Fibrates for primary prevention of cardiovascular disease events.

BACKGROUND: Fibrates are effective for modifying atherogenic dyslipidaemia, and particularly for lowering serum triglycerides. However, evidence that fibrates reduce mortality and morbidity associated with cardiovascular disease (CVD), or overall mortality and morbidity, in the primary prevention of CVD is lacking. OBJECTIVES: This Cochrane Review and meta-analysis aimed to evaluate the clinical benefits and harms of fibrates versus placebo or usual care or fibrates plus other lipid-modifying drugs versus other lipid-modifying drugs alone for the primary prevention of cardiovascular disease (CVD) morbidity and mortality. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO), and Web of Science (all from inception to 19 May 2016). We searched four clinical trial registers (last searched on 3 August 2016) with the help of an experienced professional librarian. We searched the databases to identify randomised controlled trials (RCTs) evaluating the clinical effects of fibrate therapy in the primary prevention of CVD events. We did not impose any language restrictions. SELECTION CRITERIA: We aimed to include all RCTs comparing the effects of fibrate monotherapy versus placebo or usual care, or fibrates plus other lipid-modifying drugs versus other lipid-modifying drugs alone. Included studies had a follow-up of at least six months for the primary prevention of CVD events. We excluded trials with clofibrate, because it was withdrawn from the market in 2002. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for potential study inclusion. Two review authors independently retrieved the full-text papers and extracted data. Disagreements were resolved by consensus. We calculated risk ratios (RRs) and accompanying 95% confidence intervals (CIs) for aggregate data on primary and secondary outcomes. We tested for heterogeneity with the Cochrane Q-test and used the I2 statistic to measure inconsistency of treatment effects across studies. Using the GRADE approach, we assessed the quality of the evidence and used the GRADE profiler software (GRADEpro GDT) to import data from Review Manager 5 to create 'Summary of findings' tables. MAIN RESULTS: We identified six eligible trials including 16,135 individuals. The mean age of trial populations varied across trials; between 47.3 and 62.3 years. Four trials included individuals with diabetes mellitus type 2 only. The mean treatment duration and follow-up of participants across trials was 4.8 years. We judged the risks of selection and performance bias to be low; risks of detection bias, attrition bias, and reporting bias were unclear. Reporting of adverse effects by included trials was very limited; that is why we used discontinuation of therapy due to adverse effects as a proxy for adverse effects. Patients treated with fibrates had a reduced risk for the combined primary outcome of CVD death, non-fatal myocardial infarction, or non-fatal stroke compared to patients on placebo (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.74 to 0.96; participants = 16,135; studies = 6; moderate-quality of evidence). For secondary outcomes we found RRs for fibrate therapy compared with placebo of 0.79 for combined coronary heart disease death or non-fatal myocardial infarction (95% CI 0.68 to 0.92; participants = 16,135; studies = 6; moderate-quality of evidence); 1.01 for overall mortality (95% CI 0.81 to 1.26; participants = 8471; studies = 5; low-quality of evidence); 1.01 for non-CVD mortality (95% CI 0.76 to 1.35; participants = 8471; studies = 5; low-quality of evidence); and 1.38 for discontinuation of therapy due to adverse effects (95% CI 0.71 to 2.68; participants = 4805; studies = 3; I2 = 74%; very low-quality of evidence). Data on quality of life were not available from any trial. Trials that evaluated fibrates in the background of statins (2 studies) showed no benefits in preventing cardiovascular events. AUTHORS' CONCLUSIONS: Moderate-quality evidence suggests that fibrates lower the risk for cardiovascular and coronary events in primary prevention, but the absolute treatment effects in the primary prevention setting are modest (absolute risk reductions < 1%). There is low-quality evidence that fibrates have no effect on overall or non-CVD mortality. Very low-quality evidence suggests that fibrates are not associated with increased risk for adverse effects.

Statin-associated polymyositis following omeprazole treatment.

