Key result
CYP2C19 loss-of-function alleles are not linked to death, MI, or stroke versus wild genotype.
Why the study?
The study evaluated the effect of CYP2C19 gene polymorphisms on clinical outcomes in patients after successful revascularization for acute myocardial infarction during clopidogrel therapy over 60 months of follow-up.
Does carriage of CYP2C19 loss of function alleles increase the risk of adverse ischemic events in patients with myocardial infarction treated with clopidogrel after revascularization?
Cohort (n=363)
Does carriage of CYP2C19 loss of function alleles increase the risk of adverse ischemic events in patients with myocardial infarction treated with clopidogrel after revascularization?
Effect estimate: HR 0.99 (95% CI 0.59-1.65)
Absolute Event Rate: 19% vs 20%
p-value: p=0.965
CYP2C19 loss-of-function polymorphisms (*2, *3) were not associated with an increased risk of ischemic events over 60 months in post-MI patients treated with clopidogrel after revascularization.
No association seen with CYP2C19 LOF alleles and ischemic events on clopidogrel post-MI; hypothesis-generating and should not yet change practice.
Objective: To evaluate the effect of CYP2C19 gene polymorphisms on clinical outcomes in patients after successful revascularization for acute myocardial infarction with and without ST segment elevation during clopidogrel therapy for 60 months of follow-up.Methods: From 2011 to 2012, 363 patients with acute myocardial infarction who underwent coronary revascularization were included in the study. In the postoperative period, the patients underwent genetic analysis for the CYP2C19 gene polymorphism. All patients received dual antiplatelet therapy with aspirin and clopidogrel. The 60-month follow-up period assessed the primary composite endpoint of the cumulative incidence of all-cause mortality, recurrent myocardial infarction, and stroke.Results: At 60 months after the initial intervention, 71 patients had a composite primary endpoint event (all-cause death, recurrent myocardial infarction, or stroke): 50 (20%, 95% CI 16–25) in the group patients with "wild genotype" and 21 patients of the "loss of function (LOF) *2+*3" group (19%, 95% CI 13–27). No significant relationship was observe between carriage of LOF alleles of the CYP2C19 and the primary endpoint during the 60-month follow-up (HR 0.99, 95% CI 0.59–1.65, P = .965), as well as between carriage of the homozygous CYP2C19 variant (*2/*2) and the development of myocardial infarction during the same period (HR 1.26, 95% CI 0.30–5.20, P = .752).Conclusion: No correlation was observed between the CYP2C19 gene polymorphisms (*2, *3 alleles) and the incidence of ischemic events in patients with myocardial infarction after myocardial revascularization throughout a 60-month follow-up period. Received 27 November 2022. Revised 25 September 2023. Accepted 26 September 2023. Funding: The study did not have sponsorship. Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: I.O. GrazhdankinData collection and analysis: I.O. GrazhdankinStatistical analysis: V.L. LukinovDrafting the article: I.O. Grazhdankin, A.A. Prokhorikhin, V.I. Baystrukov, E.I. Kretov, V.L. LukinovCritical revision of the article: A.M. ChernyavskiyFinal approval of the version to be published: I.O. Grazhdankin, A.A. Prokhorikhin, V.I. Baystrukov, E.I. Kretov, A.M. Chernyavskiy, V.L. Lukinov
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Grazhdankin et al. (2023) conducted a cohort in Acute myocardial infarction (n=363). CYP2C19 loss of function (*2+*3) alleles vs. CYP2C19 wild genotype was evaluated on Cumulative incidence of all-cause mortality, recurrent myocardial infarction, and stroke (HR 0.99, 95% CI 0.59-1.65, p=0.965). CYP2C19 loss-of-function alleles did not significantly affect the 60-month risk of death, recurrent MI, or stroke compared to wild genotype (HR 0.99; 95% CI 0.59-1.65; P=0.965).
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