Combination Of Fenofibrate Research Articles

Comparison of Efficacy and Safety of Fixed Dose Combination of Rosuvastatin and Choline Fenofibrate to Fixed Dose Combination of Rosuvastatin and Fenofibrate in Patients of Mixed Dyslipidemia: A Randomized, Open-label, Multicentre Clinical Trial in Indian Population.

Introduction:This study was conducted to evaluate the safety and efficacy of fixed-dose combination (FDC) of rosuvastatin and choline fenofibrate in comparison to rosuvastatin and fenofibrate FDC among Indian patients of mixed dyslipidemia. This would be a first study evaluating FDC of rosuvastatin and choline fenofibrate in Indian population.Methods:A multicenter, open-label, randomized, active controlled, comparative, parallel-design study was conducted at 12 centers spread all across India. Mixed dyslipidemic patients aged 18–70 years were randomized to FDC of rosuvastatin 10 mg and choline fenofibrate 135 mg (RCF group) and FDC of rosuvastatin 10 mg and fenofibrate 160 mg (RF group) once daily for approximately 180 days. The primary endpoint of study was percentage change in serum triglyceride level at the end of study from baseline.Results:Of 290 patients screened, 240 patients were enrolled in this study (120 patients in each group). At the end of 180 days, there was a significant reduction in triglyceride level in both the groups (−37.7% in RCF group and −37.8% reduction in RF group; P < 0.0001 for both); however, the difference between both the groups was not statistically significant (P = 0.94). Similarly, there was significant increase (P < 0.0001 for both) in high-density lipoprotein cholesterol (HDL-C) in both groups (+17.8% in RCF group and +14.9% in rosuvastatin fenofibrate RF group). Low-density lipoprotein cholesterol (LDL-C), very low-LDL (VLDL-C), and total cholesterol were also reduced significantly in both groups (P < 0.0001). However, the difference between two groups for increase in HDL-C and decrease in LDL-C, VLDL-C, and total cholesterol was not significant. Both the treatments were safe and well tolerated.Conclusion:Overall, FDC of rosuvastatin and choline fenofibrate is as safe and effective as rosuvastatin and fenofibrate combination in Indian patients with mixed dyslipidemia with added advantage improved patient compliance as it can be taken irrespective of intake of food.

Omega-3 fatty acids as adjunctive treatment for bexarotene-induced hypertriglyceridaemia in patients with cutaneous T-cell lymphoma

Bexarotene is an oral retinoid approved for treating cutaneous T-cell lymphoma (CTCL) in patients resistant to first-line systemic treatment. Hypertriglyceridaemia is an unavoidable adverse effect of bexarotene therapy, and requires monitoring because of the risk of developing pancreatitis. Therefore, prophylactic hypolipidaemic therapy, usually with a fibrate alone, is required for preventing bexarotene-induced hypertriglyceridaemia. Despite these measures, a large number of patients develop very severe hypertriglyceridaemia. To assess the lipid metabolism changes before and after the use of a combination of omega-3 fatty acids (n-3 FA) plus fenofibrate compared with fenofibrate alone as a more effective lipid-lowering therapy in patients with CTCL treated with bexarotene. From January 2005 to January 2013, we analysed all 25 patients with CTCL treated with bexarotene. The first 18 consecutively enrolled patients received fenofibrate alone as a lipid-lowering therapy, and the next 7 consecutively enrolled patients received a combination of fenofibrate and n-3 FA. Data for all 25 consecutive patients with CTCL treated with bexarotene were evaluated. Of these, 24 patients (96%) developed hypertriglyceridaemia despite the hypolipidaemic therapy, with this being very severe (> 11.2 mmol/L) in 20% of the cases. Of the 18 patients receiving fenofibrate alone, 5 (28%) developed very severe hypertriglyceridaemia, compared with none of the 7 patients treated with the n-3 FA combination. Our results suggest that the n-3 FA combination may be more effective than fibrate alone for preventing bexarotene-induced hypertriglyceridaemia.

Clinical research of fenofibrate and spironolactone for acute central serous chorioretinopathy.

To compare the effectiveness of combined fenofibrate and spironolactone with fenofibrate alone for treatment of central serous chorioretinopathy (CSCR). Totally 60 patients (60 eyes) with a history of acute CSCR were randomed into two groups: group A with combination of fenofibrate (200 mg) and spironolactone (100 mg), and group B with only fenofibrate (200 mg). They were taken half an hour before meals and once per day for 8wk. The changes of the visual acuity, subjective symptom, ocular surface disease index (OSDI), the tear film and optical coherence tomography were observed at 2, 4, 6, and 8wk before and after treatment. The best corrected visual acuity (BCVA, logMAR) was improved to 0.22 and 0.27 after treatment from baseline of 0.35 and 0.36 in groups A and B (P<0.05), respectively. After 8wk treatment, the central subfield thickness (CST), and subretinal fluid volumn (SFV) decreased significantly to 49.5% and 78.8% in group A and 37.0% and 57.2% in group B. There were significant differences of CST and SFV in both groups (all P<0.05). Fenofibrate combined with spironolactone may have more clinical efficacy in the treatment of CSCR than fenofibrate only.

The PPARα Agonist Fenofibrate Improves the Musculoskeletal Effects of Exercise in Ovariectomized Rats.

