Use Of Clofibrate Research Articles

Fibrates for secondary prevention of cardiovascular disease and stroke.

Fibrates are a class of drugs characterised by mainly lowering high triglyceride, raising high-density lipoprotein (HDL) cholesterol, and lowering the small dense fraction of low-density lipoprotein (LDL) cholesterol. Their efficacy for secondary prevention of serious vascular events is unclear, and to date no systematic review focusing on secondary prevention has been undertaken. To assess the efficacy and safety of fibrates for the prevention of serious vascular events in people with previous cardiovascular disease (CVD), including coronary heart disease and stroke. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 9, 2014) on the Cochrane Library, MEDLINE (OVID, 1946 to October week 1 2014), EMBASE (OVID, 1980 to 2014 week 41), the China Biological Medicine Database (CBM) (1978 to 2014), the Chinese National Knowledge Infrastructure (CNKI) (1979 to 2014), Chinese Science and Technique Journals Database (VIP) (1989 to 2014). We also searched other resources, such as ongoing trials registers and databases of conference abstracts, to identify further published, unpublished, and ongoing studies. We included randomised controlled trials (RCTs) in which a fibrate (for example gemfibrozil, fenofibrate) was compared with placebo or no treatment. We excluded RCTs with only laboratory outcomes. We also excluded trials comparing two different fibrates without a placebo or no-treatment control. Two review authors independently selected trials for inclusion, assessed risk of bias, and extracted the data. We contacted authors of trials for missing data. We included 13 trials involving a total of 16,112 participants. Eleven trials recruited participants with history of coronary heart disease, two trials recruited participants with history of stroke, and one trial recruited participants with a mix of people with CVD. We judged overall risk of bias to be moderate. The meta-analysis (including all fibrate trials) showed evidence for a protective effect of fibrates primarily compared to placebo for the primary composite outcome of non-fatal stroke, non-fatal myocardial infarction (MI), and vascular death (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83 to 0.94; participants = 16,064; studies = 12; I(2) = 45%, fixed effect). Fibrates were moderately effective for preventing MI occurrence (RR 0.86, 95% CI 0.80 to 0.93; participants = 13,942; studies = 10; I(2) = 24%, fixed effect). Fibrates were not effective against all-cause mortality (RR 0.98, 95% CI 0.91 to 1.06; participants = 13,653; studies = 10; I(2) = 23%), death from vascular causes (RR 0.95, 95% CI 0.86 to 1.05; participants = 13,653; studies = 10; I(2) = 11%, fixed effect), and stroke events (RR 1.03, 95% CI 0.91 to 1.16; participants = 11,719; studies = 6; I(2) = 11%, fixed effect). Excluding clofibrate trials, as the use of clofibrate was discontinued in 2012 due to safety concerns, the remaining class of fibrates were no longer effective in preventing the primary composite outcome (RR 0.90, 95% CI 0.79 to 1.03; participants = 10,320; studies = 7; I(2) = 50%, random effects). However, without clofibrate data, fibrates remained effective in preventing MI (RR 0.85, 95% CI 0.76 to 0.94; participants = 8304; studies = 6; I(2) = 47%, fixed effect). There was no increase in adverse events with fibrates compared to control. Subgroup analyses showed the benefit of fibrates on the primary composite outcome to be consistent irrespective of age, gender, and diabetes mellitus. Moderate evidence showed that the fibrate class can be effective in the secondary prevention of composite outcome of non-fatal stroke, non-fatal MI, and vascular death. However, this beneficial effect relies on the inclusion of clofibrate data, a drug that was discontinued in 2002 due to its unacceptably large adverse effects. Further trials of the use of fibrates in populations with previous stroke and also against a background treatment with statins (standard of care) are required.

Effects of clofibrate therapy on glucose tolerance, insulin secretion and serum lipids in subjects with hyperlipoproteinemia and impaired glucose tolerance. A follow-up study over a five-year period.

