Effects Of Loading-dose Homemade Rosuvastatin On Cardiac Markers After Percutaneous Coronary Intervention

ObjectivePCI (percutaneous coronary intervention) is one of main treatment methodsof coronary heart disease, and its application becomes more and morewide.Studies have shown that the PCI is accompanied with a certain amount ofmyocardial damage after the operation, the incidence rate is5-40%and theclinical manifestation is the increase of cardiac markers; the damage in mostpatients does not cause corresponding symptoms and the change ofelectrocardiogram, but it brings side effects to the prognosis of the patients andincreases both the death rate and the incidence rate of adverse events, so how toimprove the perioperative and long-term prognosis after the PCI is a focus in thecardiovascular field. Recently, some retrospective studies have shown thatgiving statins before the PCI is capable of reducing the incidence rate ofpostoperative myocardial infarction and then improving the prognosis; but thestudies are not unified in aspects such as the patient inclusion standard, the typeof the statins, the dosage and the use method. A conclusion can be obtained fromARMYDA-ACS (preoperative atorvastatin80mg+40mg followed bypostoperative40mg maintenance) and Korean studies (preoperative rosuvastatin40mg followed by postoperative10mg maintenance), which indicates that theapplication of loading-dose atorvastatin or rosuvastatin before the PCI operationobviously decreases main cardiac events of ACS (acute coronary syndrome).The loading-dose statins treatment needs to increase the drug dosage; theincrease of the side effects of the statins is dose-dependent. Either abnormalliver enzymes or rhabdomyolysis risk is dose-dependent. The most serious sideeffect of the statins manifests as myalgia or myasthenia, so it is necessary to payattention to the side effects of the drugs before choose the loading-dose statins treatment. Summaries of Brewerhb show that the atorvastatin, fluvastatin andlovastatin are accompanied with rather large increase of creatase or liverenzyme along with the increase of the drug dosage, while the rosuvastatin isaccompanied with relatively small increase of the liver enzyme and the creatasealong with the increase of the drug dosage, which shows advantages of therosuvastatin in hepatotoxicity and muscle toxicity. The long-term use ofconventional drug treatment also needs to consider drug metabolism; theinteraction of the drugs will decrease the tolerance of the drugs and increase theside effects. Both simvastatin and the atorvastatin are metabolized bycytochrome P4503A4isozyme; the drug metabolism is reduced when the drugsare used together with CYP3A4inhibitor, so the risk of cardiomyopathy isincreased by6times. Use the rosuvastatin not metabolized by the cytochromeP4503A4isozyme, so the interaction rate among the drugs is reduced. But norelevant research about the effects of the homemade rosuvastatin on thepercutaneous coronary intervention has been reported. The study researchespatients with unstable angina by a random contrast method, and use differentdosages of the homemade rosuvastatin before the operation to observe the effecton the myocardial enzyme after the PCI. The study learns the effects of differentdoses of the homemade rosuvastatin on the perioperative and long-termprognosis after the PCI operation according to observing the change of themyocardial enzyme after the PCI adopting the homemade rosuvastatin.MethodsChoose90cardiologic inpatients having the unstable angina and waitingfor the PCI treatment angina in our hospital (male49, female41, age52.5-66.9),completely satisfying a UAP (unstable angina pectoris) diagnosis standardsuggested by WHO (world health organization). All the chosen objects are notthe patients with acute myocardial infarction, the patients with troponin T orcreatine kinase MB higher than upper normal limit when being selected, thepatients with increased liver enzyme (ALT), the patients with serious renalinsufficiency, the patients with liver disease or muscle disease histories or thepatients with constraints to other statins. Randomly divide the patients withunstable angina into a homemade rosuvastatin intensive treatment group (30cases including male18and female12, age53.5-65.9, average age59.6±6.3), ahomemade rosuvastatin conventional treatment group (30cases including male 16and female14, age52.5-66.0, average age59.7±7.2), and a placebo group (30cases including male16and female16, age51.5-65.9, average age59.0±6.4).The difference in the aspects such as the age, the gender, the weight index, thesmoking proportion, the hypertension proportion, the left ventricular ejectionfraction, the blood pressure, the heart rate and the blood fat level among thethree groups is not statistically significant and has comparability. The patientsof the intensive treatment group were treated with3-7days of the homemaderosuvastatin according to40mg/d (rosuvastatin calcium tablets, NanjingXianshengdongyuan Pharmaceutical Company, specification10mg) before thePCI; the patients of the conventional treatment group took the homemaderosuvastatin according to10mg/d (rosuvastatin calcium tablets, NanjingXianshengdongyuan Pharmaceutical Company, specification10mg) before thePCI; and the patients of the placebo group did not take the statins before the PCI.The patients of the three groups receive other conventional treatment.Respectively detect the troponin T level and the CK MB level of the patients ofthe three groups before the PCI operation,6hours later after the operation and12hours later after the operation; and observe the incidence rate of adversecardiovascular events (myocardial infarction, death, and revascularization)1month later after the PCI operation. Perform statistical analysis: adopt SPSS11.5statistical software for the statistical analysis;present the measured data byaverage±standard deviation (X±S), and use independent samples t to test thecomparison between two groups; and present the measured data by percentage,and test the comparison among the groups by X2. All the tests P<0.05considerthat the difference is statistically significant.ResultsThe troponin T level and the CK MB level of the patients of the threegroups after the operation are higher than those before the operation;both theincrease incidence rate of the troponin T and that of the CK MB of the patientsof the conventional treatment group after the CPI are17.6%, which are24.5%and32.7%lower than that of the placebo group, but the difference is notstatistically significant (P>0.05); the increase incidence rate of the troponin Tand that of the CK MB of the patients of the intensive treatment group after theCPI respectively are15.2%and28.2%, which are20%and32.7%lower thanthat of the conventional treatment group and26.6%and36.7%lower than that of the placebo group, and comparison difference is statistically significant(P<0.01). The increase incidence rate of the cardiac markers of the loading-dosehomemade rosuvastatin treatment group after the PCI is obviously reduced incomparison with that of the conventional treatment group and that of theplacebo group, and the comparison difference is statistically significant(P<0.01). White blood cells in the patients of the intensive treatment group andthe white blood cells in the patients of the conventional treatment group afterthe CPI treatment are similar to the change of high-sensitivity C-reactive protein;in the followed1-month visit, both the two groups have no major adversecardiac events such as death, myocardial infarction and revascularization.ConclusionsGiving the loading-dose homemade rosuvastatin before the PCI treatmenthas good safety and has a possibility of potentially reducing the incidence of themyocardial damage after the PCI. A mechanism of obtaining benefit by using theloading-dose homemade rosuvastatin before the PCI operation is not clear,which is mainly considered to be related to pleiotropic effects of the statins atpresent. The statins also have other non-descendens blood fat effects besideshaving the function of reducing the concentration of blood cholesterol. Atpresent, the non-descendens blood fat effects are known as the pleiotropiceffects of the statins. The functions of the homemade rosuvastatin before thePCI treatment are as follows:1, an anti-inflammatory function, reducing thelevel of adhesion molecules and inflammatory factors;2, an anti-oxidationfunction, decreasing the content of free oxygen radicals and playing ananti-oxidation role;3, improving blood vessel endothelium;4, blockadingexcessive activation of neuroendocrine;5, improving myocardial remodeling;6,resisting against coagulation and platelets. Since the number of the samples issmall and the follow-up visit time is short, the functions need furtherconfirmation by large-scale clinical experiments.