Key result
In patients with coronary heart disease on clopidogrel, adverse event risk was 5.208-fold higher in intermediate metabolizers and 3.75-fold higher in poor metabolizers versus normal metabolizers.
Why the study?
Clopidogrel has significant individual differences in therapeutic effect, and carriers of the CYP2C19 deletion allele face a higher risk of adverse cardiovascular events.
Does ticagrelor improve prognosis compared to clopidogrel in patients with coronary heart disease carrying CYP2C19 loss of function alleles?
Cohort (n=170)
No
Does ticagrelor improve prognosis compared to clopidogrel in patients with coronary heart disease carrying CYP2C19 loss of function alleles?
Relative Risk: 5.208
Ticagrelor provides a better prognosis than clopidogrel in coronary heart disease patients undergoing PCI or carrying a single CYP2C19 deletion allele (intermediate metabolizers).
Should not yet change antiplatelet choice; leaves open whether CYP2C19 testing improves CHD outcomes.
Background: Clopidogrel is a traditional P2Y12 receptor inhibitor that is widely used in clinical practice, but there are significant individual differences in its therapeutic effect. Carriers of the CYP2C19 deletion allele have a higher risk of adverse cardiovascular events than non-carriers. Methods: In this study, 170 patients diagnosed with coronary heart disease (CHD) and on regular oral clopidogrel or ticagrelor antiplatelet therapy in the Department of Cardiology of Wuxi Second People’s Hospital from August to December 2019 were screened. Baseline patient data were collected, percutaneous coronary angiography (CAG) or coronary computed tomography angiography (CTA) results were recorded, CYP2C19 gene type was detected, and prognosis/outcome was assessed by telephone/outpatient/inpatient follow-up for 12 months. Results: (I) Of the 170 patients, 0.66% were the fast metabolic type, 41.45% were the normal metabolic type, 42.76% were the intermediate metabolic type, and 15.13% were the poor metabolic type. CYP2C19*2 mutation accounted for 89.29% of all mutations, CYP2C19*3 mutation accounted for 9.82%, and CYP2C19*17 mutation accounted for only 0.89%. (II) Among the patients with CHD who regularly took clopidogrel, the risk in the intermediate metabolic group was 5.208-fold higher than that of normal metabolic group, and that of the poor metabolic group was 3.75-fold higher than that of normal metabolic group; there was no significant difference between the intermediate and poor metabolic groups. (III) Prognosis was significantly associated with regular use of ticagrelor or clopidogrel by patients in the intermediate metabolic group. There was no significant correlation between poor metabolism (PM) and normal metabolism (NM). Prognosis was significantly associated with regular use of ticagrelor or clopidogrel in patients undergoing percutaneous coronary intervention (PCI), but not in patients who did not undergo PCI. Conclusions: CYP2C19 polymorphism was associated with the prognosis of patients with CHD administered antiplatelet therapy with oral clopidogrel. The incidence of poor prognosis was significantly increased with CYP2C19*2 and/or CYP2C19*3 mutations, and patients undergoing PCI or carrying a single CYP2C19 deletion allele had a better prognosis with ticagrelor as replacement therapy.
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Qian et al. (2022) conducted a cohort in Coronary heart disease (n=170). CYP2C19 loss of function allele (intermediate/poor metabolizer) vs. Normal metabolizer was evaluated on Prognosis / adverse cardiovascular events (5.208-fold higher risk). In patients with coronary heart disease on clopidogrel, adverse event risk was 5.208-fold higher in intermediate metabolizers and 3.75-fold higher in poor metabolizers versus normal metabolizers.
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