The long term effect of clofibrate treatment on the carbohydrate and lipid metabolisms and on insulin secretion was studied in subjects with primary hyperlipoproteinemia and impaired glucose tolerance. Treatment consisted of a diet and 2.0 g clofibrate per day. The body weight, triglyceride and cholesterol levels, glucose tolerance and insulin secretion of 14 patients were monitored for five years. During the first year of treatment the mean triglyceride and cholesterol levels decreased by 80% and 40% respectively. The cholesterol level became fully normal in the course of further treatment, but the triglyceride level did not. The mean reduction of body weight over the five-year period amounted to 5.0 kg. Improvement in glucose tolerance was shown by a significant increase in Conard's glucose assimilation coefficient. Glucose tolerance became completely normal in some cases. In one case diabetes mellitus became manifest. Improvement of the glucose tolerance was accompanied by reduction of glucose-stimulated insulin secretion by about 50% of the original value. The results permit the conclusion that the use of clofibrate for the long-term treatment of hyperlipoproteinemia is still justified. If hyperlipoproteinemia is accompanied by impaired glucose tolerance, clofibrate can also be regarded as having a certain antidiabetic effect during the normalisation of the "metabolic syndrome".

Recent trends in the prescribing of cholesterol lowering drugs in Australia A report from the Drug Utilization Subcommittee of the Pharmaceutical Benefits Advisory Committee

To determine the recent pattern of use of hypolipidaemic drugs in the Australian community. Drug utilisation study employing prescription data collected during the operation of the Australian Pharmaceutical Benefits Scheme (PBS). Non-hospital drug use in Australia. All patients, pensioners and non-pensioners, who received prescriptions for hypolipidaemic agents under the PBS between January 1987 and December 1989. The total number of prescriptions, average quantity dispensed with each prescription, defined daily doses (DDD) and Australian population figures for pensioners and non-pensioners were used to express the consumption of hypolipidaemic agents as DDD/1000 individuals/day. Between the March quarter 1987 and the December quarter 1989 prescribing of hypolipidaemics for the Australian community increased from 68,120 to 304,760 prescriptions per quarter, which translates to a rise in use from 1.2 to 5.2 DDD/1000 inhabitants/day. This included a rise in the use of clofibrate from 0.6 to 2.6 DDD/1000 inhabitants/day, and of cholestyramine from 0.6 to 1.9 DDD/1000 inhabitants/day. Prescribing of hypolipidaemics for pensioners increased from 29,569 to 123,440 prescriptions per quarter. This translated into a rise in use from 3.7 to 14.8 DDD/1000 pensioners/day. Notable rises were seen for clofibrate, 1.9 to 8.1 DDD/1000 pensioners/day, and cholestyramine, 1.6 to 4.7 DDD/1000 pensioners/day. In comparison published data from the Nordic countries and the United States showed a lower overall use of hypolipidaemics and declining consumption of clofibrate. The trend in Australia was unusual in that the use of clofibrate increased to a greater extent than that of the resins, cholestyramine and colestipol which are generally preferred for treatment of hypercholesterolaemia. Possible reasons for this include: the better tolerability of clofibrate; its readier availability during the study period; the recommendation by the Pharmaceutical Benefits Advisory Committee that clofibrate was the preferred drug when triglyceride levels were also elevated and the limited availability of newer hypolipidaemic agents.

Intracellular Fibrilloneogenesis in Various Dermatoses by a Local Use of Clofibrate and its Derivatives

Intracellular Fibrilloneogenesis in Various Dermatoses by a Local Use of Clofibrate and its Derivatives

Hypocholesterolemic activity of racemic dichlorophenoxypropionic acid or its enantiomers in rats.

Abundant circumstantial evidence has shown that chronic hyperlipidemia is one of the major clinical manifestations of ischemic heart disease (IHD) and many drugs have been developed which reduce serum lipids. Clofibrate has been one of the most effective drugs used for lowering serum cholesterol and reducing the morbidity of patients suffering from IHD. However, prolonged treatment with clofibrate has been reported to cause higher incidences of gastrointestinal disorders and to induce cholesterol oversaturation of bile. These deleterious side effects have resulted in a restriction of the use of clofibrate and new drugs exerting selective and non toxic hypolipidemic actions have been intensively researched. (Dichloro-2,4 phenoxy)-2 propionic acid, structurally-related to fibrates with an asymmetric carbon is well know for its herbicide effectiveness. However, nobody has investigated its possible effect on cholesterol /sup 14/C-acetate metabolism. The purpose of this study is to explore the effects of this compound on cholesterol metabolism in the rat and to compare them with those of clofibrate. It is the first time that a low concentration (0.04 mmole) of this well-known pesticide has been shown to lower plasma cholesterol when added to the diet.

