Statins are a kind of prescription drug that is widely used to treat hyperlipidemia, coronary artery disease, and other atherosclerotic diseases. A common side effect of statin use is a mild rise in liver aminotransferases, which occurs in less than 3% of patients. Statin-related liver injury is most commonly caused by atorvastatin and simvastatin, but severe liver injury is uncommon. Therefore, understanding and evaluating hepatotoxicity and weighing the benefits and risks is of great significance to better realize the protective effect of statins.
Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects* ; Atorvastatin/adverse effects* ; Simvastatin/adverse effects* ; Chemical and Drug Induced Liver Injury/drug therapy* ; Drug-Related Side Effects and Adverse Reactions/drug therapy*

BACKGROUNDResearches in arterial elasticity have increased over the past few years. We investigated the effects of simvastatin on vascular stiffness in fat fed rabbits by ultrasonography.

METHODSThirty rabbits were assigned randomly to 3 groups: normal control group (A), the cholesterol group (B), simvastatin group (C: high fat diet for 4 weeks and high fat diet + simvastatin for further 4 weeks). Stiffness coefficient, pressure strain elastic modulus and velocity of pulse waves in abdominal aorta and femoral artery were measured by ultrasonographic echo tracking at the end of the 4th and the 8th weeks.

RESULTSAt the end of the 4th week, stiffness coefficient, pressure strain elastic modulus and pulse wave velocity of femoral artery were significantly increased in group B compared with those in group A. Similarly, at the end of the 8th week, the same parameters of abdominal aorta were significantly increased in group B compared with those in group A. In contrast, stiffness coefficient, pressure strain elastic modulus and pulse wave velocity of femoral artery were significantly decreased in group C compared with those in group B, however, there was no significant difference in parameters of abdominal aorta between groups B and C.

CONCLUSIONShort term administration of simvastatin can improve the elasticity of femoral artery but not abdominal aorta.

Animals ; Anticholesteremic Agents ; therapeutic use ; Aorta, Abdominal ; drug effects ; Blood Flow Velocity ; drug effects ; Dietary Fats ; adverse effects ; Femoral Artery ; drug effects ; Rabbits ; Random Allocation ; Simvastatin ; therapeutic use

OBJECTIVETo investigate the clinical features and prognosis of rhabdomyolysis related to seizure attacks and use of statin.

METHODSThe medical records of 3 patients with established diagnosis of rhabdomyolysis were analyzed and the related literatures were reviewed.

RESULTSAll the 3 patients had seizure attacks and/or used statin before the onset of rhabdomyolysis. Two of the patients complained of back pain, and all the 3 patients had dark-colored urine. Serum levels of creatine kinase (CK) were markedly increased by over 50 times above the normal upper limit. CK level kept increasing even after proper interventions, till reaching the peak level about 3 days later. The patients improved rapidly with full recovery thereafter, and CK became normal in 2 weeks. None of the patients had renal failure.

CONCLUSIONSeizure attacks and use of statin are common risk factors for non-traumatic rhabdomyolysis. Caution needs to be taken when prescribing statin to patients with recent seizure attacks. Special attention should be given to such early symptoms as muscle pain, weakness and dark-colored urine, and CK level monitoring is advisable in such cases.

Cerebral Infarction ; drug therapy ; Creatine Kinase ; blood ; Epilepsy ; complications ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; adverse effects ; therapeutic use ; Lovastatin ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Rhabdomyolysis ; chemically induced ; enzymology ; etiology ; Simvastatin ; adverse effects ; therapeutic use

OBJECTIVEThe aim of this study was to evaluate the efficacy and safety of combination therapy with simvastatin and fenofibrate in patients with combined hyperlipidemia.

METHODSA total of 221 patients with combined hyperlipidemia were randomly assigned to receive 10 mg simvastatin (n = 72) or 200 mg fenofibrate (n = 68), or a combination of 10 mg simvastatin + 200 mg fenofibrate (n = 81) for 6 months. Lipid profiles, physical and laboratory investigations for adverse effects were assessed.

