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CYP2C19 Genotype is an Independent Predictor of Adverse Cardiovascular Outcome in Iraqi Patients on Clopidogrel After
Ameen M Mohammad, Nasir A S Al-Allawi1
1Pathology, College of Medicine, University of Duhok, Kurdistan, Iraq.
Insights
CYP2C19 genotyping significantly impacts major adverse cardiovascular events (MACE) in Iraqi patients post-PCI on clopidogrel. Genotype-guided therapy is recommended for patients with single loss-of-function alleles to reduce MACE risk.
Area of Science:
- Pharmacogenomics
- Cardiovascular Medicine
- Genetics
Background:
- Clopidogrel efficacy is influenced by CYP2C19 genotype.
- Percutaneous coronary intervention (PCI) requires effective antiplatelet therapy.
- Genetic variations in CYP2C19 affect clopidogrel metabolism and patient outcomes.
Purpose of the Study:
- To evaluate the impact of CYP2C19 genotyping on major adverse cardiovascular events (MACE) in Iraqi patients undergoing PCI and treated with clopidogrel.
- To identify predictors of MACE in this patient cohort.
- To assess the utility of genotype-guided antiplatelet therapy.
Main Methods:
- A cohort of 201 Iraqi patients undergoing PCI were genotyped for CYP2C19 alleles (*1, *17, *2, *8).
- Patients were followed for MACE occurrence while on clopidogrel.
- Univariate and multivariate analyses were performed to identify MACE predictors.
Main Results:
- CYP2C19 allele frequencies were determined: *1 (0.604), *17 (0.276), *2 (0.117), *8 (0.0026).
- MACE occurred in 8.6% of 186 patients after a median of 12 months.
- Carriage of a single CYP2C19 loss-of-function allele was a significant predictor of MACE (HR 11.88, P < 0.0005) in multivariate analysis.
Conclusions:
- CYP2C19 genotype is a significant predictor of MACE in Iraqi patients on clopidogrel after PCI.
- Genotype-guided antiplatelet therapy is favored.
- Consideration of alternative antiplatelet agents for patients with single loss-of-function alleles is recommended.
Abstract:
To determine the impact of CYP2C19 genotyping on the occurrence of major adverse cardiovascular events (MACE), in cohort of Iraqi patients on clopidogrel after percutaneous coronary intervention (PCI), a total of 201 Iraqi patients undergoing the latter procedure were enrolled. All enrollees had their CYP2C19 genotyped using polymerase chain reaction and reverse hybridization. Genotyping revealed that CYP2C19 *1, *17, *2, and *8 allele frequencies were, respectively, 0.604, 0.276, 0.117, and 0.0026. After the exclusion of those with 2 loss of function alleles, 186 patients were available for follow-up as long as they were on clopidogrel, or until MACE occurred, which was encountered in 8.6% after a median of 12 months. Among predictors associated with MACE was the carriage of one CYP2C19 loss of function allele {hazard ratio (HR) 8.6 [confidence interval (CI) 3.15-23.4]; P < 0.0005}, hypertension [HR 3.74 (CI 1.06-13.16); P = 0.04], reduced ventricular function [HR 3.88 (1.43-10.54); P = 0.008], and history of previous myocardial infarction [HR 4.9 (CI 1.48-11.33); P = 0.007] by univariate analysis, although only CYP2C19 genotype remained significant by multivariate analysis [HR 11.88 (CI 3.25-43.44); P < 0.0005]. The latter observation favors CYP2C19 genotype-guided antiplatelet therapy and extending the use of alternative antiplatelet drugs to those with single loss of function allele after percutaneous coronary intervention.
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