Statins are an extensively used class of drugs, and myopathy is an uncommon, but well-described side effect of statin therapy. Inflammatory myopathies, including polymyositis, dermatomyositis, and necrotizing autoimmune myopathy, are even more rare, but debilitating, side effects of statin therapy that are characterized by the persistence of symptoms even after discontinuation of the drug. It is important to differentiate statin-associated inflammatory myopathies from other self-limited myopathies, as the disease often requires multiple immunosuppressive therapies. Drug interactions increase the risk of statin-associated toxic myopathy, but no risk factors for statin-associated inflammatory myopathies have been established. Here we describe the case of a man, age 59 years, who had been treated with a combination of atorvastatin and gemfibrozil for approximately 5 years and developed polymyositis after treatment with omeprazole for 7 months. Symptoms did not resolve after discontinuation of the atorvastatin, gemfibrozil, and omeprazole. The patient was treated with prednisone and methotrexate followed by intravenous immunoglobulin, which resulted in normalization of creatinine kinase levels and resolution of symptoms after 14 weeks. It is unclear if polymyositis was triggered by interaction of the statin with omeprazole and/or gemfibrozil, or if it developed secondary to long-term use of atorvastatin only.

Gemfibrozil-induced myositis in a patient with normal renal function.

OBJECTIVE: To describe a case of gemfibrozil monotherapy-induced myositis in a patient with normal renal function CASE SUMMARY: A 68-year-old white man presented to his primary care clinic complaining of a 6-month history of total body pain. His past medical history was significant for hypertension, diabetes mellitus, hyperlipidemia, gastroesophageal reflux disease, benign prostatic hypertrophy, arthritis, impotence, and pancreatic cancer that required excision of part of his pancreas. His home drug regimen included bupropion 75 mg twice daily, gemfibrozil 600 mg twice daily for the past 8 months, glimiperide 1 mg daily, insulin glargine 5 units at bedtime, insulin aspart 5 units in the evening, lisinopril 10 mg daily, omeprazole 40 mg daily, pregabalin 100 mg daily, and sildenafil 100 mg as needed. Laboratory test results were significant for elevated aspartate aminotransferase (AST) 78 U/L (reference range 15-46 U/L), alanine aminotransferase (ALT) 83 U/L (13-69 U/L), and creatine kinase (CK) 3495 U/L (55-170 U/L). Serum creatinine was normal at 1.19 mg/dL. The physician determined that the elevated CK indicated myositis secondary to gemfibrozil use, and gemfibrozil was subsequently discontinued. The patient returned 1 week later to repeat the laboratory tests. Results were CK 220 U/L, AST 26 U/L, ALT 43 U/L, and serum creatinine 1.28 mg/dL. The patient was asked to return in 3 weeks to repeat the laboratory tests. At that time, CK had continued to decrease to 142 U/L, and the AST and ALT had returned to normal, at 22 and 29 U/L, respectively. The patient reported complete resolution of total body pain 3 weeks after discontinuation of gemfibrozil. Follow-up 5 weeks after discontinuation revealed no change compared to the 3-week follow-up. DISCUSSION: Myositis most often produces weakness and elevated CK levels more than 10 times the upper limit of normal. The risk of developing myositis, myopathy, or rhabdomyolysis is low (1%) when fibrates such as gemfibrozil are used as monotherapy. Evaluation of the literature revealed one case of gemfibrozil-related myositis in a patient with chronic renal failure. There is also one report of myopathy associated with gemfibrozil monotherapy in a patient with normal renal function. The present case is the first documented case of gemfibrozil monotherapy-induced myositis in a patient with normal renal function. The Naranjo probability scale indicated a probable relationship between gemfibrozil treatment and the onset of myositis in our patient. Other potential causes of myositis were ruled out by patient interview and chart review. CONCLUSIONS: Although the risk of myositis appears to be low with gemfibrozil monotherapy, clinicians should be aware of the potential for this adverse event. For patients taking gemfibrozil monotherapy who present with myalgia, discontinuation of the medication may be necessary for the alleviation of pain.

Effects of diet and gemfibrozil on posttransplant hyperlipidemia in renal transplant recipients.

