Effect of CYP2C19 genetic polymorphism on the pharmacodynamics and clinical outcomes for patients treated with ticagrelor: a systematic review with qualitative and quantitative meta-analysis

Abstract

AbstractBackgroundStudies show inconsistent results regarding the impact ofCYP2C19genotype on the pharmacodynamics (PD) and clinical outcomes of ticagrelor. With the implementation of genotype-guided individualized antiplatelet therapy, the association betweenCYP2C19polymorphism and the efficacy and safety of ticagrelor for patients is still worthy of exploring and studying.MethodsThis systematic review protocol has been registered in the PROSPERO network (No. CRD 42020158920). Electronic databases of PubMed, EmBase, and the Cochrane Library were systematically searched from inception to January 6th, 2022 to select studies investigating the impact ofCYP2C19genotype on PD and clinical outcomes of ticagrelor. The results were presented as odds ratio (OR) or weight mean difference with its 95% confidence interval (CI) by using the random-effects model. Trial sequential analysis (TSA) was used to control risk of random errors and detect the robustness of outcomes.ResultsEight studies recruited a total of 6405 patients treated with ticagrelor. Mostly trials reported no significant effect of any or noCYP2C19loss-of-function (LOF) allele (*2 or *3) on all the endpoints. Compared with no LOF allele carriers, subgroup analysis suggested any LOF allele in Asian patients was associated with a significant decreased risk of bleeding events (OR: 0.41; 95% CI: 0.22–0.75;P = 0.004). Furthermore, any LOF allele carriers didn’t yield any impact on the risk of MACEs (OR: 1.11; 95% CI: 0.76–1.64;P = 0.586), stroke (OR: 1.71; 95% CI: 0.99–2.96;P = 0.054), definite stent thrombosis (OR: 0.88; 95% CI: 0.17–4.60;P = 0.882), bleeding (OR: 0.63; 95% CI: 0.27–1.46;P = 0.281), myocardial infarction (OR: 0.81; 95% CI: 0.30–2.20;P = 0.682), and revascularization (OR: 0.81; 95% CI: 0.33–2.00;P = 0.649) in all patients. The results of TSA were indicated that more further trials would be required.ConclusionsThis qualitative and quantitative study suggested Asian patients carrying anyCYP2C19LOF allele might have a lower risk of bleeding events comparing with no LOF allele carriers when treated with ticagrelor. However, we did not prove an important role ofCYP2C19genotype on the risk of PD and clinical endpoints in the whole cohort. In future, more large-scale prospective studies and more different ethnic populations should be included.