HMG CoA reductase inhibitors as lipid-lowering agents: five years experience with lovastatin and an appraisal of simvastatin and pravastatin

The HMG CoA reductase inhibitors are the most effective drugs for treating hypercholesterolaemia currently available. They inhibit cholesterol synthesis and thus stimulate receptor-mediated uptake and degradation of low-density lipoprotein cholesterol by the liver. In 30 patients with severe hypercholesterolaemia administration of lovastatin alone or in combination with other lipid-lowering manoeuvres maintained reductions of 25 to 31 per cent in serum cholesterol over five years. The drug was easy to take and well tolerated, the only significant side effect being a reversible myopathy. Two similar compounds, simvastatin and pravastatin, exert comparable effects on serum lipids, including modest reductions in triglycerides and increases in high-density lipoprotein cholesterol. The use of these drugs seems likely to exert a beneficial effect on atherosclerosis.     

A ONE-YEAR MULTICENTRE STUDY OF SIMVASTATIN IN THE TREATMENT OF HYPERCHOLESTEROLEMIA

SUMMARY A 1-year prospective study was conducted in 475 hypercholesterolaemic men and women who received simvastatin monotherapy 10–40 mg daily for 3 months followed by additional lipid-lowering medication after this period, if necessary, to reach a target of plasma cholesterol <5.3 mmol/l. Of these, 403 subjects completed 1 year of follow-up. By the end of the 3-month monotherapy period, the following percentage mean changes were seen (with 95% confidence intervals): total cholesterol (TC) -31% (-30 to -32%), low-density lipoprotein cholesterol -39% (-38 to -40%), triglycerides -14% (-11 to -17%) and high-density lipoprotein cholesterol +12% (+11 to +14%). These levels were maintained for the remainder of the study. When subjects with a baseline TC of 6.5–7.8 mmol/l were considered (n=89), 42.7% achieved the target TC levels on simvastatin monotherapy alone. Additional hypolipidaemic medication had no significant impact on plasma lipid and lipoprotein levels. Simvastatin was well tolerated both as monotherapy and in combination.     

Ameliorating effect of coenzyme Q10, riboflavin and niacin in tamoxifen-treated postmenopausal breast cancer patients with special reference to lipids and lipoproteins

OBJECTIVES: Tamoxifen (TAM), a non-steroidal anti-estrogen that is widely used in adjuvant therapy for all stages of breast carcinomas and in chemoprevention of high-risk group. The hepatic estrogenic effect of TAM induces hypertriglyceridemia by reduced activity of lipolytic enzymes (LPL) on triglycerides. Coenzyme Q10 (Co Q10), riboflavin and niacin are proved to be potent antioxidant and protective agents against many diseases including cancer and cardiovascular diseases (CVD). In this context, the objective of the study is to find the effect of the combined modality of Co Q10 (100 mg), riboflavin (10 mg) and niacin (50 mg) with TAM (10 mg twice a day) on serum lipids and lipoprotein levels in postmenopausal women with breast cancer. DESIGN AND METHODS: The vitamin supplementation with tamoxifen was given for a period of 90 days. Blood samples were collected at the base line, 45th and 90th day during the course of treatment. Plasma total cholesterol (TC), free cholesterol (FC), ester cholesterol (EC), phospholipids (PL), triglycerides (TGL), free fatty acids (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and very low density cholesterol (VLDL-C) were estimated in 78 untreated, only TAM-treated and combinatorialy treated group along with 46 age- and sex-matched controls. RESULTS: Serum TGL and VLDL-C (p<0.001) were found to be significantly elevated and LDL-C (p<0.01), significantly reduced among TAM-treated patients as compared to the untreated breast cancer subjects. All the lipids and lipoprotein levels were found to be significantly altered in the untreated breast cancer patients when compared to their normal counterparts. All the lipid and lipoprotein abnormalities were reverted back to near normal levels on 90 days of treatment on combinatorial therapy. CONCLUSION: The study figures the altered lipid and lipoprotein levels in the untreated and TAM-treated breast cancer patients. On combination therapy with Co Q10, riboflavin and niacin, it counteracts the tamoxifen-induced hyperlipidemia to normal levels.     

