Between a Rock and a Hard Place: A High-Risk Patient with Resistance to Multiple P2Y₁₂ Antagonists

Abstract

Impaired response to P2Y₁₂ receptor antagonists, such as clopidogrel and prasugrel, can have devastating consequences for patients that require prolonged or indefinite therapy with these agents, including those with a left ventricular assist device (LVAD). While loss-of-function (LOF) alleles in CYP2C19 have been elucidated as contributing to high on treatment platelet reactivity (HTPR) during clopidogrel therapy, genetic variations in the metabolic pathway of prasugrel have not been shown to elicit this same effect. Moreover, limited studies have assessed the effect of coexisting genetic variations in pharmacokinetic and pharmacodynamic pathways. Herein, we report a left ventricular assist device patient exhibiting high on treatment platelet reactivity during clopidogrel and prasugrel therapy. Genotyping revealed variants in pharmacokinetic (CYP2B6), and pharmacodynamic pathways, with multiple variants in P2Y₁₂, the target receptor.

Keywords::

• clopidogrel
• CYP2B6
• LVAD
• prasugrel
• P2Y₁₂
• ticagrelor

Financial & competing interests disclosure

This work was supported in part by grants from the NIH (RO1HL092173, K24HL133373 and T32HG008961). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The final peer-reviewed manuscript is subject to the NIH Public Access Policy. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported in part by grants from the NIH (RO1HL092173, K24HL133373 and T32HG008961). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The final peer-reviewed manuscript is subject to the NIH Public Access Policy. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.