| BACKGROUND:Now, people pay more attention on clopidogrel resistance. Therefore, the concept of individual anti-platelet therapy has been presented. As a third-generation thienopyridines class of anti-platelet agents, Prasugrel has been recommended for prevention of thrombosis events in patients receiving emergency and elective percutaneous coronary intervention (PCI) with clopidogrel resistance. Platelet reactivity testing can evaluate the efficacy of antiplatelet drugs and predict the occurrence of clinical ischemic events. There are no large-scale trials evaluating the effect of prasugrel and clopidogrel on platelet reactivity currently.AIMS:The aim of this meta-analysis is to evaluate the efficacy and safety of prasugrel and clopidogrel by platelet reactivity in patients with coronary heart disease, and to compare platelet reactivity with the incidence of clinical events as a criterion. In this way, references can be provided for clinical rational use.METHODS:A systemic literature search in Medline, EMbase, The Cochrane Library, CNKI, WanFang, CBM, VIP databases was performed and randomized controlled trials(RCTs) involving the effect of prasugrel and clopidogrel on platelet reactivity in patients with stable coronary artery disease, acute coronary syndrome (ACS), and PCI were collected. Effect size was expressed as standard mean difference (SMD)and odds Radio (OR) with 95% confidence interval(CI). P-value and I were used to evaluate heterogeneity, besides, subgroup analysis was performed to explore the reasons for heterogeneity. Sensitivity analysis was based on the evaluation results of the literatures as well as the quality characteristics of each study, and the index of publication bias was funnel plots.RESULTS:A total of 1950 patients from 18 trials entered into this study. Combined analysis of the above findings showed the whole study has a significant heterogeneity (P<0.00001, I2= 88%). But after analyzing the method, dosage, special populations, age and other factors, the reasons for heterogeneity were positioned. Overall, platelet reactivity in patients treated with prasugrel was significantly lower than that with clopidogrel [SMD=-1.36,95% CI (-1.60,-1.12)], especially in HTPR patients and CYP2C19* 2 carriers [SMD=-1.41,95%CI (-2.22,-0.59)]. Efficacy of prasugrel was dose-dependented, and platelet reactivity in prasugrel 10mg/d was significantly less than clopidogrel 150mg/d [SMD=-1.03,95% CI (-1.27,-0.80)]. Studys were categorized according to the average age, and the platelet reactivity between prasugrel and clopidogrel had significant difference in both ages [less than 60 years old:SMD=-2.60,95% CI (-3.11,-2.09); more than 60 years old:SMD=-1.06,95% CI (-1.62,-0.50)]. In addition, These results were in agreement with those got by the incidence of clinical events.CONCLUSIONS:This study suggests that the role of prasugrel in reducing reactivity is stronger than clopidogrel in all ages, especially in HTPR patients and CYP2C19* 2 carriers, but the effect of prasugrel may reduce in the higher age group. Efficacy of prasugrel is dose-dependented. Effect of standard-dose prasugrel is stronger than high-dose clopidogrel, while low-dose prasugrel is also stronger than standard-dose clopidogrel. The incidence of adverse effects in prasugrel was higher than clopidogrel, but the incidence of major bleeding events was similar. Platelet reactivity in patients with coronary heart disease can be used as an anti-platelet drug evaluation to provide references for clinical rational use. Yet, the number of trials was still too small and more RCTs are necessary to further support these conclusions. |
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