For patients after percutaneous coronary interventions (PCI), clopidogrel combined with aspirin is a conventional dual antiplatelet therapy (DAPT) method. However, clopidogrel resistance exists in some populations, especially in East Asian populations, due to the CYP2C19 gene polymorphism. The current guidelines are very clear on DAPT method for CYP2C19 genotype of ultrarapid metabolizers (UM), extended metabolizers (EM) and poor metabolizer (PM) after PCI, but how to intermediate metabolizers (IM) choose drugs was not clear. This is the first systematic review to preferentially recommend ticagrelor for antiplatelet therapy over high-dose clopidogrel for patients carrying CYP2C19 LOF alleles after PCI with follow-up time of more than 3 months.
Abstract
What is known and objective
For patients after percutaneous coronary interventions (PCI), clopidogrel combined with aspirin is a conventional dual antiplatelet therapy (DAPT) method. Because the genetic polymorphism of CYP2C19 gene leads to clopidogrel resistance, guidelines for antiplatelet recommendations in CYP2C19 of ultrarapid metabolizers (UM), extended metabolizers (EM) and poor metabolizers (PM) are clear. However, there is no clear recommendation as to whether ticagrelor or double dose clopidogrel is the best antiplatelet regimen for CYP2C19 of intermediate metabolizers (IM). To evaluate the efficacy and safety of ticagrelor (combined with aspirin) and high-dose clopidogrel (combined with aspirin) in patients after PCI with CYP2C19 loss-of-function (LOF) alleles.
Methods
We searched the following databases to select RCTs of comparing ticagrelor with high-dose clopidogrel in patients after PCI with CYP2C19 LOF alleles: CNKI, Wanfang Data, PubMed, Clinical trials, Cochrane, Web of Science and Embase. Major adverse cardiovascular events (MACEs), platelet function and TIMI bleeding event were defined as the outcomes. revman 5.3 software was used to perform meta-analysis.
Results and discussion
A total of 14 RCTs with 2351 patients were enrolled. Meta-analysis showed that compared with high-dose clopidogrel, ticagrelor had reduced incidence of MACEs (OR = 0.32, 95% Cl: 0.23–0.44, p < 0.00001), stent thrombosis (OR: 0.24, 95%CI: 0.13–0.44, p < 0.00001), myocardial infarction OR: 0.42, 95%CI: 0.22–0.80, p = 0.008), revascularization (OR: 0.29, 95%CI: 0.10–0.82, p = 0.02) and unstable angina (OR: 0.47, 95%CI: 0.29–0.77, p = 0.003) in patients after PCI with CYP2C19 LOF alleles. A subgroup analysis showed that ticagrelor reduced the risk of MACEs compared with high-dose clopidogrel regardless of the type of metabolizer. Compared with high-dose clopidogrel, ticagrelor significantly reduced the risk of MACE with longer follow-up period (more than 3 months) without increasing the risk of bleeding (OR: 0.89, 95%CI: 0.53–1.49, p = 0.30), while ele vated dyspnoea (OR: 5.62, 95%CI: 3.07–10.28, p < 0.00001).
What is new and conclusions
For patients carrying CYP2C19 LOF alleles after PCI, ticagrelor may be better than high-dose clopidogrel in reducing the risk of MACEs, while dyspnoea incidents should be alerted.
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