JL is a 58-year-old male who began experiencing squeezing chest pain that radiated to his jaw while working in his yard. EMS were called and upon arrival to the hospital his EKG shows ST-segment elevation. He also has elevated troponins and CK-MB.
PMH: hypertension, hyperlipidemia, GERD, obesity
5’11”, 120 kg
Troponin: 14928 ng/mL (0-0.4 ng/ml)
CK-MB: 128 U/L (20-30 U/L)
Home medications: Lisinopril 20 mg PO QD, hydrochlorothiazide 12.5 mg PO QD, atorvastatin 80 mg PO QD, pantoprazole 40 mg PO QD
JL is diagnosed with a STEMI and undergoes successful PCI with stent placement. In addition to his other secondary prevention medications for MI he will be started on dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor (Plavix, Brilinta or Effient). Which of the following statements are true regarding these DAPT agents?
A. DAPT is continued indefinitely for secondary prevention of STEMI
B. Brilinta should not be used with >100 mg of aspirin/day
C. Effient is contraindicated in patients with a history of stroke or TIA
D. Plavix is a prodrug and substrate of CYP 3A4
E. Brilinta is dosed twice daily while the other agents are dosed once daily
F. Effient is a reversible inhibitor of P2Y12, while Brilinta binds irreversibly to P2Y12
G. Aspirin 325mg daily is preferred to 81 mg daily for secondary prevention of STEMI
Correct answers: B, C, E
Brand/Generic: Plavix (clopidogrel), Effient (prasugrel), Brilinta (ticagrelor)
Answer Choice A: This answer choice is incorrect because DAPT should not be continued indefinitely after STEMI. The dual therapy is only indicated for approximately one year after STEMI with stent placement. However, the daily low dose aspirin (81 mg) should be continued indefinitely for secondary prevention.
Answer Choice B: This answer choice is correct. Ticagrelor has a boxed warning for reduced efficacy with aspirin doses >100 mg/day.
Answer Choice C: This answer choice is correct. Prasugrel is contraindicated with a boxed warning for patients with a history of stroke or TIA as this increases the risk of both hemorrhagic or thrombotic stroke. It should also be used with caution for patients >75 years old or with weight <60 kg.
Answer Choice D: This answer choice is incorrect because clopidogrel is not a substrate of 3A4. It is a prodrug; however, it is metabolized by CYP 2C19. It is important to consider 2C19 polymorphisms when giving this drug as certain patients may not be able to metabolize it to its active form and therefore will not get the full therapeutic effect, which would be very important for our patient post-STEMI. Also, it is important to remember that clopidogrel will have its metabolism to its active form inhibited by 2C19 inhibitors such as omeprazole and esomeprazole. While debate rages about the clinical importance of this drug interaction, avoiding these two agents and continuing the pantoprazole would likely be the best option in this patient if a PPI is required. Use of a histamine-2 receptor antagonist, such as famotidine, could also be considered if the PPI is not required. Keep in mind that patient counseling is important here as these gastrointestinal therapies are available OTC and thus patients could unknowingly take these agents.
Answer Choice E: This answer choice is correct. The dosing of the agents is as follows assuming no reduction required for body weight:
Ticagrelor: 180 mg PO loading dose followed by 90 mg PO BID
Prasugrel: 60 mg PO loading dose followed by 10 mg PO QD
Clopidogrel: 300-600 mg PO loading dose followed by 75 mg PO QD
Answer Choice F: This answer choice is false. It is actually the other way around. Brilinta is the reversible inhibitor and binds with a more rapid and consistent onset of action as well as more rapid offset with faster platelet recovery when compared to the other agents.
Answer Choice G: This answer choice is false. Higher doses of aspirin (>160 mg) have been shown to cause more bleeding and do not provide any additional efficacy when compared to doses <160 mg, therefore aspirin 81 mg is the preferred for daily dose for secondary prevention.
Exam Competencies: Area 1 – Obtain, Interpret, or Assess Data, Medical, or Patient Information (1.5 – Signs or symptoms of medical conditions, healthy physiology, etiology of diseases, or pathophysiology), Area 2 – Identify Drug Characteristics (2.1 – Pharmacology, mechanism of action, or therapeutic class, 2.3 – Boxed warnings or REMS), Area 3 – Develop or Manage Treatment Plans (3.4 – Drug dosing or dosing adjustments; duration of therapy, 3.6 – Drug contraindications, allergies, or precautions, 3.7 – Adverse drug effects, toxicology, or overdose, 3.8 – Drug interactions, 3.10 – Drug pharmacokinetics or pharmacodynamics)
As we head into November, you should be getting the hang of these as your rotation experiences increase and your knowledge continues to solidify. Keep learning and retaining!
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