At a Glance

Unlike aspirin and Clopidogrel, there is no medical definition of Prasugrel resistance.

Prasugrel is indicated for patients that demonstrate Clopidogrel resistance or recurrent ischemic events while receiving dual antiplatelet therapy with aspirin and Clopidogrel.

Prasugrel is a third generation thienopyridine prodrug converted to an active metabolite, R-138727, by the hepatic cytochrome P450 system. Like Clopidogrel, Prasugrel acts at the platelet ADP receptor, P2Y12, to form a disulfide bond, thus, blocking ADP from binding to the receptor and providing irreversible platelet inhibition.

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What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Prasugrel is less affected by CYP2C19 genetic polymorphisms than Clopidogrel.

In contrast to Clopidogrel, Prasugrel requires a single hepatic cytochrome P450 conversion and less extensive hydrolysis. As a result, Prasugrel has a faster onset of efficacy, yields higher concentrations of its active metabolite, and produces greater inhibition of ADP-induced platelet aggregation than standard and increased doses of Clopidogrel.(Table 1)

Table 1.
Platelet aggregation inhibition to ADP
Level of inhibition not defined

Verifiy Now P2Y12 cartridge will also show decreased PRU with Prasugrel therapy.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Other antiplatelet drugs, such as aspirin, Clopidogrel, and glycoprotein IIb/IIIa antagonists, also inhibit platelet aggregation. Accurate assessment of platelet inhibition due to Prasugrel cannot be done in the presence of other antiplatelet drugs.

Other drugs metabolized in CYP450 system may affect Prasugrel metabolism and activity.

What Lab Results Are Absolutely Confirmatory?

Not applicable for Prasugrel.

What ConfirmatoryTests Should I Request for My Clinical Dx? In addition, what follow-up tests might be useful?

Repeat platelet aggregation or Verify Now P2Y12 will confirm a good response to Prasugrel. Genomic testing for CYP450 is not indicated at this time.