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Clopidogrel versus Ticagrelor in CYP2C19 Loss-of-Function Allele Noncarriers: A Real-World Study in ChinaFunding This study is funded by the National Major Scientific and Technological Special Project for “Significant New Drugs Development” during the Thirteenth Five-year Plan Period (2017ZX09304017) and Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201805).
Objective This article compares the clinical outcomes of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS) without cytochrome P450 (CYP)2C19 loss-of-function (LOF) alleles and investigates whether clopidogrel could be an alternative P2Y12 inhibitor without increasing the risk of ischemic events.
Methods Patients were divided into the clopidogrel-treated group and the ticagrelor-treated group. Inverse probability of treatment weighting (IPTW) calculated by propensity scores was used to adjust confounding covariates. The primary outcome was major adverse cardiovascular or cerebrovascular events (MACCEs) within 12 months. The secondary outcomes were MACCEs plus unstable angina, and clinically significant bleeding events.
Results Finally, 2,199 patients were included. Of them, 1,606 were treated with clopidogrel, and 593 were treated with ticagrelor. The mean age of the original cohort was 59.92 ± 9.81 years. During the 12-month follow-up period, MACCEs occurred in 89 patients (4.0%). No significant differences were observed in MACCEs (IPTW-adjusted hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.65–1.18), MACCEs plus unstable angina (IPTW-adjusted HR, 1.20; 95% CI, 0.91–1.59), or clinically significant bleeding events (IPTW-adjusted HR, 0.81; 95% CI, 0.53–1.23) between the clopidogrel- and ticagrelor-treated groups.
Conclusion In patients with ACS without CYP2C19 LOF alleles, clopidogrel was not associated with a higher risk of MACCEs when compared with ticagrelor. The main findings of this study support use of clopidogrel in CYP2C19 LOF noncarriers as an alternative P2Y12 inhibitor, which may reduce medical expenses and adverse reactions caused by more potent P2Y12 inhibitors in these patients.
Ethics Approval and Consent to Participate
All procedures performed in studies involving human participants were approved by the ethics committee of Anzhen Hospital. All participants provided their written informed consent to participate in this study.
Availability of Data and Materials
The data underlying this article will be shared on reasonable request to the corresponding author.
Y.-N.Z. and Y.Z. contributed equally to this work. (I) Conception and design: Y.L. (II) Administrative support: Y.L. (III) Determination of clinical events: W.-Z.L., Z.Z., W.-X.P. (IV) Collection and upload of data: Y.Z., Y.-N.Z., B.-D.L., J.-L.H., J.-L.Y., and Y.-F.W. (V) Data analysis and interpretation: Y.-N.Z., Y.Z., J.-L.H., and B.-D.L. (VI) Manuscript writing: Y.-N.Z., Y.Z., and W.-X.P.
Received: 31 May 2021
Accepted: 18 July 2021
Article published online:
24 August 2021
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