An Experimental Study On The Lipid-modulating Effects And Safety Of Domestic Pitavastatin Calcium

Objective: Many clinical trials have demonstrated that statins, 3-Hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitors, can prevent and reduce coronary heart disease and total mortality risk by lowering serum cholesterol level. The anti-atherosclerotic effect of statins on serum lipoproteins can be explained largely by the reduction of serum low-density lipoprotein cholesterol ( LDL-C ) levels. Therefore, various clinical practice guidelines have made lowering serum LDL-C level as the primary target of cholesterol lowering therapy. In spite of statin treatment, there are many patients in primary and secondary prevention who fail to reach the target LDL-C levels. It indicates that lipid–modulating medicine can not meet clinical demands at present. Therefore, more powerful drugs without severe adverse are thought to be needed. More recently,the newly developed pitavastatin calcium is called superstatin for well cholesterol-lowering. Abroad clinical trials have showed that pitavastatin calcium is well-tolerated and effective in lipid–modulating and more efficacious than other currently available statins in reducing TC, TG , LDL-C and increasing HDL-C. However,there is no relative report at home. This study was designed to assess the lipids-regulating effect and the safety of domestic pitavastatin calcium and compare it with simvastatin in order to provide a potentially better therapertic choice for lipid-modulating therapy.Methods:Patient's selection: The study group comprised of 36 patients who were suffering from primary hypercholesterolemia in outpatient service of the General Hospital of HeBei Province from January 2007 to August 2007, including 19 male patients and 17 female patients. Eligible patients were between the ages of eighteen and seventy-five years with serum TC level>5.72mmol/L(220mg/dl), serum LDL cholesterol level LDL–C>3.64mmol/L(140mg/dl) and serum TG level<4.52mmol/L(400mg/dl).Study participants could not concurrently take drugs known to affect lipid levels or interact with the study results. Written informed consent to participate in the study was obtained from each patient ahead of time. The following exclusion criteria were required for patients enrollment:①BMI<19kg/m2,②a history of acute conoary syndrome or cerebral apoplexy in recent 6 months,③uncontrolled hypertension(systolic blood pressure≥180mmHg or diastolic blood pressure≥110mmHg),④serious arythmia such as frequent ventricular premature beats, frequent ventricular tachycardia, second degree A-V block or third degree A-V block,⑤Patients had heart failure of New York Heart Association (NYHA) class III or IV,⑥AST and/or ALT≥2 times upper limit of normal,⑦ serum Cr>upper limit of normal,⑧myopathy or serum CK≥2 times upper limit of normal,⑨type 1 diabetes mellitus, uncontrolled type 2 diabetes mellitus (glycopenia or fasting blood sugar≥9.99mmol/L ).We adopted randomized double-blind double-imitated parallel controlled design. All patients should firstly take 2 tablets placebo (pitavastatin calcium–matched placebo or simvastatin-matched placebo) once a day for 4 weeks. After run-in period, 36 patients qualified for the test were randomly divided into 3 groups. There were 12 patients in group A, B and C(A= pitavastatin 2mg, B= simvastatin 20mg, C=pitavastatin 1mg).They took medicine orally each night for 8 weeks continuously. TC, LDL-C, HDL-C, TG, Glucose, creatine kinase,hepatic function and renal function were measured regularly at week -4, 0, before study entry and at week 4, 8, during the study period. Chief complaints were recorded during the follow-up.Statistics analysis: All data were managed by SPSS 13.0. Measurement data were expressed as mean士standard deviation. Statistical methods include repeated measurements ANOVA. LSD was used to compare the two groups. Chi-square test and Fisher exact test were used for analysis of categorical data.P value <0.05 was considered statistically significant.Results: 1 36 patients finished the trial altogether.2 After 4, 8 weeks'treatment, serum TC, LDL-C were significantly reduced striking (P<0.05) and serum TG was decreased (P>0.05), serum HDL-C was increased (P>0.05) compared with baseline (0week) among three groups. There was no more significant at the 8 week than at the 4 week to three groups in serum TC, LDL-C, TG and HDL-C level (P>0.05).3 TC, LDL-C, HDL-C, TG did not differ significantly among three groups at 0 week (P>0.05). After 4, 8 weeks'treatment, group A and B yielded significantly reduction from 0 week in serum LDL-C compared with group C respectively (P<0.05). There was no significant difference between group A and B in serum LDL-C level after 4, 8 weeks'treatment. The data also showed there was no significant difference in serum TC, TG and HDL-C level among the three groups after 4, 8 weeks'treatment (P>0.05).4 According to the LDL-C goals of therapy recommended by《China guideline for prevention and treatment of adult dyslipidemia》(2007),cases attaining the goals in group A, B and C were 83.3%, 83.3%, 75.0% at the 4 week respectively and 91.7%, 83.3%, 75.0% at the 8 week respectively. There were no significant difference in reaching LDL-C target among the there groups at 4 and 8 week(P>0.05).5 The incidence of side effects in the three groups was similar(P>0.05).Conclusions: Pitavastatin 2mg and 1mg can significantly decrease LDL-C, TC level. In decreasing LDL-C, pitavastatin 2mg was more effective than pitavastatin 1mg. The LDL-C goal achievement rate of pitavastatin was higher than that of simvastatin. The adverse event profile was similar for pitavastatin and simvastatin groups. The clinical effects of pitavastatin was exact and safe, and it was worthy of applying for the clinical treatment.