Study On The Interaction Between Atorvastatin And Clopidogrel In Patients After PCI In Follow-up Period

Backgroud and AimsWith the aging of population,changing of dietary structure and life-style in China,morbidity of the Coronary Heart Disease(CHD) has a obvious uptrend in recent years.So as to the precaution of CHD and its treatment are becoming more and more important.In clinical practice,antiatherosclerotic and antithrombotic treatments became not only the basic but also the foremost treatments of CHD.Statins,one lipid lowering drug,which possessing multiple treatment functions including counteracting inflammatory factors, improving endothelium functions,it has been proved to have good effect in primary or secondary prevention of CHD.Clopidogrel is wildly used in patients with ACS and in patients after PCI.It can inhibit platelet aggregation and thrombosis effectively,reduce occurrence rate of cardiovascular event as well as enhance long-term effect after PCI.Because of this, co-administration of statins and clopidogrel are used in perioperative period of PCI broadly.However,there is some research claiming recently that atorvastatin attenuated the antiplatelet function of clopidogrel when atorvastatin and clopidogrel co-administrate.Metabolism of these two drugs is related to cytochrome p450(mainly CYP3A4).Atorvastatin is metabolized mainly by CYP3A4 and most of its metabolite is excreted through intestine. Clopidogrel,as a prodrug,is activated by CYP3A4 to a metabolite that can lead to inhibit platelet aggregation.This mechanism of the possible drug-drug interaction between two drugs was treated as the competitive inhibition form the view of Pharmacokinetics.This viewpoint is questioned by a lot of cardiologists as well as clinicians since its introduction.In recent years,the research works on interactions between atorvastatin and clopidogrel are focused on the effects of antiplatelet function of clopidogrel when these two drugs were used together in a short time period.Another focused item is the effects of major adverse cardic events when these drugs were used together in a long time period instead.So far,there is no comprehensive reports showing on the drug-drug interactions,which one is the effect of atorvastatin on antiplatelet function of clopidogrel and another is the effect of lipid lowering and adverse reactions of atorvastatin by clopidogrel.Our research use the random and controlled methods which aimed to evaluate the effects of drug-drug interaction of different doses of atorvastatin, and general dose of clopidogrel in patients undergoing PCI in a long period treatment.We believe this will offer some scientific basises in real clinial practice regarding how to use atorvastatin and clopidogrel correctly and effectively.MethodsWe treated a total of 105 patients with CHD as the research objects during the July and December of 2007 period.There are 78 males,27 females,and age in 36-81(65.5±8.8).In between,66 patients received PCI treatments.The exclusion criteria as:platelet count less than 100×10~9/L,tendency of hemorrhage,active digestibility ulcer.cerebral vascular accidence within 1 year. counterindication of antiplatelet or anticoagulation,statins medication within 1 month and administration of glycoproteinⅡbⅢa receptor inhibitor or cilostazol during perioperative period.All patients received treatment of aspirin 300 mg/d in admission day,and a different dose of atorvastation or pravastatin was randomly used in the next day.66 patients undergoing successful PCI operation were received loading dose of 300 mg clopidogrel,followed by a maintenance dose of 75 mg/d.105 patients were separated into 5 groups,23 patients in group A with atorvastatin 20 mg/d plusing clopidogrel,20 patients in group B with atorvastatin 40 mg/d plusing clopidogrel,23 patients in group C with pravastatin 20 mg/d plusing clopidogrel,20 patients in group D with atorvastatin 20 mg / d only,19 patients in group E with atorvastatin 40 mg/d only.The platelet CD62P,CD63,maximal platelet aggregation rate(MPAR) and other plasm lipid etc were measured at the first day after admission and 1 or 3 month after treatment.The platelet CD62P,CD63 and MPAR will be used for comparation within A,B and C groups,and also TC,TG,HDL-C,LDL-C,ALT and CK was be made the comparation between A,D,B and E groups.Results1.Group balanced test:The baseline clinical characteristics did not differ significantly among 5 groups(P＞0.05).2.The level of CD62P.CD63 and MPAR comparison among group A,B and C: The level of CD62P,CD63 and MPAR was measured 3 times among group A,B and C.The differences among these groups were not significant(P＞0.05). However,1 and 3 month data of each platelet indicator declined comparing with baseline data(P＜0.05).The data of each platelet indicator did not show significant difference between 1 and 3 month(P＞0.05).Correlation analysis was done among CD62P,CD63 and MPAR,and some result was been found between CD62P and CD63(r=0.67,P＜0.05 ),between CD62P and MPAR(r=0.65,P＜0.05 ),between CD63 and MPAR(r=0.60,P＜0.05 ).Based on this,we draw the conclusion that CD62P,CD63 and MPAR had positive correlation relations each other(all P＜0.05 ).3.The level of plasma lipid,ALT and CK comparison within group A and D as well as group B and E:There was no statistic difference in the level of plasma lipid,ALT and CK within group A and D as well as group B and E during 1 or 3 month treatment afterwords(P＞0.05).ConclusionAtorvastatin below 40mg/d dose and general dose of clopidorel were used together in 3 months in patients after PCI,we can draw conclusions as below:1.Atorvastatin is not found to attenuate the antiplatelet function of clopidogrel, on the contrary,CD62P,CD63 and MPAR data of 1 and 3 month of each platelet indicators are reduced in a certain degree comparing the basline data.2.The antiplatelet function of clopidogrel remain relativelty stable within 1-3 months treatment period on using atorvastatin and clopidogrel together.3.There are no discovery on Clopidogrel affecting lipid lowering and enhancing adverse reactions of atorvastatin.4.CD62P,CD63 and MPAR have positive correlation each other during our research,In this way,CD62P,CD63 and MPAR can be used as a evaluation indicator to platelet activation and its function comprehensively.