| Background and PurposeWith improvement of people's living standards and changes in diet, the incidence of coronary heart disease increases year by year and seriously endangers the health of the people, among which acute coronary syndrome (ACS) has the highest mortality. Antiplatelet therapy is currently conventional treatment to ACS and coronary heart disease after percutaneous coronary intervention (PCI). Studies have shown that clopidogrel inhibits platelet aggregation, reduces myocardial infarction, stroke incidents, stent thrombosis and ischemic events. Statins can not only reduce the blood lipid of ACS, but also has the effect of anti-inflammation, anti-proliferation, antiplatelet aggregation and stabilizing of atherosclerotic plaque. Therefore, the combination of statins and clopidogrel is usually used in ACS treatment. But in recent years, researchers believe that atorvastatin metabolized by the liver cytochrome (CYP) 3A4 can inhibit antiplatelet function of clopidogrel that activated by CYP 3A4 in a dose-dependent manner. The issue raised wide concern in cardiovascular field and there is different view in some small-scale clinical studies on this issue.At the same time, as the statins were widely used in lipid-lowering treatment, there is increasing number of reports about their side effects. Statins are hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, which can decrease endogenous cholesterol by reducing mevalonate (MVA), the intermediate product in cholesterol synthesis. MVA is necessary for the synthesis of coenzyme Q10 (CoQ10). When MVA is absent, the cell synthesis of CoQ10 will be in disorder. Many scholars believe that the side effects of statins may have relation with their inhibition effect on CoQ10 and other important benefit factors. In recent years, there are some reports about side effects of related to combination treatment of statins and CoQ10 to patients with muscle-ache, and left ventricular diastolic dysfunction. But it is also an issue of concern about whether CoQ10 can inhibit increased transaminase caused by statin and whether the supplementary CoQ10 has effect on lipid-improving effect of statins.In this study, a randomized, control study was carried out to study the effect of different doses of atorvastatin on the antiplatelet effect of clopidogrel in patients with ACS after PCI, and to provide more data for clinical use of two types of drugs. We also observed the combined effect of CoQ10 with atorvastatin on plasma CoQ10 and liver enzyme activities and lipid levels in patients with coronary heart disease and abnormal lipid levels to explore whether the combination of two drugs is reasonable.Methods The first part of this study as follows: effect of atorvastatin on antiplatelet effect of clopidogrel. One hundred fifty patients with ACS need to receive PCI were involved in the study according to inclusion criteria. All patients were treated with 300mg/d of aspirin, 300mg loading dose followed by 75mg/d maintenance dose of clopidogrel for antiplatelet therapy. Then the patients were randomly divided into three groups. Group A: atorvastatin group (A1 20mg/d n=30, A2 40mg/d n=30, A3 80mg/d n=30). Group B: pravastatin group (20mg/d, n=30). Group C: non-statin group (n=30). Surfactant protein markers (CD62P, CD63) and maximum platelet aggregation rate (MPAR) were observed 24 h (before statin drug service) and 72 h after PCI in each group were observed and calculated about the changes.The second part of this study: combined effect of coenzyme Q10 and atorvastatin on liver enzyme activities and lipid levels. Fifty patients with coronary heart disease and abnormal lipid levels were selected and randomly divided into control group (n=25) and test group (n=25). Patients in control group took 20mg/d of atorvastatin before going to bed. Patients in test group took 30mg/d of CoQ10 in 3 times besides atorvastatin. Three months later, CoQ10 levels, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were observed before and after treatment.ResultsThe first part: 1. Statin group and non-statin group: there were no significant difference about CD62P, CD63 and MPAR in group comparison 24 h (before statin treatment) after PCI in group A, B and C (P>0.05); there were no significant difference aboutâ–³C D62P,â–³CD63 andâ–³MPAR in group comparison 72h after PCI in group A, B and C (P>0.05). 2. Different doses of atorvastatin group and non-statin group: there were no significant difference about CD62P, CD63 and MPAR in group A1, A2 and A3 when compared with that in group C 24 h after PCI (P> 0.05); there were no significant difference aboutâ–³C D62P,â–³CD63 andâ–³MPAR in group A1, A2 and A3 when compared with that in group C 72h after PCI (P> 0.05).The second part: 1. CoQ10 increased after the treatment in test group and there was significant difference compared with that before treatment (P<0.05); there was no significant increase about ALT and AST (P>0.05); TC, TG and LDL-C levels decreased significantly (P<0.01), HDL-C level increased significantly (P<0.01); 2. In control group CoQ10 significantly decreased after the treatment (P<0.01), ALT and AST levels significantly increased (P<0.01); LDL-C decreased significantly (P<0.05); there were no significant difference about TC, TG and HDL-C before and after the treatment (P>0.05); 3. Group comparison showed that there was significant difference after the treatment between test group and control group (P<0.05).Conclusions1. Atorvastatin metabolized by the liver cytochrome (CYP) 3A4 can not inhibit antiplatelet function of clopidogrel in short period and has no relation with dosage.2. Exogenous CoQ10 supplement can prevent increasing of transaminase caused by atorvastatin, and can also enhance the lipid-improving effect of statins. |
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