3.Efficacy and safety of the combination therapy of HMG CoA reductase inhibitor and fibrate in combined dyslipidemia.
Sang Min KIM ; Kyung Eun LEE ; Sung Ho LEE ; Kap Sung JUNG ; Sung Jin KIM ; Kwang Je LEE ; Sang Wook KIM ; Tae Ho KIM ; Hong Sook KO ; Chee Jeong KIM ; Wang Seong RYU
Korean Journal of Medicine 2003;65(6):682-689
BACKGROUND: The combination therapy of HMG CoA reductase inhibitor (statin) and fibrate is more effective than each ones in managing combined dyslipidemia. However, this therapy tends to be avoided due to potential risk of rhabdomyolysis. The aim of the study was to reevaluate the efficacy and safety of combination therapy. METHODS: A total 61 patients were divided into three groups according to lipid levels and medications; statin+fibrate group (n=10), statin group (n=31) and fibrate group (n=18). Patients with active hepatitis or renal dysfunction who were at high risk for complications were excluded. Lipid profiles were measured before and 2 months after medications. RESULTS: Combination therapy markedly decreased total cholesterol, low density lipoproteincholesterol (LDL-C) and triglyceride concentrations (p=0.008, p=0.028 and p=0.018 respectively), and increased high density lipoprotein-cholesterol (HDL-C)(p=0.028). The effects of this therapy on HDL-C and triglyceride were more potent than those of statin. Combination therapy was more effective in lowering LDL-C than fibrate. Serious complications such as myopathy and marked elevation of transaminase level were not observed in all groups. In statin+fibrate group, transaminase level was elevated slightly above the normal range in two cases. Creatine kinase level showed the trend to increase with borderline significance. However the levels were within normal range in 9 cases and elevated twofold in one patient. CONCLUSION: Combination therapy of statin and fibrate was effective in combined dyslipidemia and well tolerated in patients without high risk for the complications although the number of cases was small to get a conclusion.
Cholesterol
;
Creatine Kinase
;
Dyslipidemias*
;
Hepatitis
;
Humans
;
Hydroxymethylglutaryl CoA Reductases*
;
Hydroxymethylglutaryl-CoA Reductase Inhibitors
;
Hypolipidemic Agents
;
Lipoproteins
;
Muscular Diseases
;
Reference Values
;
Rhabdomyolysis
;
Triglycerides
4.A pilot study on the effect of statins, fibrates and its combination in rat nerves.
Rosales Raymond L ; Geling Olive ; Mendoza Dulce Teresa L
Philippine Journal of Neurology 2004;8(1):1-5
OBJECTIVE: To determine the histopathological effect of statins, fibrates and its combination in rat nerves
METHODOLOGY: This is a pilot experimental study. Four male albino rats were used in this study. Each rat was given therapeutic doses of simvastatin alone, gemfibrozil alone, gemfibrozil and simvastatin combination and placebo. On day 21, the sciatic nerve was harvested for histopathologic examination
RESULTS: Although not marked, the combination of simvastatin and gemfibrozil produced more axonal degeneration than did simvastatin alone or gemfibrozil alone. Axonal degeneration was documented on teased nerve fibers and epon cross sections
CONCLUSION: The use of lipid lowering agents may induce peripheral neuropathy Recommendation: This pilot study serves as rationale to proceed with an experiment not only to document neuropathy but also correlate the possible association of the pathomechanism of myotoxicity and neurotoxicity of lipid lowering agents.
Animal ; Rats ; Simvastatin ; Gemfibrozil ; Hydroxymethylglutaryl-coa Reductase Inhibitors ; Fibric Acids ; Hypolipidemic Agents ; Sciatic Nerve ; Peripheral Nervous System Diseases ; Epon ; Epoxy Resins ; Nerve Fibers
5.A dyslipidemia animal model induced by poloxamer 407 in golden hamsters and pilot study on the mechanism.
