Influence of genetic polymorphisms on platelet function, response to antiplatelet drugs and clinical outcomes in patients with coronary artery disease.

Abstract

Platelet activation and aggregation play important roles in ischemic event occurrences in patients with coronary artery disease. In the absence of a disease state and drug administration, platelet reactivity has been shown to be stable over time, indicating a high level of heritability. Interindividual variability in platelet response to agonists and in response to aspirin and clopidogrel administration along with the influence of different single nucleotide polymorphisms on platelet reactivity based on candidate gene and genome-wide association studies have been demonstrated in healthy subjects. Reduced pharmacodynamic effect and reduced clinical efficacy of clopidogrel have been well documented in high-risk coronary artery disease patients carrying a loss-of-function allele of the CYP2C19 gene. These factors are recognized by the recent American and European treatment guidelines. However, prasugrel and ticagrelor are associated with superior and predictable pharmacodynamic responses and better clinical outcomes compared with clopidogrel.

• Authors: Udaya S Tantry, Young-Hoon Jeong, Eliano P Navarese, Jacek Kubica, Paul A Gurbel
• Journal: Expert review of cardiovascular therapy (Expert Rev Cardiovasc Ther) Vol. 11 Issue 4 Pg. 447-62 (Apr 2013) ISSN: 1744-8344 [Electronic] England
• PMID: 23570358 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Piperazines
• Platelet Aggregation Inhibitors
• Purinergic P2Y Receptor Antagonists
• Thiophenes
• Clopidogrel
• Aryl Hydrocarbon Hydroxylases
• CYP2C19 protein, human
• Cytochrome P-450 CYP2C19
• Aryldialkylphosphatase
• PON1 protein, human
• Prasugrel Hydrochloride
• Ticagrelor
• Adenosine
• Ticlopidine
• Aspirin

Topics

• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• Adenosine (analogs & derivatives, metabolism, therapeutic use)
• Aryl Hydrocarbon Hydroxylases (genetics)
• Aryldialkylphosphatase (genetics)
• Aspirin (metabolism, therapeutic use)
• Blood Platelets (physiology)
• Clopidogrel
• Coronary Artery Disease (drug therapy)
• Cytochrome P-450 CYP2C19
• Humans
• Pharmacogenetics
• Piperazines (metabolism, therapeutic use)
• Platelet Activation (genetics)
• Platelet Aggregation (genetics)
• Platelet Aggregation Inhibitors (metabolism, therapeutic use)
• Polymorphism, Single Nucleotide
• Prasugrel Hydrochloride
• Purinergic P2Y Receptor Antagonists (metabolism, therapeutic use)
• Thiophenes (metabolism, therapeutic use)
• Ticagrelor
• Ticlopidine (analogs & derivatives, metabolism, therapeutic use)