II. Mechanism: Thienopyridine Class

  1. Inhibits Platelet signal transduction
  2. Inhibits Platelet aggregation
  3. Reversibly binds Adenosine Diphosphate (ADP) P2Y12-Class Receptors
    1. Inhibits G Protein
    2. Inhibits Adenyl Cyclase

III. Indications: Prevention of Thrombotic Events

  1. Cerebrovascular Accident Prevention
  2. Coronary Artery Disease Prevention (especially if Aspirin Allergy)
  3. Post-ST Elevation MI (with or without reperfusion)

IV. Contraindications

  1. Active Bleeding

V. Preparations

  1. Clopidogrel (Plavix)
    1. 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 [PubMed]
  3. Ticagrelor (Brilinta)
    1. Recommended by ACA (2016) over Clopidogrel in Acute Coronary Syndrome and stenting
    2. 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
    3. 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
    4. Adverse Effects and disadvantages
      1. Similar bleeding risk to Clopidogrel
      2. Dyspnea occurs with Brilinta use for 1 in 27 patients
      3. Requires twice daily dosing
    5. Dosing Adjustments
      1. No dosing adjustment needed in renal and mild hepatic Impairment
      2. Use caution in moderate liver disease and avoid in severe liver disease
    6. Adverse Effects
      1. Dyspnea
      2. Bleeding
      3. Dizziness or Syncope
      4. Acute Kidney Injury
      5. Other less common effects include Angioedema or Hypersensitivity, AV Block, Bradycardia, skin rash
    7. Safety
      1. Pregnancy Category C
      2. Lactation Unknown
    8. Drug Interactions: CYP3A4
    9. References
      1. (2012) Presc Lett 19(5): 27

VI. Disadvantages

  1. Clopidogrel (Plavix) is now generic ($10/month compared with $300/month for other agents)

VII. 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 with Aspirin 81 mg
  3. Impending Percutaneous Coronary Intervention (PCI)
    1. Plavix 600 mg orally once
    2. Then initiate standard 75 mg daily Plavix dose after PCI

VIII. Dosing: Ticagrelor (Brilinta)

  1. Standard dosing
    1. Brilanta 90 mg orally twice daily
  2. Acute Myocardial Infarction with or without impending PCI
    1. Loading dose: Brilanta 180 mg orally once
    2. Then initiate standard 90 mg twice daily Brilanta dose
    3. Used with Aspirin 81 mg (Dual Antiplatelet Therapy) after PCI

IX. Dosing: Prasugrel (Effient)

  1. Impending Percutaneous Coronary Intervention (PCI)
    1. Effient 60 mg orally once
    2. Then initiate standard 10 mg daily Effient dose after PCI

X. Drug Interactions: General

  1. Morphine (and presumed other Opioids)
    1. Morphine decreased (35%) and delayed (2 hours) Ticagrelor absorption
    2. May affect acute STEMI management
    3. Kubica (2016) Int J Cardiol 215:201-8 [PubMed]

XI. Drug Interactions: Proton Pump Inhibitors interacting with Clopidogrel (Plavix)

  1. Agents that reduce conversion of Plavix to active metabolite (unclear clinical impact)
    1. Omeprazole
    2. Esomeprazole
  2. Safe agents that do not appear to interact with Plavix
    1. Lansoprazole
    2. Dexlansoprazole
    3. Pantoprazole
    4. Famotidine (high dose)
  3. Limit Proton Pump Inhibitors to high risk patients
    1. Prior GI Bleed
    2. Advanced age
    3. Concurrent Aspirin, NSAIDs, Corticosteroids, or Warfarin
  4. Application
    1. Avoid Proton Pump Inhibitors unless clear indication
    2. If a Proton Pump Inhibitor is needed
      1. Choose one that that does not interfere with Cloipidogrel (e.g. Lansoprazole)
      2. Consider agent that does not interact with PPIs such as Ticagrelor (Brilanta) in place of Clopidogrel
    3. Best data suggests no increased risk of cardiovascular events with PPI and Clopidogrel
  5. References
    1. (2013) Presc Lett 20(6): 36
    2. Mehta (2011) Clin Cardiol 34(9): 528-31 [PubMed]

XII. 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)

XIII. References

  1. Filler and Lovecchio (2017) Crit Dec Emerg Med 31(7): 24
  2. Switaj (2017) Am Fam Physician 95(4): 232-40 [PubMed]

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Cost: Medications

clopidogrel (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
CLOPIDOGREL 75 MG TABLET Generic $0.06 each
plavix (on 11/23/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
PLAVIX 75 MG TABLET Generic $0.06 each
prasugrel (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
PRASUGREL 10 MG TABLET Generic $0.33 each
PRASUGREL 5 MG TABLET Generic $0.44 each
brilinta (on 1/1/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
BRILINTA 60 MG TABLET $6.81 each
BRILINTA 90 MG TABLET $6.79 each