BACKGROUND: Posttransplant hyperlipidemia increases cardiovascular morbidity and mortality rate in renal transplant recipients. It also leads to graft loss due to atherosclerosis and glomerular damage. It is essential to control hyperlipidemia in renal transplant recipients to prevent these events. METHODS: In our study, we determined lipid profiles in 59 renal transplant recipients. Twenty of the recipients had hyperlipidemia; 9 had type IV, and 11 had type II hyperlipoproteinemia. Randomly selected 14 of 20 hyperlipidemic patients consisted of the diet group and were treated with American phase 3 diet for 1 month. Randomly selected 6 of the 20 hyperlipidemic patients received their regular diet as the control group. Five diet-resistant patients in the American phase 3 diet group were given diet plus placebo for another 1 month and then they were given diet plus Gemfibrozil (600 mg twice a day) for 2 months. RESULTS: Lipid profile was normalized in 9 of the 14 patients on American phase 3 diet. The lipid profile of 5 patients in the American phase 3 diet group did not change significantly after 1-month diet. These 5 diet-resistant patients were given diet plus placebo for another 1 month, and their lipid levels again did not change significantly. Afterward, they were treated with Gemfibrozil (600 mg twice a day) plus American phase 3 diet for 2 months. At the end of this therapy period, their cholesterol level and triglyceride level decreased significantly. No change was observed in low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels. CONCLUSIONS: We conclude that American phase 3 diet and/or Gemfibrozil are effective in controlling posttransplant hyperlipidemia in renal transplant recipients.

Tamoxifen-induced severe hypertriglyceridaemia and acute pancreatitis.

Hypertriglyceridaemia is a well known risk factor for acute pancreatitis. Hypertriglyceridaemia may be primary in origin or secondary to alcohol abuse, diabetes mellitus, pregnancy or use of drugs. In this case report, the cause of acute pancreatitis was tamoxifen. We report on a patient with tamoxifen-induced acute pancreatitis and hypertriglyceridaemia who was successfully treated with insulin infusion and long-term gemfibrozil.

Lipid-modifying and pleiotropic effects of gemfibrozil, simvastatin and pravastatin in patients with dyslipidemia.

AIM: To assess the lipid-modifying and pleiotropic effects of drugs of the statin group (simvastatin and pravastatin) and the fibrate group (gemfibrozil) in dyslipidemia patients. PATIENTS AND METHODS: Fifty eight patients with primary dysli pidemia were recruited for a 12-week treatment. Forty two patients were allocated to be treated with statins (20 mg): 24 with simvastatin and 18 with pravastatin. Sixteen patients received gemfibrozil in a dose of 900 mg daily. Using enzyme, colorimetric, turbidimetric, immunoenzyme and chromogenic substrate methods, we studied the following laboratory parameters: 1) lipid parameters - total cholesterol, LDL and HDL cholesterol, triglycerides, apoli poprotein A-I, apoli poprotein B, anticardioli pin antibodies and lipid indices; 2) hemostasis, fibrinolysis and blood rheology parameters - platelet count, ADP-induced platelet aggregation, fibrinogen, platelet factor 4,antithrombin III activity, alpha2-anti plasmin concentrations, alpha2-macroglobulin, alpha1-antitripsin, plasma viscosity and hematocrit. RESULTS: Gemfibrozil elevated significantly apolipoprotein A-I, but decreased the total cholesterol, LDL cholesterol, triglycerides, the lipid indices, the ADP-induced platelet aggregation, plasminogen, alpha2-antiplasmin and hematocrit. Simvastatin treatment of patients reduced the total cholesterol, LDL cholesterol, triglycerides, two of the lipid indices, plasma viscosity and hematocrit. Pravastatin produced the same changes in the lipid parameters, but decreased apolipoprotein A-I. Plasminogen, alpha2-antiplasmin and rheological parameters decreased while antithrombin III increased. CONCLUSION: The lipid-modifying treatment with statins and fibrates, in addition to the effect on lipid metabolism, exerts a pleiotropic effect on hemostasis, fibrinolysis and blood rheology parameters.

Cost effectiveness of treating low HDL-cholesterol in the primary prevention of coronary heart disease.