Efficacy of ciprofibrate in primary type II and IV hyperlipidemia: the Italian multicenter study

The 127 diet-resistant primary hyperlipidemic patients received 100 mg of ciprofibrate daily for 12 weeks. In the 63 patients with type IIa hyperlipidemia and 41 patients with type IIb hyperlipidemia, serum levels of total cholesterol, very-low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, very-low-density lipoprotein triglycerides, and apolipoprotein (apo) B decreased significantly and levels of high-density lipoprotein cholesterol and apo A-I increased significantly. Similar changes occurred in the 23 type IV patients, except that high-density lipoprotein cholesterol levels increased significantly and apo B levels did not change. No clinically significant side effects or drug-related abnormal laboratory test results were noted. It is concluded that ciprofibrate is a safe and potent hypolipidemic agent.     

Niacin as a component of combination therapy for dyslipidemia

Dyslipidemia is one of the most important modifiable risk factors for coronary disease. Despite the availability of highly effective lipid-modifying agents, many patients still do not reach lipid targets established by national guidelines. Niacin has been known to be an effective treatment of dyslipidemia for almost half a century. Niacin substantially increases high-density lipoprotein cholesterol (HDL-C) levels while lowering levels of low-density lipoprotein cholesterol (LDL-C), triglycerides, and lipoprotein(a). In addition, niacin converts small LDL particles into more buoyant, less atherogenic LDL particles. Combined with other agents, niacin offers an important treatment option for patients with dyslipidemia. In particular, niacin complements LDL-C-lowering drugs; it is the most effective agent available for increasing HDL-C levels while lowering levels of LDL-C and triglycerides and improving other lipid risk factors such as lipoprotein(a). Combining niacin with statins or bile acid sequestrant therapy is safe and effective for improving lipid levels and decreasing coronary risk. Differences in niacin formulations dictate tolerability profiles and should be considered when selecting niacin as part of lipid therapy. Furthermore, adverse effects on glucose and insulin sensitivity should be considered when selecting candidates for niacin therapy. Adding niacin to lipid-lowering regimens is a valuable option for physicians treating patients with dyslipidemia and should be considered in appropriate patients.     

Long-term Treatment With Pravastatin Alone and in Combination With Gemfibrozil in Familial Type IIB Hyperlipoproteinemia or Combined Hyperlipidemia

BACKGROUND: Pravastatin inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase. It prevents mevalonate synthesis, reducing endogenous cholesterol production, and reduces cholesterol content in the liver, thus resulting in a down-regulation of low-density lipoprotein receptor production. Gemfibrozil reduces very low-density lipoprotein production and low-density lipoprotein-cholesterol level and increases very low-density lipoprotein catabolism. Therefore, it was suggested that combination therapy with both drugs could effect greater reduction of cholesterol levels as compared to pravastatin alone. The present study was carried out to evaluate the efficacy and safety of pravastatin as a monotherapy or in combination with gemfibrozil in the treatment of patients with familial type IIb hyperlipoproteinemia or familial combined hyperlipidemia. METHODS AND RESULTS: Forty-one patients were included in the study. All patients initially followed 6 weeks of hypolipidemic diet; subsequently they were randomized and received either 20 mg once daily of pravastatin alone (n = 13) or 20 mg of pravastatin together with 600 mg of gemfibrozil twice daily (n = 14). As a control, 14 patients were treated with diet only. The treatment lasted 24 months and clinical evaluation and laboratory tests were done at given time points. Both groups of treated patients showed an early reduction (3 months) of total (about 30% P <.01 vs controls), low-density lipoprotein (about 35%, P <.01 vs controls) and very low-density lipoprotein cholesterol levels (about 18%, P = NS). In contrast, high-density lipoprotein cholesterol levels increased significantly in patients treated with pravastatin and gemfibrozil (about 20%, P <.05 vs controls). Pravastatin treatment alone reduced the level of serum triglycerides as efficiently as in combination with gemfibrozil. Data showed a sustained normalization of lipid profile until 24 months. However, this effect was achieved in patients that had rather low levels of triglycerides. During the treatment we did not observe any difference in the incidence of possible drug-related side effects. Severe myopathy or rhabdomyolysis was not observed at the doses of the drugs used in our study. CONCLUSIONS: Therapy with pravastatin and in combination with gemfibrozil resulted in significant and sustained normalization of lipid profile in high-risk patients with familial type IIb hyperlipoproteinemia or familial combined hyperlipidemia.     

