ABSTRACT

[Objective]: To compare the effects of Xuezhikang and Simvastatin in patients with primary hyperlipidemia. Methods 108 patients with primary hyperlipidemia were randomly divided into two groups. Group 1,53 patients, took 4 Xuezhikang capsules per day (1.2g/day) for 8 weeks and Group 2, 55 patients took Simvastatin 10 mg per day for 8 weeks. At the end of 8 weeks, the lipid levels were compared with those of the baseline in each group. Results In Group 1,the serum levels of total cholesterol (TC), low-density lipoprotein (LDL) cholesterol and triglycerides (TG)decreased by 23.0%,28.0% and 28.1%(P<0.001),and in Group 2 reduced by 23.3%,29.5% and 29.5%(P<0.001) respectively. The serum levels of high-density lipoprotein (HDL) cholesterol after taking Xuezhikang increased by 5.0%(P>0.05) and after taking Simvastatin increased by 14.3%(P<0.01). No significant differences, however, were found between the two groups in TC, LDL cholesterol, TG, and HDL cholesterol. The side effects of Xuezhikang were less than those of Simvastatin. Conclusion: Xuezhikang made in China is a safe, effective and well toleraled lipid modulator.
[Key Words]: Hyperlipidemia Xuezhikang Simvastatin

INTRODUCTION

Xuezhikang is produced and refined with modern biotech methods. Researches have demonstrated that Xuezhikang comprises HMG-CoA reductase inhibitor, various unsaturated fatty acids and amino acids, which are essential to human beings. Xuezhikang has been shown in several animal models of hyperlipidemia to inhibit the increase in total cholesterol (TC), LDL cholesterol and triglyceride (TG).1 Acute and chronic toxicity studies have shown that Xuezhikang is well tolerated even at the dose much higher than the effective one.2 Clinical studies have also demonstrated that Xuezhikang significantly reduces serum plasma TC,LDL cholesterol and TG.

No significant changes in electrocardiograms or clinical laboratory measurements were observed previously.3,4 We compared Xuezhikang and Simvastatin in terms of safety parameters and efficacy of lowering lipid and lipoprotein in patients with hypercholesterolemia.

METHODS

From October 1995 to February 1996, 108 patients with primary hyperlipidemia were enrolled. They discontinued and medication for hyperlipidemia within 2 months and received dietary advice for 4 weeks. Eligible patients were recruited if their serum TC was =5.96 mmol/L and /or their TG was 2.26-4.52 mmol/L. In addition, the high-density lipoprotein (HDL) cholesterol was =1.04 mmol/L for men or =1.16 mmol/L for women.

Patients were excluded from this trial if in the last 6 months they had such conditions as myocardial infarction, stroke, severe trauma or major surgery, nephritic syndrome, hypothyroidism, acute or chronic hepatobi liary disorders, diabetes mellitus or gout. Women of childbearing or breast-feeding were also inegligible. According to the pretreatment TC and TG values, the patients were randomized into two groups.

Clinical design
The patients were treated by a single-blinded method. The treatment group was given Xuezhiking 0.6g twice a day (1.2g/d) for 8 weeks. The positive control group was treated with Simvastatin 10 mg every day at bedtime. Throughout the trial, all patients were asked to maintain their normal life styles, and dietary habits as suggested by physicians 4 weeks before the trial. Medications were allowed during the trial except those that could affect serum lipids.

Assessment of hypolipidemic efficacy
Serum lipids (TC, TG, and HDL cholesterol) were measured after fasting for at least 12 hours before enrollment and at the end of 4 and 8 weeks of the trial. Serum lipid measurements and other tests were performed in the laboratory, Division of Coronary Heart Diseases, Fuwai Hospital, CAMS. The quality control samples were used in the analyses of TC, TG and HDL cholesterol. The coefficient of variance (CV) for all of the three tests was less than 5%.The level of LDL cholesterol was calculated according to Friedewald equation: LDL cholesterol (mmol/L) =TC-(HDL cholesterol+TG/2.2).

The general efficacy was also assessed by an integrated analysis of improvement of serum lipids. The criteria for the assessment were as follows: highly effective: changes in serum lipids after treatment meet at least one of the followings: TC reduced=20%,TG reduced=40%, and HDL cholesterol increased=0.26mmol/L; effective: changes in serum lipids after the treatment meet at least one of the following: TC reduced from=10% to < 20%, TG reduced from =20% to < 40%, and HDL cholesterol increased from=0.10mmol/L to < 0.26mmol/L; ineffective: post treatment serum lipids is not changed or below the criteria for the rating of efficacy; deterioration: changes in serum lipids after the treatment meet at least one of the followings: TC or TG increased=10%, and HDL cholesterol reduced=0.10mmol/L.

Assessment of safety
The patients visited the clinic before the trial and 4 and 8 weeks after the treatment. Their compliance, general physical health, and symptoms were assessed on each visit. Physical examination (body weight, heart rate and rhythm, liver and spleen palpation), electrocardiography (ECG),and tests of complete blood counts, serum alanine aminotransferase (ALT),blood urea nitrogen (BUN), creatinine (Cr), glucose, and creatine kinase(CK)and urinalysis were performed before and 8 weeks after the treatment.