Progress in Cardiology 9

This is the ninth annual volume of Progress in Cardiology , the first having appeared in 1972. It embodies eight chapters from cardiologists and scientists here and abroad. Chapter 1 is a review by Dr M. F. Oliver of Edinburgh, Scotland, appraising six clinical trials reducing cholesterol levels in apparently healthy individuals. This review suggests the use of clofibrate or a diet that is low in cholesterol and high in unsaturated fat, or both, may create other problems while reducing cholesterol levels. Dr J. G. Sloman and co-workers, of Australia, discuss the approach to the late phase of acute myocardial infarction in the second chapter. In chapter 3, Dr B. N. Chiang and colleagues, of Taiwan, discuss the value of a combination of crosssectional echocardiography and radionuclide ventriculography in the diagnosis of ventricular aneurysm. Drs Fleming and Newsom of Cambridge, England, summarize advances in diagnosis and therapy, including prophylaxis of infective

Combined effects of clofibrate and diosgenin on cholesterol metabolism in rats

Groups of male rats were fed various doses of clofibrate and diosgenin, both alone and in combination for 1 week. Clofibrate suppressed the diosgenininduced increase in hepatic cholesterol synthesis but did not alter the effectiveness of diosgenin in reducing cholesterol absorption. Diosgenin did not affect the bioavailability of CPIB. Clofibrate reduced the diosgenin induced increase in biliary levels of cholesterol; none of the regimens altered biliary bile acids. The combination produced greater decreases in LDL cholesterol than did either compound alone; the diosgenin-induced elevation in HDL cholesterol was partially reversed by clofibrate. The data provide a basis for the combined use of clofibrate and diosgenin in the control of hyperlipoproteinemia.

Management of hypercholesterolemia: Evaluation of practical clinical approaches in healthy young adults

A work site-located clinic screened 6,000 employees (91 percent participation) and identified 146 hypercholesterolemic subjects (100 percent initial participation, 12 percent subsequent dropout rate). The subjects, aged 20 to 50 years, were randomly classified into four groups: Group A, treatment in a lipid intervention clinic with diet for 6 weeks, then diet plus clofibrate for the subsequent 18 weeks; Group B, diet treatment from a clinic nutritionist with the cooperation of the subject's private physician; Group C, referral for treatment by a private physician; and Group D, no intervention. Initial mean cholesterol was 294 mg/100 ml. At 24 weeks, all intervention groups had decreases in serum cholesterol (Group A, 12 percent; Group B, 15 percent; Group C, 17 percent; P < 0.001). The control group (D) had a small decrease in cholesterol (4 percent). Decreases in cholesterol were correlated with weight loss and decrease in fasting serum triglycerides but not with the use of clofibrate. Serum cholesterol can be reduced in healthy young adults by several practical methods.

CLOFIBRATE-INDUCED MUSCLE DAMAGE IN PATIENTS WITH CHRONIC RENAL FAILURE

Muscle weakness and tenderness together with a rise in serum creatine kinase (C.K.) were noted in five uræmic patients treated with 1-2 g of clofibrate ('Atromid-S') daily. Excessive accumulation of both total and free serum chlorophenoxyisobutyric acid (C.P.I.B.), the active circulating metabolite after clofibrate therapy, was found in three patients in whom it was sought. It is suggested that chronic renal failure should be regarded as a contraindication to the use of clofibrate for the treatment of any coexisting hyperlipidæmia. If such therapy is contemplated it must be cautiously instituted at low dosage and the patient monitored by regular assessment of serum C.K. and levels of both total and free C.P.I.B.

Combined Use of Clofibrate and Cholestyramine or DEAE Sephadex in Hypercholesterolaemia

A comparison was made of the effect of DEAE (diethylaminoethyl) Sephadex (an anion exchange resin) and cholestyramine (Questran) with and without the addition of clofibrate in normal and hypercholesterolaemic patients. DEAE Sephadex (12-15 g/day) alone appeared to be as effective as cholestyramine in lowering the plasma cholesterol by 12-15%. Clofibrate acted synergistically with DEAE Sephadex and increased the activity of the latter by over twofold. This combination proved superior to that of clofibrate and cholestyramine and has the greatest potential use in the treatment of type II pattern hyperlipoproteinaemia.