Comparison Of Antiplatelet Therapies In Patients With Clopidogrel Resistance After PCI:A Meta-analysis

Introduction:Clopidogrel in combination with aspirin treatment was the main antiplatelet therapy after PCI. Related studies had showed that the occurrence of major adverse cardiac events increased significantly in patients who have laboratory clopidogrel resistance or carryinging CYP2C19 gene variants in the process of clopidogrel dual antiplatelet therapy after PCI.So for these patients, there still were prasugrel combined aspirin,ticagrelor combined aspirin, double-dose clopidogrel combined aspirin and triple antiplatelet therapy ect. Objective:In this study,The randomized controlled clinical trials of different antiplatelet therapeutic schemes in patients with the laboratory clopidogrel resistance or carrying CYP2C19 gene variantsafter PCI were meta-anailzed, to obtain the optimal scheme of antiplatelet therapy. Methods:Through theretrieval of the Wan Fang, VIP, CNKI, PUBMED, OVID and CENTRAL database, we included randomized controlled trials about different antiplatelet therapeutic schemes in patients with the laboratory clopidogrel resistance or carrying CYP2C19 gene variantsafter PCI,MACE and bleeding events as outcomes, control group with standard-dose clopidogrel in combination with aspirin treatment. Net benefit was defined as the number in every ten thousand people about reducing MACE minus the number in every ten thousand people about increasing bleeding events. OR as a combined effect merged results after Heterogeneity analysis, the funnel chart evaluating publication bias and sensitivity analysis were carried on. Results:In terms of MACE, compared with the standard-dose clopidogrel in combination with aspirin therapy, triple antiplatelet therapy(OR 0.33, 95% CI 0.22 0.51, P < 0.00001), prasugrel dual antiplatelet therapy(OR 0.64, 95% CI 0.44 to 0.94, P = 0.02), ticagrelor dual antiplatelet therapy(OR 0.69, 95% CI 0.55 to 0.87, P = 0.002) could observably reduce the occurrence of MACE,butthe double-dose clopidogrel in combination with aspirin(OR 0.91, 95% CI 0.54 to 1.51, P = 0.70) was not better than that of the standard-dose clopidogrel dual antiplatelet therapy,there wasn’t significant statistical difference(P > 0.05). In terms of bleeding events, there wasn’t statistically significant difference in the risk of bleeding events compared control group of the above four kinds of the antiplatelet therapeutic schemes(P > 0.05). In terms of net benefit, triple antiplatelet therapy(1610 per ten thousand people benefit)had the most net benefit, followed by prasugrel dual antiplatelet therapy(210 per ten thousand people benefit) and ticagrelor dual antiplatelet therapy(150 per ten thousand people benefit), butthe net benefit of the double dose of clopidogrel dual antiplatelet therapy had negative benefit(-170 per ten thousand people benefit). Sensitivity analysis found that when we removed the various studies the direction of merged results did not change, proving the merged resultsreliable. Publication bias assessment found thatfunnel figures of ticagrelor dual antiplatelet therapy and the double dose of clopidogrel dual antiplatelet therapy were asymmetric, there may be a publication bias. Conclusion:In the crowd of the laboratory clopidogrel resistance or carrying CYP2C19 gene variantsafter PCI, considering the balance of two aspects with the curative effect and bleeding risk, the priority of the antiplatelet therapy wastriple antiplatelet therapy, prasugrel plus aspirin, ticagrelorplus aspirin, standard-dose clopidogrel plus aspirin treatment. A double-doseclopidogrel dual antiplatelet treatment had no advantage compared with the standard-doseclopidogrel dual antiplatelet treatment. More large study dataswere required to gain a higher quality of evidence in this study.