The Different Lipid Lowering Regiments On Lipid Profile And Cholesterol Metabolism Makers In Patients Undergoing Percutaneous Coronary Intervention

ObjectiveCholesterol metabolism is one of important factors which affect lipid-lowering effect. The goal of this study is to concern the effects of combined treatment using HMG-CoA reductase inhibitors (statins) and a cholesterol absorption inhibitor (ezetimibe) or statins monotherapy on lipid profile and cholesterol metabolism makers among patients undergoing percutaneous coronary intervention for coronary heart disease(CHD).MethodsIn this study, patients undergoing percutaneous coronary intervention(PCI) were randomly assigned to receive 1 of the following 12 weeks in 1:1:1 ratio:simvastatin 40mg/d(SI); atorvastatin 20mg/d(AT,);or ezetimible10mg/d plus simvastatin 20mg/d(SI/EZ). Cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), apolipoprotein A(apoA), apolipoprotein B(apoB), lipoprotein a(Lpa), high-sensitive C-reactive protein(hs-CRP), liver function, renal function were measured at baseline and at 4 weeks and 12 weeks post therapy, so were Cholesterol synthesis makers (squalene,desmosterol and lanthosterol) and cholesterol absorption makers (campersterol,stigmasterol and sitosterol) were also at baseline and at 12 weeks. Adverse reactions including gastrointestinal reaction,fatigue,myalgia,rash and so on and major adverse cardiac events(MACE)(defined as angina pectoris, nonfatal myocardial infarction, reintervention procedure[coronary artery bypass grafting, repeated PCI, PCI for a new leision])were followed up during treatment .Results1. LDL-C was significantly reduced only in SI/EZ group at 4 weeks(P<0.05), the level of both LDL-C and TC were significantly decreased after 12 weeks among three groups, LDL-C was similarly reduced in monotherapy (27.2% vs 22.6%) and in combined therapy group (32.2%)(all P>0.05). The TG level decreased after 12 weeks in SI/EZ group was higher than that both in SI group and AT group (29.5% vs 12.2% vs 5.6%, all P<0.05); compared to baseline, HDL-C increase by 4.0%,9.2% and 10.4 respectively in those groups, the level were higher both in SI/EZ group and SI group than that in SI group (all P<0.05). apo A,apo B and Lp(a) remained unchanged among three groups after treatment.2. At weeks, hs-CRP was significantly reduced only in combined therapy group(P<0.05). At the end of study, the hs-CRP level were significantly decreased in all groups (45.4% vs 50.0% vs 44.5% respectively, all P<0.05), the difference did not reach statistical significance(all P>0.05).3. The rates reaching the target level defined by China Heart Association (LDL-C<2.60mmol/L) were 60.0%,76.7% and 63.3% respectively in all groups, the rate in SI/EZ group tended to be higher than that in SI group and in AT group (93.3% vs 83.3% vs 86.7%, all P>0.05).4. After 12 weeks, the cholesterol synthesis makers, including squalene,desmosterol and lanthosterol, all significantly decreased in monotherapy groups (all P<0.05) and remain unchanged significantly in combined group (P>0.05). In contrast, the cholesterol absorption makers, including campersterol,stigmasterol and sitosterol, all significantly decreased in SI/EZ group (81% vs 48% vs 18%, all P<0.05); these absorption makers increased both in SI group and in AT group, moreover, the latter in higher than the former (all P<0.05).5. At 12 weeks, the changed tendency of the cholesterol synthesis makers:cholesterol ratios and the cholesterol absorption makers:cholesterol ratios were similar with these cholesterol makers, although the changed degree may be difference to some extent. 6. Twelve-week follow-up was available in 90(100%) of patients. The incidence of MACE after PCI in three groups were at the same(3.3%).7. None had increased peptase or creatase of clinical significance. The incidence of common adverse reactions, such as increased peptase or creatase and abdominal discomfort and so on, were similar among three groups, but the SI/EZ group had the lowest incidence.Conclusion1. The lipid profile and the hs-CRP were obviously improved among three groups. The LDL-C goal attainment and the effect on TG were better than monotherapy groups.2. Co-administration of ezetimibe and statins significantly decreased plasma levels of all of these makers, effective inhibition of cholesterol synthesis and subsequent reduction in serum cholesterol levels by statins lead to increases in serum absorption makers level, and the effect on cholesterol metabolism with atorvastatin was more powerful than that with simvastatin.3.The combined therapy can improve the clinical prognosis as statin alone do .4. Ezetimibe plus atorvastatin was well tolerated, with a safety profile similar to atorvastatin alone and to simvastatin alone, and the combined therapy had less adverse reaction.The three lipid-lowering all can significantly reduce the level of LDL-C and TG, moreover, the combined therapy can improve cholesterol metabolism. the drugs association of complementary mechanism of action should be consider a rational way, in order to raise the rate of LDL-C goal attainment and improve cholesterol metabolism. Coadministration of ezetimibe and atorvastatin offers a well-tolerated and highly efficacious new treatment option for patients with coronary heart disease, especially in patients with high risk.