[Antiplatelet therapy in coronary heart disease. Some problems and achivements]

Area of Science:

• Cardiology
• Pharmacology
• Genetics

Background:

• Standard antiplatelet therapy (aspirin plus clopidogrel) is crucial for coronary artery disease, acute coronary syndromes (ACS), and percutaneous coronary interventions (PCI).
• A significant challenge is patient resistance to clopidogrel, partly due to its metabolism by CYP450 enzymes and potential drug interactions, including with proton pump inhibitors.
• Genetic factors, such as CYP2C19 loss-of-function alleles, are linked to reduced clopidogrel efficacy, though the clinical utility of genetic testing remains debated.

Purpose of the Study:

• To review the limitations of standard antiplatelet therapy, particularly clopidogrel resistance.
• To discuss alternative strategies for guiding therapy, including platelet function testing and genetic testing.
• To evaluate the efficacy and safety of novel antiplatelet agents compared to clopidogrel.

Main Methods:

• Review of current literature on clopidogrel resistance, CYP450 metabolism, and drug interactions.
• Analysis of studies investigating platelet function tests and genetic markers (e.g., CYP2C19*2) for predicting clopidogrel response.
• Examination of clinical trial data for newer P2Y12 inhibitors (prasugrel, ticagrelor) and other antiplatelet agents.

Main Results:

• Clopidogrel resistance is a significant clinical issue, influenced by genetic variations and drug interactions.
• Platelet function testing and genetic testing show promise but lack standardized application.
• Novel P2Y12 inhibitors, particularly ticagrelor, have demonstrated superior efficacy over clopidogrel in major trials, with ticagrelor showing benefits in total mortality and manageable bleeding rates.
• Higher doses of clopidogrel have shown advantages in specific patient groups (CURRENT trial).

Conclusions:

• Limitations in standard clopidogrel therapy necessitate exploring alternative antiplatelet strategies.
• Novel agents like ticagrelor represent a significant advancement, offering improved clinical outcomes in ACS and PCI patients.
• Further research and standardization of testing methods are needed to optimize antiplatelet therapy selection.