The effects of extended-release niacin on carotid intimal media thickness, endothelial function and inflammatory markers in patients with the metabolic syndrome

BACKGROUND: Niacin is an agent that significantly increases high-density lipoprotein cholesterol (HDL-C), but its effects on surrogate markers of atherosclerosis and inflammatory markers are less clear. We studied the effects of niacin on carotid intimal media thickness (IMT), brachial artery reactivity as well as markers of inflammation and the metabolic profile of patients with metabolic syndrome. METHODS AND RESULTS: Fifty patients with the metabolic syndrome (Adult Treatment Panel (ATP) III criteria) were randomised to either extended-release niacin (1000 mg/day) or placebo. After 52 weeks of treatment, there was a change of carotid IMT of +0.009 +/- 0.003 mm in the placebo group and -0.005 +/- 0.002 mm in the niacin group (p = 0.021 between groups). Endothelial function improved by 22% in the group treated with niacin (p < 0.001), whereas no significant changes were seen in the placebo group. High sensitivity C-reactive protein decreased by 20% in the group treated with niacin for 52 weeks (p = 0.013). Niacin increased HDL-C (p < 0.001) and decreased low-density lipoprotein cholesterol and triglycerides (p < 0.001) significantly, and there were no adverse effects on fasting glucose levels after 52 weeks of treatment. CONCLUSION: Extended-release niacin therapy effects a regression in carotid intimal medial thickness and improvement in metabolic parameters (increased HDL and reduced triglycerides). Furthermore, extended-release niacin may demonstrate an anti-atherogenic effect in the metabolic syndrome by improving endothelial function and decreasing vascular inflammation.     

Treatment Effect of Niaspan, a Controlled-release Niacin, in Patients With Hypercholesterolemia: A Placebo-controlled Trial

BACKGROUND: The present study was designed to determine the efficacy and safety of Niaspan (Kos Pharmaceuticals, Inc, Hollywood, FL), a new controlled-release formulation of niacin, in the treatment of primary hyperlipidemia, the occurrence and severity of flushing events, and potential adverse effects, particularly hepatotoxicity. METHODS AND RESULTS: The study was conducted as a multicenter, randomized, double-blind, placebo-controlled, parallel comparison of Niaspan in doses of 1000 mg/day and 2000 mg/day, administered once a day at bedtime. One hundred twenty-two patients with low-density lipoprotein cholesterol levels >4.14 mM/L (160 mg/dL) with dietary intervention and high-density lipoprotein cholesterol 相似文献   

Niacin-ER and lovastatin treatment of hypercholesterolemia and mixed dyslipidemia