Statistical analysis
The data were analyzed by using the statistical software package, expressed as mean x±s. Student's t test was used to analyze the quantitative data, with the group t test for comparison of the data from the two groups, and paired t teat for comparison of continuous variables before and after the treatment. Chi-square test (odds ratio) was used to analyzing the qualitative data and the Breslow-Day test to analyze the homogeneity of odds ratios for the two groups.

RESULTS

Baseline characteristics
Of the 108 patients, 67(62%) were male. Their average age was 55.8 years (range: 30 to 79 years). Fifty patients had a history of hypertension, and 18 had coronary heart diseases (angina pectoris or myocardial infarction). No statistical differences between Xuzhikang and Simvastatin recipients were noted with regard to demographic or cardiovascular risk factors.

Effect of treatment on serum lipid and lipoprotein
Among the 108 patients, 96(47 in the Xuezhikang group and 49 in the Simvastatin group) had pretreatment TC=5.96 mmol/L. In the 108 patients (53 in the Xuzhikang group and 55 in the Simvastatin group) with pretreatment serum LDL cholesterol=3.58mmol/L, 57(29 in the Xuezhikang group and 28 in the Simvastatin group) had pretreatment serum TG=2.26 to =4.52 mmol/L, and 45 (23 in the Xuezhikang group and 22 in the Simvastatin group) had pretreatment serum HDL cholesterol<1.08 mmol/L. The ratio of non-HDL cholesterol (TC-HDL cholesterol) to HDL cholesterol was calculated for the 108 patients (53 in the Xuezhikang group and 55 in the Simvastatin group). After 4 and 8 weeks of the treatment, the lipid levels were compared with those of the baseline in each group. In the Xuezhikang group, the serun levels of TC, LDL cholesterol, TG and the ratio of non-HDL cholesterol to HDL cholesterol significantly decreased by 20.2%, 23.0%, 26.1% and 28.0%,and 33.3% and 28.1%, 29.3%, 26.5% (P<0.001) respectively. In the Simvastatin group, they were reduced by 20.5%, 23.3%, 26.1% and 29.5% and 29.4%, 29.5%,30.0% and 30.1%(P<0.001) respectively. The serum HDL cholesterol increased by 4.0% and 5.0%(p<0.05) in the Xuezhikang group and 7.3%(P<0.05) and 14.3% (P<0.01) in the Simvastatin group respectively. No significant differences were found between the two groups in TC, LDL cholesterol, TG and HDL cholesterol (Table I).

Integrated analysis of effects
The general efficacy of Xuezhikang or Simvastatin were analyzed. 41 patients in the Xuezhikang group met the criteria of highly effective and effective. In the Simvastatin group, 43 patients also met the same criteria. The total effective rate was 87.2% in the Xuezhikang group and 87.8% in the Simvastatin group. No significant difference in the total effective rate was observed between the two groups (P<0.05).

Assessment of Safety
Of the 53 patients who received Xuezhikang for 8 weeks, 2 patients (3.8%) experienced heartburn and 3 (5%-7%) tiredness. In the Simvastatin group,3 patients (5.5%) had tiredness, 3 (5.5%) constipation, 1 (1.8%) insomnia, 1 (1.8%) headache and 1 (1.8%) nausea. These symptoms resolved without specific treatment and all the patients completed their treatment. None of the 108 patients withdrawn from the trial developed any symptoms or medical conditions related to the treatment. No patient in both groups had increased serum ALT level or serum CK level two times above the upper limit of normal range (normal range: ALT = 40 IU/L, CK= 200 IU/L respectively), but one patient who had received the treatment with Simvastatin increased serum CK level from 15 IU/L to 109 IU/L with myalgia after 8 weeks.

DISCUSSION

Xuezhikang capsule is a natural HMG-CoA reductase inhibitor. Studies have shown that it significantly reduces the levels of serum TC, and TG as well as the ratio of non-HDL cholesterol to HDL cholesterol in hyperlipidemia rabbits and quails. It also can inhibit the formation of atherosclerosis clot and the deposition of lipid in the liver in hyperlipidemia rabbits. 324 patients who had received Xuezhikang capsules were compared with 122 patients who had received Jiaogulan in treating hyperlipidemia. The result indicated that Xuezhikang capsule can significantly reduce the level of serum TC, LDL cholesterol, and TG (23.0%, 28.5% and 36.5% respectively). Xuezhikang capsule is better than Jiaogulan in regulating lipids3 (P<0.001). Simvastatin has been proved one of the most potent HMG-CoA reductase inhibitor in reducing the level of serum TC. A Scandinavian study indicated that Simvastatin is valuable in reducing the total mortality and the deaths due to coronary heart disease. We selected Simvastatin as the positive control drug. There was no significant difference between Xuezhikang capsule and Simvastatin in reducing the level of serum TC, LDL cholesterol, TG as well as the ratio of non-HDL cholesterol to HDL cholesterol (P<0.05). The side effects of Xuezhikang capsule were less than those of Simvastatin. Four Xuezhikang capsules per day (1.2g/day) were similar to simvastatin 10 mg per day in regulating the level of lipids. Xuezhikang capsule is considered a natural effective lipid modulator.

REFERENCES