BACKGROUND: A low serum level of high-density lipoprotein (HDL)-cholesterol is an independent risk factor for coronary heart disease (CHD). Fibrates, particularly gemfibrozil, have been shown to raise HDL-cholesterol levels and reduce the incidence of CHD. The literature on fibrate cost effectiveness is quite limited. OBJECTIVE: The objective of this analysis is to determine the cost effectiveness of the fibrates gemfibrozil and fenofibrate in the primary prevention of CHD. The target population includes patients with low levels of HDL-cholesterol, but without pre-existing CHD or other CHD risk factors sufficiently elevated to indicate drug therapy. STUDY DESIGN AND METHODS: From a societal perspective, a lifetime incremental cost-effectiveness model was developed to calculate baseline and treatment costs, life-years gained and QALYs gained. Model parameter values were taken from existing literature. In this 'backward induction' model, the expected costs and outcomes for each 5-year time-interval are utilised in subsequent 5-year time period calculations over the patient's entire lifetime. The study population consisted of a hypothetical cohort of males and females in the US aged 45-74 years, with low levels of HDL-cholesterol and no prior history of CHD. The base-case CHD risk factors for this population were obtained from the VA-HIT (Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial) population baseline characteristics, but assuming no prior CHD history. Estimates for the reduction in CHD risk associated with fibrate therapy reduction are also taken from the VA-HIT study. RESULTS: Using a societal cost-effectiveness threshold of US$50, 000 per QALY, primary prevention of CHD in patients with low HDL-cholesterol levels using generic gemfibrozil therapy is cost effective for all age and sex categories, in contrast to fenofibrate therapy, which is cost effective for males, but not for females at baseline risks levels. In the base-case scenario, because of their higher CHD lifetime risk, it is more cost effective to treat males than females with either gemfibrozil or fenofibrate. For males and females the cost per QALY decreases with age for most age intervals. Gemfibrozil is more cost effective than fenofibrate for all age-sex categories because of the assumed equal efficacy and the higher fenofibrate drug cost. In the comparison scenario, generic lovastatin was more cost effective than gemfibrozil for men except at age 45 years and women at all ages, and more cost effective than fenofibrate for both men and women. CONCLUSIONS: This analysis suggests that fibrate therapy, particularly with generic gemfibrozil, is cost effective in the primary prevention of CHD in individuals with low HDL-cholesterol levels, with or without elevated triglyceride levels. Certain patient subgroups, such as those with elevated triglyceride levels, smokers and those with diabetes mellitus are likely to achieve both CHD risk reduction and overall savings in net expected medical care costs. Comparable cost-effectiveness results are also shown for lovastatin therapy in the target patient population. Gemfibrozil dominates fenofibrate because of the lower cost of therapy (direct and indirect costs). These conclusions are robust to reasonable changes in model parameter values.

The role of lipid management in diabetes.

This article discusses the role of lipid management in diabetes.

Patients with low levels of high-density lipoprotein cholesterol: to treat or not to treat?

Clinical evidence indicates that a low level of high-density lipoprotein cholesterol (HDL-C) is a major risk of atherosclerosis. Raising HDL-C reduces this risk significantly, making HDL-C levels an important target of treatment for dyslipidaemia, especially in pre-existent atherosclerosis. HDL-C is protective against atherosclerosis, largely due to its function of reverse cholesterol transport. Additionally, some important roles include fibrinolysis, antioxidant functions, and reduction of platelet aggregability. A number of agents potentially modify HDL favourably. Niacin is the most potent HDL-C raising agent currently available in clinical practice, followed by fibrates. CETP inhibitors show greater HDL-C rising, but are still used in trial settings only. HDL mimetic agents are another group of agents that offer much promise. Clinical outcome data are awaited for these newer therapeutic agents.

Evaluation of effects of unmodified niacin on fasting and postprandial plasma lipids in normolipidemic men with hypoalphalipoproteinemia.

