Background:
CYP2C19 loss-of-function (LOF) alleles reduce the effectiveness of
clopidogrel in patients undergoing
percutaneous coronary intervention for
acute coronary syndrome. However, the clinical impact of implementing
CYP2C19 gene-guided
pharmacotherapy is unclear, especially among the Chinese population. The purpose of this study was to evaluate P2Y12 receptor inhibitor selection and clinical outcomes upon implementation of
CYP2C19 genotype-guided
pharmacotherapy in current clinical practice. Methods: This was a single-center observational cohort study. Adult
percutaneous coronary intervention patients who received
CYP2C19 genetic testing (*2, *3, *17 alleles) were included.
Ticagrelor was recommended for patients with a LOF allele. Factors related to P2Y12 inhibitor selection were determined by logistic regression. The primary endpoint was major cardiac or cerebrovascular adverse events (MACCE) within 12 months. MACCE and clinically significant
bleeding events (BARC ≥2) in the LOF-
clopidogrel group, non-LOF-
clopidogrel group, and non-LOF-
ticagrelor group were compared with those in the LOF-
ticagrelor group. The inverse probability of treatment weighting (IPTW) was adjusted in a Cox regression analysis to eliminate confounding factors. Results: Among 1,361 patients, 826 (60.7%) had a LOF allele. Patients with a LOF allele were more likely to be prescribed
ticagrelor (multivariate-adjusted OR 1.349; 95% CI 1.040 to 1.751; p = 0.024). The MACCE rate was higher in the LOF-
clopidogrel group than in the LOF-
ticagrelor group (7.8 vs. 4.0%; log-rank p = 0.029; IPTW-adjusted HR 2.138; 95% CI 1.300-3.515). Compared with the LOF-
ticagrelor group, the non-LOF-
clopidogrel group showed no significant difference in MACCE rate (5.8 vs. 4.0%; log-rank p = 0.272; IPTW-adjusted HR 1.531; 95% CI 0.864-2.714). Among the patients treated with
ticagrelor, there was no significant difference in the MACCE rate between the LOF group and non-LOF group (4.3 vs. 4.0%; log-rank p = 0.846; IPTW-adjusted HR 1.184; 95% CI 0.582-2.410). There was no significant difference in the incidence of clinically significant
bleeding events among the four groups. Conclusion: This study confirms that efficiently returned
CYP2C19 genotype results did partially guide cardiologists to prescribe
ticagrelor for patients with a LOF allele, and that
clopidogrel had a higher risk of MACCE than
ticagrelor in these patients, which provides support for the implementation of
CYP2C19 gene-guided antiplatelet
therapy in clinical practice.