OBJECTIVE: To review the currently available information on the once-daily combination of niacin extended-release (ER)/lovastatin in the treatment of patients with hypercholesterolemia and mixed dyslipidemia at high risk for cardiovascular events. DATA SOURCES: MEDLINE (1966-July 2002) was searched for primary and review articles. Data from the manufacturer were also included. STUDY SELECTION/DATA EXTRACTION: All articles and product labeling deemed relevant to the combination of niacin and statins (i.e., lovastatin) were included for review. English-language studies selected for inclusion were limited to those with human subjects. DATA SYNTHESIS: The Food and Drug Administration approved a new fixed-dose combination of niacin-ER/lovastatin, which is administered once daily. The efficacy and safety of the combined agent have been proven to be similar to either component used alone or in combination for management of hyperlipidemia and mixed dyslipidemia. CONCLUSIONS: Elevated low-density lipoprotein cholesterol (LDL-C) is independently associated with a higher risk for cardiovascular events. Lowering of elevated LDL-C concentrations with statin monotherapy may be insufficient in patients at high risk for cardiovascular events. In fact, consideration of elevated triglycerides (TGs) and/or low concentrations of high-density lipoprotein cholesterol (HDL-C) in patients with elevated LDL-C places them at greater risk. The addition of niacin may enhance or improve the lipid profile of those who require a further decrease of TGs and/or increase of HDL-C even after stable statin therapy. Niacin-ER offers efficacy similar to that of immediate-release niacin, but minimal myopathy and hepatotoxicity (compared with sustained-release niacin). Although no clinical outcomes are available, current evidence shows that the combination product offers adequate lowering of LDL-C and TGs and increasing HDL-C. The data suggest that therapy with the niacin-ER and lovastatin combination product is safe and does not increase the incidence of adverse effects.     

Fenofibrate decreases plasma fibrinogen, improves lipid profile, and reduces uricemia.

Plasma fibrinogen has been found to be a major cardiovascular disease risk factor. This 2-year trial was designed to assess the effect of fenofibrate on fibrinogen and, as secondary end points, on lipid profile and uric acid in patients with dyslipidemia. Eighty subjects (40 women and 40 men) were admitted to either a control or an active group. Sixty-seven (84%) had sole hypercholesterolemia, 13 (16%) subjects had mixed dyslipidemia. The effect attributable to fenofibrate was a decrease of 15% in fibrinogen, 26% in the ratio low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (-20% low-density lipoprotein cholesterol, +10% high-density lipoprotein cholesterol), 34% in triglycerides (median), and 13% in uric acid (P < .0001 for all). Fenofibrate simultaneously affected hemostasis (by lowering fibrinogenemia) and lipid profile. Because fenofibrate has few adverse effects, it could be a fair option for patients who need polytherapy and do not tolerate resins or niacin. Its clinical efficacy should be tested in long-term studies to assess its real capacity to prevent cardiovascular events.     

丹红注射液联合小剂量辛伐他汀对急性冠脉综合征的降脂效果

目的探讨丹红注射液联合小剂量辛伐他汀对急性冠脉综合征的降脂效果。方法将急性冠脉综合征患者70例按随机数字表法分为2组:对照组35例给予辛伐他汀降脂,观察组35例给予丹红注射液联合小剂量辛伐他汀降脂,评估两者降脂效果。结果治疗后观察组患者TC、TG、LDL-C及hs-CRP明显低于对照组(P<0.05),观察组患者血脂达标率明显高于对照组(97.14%比77.14%,P<0.05)。结论丹红注射液联合小剂量辛伐他汀在急性冠脉综合征中降脂的临床效果明确,值得应用。     

An evaluation of pharmaceutical treatment of dyslipidaemia among patients without diagnosed atherosclerotic disease in Belgium

The aim of this study was to assess the lipoprotein levels in patients without diagnosed atherosclerotic disease but treated with lipid-lowering drugs. During February and March 2002 all demands for continuation of reimbursement of lipid-lowering drugs were recorded at two regional offices of health insurance associations. A total of 1973 patients without diagnosed atherosclerotic disease were included (mean age 66 years). Mean total cholesterol (TC) was 5.39 mmol/l, high-density lipoprotein cholesterol (HDL-C) 1.50 mmol/l, low-density lipoprotein cholesterol (LDL-C) 3.16 mmol/l and triglycerides (TG) 1.59 mmol/l. Thirty-four per cent of the treated patients reached the TC target of 5.0 mmol/l or less. The LDL-C target level of 3.0 mmol/l or less was reached by 45% of the patients. Of the patients receiving a statin, 61% were not treated with the optimal doses. The treatment was adjusted in 15% of the patients who did not reach the combined endpoint.     