PURPOSE: The aim of this study was to define the effects of unmodified niacin on basal lipids and lipoproteins and on the plasma triglyceride response to a fatty meal--postprandial or alimentary lipemia--in individuals with low levels of high-density lipoprotein cholesterol (HDL-C) and normal fasting cholesterol and triglyceride concentrations (normolipidemic hypoalphalipoproteinemia, isolated low HDL-C). PATIENTS AND METHODS: Twenty-eight normolipidemic men (total plasma cholesterol concentration [TC] < 230 mg/dL [< 6 mmol/L], plasma triglyceride [Tg] < 250 mg/dL [2.75 mmol/L]) with low plasma concentrations of HDL-C were randomly assigned to increasing doses of crystalline niacin (up to 3,000 mg/d) or no drug for 12 weeks, then crossed over to the alternate regimen. Outcome measures included changes in plasma lipoproteins and alimentary lipemia. RESULTS: Fifteen participants completed the study. Mean baseline HDL-C +/- SD was 31.7 +/- 6.2 mg/dL (0.82 +/- 0.16 mmol/L). Mean baseline TC, plasma concentration of low-density lipoprotein cholesterol (LDL-C), and Tg were 192 +/- 29.4 mg/dL (4.97 +/- 0.76 mmol/L), 123 +/- 27 mg/dL (3.17 +/- 0.69 mmol/L), and 197 +/- 75 mg/dL (2.17 +/- 0.83 mmol/L), respectively. Unmodified niacin treatment resulted in significant (P < 0.001) reductions of 14% in TC (to 165 mg/dL, 4.26 mmol/L), 40% in Tg (to 119 mg/dL, 1.31 mmol/L), and 18% in LDL-C (to 101 mg/dL, 2.60 mmol/L) and significant increases of 30% in HDL-C (to 42 mg/dL, 1.07 mmol/L), 100% in HDL2 cholesterol (from 5 mg/dL to 9 mg/dL, 0.12 mmol/L to 0.24 mmol/L), and 21% in HDL3 cholesterol (from 27 mg/dL to 33 mg/dL, 0.70 mmol/L to 0.85 mmol/L). Unmodified niacin treatment reduced alimentary lipemia by 45% (P < 0.02). CONCLUSIONS: Crystalline niacin effectively raises HDL-C, lowers LDL-C, and reduces alimentary lipemia in patients with isolated low HDL-C. However, many patients have difficulty tolerating the drug, and supervision may be required to sustain patient compliance and avoid toxicity.

Drug treatment of dyslipoproteinemia.

The bile-acid sequestrants, nicotinic acid and lovastatin, are the most effective drugs for lowering LDL-cholesterol. Nicotinic acid and gemfibrozil are more effective for lowering triglycerides and increasing HDL. Important considerations for proper selection of drugs in the treatment of the various dyslipoproteinemias are presented. Currently available drugs now permit effective control of blood lipid and lipoprotein levels.

The Veterans Affairs High-Density Lipoprotein Intervention Trial: baseline characteristics of normocholesterolemic men with coronary artery disease and low levels of high-density lipoprotein cholesterol. Veterans Affairs Cooperative Studies Program High-Density Lipoprotein Intervention Trial Study Group.

This report describes the baseline characteristics of the 2,531 patients with coronary artery disease enrolled in the Veterans Affairs Cooperative Studies Program High Density Lipoprotein Intervention Trial. The population is characterized by a large percentage of elderly patients, diabetic patients, and patients with the clinical characteristics of the insulin-resistance syndrome.

Safety and efficacy of long-term statin-fibrate combinations in patients with refractory familial combined hyperlipidemia.

