The Interface of Therapeutics and Genomics in Cardiovascular Medicine

Abstract

Pharmacogenomics has a burgeoning role in cardiovascular medicine, from warfarin dosing to antiplatelet choice, with recent developments in sequencing bringing the promise of personalised medicine ever closer to the bedside. Further scientific evidence, real-world clinical trials, and economic modelling are needed to fully realise this potential. Additionally, tools such as polygenic risk scores, and results from Mendelian randomisation analyses, are only in the early stages of clinical translation and merit further investigation. Genetically targeted rational drug design has a strong evidence base and, due to the nature of genetic data, academia, direct-to-consumer companies, healthcare systems, and industry may meet in an unprecedented manner. Data sharing navigation may prove problematic. The present manuscript addresses these issues and concludes a need for further guidance to be provided to prescribers by professional bodies to aid in the consideration of such complexities and guide translation of scientific knowledge to personalised clinical action, thereby striving to improve patient care. Additionally, technologic infrastructure equipped to handle such large complex data must be adapted to pharmacogenomics and made user friendly for prescribers and patients alike.

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

“…Most of these drugs are taken in a polypharmacy fashion (>6 drugs/day), with the consequent increase in DDIs and ADRs [101]. In patients with these health conditions, PGx pre-emptive testing is highly recommended to improve efficacy and minimize toxicity [102]; however, the PGx of cardiovascular and related disorders in practice is still in a very primitive stage, despite the abundance of information available for the personalized use of cardiovascular drugs [23,103] (Tables 1-3).…”

Ethnic Diversity and Warfarin Pharmacogenomics

“…The seven acenocoumarol and phenprocoumon pharmacogenetic dosing algorithms were developed in European (Germany, Greece, Netherlands, Spain) and Asian (India) countries which means, like warfarin, they do not reflect ethnic diversity. In the broader cardiovascular field, clopidogrel and statins are other drugs that are currently ready for pharmacogenomic implementation ( Magavern et al, 2021 ), and are discussed further below.…”

Precision Medicine and Adverse Drug Reactions Related to Cardiovascular Drugs

“…An example of this includes the common rs9923231 reduction-of-expression variant. Patients who have this variant require much lower doses of warfarin due to increased drug sensitivity [6,8].…”

“…Reduced hepatic uptake of simvastatin results in larger systemic concentrations [16]. Interestingly, despite known associations between SLCO1B1 and other statins, such as atorvastatin, the link to muscle toxicity is much weaker [8].…”