From Editor-in-Chief

As I welcome you to the pages of the latest issue of our journal, which features articles on various areas of pharmacogenetics, including those related to patients with cardiovascular diseases, in my message as Editor-in-Chief I would like to focus on one of the most dynamically developing and clinically significant fields — pharmacogenetics in cardiology. Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, and despite advances in treatment, standardized evidence-based approaches often fail to account for individual patient characteristics, primarily genetic ones. It is here that personalized medicine, which utilizes genetic information to optimize therapy, comes to the forefront.

As a recent extensive review in Arteriosclerosis, Thrombosis, and Vascular Biology (Sanghvi et al., 2025) [1] eloquently demonstrates, the integration of genomics into routine cardiology practice is already changing the paradigm of patient care. Pharmacogenetics has ceased to be a domain of purely academic interest and has become a powerful tool for enhancing the efficacy and safety of widely prescribed medications.

In this context, three pillars of cardiovascular pharmacogenetics can be identified:

1. Antiplatelet Therapy: The Example of Clopidogrel. The classic and most thoroughly investigated example is the impact of CYP2C19 gene polymorphisms on the effectiveness of clopidogrel. Patients who carry "slow" alleles of this gene, responsible for converting the prodrug into its active metabolite, have a significantly increased risk of thrombotic events. International guidelines already recommend pharmacogenetic testing before prescribing clopidogrel, particularly in cases of acute coronary syndrome (ACS) and percutaneous coronary interventions (PCI). However, data indicate that even when information about a patient's CYP2C19 metabolizer status is available, many physicians are reluctant to alter treatment regimens. This highlights the need for better education and the integration of these tests into clinical algorithms.

2. Beta-Blockers: The Role of CYP2D6. Another key player is the CYP2D6 enzyme, which metabolizes beta-blockers such as metoprolol. A patient's genetic status regarding CYP2D6 influences the plasma concentration of the drug. Individuals with slow metabolism exhibit a higher incidence of bradycardia. An important clinical nuance is the phenomenon of phenoconversion, where the co-administration of potent CYP2D6 inhibitors (e.g., certain antidepressants) can effectively "convert" a rapid metabolizer into a slow one, unpredictably altering the profile of efficacy and toxicity.

3. Innovative Drugs: Mavacamten. The advent of targeted therapies, such as the cardiac myosin inhibitor mavacamten for the treatment of obstructive hypertrophic cardiomyopathy, has immediately placed pharmacogenetics at the core of their application. As this drug is significantly metabolized via CYP2C19, regulatory bodies (e.g., the European Medicines Agency) recommend determining the patient's genotype prior to initiating therapy. This allows for dose individualization and minimizes the risk of dose-dependent systolic dysfunction, especially in "slow metabolizers" for whom the drug's half-life can be prolonged several-fold.

Challenges and Prospects

Despite the obvious successes, serious challenges lie ahead.

First, the gap between guidelines and actual clinical practice must be bridged.

Second, the issue of representativeness is acute: most pharmacogenetic studies have been conducted on populations of European descent, which limits the applicability of their findings to other ethnic groups. This is particularly relevant for Russia as a multinational state. We must actively work to include diverse populations in research.

Third, pharmacogenetics is only one part of a broader genomic landscape. Data from genome-wide association studies (GWAS) are opening opportunities for identifying new pharmacogenetic markers.

Conclusion

It appears that pharmacogenetics is experiencing its heyday in cardiology. It provides us with concrete tools to make the prescription of both "standard" and "innovative" drugs more precise and safer. Our shared task as scientists, clinicians, and regulators is to ensure the seamless integration of this knowledge into everyday practice, making personalized cardiology accessible and effective for every patient.