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PubMed1999

Comparison of therapy with simvastatin 80 mg and atorvastatin 80 mg in patients with familial hypercholesterolaemia.

This study compared the efficacy of simvastatin 80 mg and atorvastatin 80 mg in the treatment of 26 patients with familial hypercholesterolaemia over 12 weeks using an open crossover trial format. Both, similarly, reduced LDL by 47 +/- 13% and 43 +/- 16% and median triglycerides by 22% and 27% respectively. However, atorvastatin reduced HDL by 2 +/- 24% compared with 8 +/- 30% increase with simvastatin (p = 0.05) affecting the LDL:HDL ratio achieved (4.478 +/- 1.56 vs 3.74 +/- 0.93, p = 0.001). Atorvastatin raised median fibrinogen by 15% compared with a non-significant 5% increase with simvastatin (p = 0.05). Simvastatin reduced lipoprotein (a) by a median 20% compared with baseline (p = 0.05) compared with 5% for atorvastatin. Side-effects, mostly gastrointestinal, were seen in four patients (16%) with atorvastatin compared with one case of myalgia with simvastatin (4%). We conclude both drugs are equally effective in LDL reduction but that simvastatin is superior in raising HDL and causes fewer side-effects. These results require confirmation in larger studies.

Adult↗
PubMed2001

Cholesterol metabolism in primary biliary cirrhosis during simvastatin and UDCA administration.

Little is known about the effects of cholesterol-lowering agents in hypercholesterolemic patients with primary biliary cirrhosis (PBC). The aim of this study was to compare the changes induced by simvastatin and ursodeoxycholic acid (UDCA) on cholesterol metabolism in patients with PBC and preserved liver function. Six patients with PBC were administered simvastatin (40 mg/day) for 30 days and, after a washout period of 30 days, ursodeoxycholic acid (600 mg/day) for 30 days. Serum levels of lathosterol, campesterol, 7 alpha-hydroxycholesterol, and 27-hydroxycholesterol were measured by gas chromatography-mass spectrometry. During simvastatin administration, reduction of cholesterol levels (34% in 30 days) was paralleled by the decrease of lathosterol (55%), whereas concentrations of campesterol and of the two hydroxysterols were not substantially modified. During ursodeoxycholic acid administration, a trend toward a decrease of serum cholesterol concentrations was observed after only one year of treatment, and these changes were paralleled by the decrease of campesterol serum levels. Both simvastatin and UDCA were well tolerated, and a reduction of serum liver enzyme levels occurred with the latter. Simvastatin proved to be safe and effective in reducing serum cholesterol levels in patients with PBC by an inhibitory effect on cholesterol synthesis occurring within 24 h. --Del Puppo, M., M. Galli Kienle, A. Crosignani, M. L. Petroni, B. Amati, M. Zuin, and M. Podda. Cholesterol metabolism in primary biliary cirrhosis during simvastatin and UDCA administration. J. Lipid Res. 2001. 42: 437--441.

Aged↗
PubMedDate not supplied

Lipid-lowering effect of simvastatin in patients of type 2 diabetes mellitus.