Quan LIU ; Shuai-nan LIU ; Lin-yi LI ; Zhi-yu CHEN ; Lei LEI ; Ning ZHANG ; Zhu-fang SHEN
Acta Pharmaceutica Sinica 2011;46(4):406-411
The aim of this study is to establish a simple and stable model like poloxamer 407 (P-407)-induced dyslipidemia of golden hamster model, and investigate the mechanism of lipid metabolism disturbance in this model. PPARalpha agonist and HMG-CoA reductase inhibitor were administrated to validate the efficacy on regulating lipid metabolism in the dyslipidemia golden hamster model. Six weeks male golden hamsters were chosen to inject P-407 intraperitoneally at a bolus dose of 300 mg x kg(-1), an intermittent injection at a dose of 200 mg x kg(-1) every 72 hours after the bolus. The results showed that P-407-induced golden hamster model characterized as increased serum triglyceride (TG), total cholesterol (TC), free cholesterol (free-CHO), cholesteryl ester (CE), free fatty acids (FFA) and apoB levels, and the hyperlipidemia state maintained at a stable level persistently. Meanwhile, augmented malondialdehyde (MDA) and nitric oxide (NO) level was observed. LCAT and SR-B I mRNA levels in liver of model group were down-regulated (expression ratio is 0.426; 0.783), while HMG-CoA reductase mRNA level was up-regulated (expression ratio is 1.493) compared with those of the normal group. The serum cholesterol and triglyceride levels were significantly lower in P-407-induced dyslipidemia hamster model after treated with atorvastatin (Ato) at a dose of 50 mg x kg(1) or fenofibrate (Fen) at 100 mg x kg(-1) for two weeks. These findings suggest that serum lipid distribution in dyslipidemia golden hamster is similar to that of human, and which may be relevant to the disturbance of the enzymes expression involved in lipid metabolism in liver. Results obtained from this study support the concept that dyslipidemia golden hamster may be an adequate animal model to evaluate the efficacy of lipid-lowering agents.
Animals
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Anticholesteremic Agents
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pharmacology
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Atorvastatin Calcium
;
CD36 Antigens
;
genetics
;
metabolism
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Cricetinae
;
Disease Models, Animal
;
Dyslipidemias
;
chemically induced
;
metabolism
;
Fenofibrate
;
pharmacology
;
Heptanoic Acids
;
pharmacology
;
Hydroxymethylglutaryl CoA Reductases
;
genetics
;
metabolism
;
Hydroxymethylglutaryl-CoA Reductase Inhibitors
;
pharmacology
;
Hypolipidemic Agents
;
pharmacology
;
Lipid Metabolism
;
Liver
;
metabolism
;
Male
;
Malondialdehyde
;
metabolism
;
Mesocricetus
;
Nitric Oxide
;
metabolism
;
PPAR alpha
;
agonists
;
Phosphatidylcholine-Sterol O-Acyltransferase
;
genetics
;
metabolism
;
Poloxamer
;
Pyrroles
;
pharmacology
;
RNA, Messenger
;
metabolism
;
Superoxide Dismutase
;
metabolism
6.A meta-analysis on the safety of combination therapy with fenofibrate and statins.
Qiang GENG ; Jing-yi REN ; Su-fang LI ; Hong CHEN
Chinese Journal of Cardiology 2013;41(12):1063-1068
OBJECTIVEThe aim of this study was to assess the safety of fenofibrate-statin combination therapy.
METHODSMedline, Cochrane Library, Web of Knowledge and CNKI were searched for 2184 randomized controlled trials. Finally, twenty-six studies with a total of 9494 participants were included in this analysis.
RESULTSCompared with statins group, the fenofibrate-statin group had significantly higher incidence of aminotransferase elevations (OR 1.67, 95%CI 1.22-2.30, P < 0.05) . The two groups had identical incidence of creatin kinase elevations (OR 0.86, 95%CI 0.62-1.20, P > 0.05) , muscle-associated adverse events (OR 0.98, 95%CI 0.88-1.09, P > 0.05) and withdrawals due to hepatotoxicity or muscle toxicity. The safety of fenofibrate + standard-dose statin regimens were similar to those in fenofibrate-statin group.
CONCLUSIONCombined fenofibrate-statin treatment is generally safe and well tolerated, liver function should be monitored before and during and after therapy.
Adult ; Aged ; Aged, 80 and over ; Combined Modality Therapy ; Fenofibrate ; therapeutic use ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; therapeutic use ; Hypolipidemic Agents ; therapeutic use ; Male ; Middle Aged ; Randomized Controlled Trials as Topic
7.Real world use of statins for secondary prevention in patients with high risk coronary heart disease in China.
Hong-Juan LI ; Jun LIU ; Jing LIU ; Wei WANG ; Lan-Ping QIN ; Yan LI ; Miao WANG ; Jia-Yi SUN ; Yue QI ; Dong ZHAO
Chinese Journal of Cardiology 2010;38(11):1033-1037
OBJECTIVETo observe the real world statins use for secondary prevention in patients with high risk coronary heart disease (CHD) in China.
