Comparative Analysis Of Clinical Effects Of Routine Dose Different Statins After PCI And Related Mechanism

Coronary heart disease (CHD) is one of the leading causes of cardiac death, and itrepresents an increasing burden on healthcare resources worldwide. Percutaneouscoronary intervention (PCI) is an important means of treatment of acute myocardialinfarction and has get considerable progress and development, such as its technicaloperations, equipment design, perioperative management, and other aspects.However, PCI may lead to microcirculatory thrombosis and no flow. To reduce therisk of adverse events associated with invasive procedures, statin pre-treatmentbefore PCI have been demonstrated to be beneficial. Statins can efficiently low thecholesterol levels and exert many effects, including improvement of endothelialfunction, decreasing of vascular inflammation, inhibition of smooth muscleproliferation, and immunomodulation. Previous clinical studies have shown thathigh-dose statin pre-treatment before PCI may improve clinical outcomes byreducing periprocedural myocardial infarctions in patients with stable anginapectoris or acute coronary syndrome (ACS). Recently, many studies about statins arefocusing on the benefit from statins of maximum tolerance dose, while the studiesabout efficacy or safety of routine dose statins after PCI are rare. In this work, weconducted a prospective randomized trial to discuss the effects of routine dose statinsto patients after PCI and observe the statins’ side effects. In addition, moleculardynamics simulation is used to explain the side effects of statins. Specific studiesinclude the following two parts:1. A total of117patients with CHD post successful PCI were randomly dividedinto three groups: simvastatin20mg/day (group A), atorvastatin20mg/day (groupB), rosuvastatin10mg/day (group C). Blood were taken at baseline and one monthfor serum TG, CHOL, HDL-C, LDLC, ALT, GLU, BUN, CREA，CK. The incidenceof major adverse events, such as death, re-infarction, repeat PCI, myalgia were also observed. The results show that the values of CHOL, LDL-C in three groupsdecrease significantly compared to baseline, while it displays no statisticallysignificant difference between three groups. In addition, there were no significantchanges of the levels of ALT GLU, BUN, CREA, and no serious adverse effects ofstatin therapy after PCI in three groups. Thus the routine dose of statins is effectiveand safe to patients post PCI.2. We hypothesize that the discrepancy of CYP3A4-mediated drug interactions inclinical is ascribable to different bind energy of simvastatin and atorvastatin toCYP3A enzymes. Thus, we analysis the bind energies and sites between simvastatinand atorvastatin into CYP3A4. The three-dimensional (3D) models of simvastatinand atorvastatin into CYP3A4enzyme were constructed based on the crystalstructure (PDB ID:3UA1) and refined by molecular dynamics (MD) simulations.The results showed that simvastatin and atorvastatin can stably bound into the activesite of CYP3A4enzyme. The hydrogen bonds and hydrophobic interactions playedan important role in the stabilities of the conformation of the complexes. Comparedwith simvastatin, atorvastatin showed stronger binding capacity to CYP3A4. Thusthe impact of CYP3A inhibitors on atorvastatin pharmacokinetics is significantlysmaller than that of simvastatin. That is why the drug interactions discrepancy ofsimvastatin and atorvastatin caused during the CYP3A4-mediated precess. It is inwell agreement with the clinical results that atorvastatin is more non-sensitive to theCYP3A4-mediated drug.