No monotherapy is able to tackle effectively all atherogenic features of familial combined hyperlipidemia: high low-density lipoprotein (LDL) cholesterol, triglycerides (TG), and plasma fibrinogen, as well as low high-density lipoprotein (HDL) cholesterol. The present study investigated the safety and efficacy of combined pravastotin or simvastatin with gemfibrozil or ciprofibrate treatment on total cholesterol, LDL, TG, plasma fibrinogen, and apoproteins B and A-I in patients with refractory familial combined hyperlipidemia, with or without coronary artery disease. From the initial 420 patients included in the study, 389 (294 men and 95 women, mean age 51 years [range 30 to 65]) completed the study. These patients were followed for a mean period of 29 months (1 year [n = 107], 2 years [n = 102], 3 years [n = 95], and 4 years [n = 85]). Patients given a hypolipidemic diet were randomly assigned to pravastatin + gemfibrozil (n = 135, 20 and 1,200 mg/day, respectively), simvastatin + gemfibrozil (n = 130, 20 and 1,200 mg), or simvastotin + ciprofibrate (n = 124, 20 and 100 mg). Lipid parameters, apoproteins B and A-I, and plasma fibrinogen were assessed every 3 months. Physical and laboratory investigations for adverse effects were performed every month for the first 3 months and every 3 months thereafter. No patient exhibited myopathy or rhabdomyolysis. Five patients (1.3%) were withdrawn from the study because of high transaminases (more than threefold the upper normal limit). Five nonfatal coronary artery disease events were recorded. All 3 combination treatments were more effective in normalizing lipid profile than any monotherapy in the past. Simvastatin + ciprofibrate was more effective than pravastatin + gemfibrozil in reducing LDL, TG, and plasma fibrinogen levels. Simvastatin + gemfibrozil increased HDL levels more than the other 2. The apoprotein B decrease was analogous to the LDL reduction by all combinations, whereas apoprotein A-I was increased more with simvastatin + gemfibrozil. The data suggest that the statin-fibrate combinations used in the study are safe and have a favorable effect on all major coronary artery disease risk factors in patients with refractory familial combined hyperlipidemia with or without coronary artery disease. Early detection of the rare drug-induced reversible hepatotoxicity calls for close monitoring of patients.

Role of fibrates in reducing coronary risk: a UK Consensus.

This paper presents the consensus reached by a panel of experts on the role of fibrates in reducing coronary heart disease (CHD). The emphasis is on the application of these agents in clinical practice. Evidence that low levels of high-density lipoprotein cholesterol (HDL-C) play a major role in the development of CHD, plus the roles of lifestyle modification and statin treatment in raising HDL-C, are briefly reviewed. Current thinking on single agent and combination therapies with fibrates is discussed with particular relevance to patients with low baseline HDL-C- whether receiving statins or not - and those with features of the metabolic syndrome. Recommendations on the practical use of fibrates are made in the light of recently published international guidelines on HDL-C management and the relevant evidence base.

Effect of gemfibrozil versus lovastatin on increased serum lipoprotein(a) levels of patients with hypercholesterolemia.

The aim of this study was to determine the effect of gemfibrozil, compared with lovastatin, in patients with high levels of lipoprotein(a) and on plasma lipid profile. Twenty-seven nondiabetic patients with high levels of plasma lipids and lipoprotein(a), 19 male and eight female, aged 37-68 (mean +/- S.D. 54.2 +/- 7.5) years, were randomly assigned to 2 weeks of treatment with gemfibrozil 600 mg twice daily (14 pts.) or lovastatin 40-80 mg once daily (13 pts.). Patients had fasting plasma total cholesterol levels > or = 6.2 mmol/l, low-density lipoprotein > 4.14 mmol/l and lipoprotein(a) > 0.62 mmol/l. All patients but one had triglycerides > 2.82 mmol/l. There were no statistical differences between both groups in terms of age, sex, clinical diagnosis and previous medication. After 3 months of treatment, gemfibrozil reduced triglycerides (47.9% vs. 24.5%; P < 0.001), very low density lipoprotein (43.9% vs. 24.6%; P < 0.05), lipoprotein(a) (25.3% vs. 4.9%; P < 0.05) and increased high-density lipoprotein (34.4% vs. 11%; P < 0.01) more than lovastatin. Gemfibrozil and lovastatin reduced comparably total cholesterol (21.4% vs. 29.0%; P = NS) and low-density lipoprotein (26.5% vs. 37.3%; P = NS). The plasma levels of high-density lipoprotein and lipoprotein(a) were unchanged significantly by lovastatin. In conclusion, besides well-known efficacy in hyperlipidemia treatment, gemfibrozil also increased high-density lipoprotein and reduced lipoprotein(a), which may have important epidemiologic implications.