Serum lipoprotein profile in patients with cancer. A comparison with non-cancer subjects

The association of cancer with low serum total cholesterol is well established. Less clear is the relationship of cancer with the cholesterol distribution among the different lipoprotein classes. Conflicting results have been reported on low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and serum triglyceride levels in different types of tumor. Total serum cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and serum triglycerides were analyzed in 530 patients with newly diagnosed cancer (97 with hematological malignancies, 92 with tumor of the lung, 108 of the upper digestive system, 103 of colon, 32 of breast, and 98 of the genitourinary system) and in 415 non-cancer subjects. Anthropometric (body mass index) and biochemical (serum albumin) indices of nutritional status were also determined in all subjects. Total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, serum albumin, and body mass index were significantly lower in cancer than in non cancer-subjects. The lowest values of total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol were recorded in patients with hematological malignancies and the highest in patients with breast tumor. All the cancer groups, with the exception of women with breast cancer, showed significantly lower total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol than age- and sex-matched non-cancer subjects. Multiple regression analysis with low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides as dependent variables and sex, age, body mass index, albumin, and cancer (dummy variable) as independent variables, showed that cancer was independently associated with low levels of low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol and with high values of serum triglycerides. Total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, serum triglycerides, body mass index and serum albumin were significantly lower in patients with metastatic than in patients with non-metastatic solid tumor. The significant difference in low-density lipoprotein-cholesterol and serum triglycerides between patients with metastatic and non-metastatic cancer was lost when lipoprotein cholesterol and serum triglyceride levels were adjusted for nutritional variables. The lipid profile in cancer patients is characterized by low low-density lipoprotein-cholesterol, low high-density lipoprotein-cholesterol and relatively high serum triglycerides. The abnormality is a common feature of both hematological and solid tumors and is not entirely explained by poor nutrition.     

The effects of triple vs. dual and monotherapy with rosiglitazone, glimepiride, and atorvastatin on lipid profile and glycemic control in type 2 diabetes mellitus rats

The present study was undertaken to investigate the effects of triple oral therapy and different combination of rosiglitazone, atorvastatin, and glimepiride on streptozotocin (STZ)-induced diabetic rats. The various biochemical parameters studied included glycosylated hemoglobin (A1c), fasting plasma sugar levels, triglycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and very low-density lipoprotein (VLDL) cholesterol in diabetic and normal rats. The present study demonstrates that atorvastatin could increase the effect of rosiglitazone and glimepiride and lipid-lowering effect of combination of rosiglitazone and glimepiride (GLIM). According to our finding, similar results for rosiglitazone plus atorvastatin were obtained in terms of correcting lipid parameters, whereas the suppressive action of triple oral therapy of rosiglitazone and glimepiride, and atorvastatin on blood glucose, total cholesterol, LDL, VLDL, HDL cholesterol, and triglyceride was more beneficial than that of dual therapy of different combinations and monotherapy.     

Clinical update on the use of niacin for the treatment of dyslipidemia

PURPOSE: To provide nurse practitioners (NPs) with clinical and practical information about the use of niacin in the treatment of dyslipidemia. DATA SOURCES: Research-based and review articles in the medical literature and National Cholesterol Education Program guidelines. CONCLUSIONS: Niacin provides beneficial effects on all major lipid fractions, particularly high-density lipoprotein cholesterol and triglycerides. Niacin also reduces low-density lipoprotein (LDL) cholesterol; lipoprotein (a); and the number of highly atherogenic small, dense LDL particles. Niacin promotes angiographic regression when used in combination with other drugs that lower LDL cholesterol and can reduce cardiovascular risk in patients with coronary heart disease. Several niacin formulations are available, but the safety (i.e., from hepatotoxicity) and tolerability (i.e., severity of flushing) of these niacin formulations may differ. IMPLICATIONS FOR PRACTICE: Niacin therapy is appropriate for many types of lipid abnormalities, including complex dyslipidemias. NPs can take several steps to minimize potential side effects of niacin therapy and to ensure that patients adhere to this important intervention.     