RESULTS(1) Combination treatment were more effective in normalizing lipid profile than any monotherapy. Serum TC, LDL-C, and TG were reduced by 30%, 37% and 56% respectively, whilst HDL-C significantly increased by 24% (all P < 0.01). The improvement in TG and HDL-C achieved by combination treatment was superior to fenofibrate or simvastatin alone. (2) The success rate of TC, LDL-C and TG control in the combination therapy group were 51%, 55% and 61% respectively, with an overall success rate (all three together) of 45%, which was superior to either drug given as monotherapy. (3) All treatments were well tolerated with no increase in adverse events for combination therapy versus monotherapy.

CONCLUSIONThe results of this study demonstrated that combination therapy with fenofibrate (200 mg/day) and low-dose simvastatin (10 mg/day) is more effective than monotherapy in patients with combined hyperlipidemia, and is generally safe and well tolerated.

Drug Therapy, Combination ; Female ; Fenofibrate ; administration & dosage ; adverse effects ; therapeutic use ; Humans ; Hyperlipoproteinemia Type V ; drug therapy ; Hypolipidemic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Simvastatin ; administration & dosage ; adverse effects ; therapeutic use

Aspirin ; therapeutic use ; Bisoprolol ; therapeutic use ; Cardiomyopathies ; chemically induced ; etiology ; Cardiotonic Agents ; adverse effects ; Chest Pain ; diagnostic imaging ; Dobutamine ; adverse effects ; Echocardiography, Stress ; adverse effects ; Enalapril ; therapeutic use ; Humans ; Male ; Middle Aged ; Simvastatin ; therapeutic use

BACKGROUNDCigarette smoking has an influence on both arterial-type and venous-type thrombosis. However, little is known about the direct effect of cigarette smoke extract (CSE) on fibrinolytic activity of human umbilical vein endothelial cells (HUVECs). Most recently, simvastatin has been marked in its effect on endothelial cells protection and anticoagulation. In this study, the effect of CSE on the expression of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in HUVECs was addressed. The role of simvastatin in CSE-induced fibrinolytic activity changes was investigated as well.

METHODSThe fourth to fifth generation of HUVECs were incubated respectively with 0, 5%, 10% and 20% CSE for 6 hours or exposed to 5% CSE for 0, 4, 6, 8, 12, 24 hours to determine the expression changes of t-PA and PAI-1 protein. Meanwhile, cells were also accordingly exposed either to 5% CSE alone or simvastatin pre-treated and 5% CSE for 24 hours to assess the role of simvastatin in CSE-induced t-PA and PAI-1 protein and mRNA expression in HUVECs. RT-PCR and ELISA techniques were used for detecting the t-PA or PAI-1 mRNA and protein.

RESULTSAfter 6-hour exposure to CSE, the expression levels of t-PA protein in 10% and 20% CSE-treated groups reduced significantly ((0.0365 +/- 0.0083) ng/ml, (0.0255 +/- 0.0087) ng/ml) when compared with that of control group ((0.0660 +/- 0.0120) ng/ml) (P < 0.05). In contrast, the levels of PAI-1 protein in 5%, 10% and 20% CSE-treated groups increased remarkably ((13.3225 +/- 0.5680) ng/ml, (14.2675 +/- 1.5380) ng/ml, (14.4292 +/- 1.6230) ng/ml) when compared with that of control group ((8.5193 +/- 0.7537) ng/ml) (P < 0.05). After stimulation with 5% CSE for 0, 4, 6, 8, 12, 24 hours, the levels of PAI-1 protein increased over time and reached the peak at 24 hours ((14.6400 +/- 1.0651) ng/ml), which was significantly higher than that of control group ((12.0656 +/- 0.6148) ng/ml) (P < 0.05). Additionally, CSE could up-regulate PAI-1 expression at both the mRNA and the protein levels. The levels of PAI-1 mRNA and protein increased significantly in 5% CSE-treated group ((8.8030 +/- 0.4745) ng/ml, (1.8155 +/- 0.0412) ng/ml) compared with those of control groups ((5.0588 +/- 0.2315) ng/ml, (1.3030 +/- 0.0647) ng/ml) (P < 0.01), and decreased after 2-hour simvastatin pre-treatment ((5.4875 +/- 0.3166) ng/ml, (1.3975 +/- 0.0297) ng/ml) (P < 0.01). No significant difference was found at the levels of t-PA protein and mRNA (P > 0.05).

