What is Pharmacogenomics (PGx)?

• PGx studies how genetic variations affect an individual’s response to medications, focusing on:
  • Drug efficacy.
  • Risk of adverse effects.
  • Personalised treatment plans.

Key Examples in Cardiovascular Medicine

1. Clopidogrel

   • Purpose: Prevents blood clots in conditions like coronary artery disease or post-angioplasty.
   • Genetic Variation: CYP2C19 loss-of-function variants impair the activation of clopidogrel, reducing its effectiveness.
   • Clinical Impact: Patients with these variants are at a higher risk for stent thrombosis and adverse cardiovascular events.
   • FDA Guidance: Includes a black box warning recommending alternative therapies for patients with these variants.

2. Warfarin

   • Purpose: Anticoagulant used to prevent blood clots.
   • Genetic Variants:
     • CYP2C9 affects warfarin metabolism.
     • VKORC1 influences sensitivity to warfarin.
   • Clinical Impact: Genetic testing helps tailor the dose to avoid bleeding or clotting complications.

3. Statins

   • Purpose: Lowers cholesterol to reduce cardiovascular risk.
   • Genetic Variation: SLCO1B1 variants increase the risk of statin-induced myopathy, particularly with simvastatin.
   • Clinical Application: Lower doses or alternative statins may be prescribed based on genetic testing.

4. Beta-Blockers

   • Purpose: Treat high blood pressure, arrhythmias, and heart failure.
   • Genetic Variants: ADRB1 and CYP2D6 influence drug efficacy and metabolism.
   • Clinical Impact: Genetic testing may predict response to beta-blockers.

Clinical Applications of PGx

• Optimising Drug Selection: Choose medications aligned with genetic profiles.
• Personalised Dosing: Adjust doses for drugs like warfarin to maintain efficacy and safety.
• Improving Patient Outcomes: Enhance therapeutic effects while minimising side effects.

Challenges

• Identifying clinically actionable variants.
• Cost and accessibility of genetic testing.
• Interpreting and integrating genetic data into clinical practice.

Genetic Testing for Hypertrophic Cardiomyopathy (HCM)

What is HCM?

• A genetic heart condition causing thickening of the heart muscle.
• Can lead to obstruction of blood flow, arrhythmias, or sudden cardiac death.

Role of Genetic Testing in HCM

• Process:
  • Analyses DNA for mutations in genes linked to HCM.
  • Typically screens 30-50 genes associated with the condition.
• Cascade Testing:
  • Tests first-degree relatives of affected individuals to identify at-risk family members.
• Genetic Counselling:
  • Pre-test: Explains the purpose and implications of testing.
  • Post-test: Helps interpret results and guides medical or lifestyle decisions.

Benefits of Genetic Testing

• Definitive Diagnosis:
  • Confirms HCM in ambiguous cases.
• Risk Stratification:
  • Identifies individuals at risk for severe complications, enabling early intervention.
• Family Screening:
  • Helps detect at-risk relatives for early management.
• Reproductive Planning:
  • Options like preimplantation genetic diagnosis (PGD) reduce the risk of passing mutations to offspring.

Screening for HCM

• Distinct from Genetic Testing: Includes clinical evaluations like:
  • Physical examination.
  • ECG for electrical activity.
  • Echocardiography for structural assessment.

Role of Pharmacy Students

1. PGx in Practice:

   • Counsel patients about the importance of genetic testing.
   • Collaborate with healthcare teams to integrate PGx into therapy selection.
   • Monitor for adverse effects linked to genetic predispositions.

2. HCM and Genetic Testing:

   • Support cascade testing programs.
   • Educate families about the implications of genetic findings.
   • Ensure medications prescribed align with the patient’s genetic profile.

Conclusion

• PGx and genetic testing are revolutionising cardiovascular care by enabling personalized medicine.
• Pharmacy students must understand the implications of genetic findings for drug response and disease management to optimise patient outcomes.
• Collaboration across interdisciplinary teams ensures that genetic testing and PGx applications are integrated into routine clinical care.

References

1. Johnson, J. A., & Cavallari, L. H. (2014). Pharmacogenomics and cardiovascular disease: Implications for personalized medicine.
2. Ingles, J., & Semsarian, C. (2021). Genetic testing for inherited cardiovascular diseases.
3. Cardiomyopathy UK. (2023). Genetic Testing in Cardiomyopathy.
4. British Heart Foundation. Hypertrophic Cardiomyopathy National Cascade Testing.
5. American Heart Association. Genetic Testing for HCM.