[Algorithm for selection of individual therapy with clopidogrel in vascular surgical practice]

Area of Science:

• Cardiovascular Medicine
• Pharmacology
• Genetics

Background:

• Permanent antiplatelet therapy is indicated for lower limb artery diseases and high-risk cardiovascular patients.
• Individual sensitivity to antiplatelet agents like clopidogrel poses a clinical challenge.
• Clopidogrel, a thienopyridine prodrug, requires two-stage metabolism via cytochrome P450 2C19 (CYP2C19) to exert its antiplatelet effect.

Purpose of the Study:

• To develop an individualized dosing algorithm for clopidogrel in patients with atherosclerosis of lower limb arteries.
• To enhance the efficacy and safety of antiplatelet therapy by considering individual patient factors.
• To correlate platelet aggregation levels and CYP2C19 genetic variations with clopidogrel response.

Main Methods:

• Analysis of patient case histories with atherosclerosis of lower limb arteries.
• Assessment of platelet aggregation levels in response to various inducers (ADP, collagen, arachidonic acid).
• Molecular-genetic testing for cytochrome CYP2C19 gene variations.

Main Results:

• An evidence-supported basis for long-term clopidogrel use in lower limb artery atherosclerosis was established.
• A novel algorithm for individualized clopidogrel dosing was developed, incorporating platelet aggregation data.
• Dose correction based on CYP2C19 genetic testing results was integrated into the algorithm.
• The algorithm aims to maximize treatment efficacy and patient safety.

Conclusions:

• Individualized clopidogrel dosing, guided by platelet aggregation and CYP2C19 genotype, is essential for optimizing antiplatelet therapy.
• This approach addresses variable patient sensitivity and improves therapeutic outcomes in lower limb artery disease.
• The developed algorithm offers a personalized strategy for clopidogrel management.