BACKGROUND: Dyslipidemia is an important factor in causation of macrovascular disease in type 2 diabetics. The role of simvastatin in the management of dyslipidemia in patients with type 2 diabetes mellitus is not very well elucidated, particularly in the context of the recent American Diabetes Association criteria 2001. The American Diabetes Association suggests that aggressive therapy of diabetic dyslipidemia will reduce the risk of coronary heart disease in diabetics and that optimal levels are serum low-density lipoprotein cholesterol <2.60 mmol/L (< 100 mg/dl), high-density lipoprotein cholesterol >1.1 5 mmol/L (>45 mg/dl) and triglycerides <2.30 mmol/L, (<200 mg/dl). This study was planned to compare the effect of simvastatin together with behavioral modification and behavioral modification alone, in age, sex and body mass index matched patients with type 2 diabetes mellitus with dyslipidemia, in reaching the target levels of various lipids as suggested by the American Diabetes Association criteria 2001. METHODS AND RESULTS: An open-label, prospective study was conducted on 80 patients with type 2 diabetes mellitus, who had fair to moderate glycemic control with a total glycated hemoglobin < 10%. The patients in the control group (n=40) were treated with only behavioral modifications like calorie control and daily walking for 30 minutes, and no lipid-lowering agent was given. The lipid profile was re-evaluated after 6 and 12 weeks. The patients in the test group (n=40) were advised behavioral modification and given simvastatin. The starting dose was 10 mg at bed time. After 6 weeks of simvastatin therapy, a lipid profile was done. If the goal of low-density lipoprotein cholesterol < 100 mg/dl and/or triglycerides <200 mg/dl and/or high-density lipoprotein cholesterol >45 mg/dl was not achieved, the dose of simvastatin was increased to 20 mg at bedtime for another 6 weeks. It was observed that low-density lipoprotein dyslipidemia was most prevalent. In the control group, a favorable alteration in lipid levels was brought about but none was statistically significant and the American Diabetes Association goals were not achieved in any of the patients. In the test group, there was a significant and favorable alteration in all lipid moieties, and the target levels were achieved in 80% of patients after 12 weeks. There was no significant alteration in glycemic control and liver functions. Myopathy and epigastric pain were seen in 1 patient in each group. CONCLUSIONS: In our study, behavioral modification alone did not achieve the target levels of various lipids in diabetic dyslipidemia as per the American Diabetes Association guidelines. Hence, pharmacological therapy with statins should be resorted to in patients with type 2 diabetes mellitus who carry a high risk of coronary heart disease. Simvastatin is a safe and efficacious lipid-lowering drug.

Adult↗
PubMed2002

Comparing the efficacy and safety of atorvastatin and simvastatin in Asians with elevated low-density lipoprotein-cholesterol--a multinational, multicenter, double-blind study.

BACKGROUND AND PURPOSE: There have been few reports on the efficacy and safety of statins in the Asian population. The study objectives were to compare the efficacy and safety of atorvastatin and simvastatin in Asian people. MATERIALS AND METHODS: This was a 16-week, double-blind, double-dummy, randomized, multicenter study involving eight medical centers in six Asian countries or areas. After a 6-week, diet-controlled, placebo lead-in period, 157 patients with low-density lipoprotein cholesterol (LDL-C) of between 160 and 250 mg/dL and serum triglyceride (TG) of less than 400 mg/dL were randomized to receive 10 mg of either atorvastatin (n = 79) or simvastatin (n = 78). After 8 weeks of treatment, all patients had the dose of study medication increased to 20 mg, irrespective of LDL-C concentration. Data obtained by monitoring lipid profiles, adverse events, and laboratory tests during the 16 weeks of study were used to assess the efficacy and safety of both treatments. RESULTS: After 8 weeks of treatment, LDL-C concentrations were reduced by 42.5% from baseline in patients receiving atorvastatin and 34.8% in those receiving simvastatin (p = 0.0006). Patients treated with atorvastatin also had a significantly greater reduction in very-low-density lipoprotein cholesterol (VLDL-C), TG, and total cholesterol (TC) after 8 weeks of treatment. The significantly greater reductions in LDL-C, VLDL-C, TG, and TC from baseline achieved with atorvastatin were still observed after an additional 8 weeks of treatment with 20 mg study medication. Both drugs increased high-density lipoprotein cholesterol (HDL-C) concentrations after 16 weeks of treatment, with no significant difference between the two treatments. After 16 weeks of treatment, 93% of atorvastatin and 85% of simvastatin patients had achieved their National Cholesterol Education Program LDL-C goals. No deaths occurred in the study population and the incidence of treatment-emergent adverse events was the same in the two groups (28%). Only one patient who was treated with simvastatin had a transaminase or creatine phosphokinase concentration that was more than three-fold the upper limit of normal. CONCLUSIONS: Asian people with primary hypercholesterolemia treated with atorvastatin had lower LDL-C, VLDL-C, TG, and TC after 8 weeks and 16 weeks of treatment than those treated with simvastatin. Both drugs demonstrated acceptable safety profiles.

Adult↗
PubMed2002

[Simvastatin (40 mg/day) in patients with hereditary hypercholesterolemia: effect on high density lipoprotein cholesterol].

