NAPLEX Question of the Week: P2Y12 Inhibitors

Antiplatelet agents are the subject of our question of the week!
NAPLEX Question of the Week: P2Y12 Inhibitors
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LB is a 75 yo male patient under your care who came in with a ST Elevation Myocardial Infarction (STEMI) and will require Dual Antiplatelet Therapy (DAPT). The patient is post percutaneous coronary intervention (PCI) treatment and is resting in the cardiac care unit for monitoring before being discharged home. The cardiologist will be discharging the patient on the following medications:

Metoprolol tartrate 25 mg PO BID, Aspirin 81 mg PO QD, Crestor 40 mg PO QD, Amlodipine 5 mg PO QD

PMH: CAD, Hypertension, Hyperlipidemia, Osteoarthritis, Previous CVA 7 years ago

Allergies: Lisinopril-lip swelling

In addition, the cardiologist is considering which P2Y12 inhibitor to also place the patient on upon discharge with aspirin for DAPT. 

Which of the following statements are true with regards to P2Y12 inhibitors? Select all that apply. 

A. Effient would be contraindicated in LB due to the patient's prior medical history of CVA.

B. The maximum dose of aspirin when used concomitantly with Plavix is less than 100 mg/day. 

C. Brilinta may cause self-limiting dyspnea during therapy.

D. Effient is indicated for both acute coronary syndrome managed medically or managed in conjunction with PCI.

E. Clopidogrel is a prodrug metabolized by CYP2C9 to an active metabolite and concomitant use with omeprazole may reduce its antiplatelet activity. 

Generics/Brands Covered: Clopidogrel (Plavix), Metoprolol tartrate (Lopressor), Rosuvastatin (Crestor), Amlodipine (Norvasc), Prasugrel (Effient), Ticagrelor (Brilinta), Omeprazole (Prilosec)

Rationale: The choice of a P2Y12 inhibitor is important, because it reduces the risk of a future cardiac event for patients post acute myocardial infarction, typically in combination with aspirin for a set period of time, generally about 9-12 months but can be longer. Further, the selection of the agent will largely depend on patient specific factors so it is important to keep in mind the clinical pearls associated with each P2Y12 inhibitor. Specifically, consider when or if your patient will need another surgery, if the patient is older or low in body weight, if the patient has a history of stroke or ongoing major bleeding, as well as what other medications a patient is taking. All of these factors can influence which P2Y12 inhibitor to choose so the patient is getting adequate anti-thrombosis as well as reducing drug interactions and adverse effects such as bleeding. 

Answer A is correct. Prasugrel is contraindicated for patients with a history of cerebrovascular accident or transient ischemic attack due to increased risk of stroke in prior studies. 

Answer B is incorrect. The P2Y12 inhibitor that should be used with no more than 100 mg of aspirin per day is actually ticagrelor, not Plavix. 

Answer C is correct. Patients can experience self-limiting dyspnea during therapy. 

Answer D is incorrect.  Prasugrel is only indicated for patients who have been managed with PCI for their acute coronary syndrome. However, both Plavix and ticagrelor can be used in patients being medically managed for acute coronary syndrome. 

Answer E is incorrect. Omeprazole is a CYP2C19 inhibitor and clopidogrel is a CYP2C19 substrate as well as a prodrug which requires activation to the active metabolite. This means clopidogrel’s efficacy could possibly be diminished if used in conjunction with omeprazole. This is a much debated topic as most of the data are not high quality demonstrating worse outcomes with this drug interaction, but does show decreased platelet reactivity in vitro.  However the question states this is CYP2C9, not CYP2C19 and therefore would be incorrect. CYP2C9 is very important for Coumadin drug interactions as this is the enzyme primarily responsible for metabolizing the S-warfarin (most potent isomer). 

Correct Answers: A and C

NAPLEX Core Competencies covered:

2.1 Pharmacology, mechanism of action, or therapeutic class

2.2 Brand or Generic

3.3 Medication indication

3.4 Drug dosing, Dosing adjustments

3.6 Drug contraindications

3.8 Drug interactions

Sources:  

Plavix Package insert-https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020839s042lbl.pdf

Effient Package Insert: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022307s003lbl.pdf

Brilinta Package Insert:

https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022433s020lbl.pdf

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