Key result
Carrying one CYP2C19 loss-of-function allele linked to ~12-fold higher MACE risk on clopidogrel post-PCI.
Why the study?
Does carriage of a CYP2C19 loss of function allele increase the risk of MACE in Iraqi patients on clopidogrel after PCI?
Cohort (n=201)
Does carriage of a CYP2C19 loss of function allele increase the risk of MACE in Iraqi patients on clopidogrel after PCI?
Effect estimate: HR 11.88 (95% CI 3.25-43.44)
p-value: p=< 0.0005
Carriage of a single CYP2C19 loss of function allele is a strong independent predictor of MACE in Iraqi patients receiving clopidogrel after PCI, supporting genotype-guided antiplatelet therapy.
May warrant CYP2C19 testing in Iraqi post-PCI patients on clopidogrel; hypothesis-generating and requires confirmation in larger trials.
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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Mohammad et al. (2018) conducted a cohort in Post-percutaneous coronary intervention on clopidogrel (n=201). Carriage of one CYP2C19 loss of function allele was evaluated on Major adverse cardiovascular events (MACE) (HR 11.88, 95% CI 3.25-43.44, p=< 0.0005). Carriage of one CYP2C19 loss of function allele independently predicted major adverse cardiovascular events in patients on clopidogrel after PCI (HR 11.88; 95% CI 3.25-43.44; P<0.0005).
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