AIM: To study effect of simvastatin of the level of high density lipoprotein (HDL) cholesterol (CH). MATERIAL AND METHODS: Simvastatin (40 mg/day) was given for 3 months to 15 patients (3 men, 12 women, mean age 56-/+10.3 years) with hereditary type II hypercholesterolemia after washout from lipid lowering therapy. Initial level of HDL CH was below and above 1.0 mmol/l in 7 and 8 patients, respectively. Blood lipids, activity of liver enzymes and creatine kinase were determined after 1 and 3 months of therapy with simvastatin. Safety and tolerability of simvastatin were also studied. RESULTS: Simvastatin was well tolerated. In 1 patient the drug was stopped because of pain in the liver and nausea. In patients with initially low HDL CH levels of total and low density lipoprotein (LDL) CH significantly decreased by 29.6 and 36.8%, respectively, after 3 months, while level of HDL CH increased by 20% after 1 month of therapy. In patients with initially normal HDL CH levels of total and LDL CH significantly decreased by 31.1 and 32.6%, respectively, while those of triglycerides and HDL CH did not change. CONCLUSION: In patients with hereditary hypercholesterolemia 40 mg/day of simvastatin besides pronounced lowering of LDL CH level caused significant increase of HDL CH (up to 20% in 1 month) in patients with initially low level of this parameter.

Anticholesteremic Agents↗
PubMed2003

[Simvastatin induces osteoblastic differentiation of bone marrow stromal cells].

OBJECTIVE: To observe the effect of simvastatin on osteoblastic cell differentiation of bone marrow stromal cells in vitro, and to elucidate the mechanisms of anabolic effect of simvastatin on bone formation. METHODS: Bone marrow stromal cells from femur and tibia of adult female BALB-C mice were cultured in vitro, after being treated with different concentrations of simvastatin for 72 h, changes of mRNA level of osteocalcin (OCN) were detected by RT-PCR, change of OCN, and osteopontin (OPN) expression were examined by Western blot, and the changes of cellular alkaline phosphatase activity (ALP) were examined by histochemistry and enzymologic measurement. RESULTS: After bone marrow stromal cells were treated with different concentration of simvastatin for 72 h, level of OCN mRNA increased, and expression of OCN and OPN also increased in a concentration-dependent manner, and cellular ALP activity significantly increased in a concentration-dependent manner. CONCLUSION: Simvastatin can stimulate osteoblastic differentiation, and improve cellular ALPase activity with high expression of osteocalcin and osteopontin in vitro. These may be parts of the mechanism of anabolic effect of simvastatin on bone formation.

Alkaline Phosphatase↗
PubMed1992

Simvastatin in non-insulin-dependent diabetic patients with hypercholesterolaemia.

The objective of this study was to evaluate the lipid-lowering effect of simvastatin in non-insulin-dependent diabetes mellitus (NIDDM) patients with hypercholesterolaemia while possible clinical and biochemical adverse effects were monitored for. Forty-three NIDDM patients with hypercholesterolaemia (total cholesterol > 6.5 mmol/l) used simvastatin after a detailed clinical laboratory evaluation as well as a 4-week wash-out period and a 4-week placebo baseline period. Simvastatin treatment was initiated with a 10 mg dose for 6 weeks; this was increased to 20 mg and 40 mg at 12 and 18 weeks of follow-up respectively if the total cholesterol level had not decreased to below 5.17 mmol/l. Patients were placed on a lipid-lowering diet and continued to take any regular non-lipid-lowering medication throughout the trial; side-effects were monitored at 6-week intervals until patients had taken simvastatin for 24 weeks. The mean total cholesterol level was reduced by 22.2% at the first follow-up visit, and by 24.2%, 23.3%, and 28.5% at the second, third and fourth follow-up visits respectively compared with base-line levels. A dose of 10 mg simvastatin brought about a reduction in total cholesterol similar to those found with higher doses. The mean triglyceride level was reduced by 20.9% with 20 mg simvastatin. The high-density lipoprotein cholesterol level was not altered significantly and neither was the control of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

[Effects of simvastatin only or in combination with continuous combined hormone replacement therapy on lipid levels in hypercholesterolemic women].