Optimal management of cholesterol levels and the prevention of coronary heart disease in women

Coronary heart disease, the leading cause of death in women, is largely preventable. Lifestyle modifications (e.g., diet and exercise) are the cornerstone of primary and secondary prevention. Elevated levels of low-density lipoprotein cholesterol and triglycerides and low levels of high-density lipoprotein cholesterol are significant risk factors for coronary heart disease. Abundant data show inadequate utilization of lipid-lowering therapy in women. Even when women are given lipid-lowering agents, target levels often are not achieved. Recent guidelines from the American Heart Association and the American College of Cardiology encourage a more aggressive approach to lipid lowering in women. The National Cholesterol Education Program Adult Treatment Panel III also supports this strategy and significantly expands the number of women who qualify for intervention.     

Atorvastatin, a New HMG-CoA Reductase Inhibitor as Monotherapy and Combined With Colestipol

BACKGROUND: Atorvastatin, a new HMG-CoA reductase inhibitor in clinical development has demonstrated an acceptable safety profile and marked cholesterol and triglyceride reduction at doses ranging from 10-80 mg/day. Since bile acid sequestering resins are often used in combination with HMGRIs to enhance cholesterol reduction, this trial was conducted to explore the use of atorvastatin alone and combined with colestipol in patients with primary hyperlipidemia. METHODS AND RESULTS: One hundred six patients with low-density lipoprotein (LDL) cholesterol >4.1 mM/L (160 mg/dL) and plasma triglycerides <3.9 mM/L (350 mg/dL) were randomized to treatment consisting of 20 g/day colestipol, 10 mg/day atorvastatin, or 10 mg/day atorvastatin plus 20 g/day colestipol for 12 weeks. Percent change from baseline in lipid variables were measured. The atorvastatin group showed a significant reduction in LDL cholesterol of 35% after 12 weeks. Combination therapy provided an additional 10% reduction in LDL cholesterol over that observed for atorvastatin alone. Twenty-one percent of all patients in the atorvastatin monotherapy group experienced associated adverse events compared with 60% in the combination therapy group. Ninety percent of atorvastatin monotherapy patients were compliant at every visit compared with 75% receiving combination therapy. CONCLUSIONS: Although the combination of atorvastatin plus colestipol was more effective in lowering LDL cholesterol than atorvastatin alone, atorvastatin 10 mg/day monotherapy provided a better safety profile and improved patient compliance, which may result in improved long-term cholesterol control.     

An open-label comparison of the effects of simvastatin and niacin alone and combined on the lipid profile and lipoprotein (a) level in an Indian population with dyslipidemia

Abstract

Background:

Patients with dyslipidemia often require the use of >1 lipid-altering agent to achieve the target levels recommended by the National Cholesterol Education Program Adult Treatment Panel III.

Objective:

The aim of this study was to compare the effects of simvastatin and niacin alone and combined on the lipid profile and lipoprotein (a) (Lp[a]) level in an Indian population with dyslipidemia.

Methods:

This 12-week, open-label, nonrandomized study was conducted at the Departments of Pharmacology and Medicine, Government Medical College, Amritsar (Punjab), India. Patients aged 30 to 70 years with dyslipidemia were eligible. Patients were assigned to 1 of 3 treatment groups. Group 1 received simvastatin 20 mg/d for 12 weeks. Group 2 received niacin at doses of 375 mg/d for 1 week, 500 mg/d for 1 week, and 500 mg BID for 10 weeks. Group 3 received simvastatin 10 mg/d plus niacin (375 mg for 1 week and 500 mg for 11 weeks). The lipid profile (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) and Lp(a) were measured before the start of therapy and at 6 and 12 weeks of treatment. Percentage changes from baseline were calculated. Adverse effects (AEs) were recorded at weeks 6 and 12 and through spontaneous reporting.

