Limited Visibility and Perception of the Clinical Relevance of Clopidogrel Pharmacogenetics in Cardiology Literature

Clopidogrel is an antiplatelet agent widely utilized in cardiology. It is a prodrug activated in the liver by the cytochrome P450 isoform CYP2C19. Variability in the CYPC2C19 gene influences the activation and efficacy of clopidogrel. This is covered in guidelines from the Clinical Pharmacogenetics Implementation Consortium, the Dutch Pharmacogenetics Working Group, and more recently the UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics. Despite this extensive guidance, pharmacogenetic information is rarely used to guide clopidogrel prescription in cardiology patients. The present study assesses the visibility of the pharmacogenetic guidelines in the cardiology literature. We analyzed citations of the clopidogrel pharmacogenetic guidelines in the cardiology literature and in the cardiology guidelines/position statements on the treatment of acute coronary syndromes and stable coronary artery disease. Citations of these guidelines were found to be limited in the cardiology literature. Only 3 out of 19 cardiology guidelines/position statements refer to the pharmacogenetic guidelines. 58% of the cardiology guidelines/position statements mention clopidogrel pharmacogenetics but suggest that the use of pre-emptive genotyping for CYP2C19 variants to guide clopidogrel prescription is of limited clinical relevance. Genetically determined variation in clopidogrel efficacy has poor visibility in the cardiology literature and clinical guidelines. It is perceived to have limited benefits for clinical practice despite mounting evidence from randomized controlled trials and systematic reviews/meta-analyses.