CONCLUSIONSCSE inhibits the fibrinolytic activity of HUVECs in vitro. Simvastatin plays a protective role in CSE-induced fibrinolytic malfunction.

Cells, Cultured ; Endothelial Cells ; metabolism ; Fibrinolysis ; drug effects ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; pharmacology ; Plasminogen Activator Inhibitor 1 ; analysis ; biosynthesis ; genetics ; Simvastatin ; pharmacology ; Smoke ; adverse effects ; Tissue Plasminogen Activator ; analysis ; biosynthesis ; genetics ; Tobacco ; adverse effects ; Umbilical Veins ; cytology

BACKGROUND/AIMS: The efficacy and safety of a combination of ezetimibe and low-dose statin as primary treatment for dyslipidemia in renal transplant patients were evaluated prospectively. METHODS: The study enrolled 77 renal transplant recipients with dyslipidemia. They were given ezetimibe (10 mg) and simvastatin (10 mg) for 6 months as the initial treatment for dyslipidemia. Efficacy and safety were evaluated using lipid profiles, trough calcineurin inhibitor levels, allograft function, and adverse effects. The effects on proteinuria and high sensitivity C-reactive protein (hsCRP) levels were also evaluated. RESULTS: Ezetimibe and low-dose simvastatin significantly decreased the levels of total cholesterol (34.6%), triglyceride (16.0%), and low-density lipoprotein cholesterol (LDL-C) (47.6%), and 82.5% of the patients reached the target LDL-C level of <100 mg/dL. No significant change in the trough calcineurin inhibitor levels or allograft function occurred, and no serious adverse effects were observed. Fourteen patients (18.2%) discontinued treatment; eight patients (11.7%) developed muscle pain or weakness without an increase in creatinine kinase levels, and two patients (2.6%) developed elevated liver transaminase levels. The proteinuria and hsCRP levels did not change significantly. CONCLUSIONS: Ezetimibe and low-dose statin treatment is safe and effective as a primary treatment for dyslipidemia in renal transplant patients.
Adult ; Azetidines/*administration & dosage/adverse effects ; C-Reactive Protein/analysis ; Cholesterol, LDL/blood ; Dyslipidemias/blood/*drug therapy ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*administration & dosage ; *Kidney Transplantation ; Male ; Middle Aged ; Prospective Studies ; Simvastatin/*administration & dosage/adverse effects

OBJECTIVETo evaluate the effectiveness and safety of Taizhi'an (TZA) capsule combined with Simvastatin (Sim) in treating hyperlipidemia in diabetes mellitus (DM) patients.

METHODSEighty cases of type 2 DM patients with hyperlipidemia were randomized into two groups, 40 in each group. The patients in the treated group took orally TZA capsules at the dose of 0.9 g 3 times a day and Sim 10 mg at bedtime. And the patients in the control group were treated with Sim 20 mg alone at bedtime. Both regimens lasted for 12 weeks. Before and after the study the changes of blood lipid levels and adverse reaction were investigated.

RESULTSThe serum levels of total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) were decreased respectively by 28.8%, 18.2% and 26.3% in the treated group; and by 29.4%, 19.4% and 24.6% in the control group. On the contrary, high density lipoprotein-cholesterol (HDL-C) was increased by 23.5% in the treated group and by 29.4% in the control group. All these changes were statistically significant before and after treatment (all P < 0.05), but they did not differ statistically between the two groups (P > 0.05). There was no significant changes in hemoglobin A(1)c (HbA(1)c). Patients in the treated group did not develop any adverse reactions. However, ALT was found to be higher above the normal range in 5% of the patients in the control group.