OBJECTIVE: To evaluate the effects of simvastatin only or combined with continuous transdermal hormone replacement therapy (HRT) on the serum lipid profile in hypercholesterolaemic women. MATERIAL AND METHODS: The study population consisted of 75 women after menopause, ranging in age from 45 to 62. The patients were divided into five groups: group I--women receiving HRT (Systen Sequi, Cilag); group II--HRT + statin (Systen Sequi, Cilag + Zocor, MSD); group III--HRT (Systen Conti, Cilag); group IV--HRT + statin (Systen Conti, Cilag + Zocor, MSD) and group V--statin only (Zocor, MSD). Before and after 3 and 6 months therapy serum total cholesterol (TC), triglycerides (TG), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) was measured. RESULTS: The combination of simvastatin + HRT or simvastatin only decreased significantly TC and LDL-C, and increased HDL-C levels at 3 months (groups II, IV and V). A comparative analysis revealed that HRT effect on TC, LDL-C and HDL-C was significantly observed after 6 months (group I and III). TG levels significantly decreased after 6 months of therapy (simvastatin + HRT) in groups II and IV. CONCLUSIONS: The combination of simvastatin and HRT seems to be more effective than simvastatin only in the treatment of hypercholesterolaemia in women.

Anticholesteremic Agents↗
PubMed2003

Effects of simvastatin on pro-inflammatory cytokines in patients with hypercholesterolemia.

BACKGROUND: The role of inflammation in the development of atherosclerosis and its complications has been recently documented. Pro-inflammatory cytokines are among many postulated factors. It is possible that the imbalance between protective cytokines and cytokines affecting endothelial function is one of the underlying mechanisms of myocardial ischaemia. AIM: To examine the effects of simvastatin on IL-2 and TNFalpha levels in patients with hypercholesterolemia. METHODS: The study group consisted of 64 males (age 20-65 years) with hypercholesterolemia. The control group was composed of 10 healthy male volunteers (age 25-40 years) with normal lipid profile. Total cholesterol, LDL-cholesterol, IL-2 and TNFalpha were measured in both groups at baseline, after three months of dietary treatment, and after a further three months of simvastatin therapy. RESULTS: Simvastatin caused a significant decrease in the total and LDL-cholesterol levels compared both with baseline measurements (p=0.0001) and after dietary treatment (p=0.0001). Moreover, simvastatin significantly reduced the IL-2 plasma concentration (p=0.0003). There were no significant differences between IL-2 levels before and following dietary treatment. The TNFalpha serum concentration significantly decreased following the implementation of diet (p=0.0001). Subsequent simvastatin therapy caused further decrease in the TNFalpha serum concentration but this difference did not achieve statistical significance. CONCLUSIONS: A hypolipemic diet significantly decreases TNFalpha serum concentration without affecting the IL-2 level. The subsequent simvastatin therapy significantly reduces IL-2 but not TNFalpha when compared with the post-diet values.

Adult↗
PubMed2003

Effects of simvastatin treatment on oxidant/antioxidant state and ultrastructure of diabetic rat myocardium.

In the present study we investigated the effects of simvastatin treatment on lipid metabolism and peroxidation, antioxidant enzyme activities and ultrastructure of the diabetic rat myocardium. Diabetes was induced by single injection of streptozotocin (45 mg/kg i.p.). Eight weeks after induction of diabetes, a subgroup of control and of diabetic rats was treated with simvastatin for 4 weeks (10 mg/kg/day, orally). Blood glucose, plasma cholesterol and triacylglycerol, as well as levels of cardiac thiobarbituric acid reactive substances (TBARS) were significantly increased in diabetic rats. The activities of antioxidant enzymes, catalase (CAT) and glutathione peroxidase (GSHPx), were also elevated in the diabetic myocardium. Treatment with simvastatin markedly reduced serum triacylglycerol and cholesterol, and partially controlled hyperglycemia in diabetic animals. The increased activation of antioxidant enzymes and the excess of lipid peroxidation measured by TBARS were completely reversed by simvastatin treatment. Diabetic rats displayed ultrastructural ischemia-like alterations of cardiomyocytes and capillaries, which support oxidative stress-induced tissue remodelling. In the diabetic myocardium simvastatin treatment partly attenuated angiopathic and atherogenic processes, detected by electron microscopy. These results suggest that simvastatin, known as a lipid-lowering drug, may positively affect diabetes induced cardiovascular complications via reducing risks of atherosclerotic pathological processes, such as imbalance between oxidant and antioxidant state.