Results:

Ninety patients were enrolled (50 men, 40 women; 30 patients per treatment group). In group 1, the mean (SD) percentage decrease in LDL-C level at 12 weeks was 42.79% (16.29%) (P < 0.05), but no significant change was seen in group 2 or 3. The mean (SD) percentage increases in HDL-C level were 18.43% (13.28%) and 20.82% (17.57%) in groups 2 and 3, respectively (both, P < 0.05), but no significant change was seen in group 1. TC levels decreased by a mean (SD) of 32.97% (13.66%) in group 1 (P < 0.05), but no significant change was seen in group 2 or 3. TG and Lp(a) levels did not change significantly in any of the 3 treatment groups. Flushing, myalgia, and dyspepsia were the most common AEs in patients receiving niacin.

Conclusions:

In this study in Indian patients with dyslipidemia, simvastatin-niacin combination therapy was associated with greater changes in lipid profile compared with either agent used alone. Niacin was also associated with greater changes in Lp(a) levels. AEs were less prevalent with combination therapy than with niacin alone.Key words: dyslipidemia, simvastatin, niacin, combination therapy     

Mathematical evaluation of methods for estimation of the concentration of the major lipid components of human serum lipoproteins.

The concentration of total cholesterol and triglycerides in the three major lipoprotein classes of human serum was measured in 136 men, randomly selected from an industrial population, by a quantitative method of lipoprotein electrophoresis on agarose gel and of fractions separated by preparative ultracentrifugation. Correlation coefficients for the two estimates were 0.98 for triglycerides in very low-density lipoproteins, 0.93 for total cholesterol in low-density lipoproteins, and 0.75 for total cholesterol in high-density lipoproteins. Data obtained form the analyses of the ultracentrifugal fractions were used to develop regression equations that predict the concentrations of total cholesterol and triglycerides in the lipoprotein classes from their concentrations in whole serum. These equations take into account the inverse curvilinear relationship between total cholesterol in high-density lipoproteins and serum tiriglyceride concentration. When applied to a separate sample of 530 men, the predicted values for triglycerides in very low-density lipoproteins and total cholesterol in low-density lipoproteins correlated as well with ultracentrifugal values as did the electrophoretic estimates. However, for total cholesterol in high-density lipoproteins, the electrophoretic method was superior. Similar regression equations were developed from ultracentrifugal lipoprotein analyses in 158 women from the same industrial population. Although the concentration of total cholesterol in the low-density lipoproteins estimated by both electrophoresis and the regression equations agreed closely in most cases with the ultracentrifugal values, errors exceeded 10% with sufficient frequency to limit the value of the estimates for this purpose. In both men and women, the ratio of total cholesterol to triglycerides in high-density lipoproteins was a hyperbolic function of serum triglyceride concentration, suggesting that cholesteryl esters in the core of this lipoprotein are progressively replaced by triglycerides as the concentration of triglycerides in very low-density lipoproteins increases. This altered composition of nonpolar lipids accounts, at least in part, for the reduction of cholesterol in high-density lipoproteins in hyperlipemic individuals.     

Lack of effect of hepatic enzyme induction on metabolic control in patients with type 2 (non-insulin-dependent) diabetes

A placebo-controlled, double-blind crossover study was carried out in 11 non-insulin-dependent (type 2) diabetic patients to find out the effects of a hepatic enzyme inducer (phenobarbital, 100 mg/day for 2 months) on the metabolic control, plasma C-peptide, insulin, serum, and lipoprotein lipid levels. Phenobarbital induced a significant increase in hepatic antipyrine metabolizing activity, but no significant changes were found in fasting or postload blood glucose, plasma C-peptide, or insulin levels during the study. There was a significant increase in serum total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, as well as in serum total and very low-density lipoprotein triglycerides, during phenobarbital treatment as compared with placebo.