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Published on: April 1, 2019
Genetics in the Clinical Decision of Antiplatelet Treatment
Gerasimos Siasos1, Marina Zaromitidou, Evangelos Oikonomou
1Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School and Harvard-MIT Biomedical Engineering Center, Massachusetts Institute of Technology, Boston, MA, United States.
Background:
Coronary artery disease remains the leading cause of death globally. Dual antiplatelet treatment with aspirin and aP2Y12 receptor significantly reduces thrombotic events. However, antiplatelet drug response displays considerable interindividual variability.
Methods:
Genetic factors account for up to 70% of impaired drug response. A number of genes encoding proteins involved in the pharmacokinetic pathway have been found to alter drug response.
Results:
According to most studies, CYP2C19 gene is the strongest genetic determinant. The novel antiplatelet agents prasugrel and ticagrelor, seem to overcome genetic restrictions but in expense of increased bleeding rates. Achieving a balance between adequate platelet inhibition and bleeding complications is challenging.
Conclusion:
Genetic screening may provide valuable guidance towards an efficient antiplatelet treatment. However, the lack of randomized controls trials testing the effect of a genotype-guided therapy, forbids the implementation of genetic testing into clinical practice.
Insights
Genetic factors significantly impact antiplatelet drug response in coronary artery disease patients. While CYP2C19 is a key gene, genotype-guided therapy lacks clinical trial evidence for widespread use.
Area of Science:
- Pharmacogenomics
- Cardiovascular Medicine
- Drug Metabolism
Background:
- Coronary artery disease (CAD) is a leading global cause of mortality.
- Dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitors reduces thrombotic events but shows significant interindividual variability.
- Understanding factors influencing DAPT response is critical for patient outcomes.
Purpose of the Study:
- To review the role of genetic factors in antiplatelet drug response.
- To discuss the implications of genetic variability on DAPT efficacy and safety.
- To evaluate the potential of genotype-guided antiplatelet therapy.
Main Methods:
- Literature review focusing on genetic determinants of antiplatelet drug response.
- Analysis of studies investigating gene-drug interactions in DAPT.
- Evaluation of clinical trial data and guidelines regarding genetic testing.
Main Results:
- Genetic factors contribute up to 70% to impaired antiplatelet drug response.
- The CYP2C19 gene is identified as a major determinant of drug metabolism and response.
- Novel agents like prasugrel and ticagrelor may overcome some genetic limitations but increase bleeding risk.
Conclusions:
- Genetic screening holds promise for optimizing antiplatelet therapy.
- Balancing platelet inhibition and bleeding risk remains a clinical challenge.
- The absence of randomized controlled trials for genotype-guided therapy currently limits its clinical implementation.
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