Pharmacogenomics (PGx) is transforming cardiovascular medicine by enabling personalized treatment approaches based on a patient’s genetic profile. In particular, PGx is helping cardiologists optimize the use of antiplatelet, anticoagulant, and beta-blocker therapies in patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). While numerous critical aspects are involved in practical cardiovascular medicine treatment, the PGx (pharmacogenomics) tests may also help doctors administer tailored treatments and minimize trial and error.

Genetic Makeup and Cardiovascular Treatment:

Similar to most medicines, cardiovascular medicines are also metabolized by enzymes in our body. Metabolizers are typically divided into 3 categories, i.e., Rapid, Normal, and Poor. However, there are four types of metabolizers, i.e., ultrarapid metabolizers, normal metabolizers, intermediate metabolizers, and poor metabolizers. Based on the different metabolic systems, our bodies may respond differently to medications.

PGx in Antiplatelet Therapy: A Focus on CYP2C19 Variability

Antiplatelet therapy is a cornerstone of ACS management and involves drugs such as clopidogrel and prasugrel, which are metabolized by the liver enzyme CYP2C19 into active forms. However, due to genetic polymorphisms in CYP2C19, patients can be classified as:

• Poor metabolizers: Reduced conversion of clopidogrel into its active form, leading to diminished platelet inhibition and higher thrombotic risk.
• Extensive metabolizers: Normal drug metabolism and expected therapeutic response.
• Ultrarapid metabolizers: Overactivation of the drug, resulting in increased bleeding risk.

Practical Implications for Cardiologists:

1. Clopidogrel is less effective in patients with CYP2C19 loss-of-function alleles. In these patients, switching to prasugrel or ticagrelor, which are not CYP2C19-dependent, is recommended.
2. PGx-guided therapy helps reduce the risk of adverse events by tailoring antiplatelet regimens based on genetic testing results.

PGx tests from RPh LABS give insights into your genetic makeup, showing how your body may respond to 250+ medications. This test is non-invasive, only requires a saliva cheek swab, and can be performed right from the comfort of a patient’s home. Here is how it works.

PGx in Anticoagulant Therapy:

Anticoagulation in non-ST elevation acute coronary syndrome (NSTE-ACS) or PCI requires careful balancing of thrombotic and bleeding risks. The primary anticoagulants used include:

• Unfractionated heparin (UFH)
• Low molecular weight heparin (LMWH)
• Bivalirudin
• Fondaparinux

PGx insights are increasingly valuable in guiding dosing for newer oral anticoagulants, particularly dabigatran, apixaban, and rivaroxaban, which are used in conditions such as atrial fibrillation (AF) but also considered in post-ACS scenarios.

Recommendations for Clinical Practice:

• Patients with genetic variations affecting clotting factor synthesis or metabolism may require dose adjustments or alternative therapies.
• PGx-based anticoagulant selection minimizes bleeding complications while maintaining effective thrombus prevention.

Beta-Blocker Therapy: Genetic Influences on Efficacy

Beta-blockers are critical in post-MI and heart failure management. However, their efficacy can vary significantly depending on genetic factors affecting beta-adrenergic receptors and drug metabolism. For example:

• Beta-1 adrenergic receptor polymorphisms can alter a patient’s response to commonly used beta-blockers like metoprolol or bisoprolol.
• Genetic variants in CYP2D6, the enzyme responsible for metabolizing many beta-blockers, can categorize patients as poor or ultrarapid metabolizers, impacting drug clearance and efficacy.

Clinical Takeaways:

• Poor metabolizers may have higher plasma levels of beta-blockers, increasing the risk of Hypotension (low blood pressure), or Bradycardia, a slow heartbeat condition in which the heart gives 60 beats per minute or even less.
• Ultrarapid metabolizers may require higher doses to achieve the desired therapeutic effect.

Implementation of CYP2C19 Genotyping

A study investigated the impact of CYP2C19 genotype-guided pharmacotherapy on clinical outcomes in Chinese patients undergoing percutaneous coronary intervention. It found that patients with CYP2C19 loss-of-function alleles were more likely to receive ticagrelor, and this was associated with a lower risk of major adverse cardiac events compared to those receiving clopidogrel. These findings support the implementation of CYP2C19 genotyping (analysis of genome variations) to optimize antiplatelet therapy and improve patient outcomes.

The Future of Cardiovascular Medicine with PGx

With advances in genetic testing and growing clinical evidence, cardiologists can expect to see increased precision in treatments, fewer adverse events, and better long-term patient outcomes.
Pharmacogenetics (PGx) integrates genetic insights with clinical expertise to provide optimal care. As more genetic data becomes available, the scope of PGx in cardiovascular medicine is expected to expand, ultimately improving survival rates and patient quality of life.

Conclusion

Practical Cardiovascular Medicine involves certain crucial points that most cardiovascular specialists are already aware of. Pharmacogenomics testing acts as an extra shield to minimize trial and error in cardiovascular medicine by offering personalized treatment options tailored to an individual’s genetic makeup. By adopting PGx-guided strategies, healthcare providers can stay at the forefront of modern cardiovascular care, ensuring that treatments are not only effective but also safe and personalized.

Reference

https://pubmed.ncbi.nlm.nih.gov/33551797/

https://onlinelibrary.wiley.com/doi/book/10.1002/9781119832737

Disclaimer: This blog is for informational purposes only. Please always consult a doctor before taking any medical action.