Limited visibility and uptake of the clopidogrel pharmacogenomic guidelines among cardiologists

Abstract Background Clopidogrel is an antiplatelet agent widely utilised in the treatment of acute coronary syndromes and following coronary interventions. Clopidogrel is a prodrug activated in the liver, mostly by cytochrome P450 2C19 that is encoded by a gene (CYP2C19). Variability in CYPC2C19 affects enzymatic activity and leads to variability in the activation and efficacy of clopidogrel. In 2011, the Clinical Pharmacogenetics Implementation Consortium (CPIC) produced the first set of detailed guidelines on the use of genetic testing to guide the clinical utilization of clopidogrel. Updates on these guidelines were published in 2013 and 2022. However, pre-prescription genetic testing is seldom performed. Purpose To establish whether these pharmacogenomics guidelines have visibility within the cardiovascular (CVD)community and have been incorporated into CVD guidelines. Methods (i) We examine the impact of the CPIC Clopidogrel guidelines released in 2013 and 2022 by looking at the citation patterns in CVD journals indexed in PubMed. (ii) We reviewed the guidelines released by the European Society of Cardiology and the American College of Cardiology on the management of coronary interventions and coronary artery disease over the last 15 years to establish whether CPIC guidelines are making any impact on practice. Results The CPIC 2022 guidelines were cited by 88 articles (49 journals) of which 13 citations (14.7%) appear in CVD journals. None of these citations are in the five major journals in which CVD guideline statements are most frequently published (Nature Review Cardiology, European Heart Journal, Circulation, Journal of the American College of Cardiology, and Journal of the American Medical Association - Cardiology). The 2013 guideline received 366 citations (183 PubMed journals). Of these, 47 were in cardiology journals (12.8%), but only 4 citations were in one of the same five major cardiology journals (2 in Nature Review Cardiology, 1 in Circulation and 1 in JAMA Cardiology). Of the 14 guidelines published by the ESC and ACC over the last 14 years, none cited the CPIC clopidogrel guidelines. Only 6 out of the 14 guidelines mentioned that the efficacy of clopidogrel was modulated by genetic factors but none of them included details or practical implications. Conclusion(s) Whilst sufficient time has not yet elapsed for the 2022 CPIC guidelines to have an impact on the specialist literature, the 2013 guidelines have had limited visibility within the CVD community. Undoubtedly, given the potential contribution of PGx, discussions on its uptakes are ongoing thus far, without resolution. Some considerations of clopidogrel genetics are diffusing into the specialty; however, from the citation evidence, it appears that CPIC clopidogrel guidelines of any vintage have had limited impact in terms of adoption and/or endorsement by cardiologists.