Effects Of Statins On Platelet Inhibition By Clopidogrel A Meta Analysis

BackgroudDual antiplatelet therapy combining aspirin and clopidogrel is the standard regimen for patients who have acute coronary syndromes (ACS) or are undergoing percutaneous coronary intervention (PCI). Clopidogrel can significantly decrease the rate of MI,stroke and stent thrombosis compared with aspirin.But some patients display the clinical phenomenon of clopidogrel resistance,defined as the occurance of clinical event of arterial thrombosis. Clopidogrel resistance significantly increase the patients’risk of cardiovascular events. Clopidogrel inhibits the activity of platelet by blocking the ADP receptor P2Y12. Clopidogrel is administered as a prodrug and the active metabolite is generated by the cytochrome P450system. Therefore,inadequate responses to clopidogrel may be caused by polymorphisms of the cytochrome P450enzymes and interaction/competition with other drugs metabolized by the cytochrome P450system.The3-hydroxy-3-methylglutaryl-coenzyme A(HMG CoA) reductase inhibitors (statins) have multiple effects of decreaseing the level of cholesterol in vivo, anti-inflammatory, stable the atherosclerotic plaque and improve the function of endothelial cell.Several studies have confirmed good clinical benefit in the primary and secondry prevention of coronary atherosclerosis disease with statins.Statins can be divided into two categories according to their different metabolic enzymes in vivo, i.e. atorvastatin, simvastatin and lovastatin that mainly metabolized by CYP3A4and rosuvastatin, fluvastatin and pravastatin that not mainly metabolized by CYP3A4. Some studies have showed that statins metabolized by CYP3A4can decrease the inhibition effect of platelet by clopidogrel and that is one of the potential factors of clopidogrel resistance.Recently there is no large scale clinical randomized controlled trials about the effects of statins on platelet inhibition by clopidogrel. In view of the contradictory results of current study and the widely use combining statins and clopidogrel,it is necessary to make a systematic review about the effects of statins on platelet inhibition by clopidogrel and guide to make better clinical treatment strategies.ObjectiveTo evaluate the effects of statins metabolized by different enzymes on the platelet function and major adverse cardiovascular events when combined with clopidogrel.MethodWe search the databases including PubMed,Cochrane library,CNKI,Wanfang,CBM and VIP to identify clinical randomized control trials in which the effects of statins metabolized by different enzymes on the platelet function when combined with clopidogrel are studied and search the references of the literatures.The english key terms are statins,hydroxymethylglutaryl-coa reductase inhibitors,clopidogrel,plavix and platelet.We include related studies according to the inclusion criteria and exclusion criteria and assess the quality of literatures.The data of patients’ drug use and evaluation of platelet function is extracted.The RevMan5.0software is used for data analysis.ResultsThis meta analysis include15RCTs, involved2387patients.The analysis results show that there is no significant difference in ADP-induced platelet aggregation when statins combining clopidogrel are used(WMD=-0.24,95%CI(-1.77～1.29), P=0.76). Subgroups analysis show that there is no significant difference in ADP-induced platelet aggregation when low-dose atorvastatin combining clopidogrel are used(WMD=-0.81,95%CI(-0.88～2.49), P=0.35), there is no significant difference in ADP-induced platelet aggregation when high-dose atorvastatin combining clopidogrel are used(WMD=-0.76,95%CI(-6.65-5.13), P=0.80). There is no significant difference in the incidence of MACE when statins combining clopidogrel are used(OR=0.82,95%CI(0.50-1.36), P=0.44).But the level of platelet P-selectin is lower in patients receiving CYP3A4metabolized statins(WMD=-0.82,95%CI(-1.46～-0.18), P=0.01).ConclusionThere is no influence on the ADP induced platelete aggregation when both of statins metabolized by different enzymes and clopidogrel are used; the level of P-selectin is lower in patients receiving clopidogrel and CYP3A4metabolized statins; there is no influence on the incidence of MACE when both of statins metabolized by different enzymes and clopidogrel are used. Limited by the quantity and quality of the included studies, the above conclusions still need larger clinical randomized controlled trials to verify.