Animals↗
PubMed1992

Efficacy and cost-effectiveness of simvastatin and gemfibrozil in the treatment of hyperlipidaemia.

The aim of this study is to compare the efficacy and cost-effectiveness of simvastatin with gemfibrozil in regulating the serum lipid profiles in the local population. In this study, we reviewed the effect of medication on 75 patients with hypercholesterolaemia with or without hypertriglyceridaemia; 26 patients were on simvastatin 10 mg nightly, 24 patients were on gemfibrozil 300 mg twice daily and 25 patients were on gemfibrozil 600 mg twice daily. The average follow-up period was 10.8 weeks, 19.0 weeks and 16.2 weeks for simvastatin 10 mg, gemfibrozil 300 mg and gemfibrozil 600 mg groups respectively. Prior to drug therapy, patients were put on dietary control. The pre-treatment and post-treatment serum lipid profiles were monitored. The mean changes in the lipid profiles of the patients on gemfibrozil 600 mg twice daily were a 21.6% reduction in total cholesterol, a 21.8% reduction in low-density lipoprotein cholesterol (LDL-C), a 46.3% reduction in serum triglyceride and an 11.2% increase in high density lipoprotein cholesterol (HDL-C). The patients in all three groups had raised HDL-C and lowered triglyceride levels post-treatment but patients on gemfibrozil had a greater increase in HDL-C and a greater decrease in triglycerides as compared to the simvastatin group. In comparison to gemfibrozil, simvastatin was more efficacious in the reduction of LDL-C. The mean reduction in the LDL-C was 21.8% for gemfibrozil 600 mg twice daily group as compared to 28.0% for simvastatin 10 mg nightly group.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-Benefit Analysis↗
PubMed2005

Comparison between duration dependent effects of Simvastatin and Gemfibrozil on dyslipidemia in patients with type 2 diabetes.

OBJECTIVE: To observe the duration dependent effects of two important classes of lipid lowering drugs i.e. simvastatin and gemfibrozil in type 2 diabetic patients with dyslipidemia in Pakistani population. METHODS: Seventy type 2 diabetic patients with newly diagnosed dyslipidemia were enrolled and were divided randomly into two groups each, with 35 patients. Group I patients was given tablets Simvastatin 20 mg once daily and group II patients received tablet Gemfibrozil 600 mg twice daily. The study period comprised of 12 weeks. Fasting lipid profile and fasting blood sugar was analyzed on week 0 (day of inclusion), week 6 and week 12. RESULTS: At week 12 simvastatin decreased serum LDL cholesterol by 36.97 percent (P < 0.001). In contrast gemfibrozil did not reduce it significantly with a reduction of only 1.33 percent (P = N.S). Simvastatin reduced serum total cholesterol and serum triglyceride by 29.88 percent (P < 0.001) and 21.78 percent (P < 0.001) respectively and increased serum HDL cholesterol by 16.67 percent (P < 0.001). While gemfibrozil decreased serum total cholesterol by 9.14 percent (P < 0.001) and serum triglyceride by 30.84 percent (P < 0.001). Gemfibrozil raised serum HDL cholesterol levels by 18.08 percent (P < 0.001). CONCLUSION: Significant changes were observed in all lipid parameters with both simvastatin and gemfibrozil with regard to duration of treatment. Simvastatin was found to be more effective in lowering serum total cholesterol and LDL cholesterol levels in comparison to gemfibrozil, which was found to be more effective in lowering serum triglyceride and elevating serum HDL cholesterol levels. Both of these drugs were well tolerated and none of the patients exhibited any significant adverse effects. Both can be given as monotherapy in patients with type 2 diabetes mellitus and abnormal lipid profile.

Adult↗
PubMed2006

[Effect of 6-month therapy with simvastatin on lipid transport function of the blood and the state of endothelium in patients with diabetes and hypertension].

