Key result
CYP2C19 loss-of-function alleles were not significantly associated with an increased risk of major adverse cardiac events in patients treated with clopidogrel following percutaneous coronary intervention (HR 1.18).
Why the study?
While CYP2C19 loss-of-function alleles decrease clopidogrel efficacy after PCI for ACS, the impact of genotype in stable ischemic heart disease is unclear.
Does CYP2C19 loss-of-function genotype increase the risk of major adverse cardiac events in patients treated with clopidogrel following PCI for ACS or SIHD?
Cohort (n=4,461)
Yes
Does CYP2C19 loss-of-function genotype increase the risk of major adverse cardiac events in patients treated with clopidogrel following PCI for ACS or SIHD?
Hazard Ratio: 1.18 (95% CI 0.97–1.45)
p-value: p=0.096
CYP2C19 loss-of-function genotype is not significantly associated with increased MACE in patients with stable ischemic heart disease treated with clopidogrel after PCI, suggesting genotype-guided therapy may not be warranted in this subgroup.
No significant MACE link with CYP2C19 LOF alleles in SIHD cohort; leaves open whether genotyping improves clopidogrel outcomes post-PCI.
Background CYP2C19 loss-of-function (LOF) alleles decrease the antiplatelet effect of clopidogrel following percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndrome (ACS). The impact of genotype in stable ischemic heart disease (SIHD) is unclear. Objectives Determine the association of CYP2C19 genotype with major adverse cardiac events (MACE) after PCI for ACS or SIHD. Methods Million Veterans Program (MVP) participants age <65 years with a PCI documented in the VA Clinical Assessment, Reporting and Tracking (CART) Program between 1/1/2009 to 9/30/2017, treated with clopidogrel were included. Time to MACE defined as the composite of all-cause death, stroke or myocardial infarction within 12 months following PCI. Results Among 4,461 Veterans (mean age 59.1 ± 5.1 years, 18% Black); 44% had ACS, 56% had SIHD and 29% carried a CYP2C19 LOF allele. 301 patients (6.7%) experienced MACE while being treated with clopidogrel, 155 (7.9%) in the ACS group and 146 (5.9%) in the SIHD group. Overall, MACE was not significantly different between LOF carriers vs. noncarriers (adjusted hazard ratio [HR] 1.18, confidence interval [95%CI] 0.97-1.45, p=0.096). Among patients presenting with ACS, MACE risk in LOF carriers versus non-carriers was numerically higher (HR 1.30, 95%CI 0.98-1.73, p=0.067). There was no difference in MACE risk in patients with SIHD (HR 1.09, 95%CI 0.82-1.44; p=0.565). Conclusions CYP2C19 LOF carriers presenting with ACS treated with clopidogrel following PCI experienced a numerically greater elevated risk of MACE events. CYP2C19 LOF genotype is not associated with MACE among patients presenting with SIHD.
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Chanfreau‐Coffinier et al. (2023) conducted a cohort in Acute coronary syndrome or stable ischemic heart disease requiring PCI (n=4,461). CYP2C19 loss-of-function (LOF) alleles vs. CYP2C19 non-carriers was evaluated on Major adverse cardiac events (MACE) defined as the composite of all-cause death, stroke or myocardial infarction within 12 months following PCI (HR 1.18, 95% CI 0.97-1.45, p=0.096). CYP2C19 loss-of-function alleles were not significantly associated with an increased risk of major adverse cardiac events in patients treated with clopidogrel following percutaneous coronary intervention (HR 1.18).
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