METHODSSixty-four hospitals across 31 provinces of China including 32 secondary hospitals and 32 tertiary hospitals were selected for baseline survey. Fifty consecutive outpatients with established history of acute coronary syndrome were recruited in each hospital. Information of these patients including statins use was collected.
RESULTSA total of 2516 high risk CHD outpatients were involved in present report. Mean age of the patients was (65 ± 10) years and 69.4% patients were male. Fifty-seven point nine percent patients were treated with a statin at the time of interview and recommended low-density lipoprotein-cholesterol (LDL-C) target was achieved in 29.8% patients. Percent of statin use and achieving LDL-C goal was significantly higher in male outpatients than in female outpatients. Outpatients admitted in tertiary hospitals were more likely to have achieved their LDL-C targets than those admitted in secondary hospitals. Statin use was more often for patients in South China than patients in North China. The percentage reaching the optimal LDL-C treatment target was the highest in Central China (38.5%) and the lowest in Northeast China (18.5%). At this interview, 68.2% outpatients were prescribed statins and 24.1% prescribed doses of statins were sub-minimal.
CONCLUSIONThere was a gap between real world statin use and guideline recommendations for secondary prevention in high risk CHD patients in China.
Aged ; China ; Coronary Disease ; drug therapy ; prevention & control ; Cost-Benefit Analysis ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; therapeutic use ; Hypolipidemic Agents ; Male ; Middle Aged ; Practice Guidelines as Topic ; Secondary Prevention
8.Low-density lipoprotein cholesterol levels and lipid-lowering treatment status among young and middle-aged ultra-high-risk patients with acute coronary syndrome in China.
Jun LIU ; Dong ZHAO ; Yong Chen HAO ; Na YANG ; Zhao Qing SUN ; Jing LIU
Chinese Journal of Cardiology 2022;50(12):1161-1168
Objective: To assess low-density lipoprotein cholesterol (LDL-C) levels and use of lipid-lowering treatment among young and middle-aged ultra-high-risk patients with acute coronary syndrome (ACS) in China. Methods: The study was based on the"Improving Care for Cardiovascular Disease in China (CCC)-ACS"project, a collaborative registry by and Chinese Society of Cardiology (CSC) and the American Heart Association. Hospitalized-patients with ACS were consecutively enrolled from 159 tertiary and 82 secondary hospitals across China, related clinical information was collected. This study included young and middle-aged hospitalized patients (18-59 years) with ACS from November 2014 to December 2019 registered in CCC-ACS project. Ultra-high-risk was defined according to Chinese expert consensus on lipid management of ultra-high-risk atherosclerotic cardiovascular disease (ASCVD) patients of CSC. The mean LDL-C levels at admission, pre-hospital lipid-lowering therapy and proportion of patients with LDL-C target achieved were analyzed. Results: A total of 42 230 patients younger than 60 years with ACS were included in this study. The mean age was (50.4±6.9) years, and 86.8% (36 676/42 230) of the ACS patients were male. Among them, 86.9% (36 687/42 230) met the criteria of ultra-high-risk. The mean level of LDL-C at admission was (2.8±1.0)mmol/L, only 5.3 % (1 948/36 687) patients achieved the targeted goal of LDL-C<1.4 mmol/L. Among the ultra-high-risk ASCVD patients, 17.5% (6 430/36 687) received lipid-lowering drugs before hospitalization, 96.4% (6 198/6 430) of whom received statins monotherapy. Among patients receiving pre-hospital statins, only 9.9% (626/6 323) patients reached an LDL-C<1.4 mmol/L at admission. Conclusions: The majority of young and middle-aged hospitalized patients with ACS are ultra-high-risk patients for ASCVD in China. Pre-hospital lipid-lowering drugs use is lower in these ultra-high-risk ASCVD patients and most patients do not reach the new LDL-C target level at admission.
Middle Aged
;
United States
;
Humans
;
Male
;
Adult
;
Female
;
Cholesterol, LDL
;
Acute Coronary Syndrome/drug therapy*
;
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
;
China
;
Atherosclerosis/drug therapy*
;
Hypolipidemic Agents/therapeutic use*
10.Effect of Taizhi'an capsule combined with Simvastatin on hyperlipidemia in diabetic patients.
Chinese journal of integrative medicine 2006;12(1):24-28
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