The state of lipid transport function of the blood, blood contents of stable nitrogen metabolites, and proinflammatory cytokines (TNF-a and IL-1b) during therapy with simvastatin were studied in 29 patients receiving combination antihypertensive therapy with angiotensin converting enzyme inhibitors (ACEI) and verapamil. Lipid lowering action of simvastatin was realized just in 1 month of treatment and remained sustained for half a year (average duration). 6 months after addition of simvastatin to antihypertensive therapy substantial (58.4%, p=0.044) rise of plasma content of stable nitrogen metabolites took place. At the same time therapy with metoprolol in a similar group of patients exerted no considerable effect on blood plasma concentration of nitrate and nitrite anions. Lowering of median values of TNF-alpha from 20.13 (12.67-52.80) to 11.34 (3.31-31.29) pg/ml (p<0.0038) was also noted at the background of combination antihypertensive therapy. This happened without distinct affair with degree of lipid lowering action of simvastatin. The results of the study document positive effect of half year treatment of patients with concomitant hypertension and diabetes with simvastatin (10-20 mg/day) in combination with ACEI and verapamil on metabolism of nitric oxide and plasma content of TNF-alpha which realizes independently from degree of hypolipidemic action of simvastatin.

Biomarkers↗
PubMedDate not supplied

Influence of simvastatin at high dose and nifedipine on hemodynamic parameters in rabbits.

Recent findings in vitro have shown that statins could reduce cardiomyocyte viability. The correlation between statin cardiotoxicity, assessed in vitro, and cardiac efficiency, investigated in vivo has not been estimated so far. The aim of the present experiment was to establish the impact of high-dose simvastatin on the hemodynamic parameters, especially on myocardium efficiency, after continuous infusion of dopamine. Moreover, hemodynamic interaction between simvastatin and nifedipine, metabolized by the same izoenzyme CYP3A4 was examined. The experiments were performed on twenty seven New Zealand white rabbits. The animals were divided into four groups receiving: 0.2% methylcellulose (MC) (control group), nifedipine, simvastatin or simvastatin + nifedipine, for 14 days (p.o.). The following hemodynamic parameters were estimated: cardiac output index (COI), heart rate (HR), systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP) and total peripheral resistance index (TPRI). The registration of hemodynamic parameters was performed by Doppler method (Hugo Sachs Electronic Haemodyn). Dopamine did not cause a statistically significant increase in COI in rabbits receiving simvastatin alone or concomitantly with nifedipine. Nifedipine significantly lowered COI, BP and HR in rabbits if given simultaneously with simvastatin. In conclusion, administration of nifedipine may elicit detrimental impact on statin therapy, resulting in the worsening of cardiac performance. This may suggest another mechanism of drug-drug interaction than the one based on CYP3A4 inhibition.

Animals↗
PubMed2006

Simvastatin treatment improves endothelial function and increases fibrinolysis in patients with hypercholestrolemia.

OBJECTIVES: Statins reduce cardiovascular events by cholesterol-lowering as well as nonlipid-related actions. Thrombin activatable fibrinolysis inhibitor (TAFI) is a recently identified independent risk factor of thrombosis. Endothelial dysfunction is also a strong predictor of cardiovascular events. The aim of this study was to assess the effects of simvastatin treatment on circulating TAFI concentrations and endothelial function in patients with hypercholesterolemia. METHODS: Thirty-five patients (19 female, mean age 48 +/- 7 years) with hyperlipidemia were recruited into the study. Simvastatin was administered, 40 mg daily, for eight weeks to all subjects. Study subjects did not receive any medication except for lipid-lowering therapy during the follow-up period. Endothelial function was evaluated by flow-mediated dilation (FMD) from the brachial artery of the patients. Plasma lipid parameters, TAFI levels and endothelial function were measured before and after simvastatin treatment. RESULTS: Treatment with simvastatin showed a significant decrement in plasma total cholesterol, LDL cholesterol and triglyceride levels (p<0.05). Plasma TAFI levels were also significantly decreased after simvastatin treatment [median 17.0 (range 0.4-93.7) mcg/mL versus median 6.9 (range 0.8-63.0) mcg/mL, p<0.001]. Mean FMD was measured 7.7 +/- 2.5% at baseline and significantly improved after treatment (13.0 +/- 1.4%) (p=0.001). CONCLUSION: Our findings of decreased TAFI levels may reflect the beneficial effect of simvastatin treatment on fibrinolysis, and improved endothelial function may suggest the improved future cardiovascular events in hyperlipidemic patients.

Anticholesteremic Agents↗
PubMed2006

[Effects of xuezhikang and simvastatin on cerebral ischemia-reperfusion injury in rat].

