JP is a 71-year-old male with a history of hypertension, ischemic stroke, GERD, depression, and insomnia. Current medications include amlodipine 10 mg PO daily, lisinopril 20 mg PO daily, aspirin 81 mg PO daily, rosuvastatin 20 mg PO daily, omeprazole 40 mg PO daily, and trazodone 100 mg PO QHS. JP presented to the hospital today with chest pain, shortness of breath, and diaphoresis. STEMI was confirmed by EKG, so PCI and drug eluting stent placement were performed. The team now wants to start dual antiplatelet therapy. An order is sent to the pharmacy for ticagrelor 90 mg PO BID in addition to the existing aspirin regimen. Which of the following is the most appropriate action?

A. Verify the order as written.

B. Do not verify the order. Recommend that the frequency be changed to ticagrelor 90 mg PO daily.

C. Do not verify the order. Recommend that ticagrelor be changed to apixaban 5 mg PO BID.

D. Do not verify the order. Recommend that ticagrelor be changed to prasugrel 10 mg PO daily.

Answer with rationale:

The correct answer is A.

After a patient undergoes PCI for MI, several maintenance medications are necessary. This often, depending on the type of stent placed,  includes a year of dual antiplatelet therapy (DAPT), which consists of aspirin and a P2Y12 inhibitor. Options for the second antiplatelet agent include clopidogrel (Plavix), prasugrel (Effient), or ticagrelor (Brilinta). Indications for antiplatelets are distinct from those of anticoagulants, like apixaban. Anticoagulants are used primarily to prevent VTE recurrence or to prevent stroke in atrial fibrillation patients. Rivaroxaban (Xarelto) is FDA approved in combination with aspirin for patients with stable documented CAD based on the COMPASS trial, but this patient immediately post STEMI would not meet criteria for this indication and apixaban (Eliquis) does not have any indication post STEMI.  Therefore answer C is incorrect.

Clopidogrel is the P2Y12 inhibitor most commonly used, but it would be controversial in this patient due to its interaction with omeprazole. Although the clinical significance of this interaction has been questioned, the clopidogrel labeling recommends avoiding use with omeprazole, which inhibits CYP2C19 and may reduce conversion of clopidogrel to its active metabolite.

Compared to clopidogrel, both prasugrel and ticagrelor have been found to be associated with less cardiovascular death and MI but more bleeding when used following acute coronary syndromes. Like clopidogrel, prasugrel is a prodrug, but conversion to its active metabolite is not dependent upon CYP2C19. Prasugrel does carry a boxed warning that recommends against use in patients with a history of stroke due to increased bleeding risk in these patients. Therefore answer D is incorrect.

The order for ticagrelor is written for the correct dose and frequency of 90 mg BID. Answer B is incorrect. There are a couple of factors that could disqualify patients from ticagrelor therapy. Ticagrelor should not be used with aspirin doses >100 mg/day because this can interfere with the antiplatelet effect of ticagrelor. Ticagrelor is primarily metabolized by CYP3A4, so it should also not be used with strong inhibitors or inducers of this enzyme. These factors are not present in this patient, so ticagrelor would be an appropriate choice at the prescribed dose and frequency. Therefore answer A is correct.

Reference:

Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017;377:1319-1330.