Effects of a lipid lowering fibrate and hormone replacement therapy on serum lipids and lipoproteins in overweight postmenopausal women with elevated triglycerides.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in women after menopause. In essence major risk factors for CVD are similar in women as for men inclusive of serum lipid perturbations. The effects of estrogens and hormone replacement therapy on lipid metabolism is widely discussed and warrant further evaluation especially when combined with other lipid lowering drugs. STUDY DESIGN: Postmenopausal women were studied by an open randomised study during 9 months. Subjects were recruited from outpatient clinics in a rural area of Sweden. Major inclusive criteria comprised body mass index (BMI) >28, serum triglycerides >1.5 mmol/l. Participants were at least 12 months postmenopause with a concomitant serum Follicle Stimulating Hormone (FSH) above 28 IU/l. After inclusion in the study patients were instructed to adhere to a low-fat and caloric diet for 3 months and after this period randomised into two groups of intervention; a lipidlowering fibrate (LLF) group and one hormone replacement therapy group (HRT). The LLF group was given gemfibrozil 600 mg orally twice daily and HRT group received 2 mg oestradiol in combination with 1 mg norethisterone acetate as a continuous combined therapy once daily. After 3 months, the LLF group added the HRT regimen and patients in the HRT group added gemfibrozil. Hence, all participants received the regimens combined for the last 6 months of the study. RESULTS: Serum s-cholesterol was markedly decreased in both groups during the first 3 months of single treatment (P<0.0001). This decrease reflected a reduction especially of calculated low density lipoprotein (LDL) s-cholesterol (P<0.001). High density lipoprotein (HDL) s-cholesterol was reduced in the HRT group (P<0.005) but increased (P<0.004) in the LLF group. Triglycerides were also decreased by both treatments but more marked in the LLF group (P<0.0001) than in the HRT group (P<0.02). After 9 months the reduction remained in both groups but no additive effects were encountered in any of the groups. CONCLUSION: The effects by gemfibrozil on s-cholesterol and triglycerides levels seem to be superior to continuous combined HRT in overweight women with elevated triglycerides. The combination of the two drugs did not seem to offer any additional benefit concerning the routine serum lipid or lipoprotein profile.

Dyslipidemia and coronary artery disease.

Genetically determined and metabolically induced disturbances in lipid metabolism, as manifested in several types of dyslipidemia, have been shown to be causally related to the development of coronary artery disease (CAD). A diversity of clinical and angiographic studies has been made to evaluate the linkage between plasma lipid-control therapy in the development of initial and recurrent cardiovascular events. The plan of treatment invariably begins with a low-fat, low-cholesterol diet before initiation of drug therapy. However, many patients have difficulty in adhering to the low-fat diet. Fortunately, metabolic studies show that foods which contain fats rich in stearic (saturated) and oleic (monounsaturated) fatty acids may be given in limited amounts to boost patients' compliance to a low-fat diet and to prevent their blood lipids from rising to abnormal levels. A bile acid sequestrant (cholestyramine or colestipol) is the first-line drug for control of hypercholesterolemia. Either gemfibrozil or gemfibrozil plus niacin is prescribed to raise high-density lipoprotein (HDL) levels of CAD patients. Approval of two HMG CoA reductase inhibitors, pravastatin and simvastatin, by the FDA gives physicians the additional flexibility of employing a single or a combination drug therapy for optimal control of dyslipidemia. The association of low serum cholesterol level (< 160 mg/dl) with increase in noncardiac mortality has prompted health professionals to consider modifying the universal screening and treatment of serum cholesterol in children and young women and to use hypolipidemic drugs in patients judiciously.

Successful pregnancy in a woman with lipoatrophic diabetes mellitus. A case report.

BACKGROUND: Lipoatrophic diabetes mellitus is a rare insulin-resistance syndrome. A successful pregnancy occurred in a woman with lipoatrophic diabetes with no antepartum or intrapartum complications except hypertriglyceridemia, treated with gemfibrozil. CASE: A 29-year-old primigravida had lipoatrophic diabetes most consistent with congenital partial lipodystrophy (Kobberling-Dunnigan syndrome). The antenatal course was remarkable only for a midtrimester rise in serum triglycerides. The patient underwent oxytocin induction and an uncomplicated vaginal delivery. CONCLUSION: This case demonstrates that women with lipoatrophic diabetes who are otherwise healthy should not be discouraged from trying to conceive. Blood lipids should be checked periodically and hypertriglyceridemia treated to prevent pancreatitis. Gemfibrozil was used in this patient without apparent adverse effects.