The role of pharmacogenomics in contemporary cardiovascular therapy: a position statement from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy

Abstract

There is a strong and ever-growing body of evidence regarding the use of pharmacogenomics to inform cardiovascular pharmacology. However, there is no common position taken by international cardiovascular societies to unite diverse availability, interpretation and application of such data, nor is there recognition of the challenges of variation in clinical practice between countries within Europe. Aside from the considerable barriers to implementing pharmacogenomic testing and the complexities of clinically actioning results, there are differences in the availability of resources and expertise internationally within Europe. Diverse legal and ethical approaches to genomic testing and clinical therapeutic application also require serious thought. As direct-to-consumer genomic testing becomes more common, it can be anticipated that data may be brought in by patients themselves, which will require critical assessment by the clinical cardiovascular prescriber. In a modern, pluralistic and multi-ethnic Europe, self-identified race/ethnicity may not be concordant with genetically detected ancestry and thus may not accurately convey polymorphism prevalence. Given the broad relevance of pharmacogenomics to areas such as thrombosis and coagulation, interventional cardiology, heart failure, arrhythmias, clinical trials, and policy/regulatory activity within cardiovascular medicine, as well as to genomic and pharmacology subspecialists, this position statement attempts to address these issues at a wide-ranging level.

Pharmacogenetics to Avoid Adverse Reactions in Cardiology: Ready for Implementation?

“…DPWG is by far the group that reviewed more cardiovascular drug-gene pairs [23] and also the one that has issued more therapeutic recommendations [10].…”

“…Common genetic variants in CYP2C9, VKORC1, CYP4F2, in addition to known nongenetic factors, account for 50-60% of the variability in warfarin dosage [10].…”

“…The latest position statement from the ESC on the role of pharmacogenomics in contemporary cardiovascular therapy insists that CYP2C19 genotyping is only recommended in high-risk cardiovascular situations (e.g., ACS undergoing percutaneous intervention, patients at a high risk of thrombosis or bleeding or patients with recurrent adverse events) and not to systematically tailor the selection of antiaggregation therapy [10]. However, it does recognize that clopidogrel should be avoided in those patients that are known to be intermediate or poor metabolizers due to the risk of ineffectiveness.…”

“…The Spanish Society of Pharmacogenetics and Pharmacogenomics has also included in its strategic plan the publication of practice guidelines for relevant drug-gene pairs [9]. Recently, the European Society of Cardiology issued a position statement on the role of Pharmacogenomics in contemporary cardiovascular therapy [10]. However, in most cases there are no official recommendations provided by the drug agencies.…”

“…The recently published ESC position paper states that prospective genotyping prior to warfarin initiation is advisable. Their recommendation is to genotype for all the relevant CYP2C9, VKORC1 and CYP4F2 alleles irrespective of patient's ethnicity and adjust the initial dosage with a universal algorithm, that still needs to be developed and properly validated [10].…”