not initiate in emergency department due to bleeding risk
      5. References
         1. Wiviott (2007) N Engl J Med 357(20):2001-15
   3. Ticagrelor (Brilinta)
      1. Per 1000 ACS patients, Ticagrelor prevents more adverse CV events than Clopidogrel
         1. Prevents 11 more cardiovascular deaths
         2. Prevents 11 more Myocardial Infarctions
         3. Prevents 6 more stent thromboses
      2. Majority of cardiovascular benefit is within first few weeks after Acute Coronary Syndrome
         1. Patients on Clopidogrel already will be unlikely to benefit from switch to Ticagrelor
         2. Discuss antiplatelet agent choice with cardiology at time of Acute Coronary Syndrome
      3. Adverse Effects and disadvantages
         1. Similar bleeding risk to Clopidogrel
         2. Dyspnea occurs with Brilinta use
         3. Requires twice daily dosing
      4. References
         1. (2012) Presc Lett 19(5): 27
5. Disadvantages
   1. Expensive
6. Dosing: Clopidogrel (Plavix)
   1. Standard dosing
      1. Plavix 75 mg orally daily
   2. Acute Myocardial Infarction
      1. Loading dose: Plavix 300 mg (if age <75 years)
      2. Then initiate standard 75 mg daily Plavix dose
   3. Impending Percutaneous Coronary Intervention (PCI)
      1. Plavix 600 mg orally once
      2. Then initiate standard 75 mg daily Plavix dose after PCI
7. Dosing: Ticagrelor (Brilanta)
   1. Standard dosing
      1. Brilanta 90 mg orally twice daily
   2. Acute Myocardial Infarction with or without impending PCI
      1. Brilanta 180 mg orally once
      2. Then initiate standard 90 mg twice daily Brilanta dose
8. Drug Interactions
   1. Proton Pump Inhibitors
      1. Risk: Omeprazole and Esomeprazole reduce conversion of Plavix to active metabolite (unclear clinical impact)
      2. Safe: Lansoprazole, Dexlansoprazole, Pantoprazole and Famotidine (high dose) do not appear to interact with Plavix
      3. Limit Proton Pump Inhibitors to high risk patients
         1. Prior GI Bleed
         2. Advanced age
         3. Concurrent Aspirin, NSAIDs, Corticosteroids, or Warfarin
      4. Mehta (2011) Clin Cardiol 34(9): 528-31
9. Management: Reversal
   1. Platelet Transfusion 2 units (12 pack)
   2. Consider Desmopressin (DDAVP) 0.3 mcg/kg (expert opinion)
   3. Consider Recombinant activated Clotting Factor VII (rFVIIa) 30-90 mcg/kg (expert opinion)