CONCLUSIONIn treating hyperlipidemia in DM patients, combination of TZA with Sim 10 mg taken daily achieved satisfactory efficacy which was similar to Sim 20 mg daily alone. But the combination therapy conducted in the treated group proved to be better in safety, and could overcome adverse reactions resulting from Sim that was seen in the control group.

Adult ; Aged ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Diabetes Mellitus, Type 2 ; blood ; complications ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Female ; Glycated Hemoglobin A ; analysis ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; administration & dosage ; adverse effects ; Hyperlipidemias ; blood ; complications ; drug therapy ; Hypolipidemic Agents ; administration & dosage ; adverse effects ; Male ; Middle Aged ; Phytotherapy ; Simvastatin ; administration & dosage ; adverse effects ; Triglycerides ; blood

Dental surgery is very common, and it is important for our dental colleagues to understand the medical history and chronic medications of our co-managed patients. Antibiotic prophylaxis is currently recommended only for patients at high risk for infective endocarditis when undergoing high-risk dental procedures. Good dental hygiene can prevent more infective endocarditis than prophylactic antibiotic therapy, as transient bacteraemia is common in daily activities such as the brushing and flossing of teeth. Most dental surgeries can generally be performed on patients taking a daily dose of aspirin, but the dentist must be able to assess the risk-benefit ratio of employing local measures of haemostasis versus stopping the antiplatelet therapy. Patients on antiplatelet with recent coronary artery stenting should be referred to their primary cardiologist regarding the cessation of these agents before any surgery.
Angioplasty ; Antibiotic Prophylaxis ; methods ; Aspirin ; therapeutic use ; Dental Care for Chronically Ill ; methods ; Dentists ; Drug Interactions ; Endocarditis ; prevention & control ; Humans ; Hyperlipidemias ; complications ; Macrolides ; adverse effects ; Male ; Mitral Valve Prolapse ; complications ; Myocardial Ischemia ; complications ; Platelet Aggregation Inhibitors ; adverse effects ; Simvastatin ; adverse effects ; Streptococcal Infections ; prevention & control ; Tooth Extraction ; methods ; Viridans Streptococci ; metabolism

HMG-CoA reductase inhibitors (statins) are widely used to treat hypercholesterolemia. Among the adverse effects associated with these drugs are statin-associated myopathies, ranging from asymptomatic elevation of serum creatine kinase to fatal rhabdomyolysis. Fluvastatin-induced fatal rhabdomyolysis has not been previously reported. We describe here a patient with liver cirrhosis who experienced fluvastatin-induced fatal rhabdomyolysis. This patient had been treated with simvastatin (20 mg/day) for coronary artery disease and was switched to fluvastatin (20 mg/day) 10 days before admission. He was also taking aspirin, betaxolol, candesartan, lactulose, and entecavir. Rhabdomyolysis was complicated and continued to progress. He was treated with massive hydration, urine alkalization, intravenous furosemide, and continuous renal replacement therapy for acute renal failure, but eventually died due to rhabdomyolysis complicated by hepatic failure. In conclusion, fluvastatin should be used with caution in patients with liver cirrhosis, especially with other medications metabolized with CYP2C9.
Coronary Artery Disease/complications/*drug therapy ; Fatal Outcome ; Fatty Acids, Monounsaturated/administration & dosage/*adverse effects/therapeutic use ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage/*adverse effects/therapeutic use ; Indoles/administration & dosage/*adverse effects/therapeutic use ; Liver Cirrhosis/*complications ; Male ; Middle Aged ; Rhabdomyolysis/*chemically induced ; Simvastatin/administration & dosage/therapeutic use