OBJECTIVE: To observe the effects of Xuezhikang and simvastatin on cerebral ischemia/reperfusion injury in rat, as well as the influences after intervention with L-NAME. METHOD: Rats were given orally with Xuezhikang and simvastatin or vehicle for 2 weeks, and then subjected to middle cerebral artery occlusion for 120 min using intraluminal filament model. L-NAME were injected into the lateral ventricles in half of the rats treated with Xuezhikang and simvastatin 45 min before the ischemia. The neurological deficits examinations were performed at 2, 24, 48 h after reperfusion. After the last examination the animals were sacrificed, the infarct volumes were determined by TTC staining, and MDA levels were also measured. RESULT: Xuezhikang and simvastatin both significantly reduced the infarct volume and improved the functional recovery when compared to vehicle. Xuezhikang and simvastatin both significantly decreased the MDA accumulation after reperfusion. L-NAME partially inhibited the protective effect of Xuezhikang but nearly completely abolished the protective effect of simvastatin. CONCLUSION: Xuezhikang has protective effects on ischemic brain damage in rats, which the beneficial effects are partly due to the statins components. The other components in Xuezhikang may also account for the neuroprotective effects, which is worth further investigations.

Animals↗
PubMedDate not supplied

Simvastatin versus pravastatin: efficacy and tolerability in patients with primary hypercholesterolemia.

One hundred patients with primary hypercholesterolemia (total plasma cholesterol greater than or equal to 6.2 mmol/L [240 mg/dl]) were enrolled in an open, randomized, parallel comparative study of simvastatin and pravastatin. All patients started or continued a standard lipid-lowering diet for at least six weeks prior to entry into the four-week placebo baseline period. Fifty patients received simvastatin and 50 patients received pravastatin, both at the recommended starting dose of 10 mg/day, for a treatment period of six weeks. Total cholesterol levels were reduced by 24% (from 7.59 mmol/L to 5.80 mmol/L) with simvastatin, and by 15% (from 7.48 mmol/L to 6.35 mmol/L) with pravastatin. Low-density-lipoprotein cholesterol levels were reduced by 33% and 22% and high-density-lipoprotein cholesterol levels were increased by 10% and 7% with simvastatin and pravastatin, respectively. Plasma total triglyceride levels were reduced by 12% with simvastatin and by 6% with pravastatin. Adverse experiences were similar between treatment groups and both drugs were well tolerated. No patients were withdrawn from the study due to clinical adverse experiences; one patient in the pravastatin group required a reduction in dose to 5 mg/day due to insomnia. At the recommended starting dose, simvastatin had a significantly greater lipid-lowering effect than pravastatin. These results may have implications for the appropriate lipid-reduction therapy for patients at risk of coronary heart disease.

Adolescent↗
PubMed1990

[The effects of the cholesterol synthesis inhibitor simvastatin in patients with hypercholesterolemia with and without diabetes mellitus].

We studied the short-term effects of simvastatin on lipid variables in 33 dyslipidemic patients without and 18 with diabetes mellitus who were on a lipid-lowering diet for at least 3 months. Six diabetic patients had type I, and 12 had type II diabetes mellitus, of whom 5 were using insulin. In the whole group total cholesterol decreased by 28%, from 9.35 (SD 2.10) mmol/l to 6.69 (SD 1.47) mmol/l after 3 months and 6.60 (SD 1.27) mmol/l after 6 months (mean daily dose of simvastatin 21 (SD 12) mg). Calculated LDL-cholesterol showed a decrease of 38%, HDL-cholesterol increased by 10% and plasma triglycerides decreased by 13%. In patients receiving 10, 20, or 40 mg simvastatin daily, the following changes were observed: total cholesterol -26, -31 and -34% and LDL-cholesterol -37, -38 and -39%, respectively. The effect of simvastatin in the diabetic patients was comparable with that in the non-diabetic individuals, although in the diabetics LDL-cholesterol before therapy was lower, as was the daily dose of simvastatin after 6 months (14 versus 24 mg). In the diabetic patients blood glucose control, measured as HbA1c, was not affected. One patient discontinued therapy because of stomach complaints. Our results show that a low daily dose (10 mg) of simvastatin effectively lowers plasma total and LDL-cholesterol and that the drug can be safely used in diabetic patients.

Anticholesteremic Agents↗