An Introductory Tutorial on Cardiovascular Pharmacogenetics for Healthcare Providers

Abstract

Pharmacogenetics can improve clinical outcomes by reducing adverse drug effects and enhancing therapeutic efficacy for commonly used drugs that treat a wide range of cardiovascular diseases. One of the major barriers to the clinical implementation of cardiovascular pharmacogenetics is limited education on this field for current healthcare providers and students. The abundance of pharmacogenetic literature underscores its promise, but it can also be challenging to learn such a wealth of information. Moreover, current clinical recommendations for cardiovascular pharmacogenetics can be confusing because they are outdated, incomplete, or inconsistent. A myriad of misconceptions about the promise and feasibility of cardiovascular pharmacogenetics among healthcare providers also has halted clinical implementation. Therefore, the main goal of this tutorial is to provide introductory education on the use of cardiovascular pharmacogenetics in clinical practice. The target audience is any healthcare provider (or student) with patients that use or have indications for cardiovascular drugs. This tutorial is organized into the following 6 steps: (1) understand basic concepts in pharmacogenetics; (2) gain foundational knowledge of cardiovascular pharmacogenetics; (3) learn the different organizations that release cardiovascular pharmacogenetic guidelines and recommendations; (4) know the current cardiovascular drugs/drug classes to focus on clinically and the supporting evidence; (5) discuss an example patient case of cardiovascular pharmacogenetics; and (6) develop an appreciation for emerging areas in cardiovascular pharmacogenetics. Ultimately, improved education among healthcare providers on cardiovascular pharmacogenetics will lead to a greater understanding for its potential in improving outcomes for a leading cause of morbidity and mortality.

Moving towards the implementation of pharmacogenetic testing in Quebec

“…Twenty-seven medications are frequently cited in ADRs and approximately 60% of them are associated with at least one drug-metabolizing enzyme with known PGx variants ( Mroz et al, 2021 ). As a randomized controlled trial shows a 30% decrease in clinically significant ADRs by implementing pre-emptive panel-based PGx-guided prescriptions ( Oni-Orisan et al, 2023 ; Swen et al, 2023 ), we believe the rapid implementation of PGx is more than relevant.…”

“…However, the CPIC and the DPWG provide freely accessible, evidence-based, peer-reviewed, and updated PGx clinical guidelines to support healthcare professionals in implementing PGx into their practice ( Relling and Klein, 2011 ; Swen et al, 2011 ). As of late 2022, the CPIC has published 26 guidelines while the DPWG has published 47 guidelines ( McDermott et al, 2023 ; Oni-Orisan et al, 2023 ). This situation suggests communication issues between scientific committees and HCPs.…”

“…The Genetic Non-Discrimination Act (GNA) makes it a criminal offence for a service provider or anyone entering into a contract with a person to require or compel that person to take or disclose the results of, a genetic test ( Branch, 2017 ). This law needs to be made aware as it prevents, as seen in our American counterpart, social discrimination using genetic information by individuals or organizations such as insurance companies ( De Denus et al, 2013 ; Branch, 2017 ; Hayashi et al, 2022 ; Oni-Orisan et al, 2023 ). Continuing with ethical considerations, to guarantee a secure, interoperable and accessible centralized database and digital ecosystem ( Albalwy et al, 2022 ), a multitude of experts and committees are needed.…”

“…Quebec PCPs and pharmacists agreed that PGx test results must be obtained rapidly to be valuable ( Frigon et al, 2019 ). It is unanimous, in literature, that a pre-emptive model of genomic testing has the added benefit of timelessness as genetic data does not change ( ODonnell et al, 2012 ; Johnson et al, 2013 ; Bielinski et al, 2014 ; Hoffman et al, 2014 ; Rasmussen-Torvik et al, 2014 ; Van Driest et al, 2014 ; Rosenman et al, 2017 ; Van Der Wouden et al, 2017 ; Chumnumwat et al, 2019 ; Duarte et al, 2021 ; Albalwy et al, 2022 ; Hayashi et al, 2022 ; Morris et al, 2022 ; Huang et al, 2023 ; Kabbani et al, 2023 ; McDermott et al, 2023 ; Oni-Orisan et al, 2023 ). Except for the first prescription of a PGx test, there is no waiting period in therapeutic decision-making.…”

“…The field of pharmacogenetics (PGx) holds the promise to personalize clinical practice using genetic variants to optimize treatment, prevent adverse drug reactions (ADRs), and reduce avoidable costs for the healthcare system and patients. Indeed, studies show that approximately 91%–99% of the population carry at least one actionable pharmacogenetic variant, which is defined as being clinically significant in therapeutic efficacy or risk of ADRs ( Van Driest et al, 2014 ; Van Der Wouden et al, 2017 ; Mroz et al, 2021 ; Tafazoli et al, 2021 ; Morris et al, 2022 ; Huang et al, 2023 ; Kabbani et al, 2023 ; Oni-Orisan et al, 2023 ). To date, a large number of genetic variants have demonstrated a clinical utility and are incorporated for genetic testing into at least 430 drug labels (including 130 drugs used in oncology) by the United States Food and Drug Administration (FDA) and 182 by Health Canada ( PharmGKB, 2023 ).…”