The musculoskeletal effects of exercise are attenuated by estrogen deficiency. The peroxisome proliferator-activated receptor-α agonist fenofibrate exerts beneficial effects in bone and muscle. We therefore examined whether fenofibrate could enhance the musculoskeletal training response during estrogen deficiency. We investigated the combined effects of 8 weeks of fenofibrate and jumping exercise in ovariectomized (OVX) Sprague Dawley rats. Female rats were allocated to a sham-operated group and four OVX groups; fenofibrate (OVX-Fen), exercise (OVX-Ex), combined fenofibrate and exercise (OVX-FenEx), and a control group (OVX-Ctr) (n = 12/group). Fenofibrate (90 mg/kg/d) or methylcellulose was given by gavage. The combination of exercise and fenofibrate resulted in enhanced femoral bone mineral density (BMD) and improved bone microarchitecture compared with fenofibrate alone as well as increased trabecular BMD compared with OVX-Ctr. These effects were not seen in the OVX-Ex group. Femoral BMD was normalized in both exercise groups relative to sham and increased more in all intervention groups compared with OVX-Ctr. A higher plasma level of the bone formation marker type 1 collagen amino propeptide was observed in the OVX-Fen and OVX-FenEx groups compared with controls. Lean mass and soleus muscle weight were higher in the OVX-FenEx group than in the OVX-Ctr group, which coincided with lower mRNA levels of Atrogin1. These results suggest that peroxisome proliferator-activated receptor-α activation improves the musculoskeletal effects of exercise during estrogen deficiency.

Chronic oral administration of low-dose combination of fenofibrate and rosuvastatin protects the rat heart against experimentally induced acute myocardial infarction.

Fenofibrate and rosuvastatin at low doses might have experimental pleiotropic benefits. This study investigated the combined effect of low doses of fenofibrate and rosuvastatin in isoproterenol-induced experimental myocardial infarction. Rats administered isoproterenol (85 mg/kg/day, s.c.) for 2 days (day 29 and day 30) of 30 days experimental protocol developed significant myocardial infarction that was accompanied with high myocardial oxidative stress and lipid peroxidation, elevated serum markers of cardiac injury, lipid abnormalities, and elevated circulatory levels of C-reactive protein. Pretreatment with low doses of fenofibrate (30 mg/kg/day p.o., 30 days) and rosuvastatin (2 mg/kg/day p.o., 30 days) both alone or in combination markedly prevented isoproterenol-induced myocardial infarction and associated abnormalities while the low-dose combination of fenofibrate and rosuvastatin was more effective. Histopathological study in isoproterenol control rat heart showed necrosis with edema and acute inflammation at the margins of necrotic area. The rat heart from low-dose fenofibrate and rosuvastatin pretreated group showed scanty inflammation and no ischemia. In conclusion, fenofibrate and rosuvastatin pretreatment in low doses might have a therapeutic potential to prevent the pathogenesis of myocardial infarction. Moreover, their combined treatment option might offer superior therapeutic benefits via a marked reduction in myocardial infarct size and oxidative stress, suggesting a possibility of their pleiotropic cardioprotective action at low doses.

Targeted Proteomics Identifies Paraoxonase/Arylesterase 1 (PON1) and Apolipoprotein Cs as Potential Risk Factors for Hypoalphalipoproteinemia in Diabetic Subjects Treated with Fenofibrate and Rosiglitazone

Low levels of high-density lipoprotein cholesterol (HDL-C) and high triglyceride levels contribute to the excess rate of cardiovascular events seen in subjects with type 2 diabetes. Fenofibrate treatment partially reverses dyslipidemia in these subjects. However, a paradoxical marked reduction in HDL-C and HDL's major protein, apolipoprotein A-I, is a complication of fenofibrate in combination with rosiglitazone, an insulin-sensitizing agent. Risk factors for this condition, termed hypoalphalipoproteinemia, have yet to be identified. Using a case-control study design with subjects enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, we tested the hypothesis that alterations in HDL's protein cargo predispose diabetic subjects to fenofibrate/rosiglitazone-induced hypoalphalipoproteinemia. HDL was isolated from blood obtained from controls (no decreases or increase in HDL-C while receiving fenofibrate/rosiglitazone therapy) and cases (developed hypoalphalipoproteinemia after fenofibrate/rosiglitazone treatment) participating in the ACCORD study before they began fenofibrate/rosiglitazone treatment. HDL proteins were quantified by targeted parallel reaction monitoring (PRM) and selected reaction monitoring (SRM) with isotope dilution. This approach demonstrated marked increases in the relative concentrations of paraoxonase/arylesterase 1 (PON1), apolipoprotein C-II (APOC2), apolipoprotein C-I, and apolipoprotein H in the HDL of subjects who developed hypoalphalipoproteinemia. The case and control subjects did not differ significantly in baseline HDL-C levels or other traditional lipid risk factors. We used orthogonal biochemical techniques to confirm increased levels of PON1 and APOC2. Our observations suggest that an imbalance in HDL proteins predisposes diabetic subjects to develop hypoalphalipoproteinemia on fenofibrate/rosiglitazone therapy.

Comparative Study of Atorvastatin and Rosuvastatin in Combination with Fenofibrate in mixed Hyperlipidemia

International Journal of Pharmacology and Clinical Sciences,2016,5,1,25-31.DOI:10.5530/ijpcs.5.1.5Published:March 2016Type:Research ArticlesAuthors:Rohit Dixit, and Shankar Jagan Author(s) affiliations:Rohit Dixit1 and Shankar Jagan2 1Department of Pharmacology, Navodaya Medical College, INDIA. 2Medical Review Safety Physician, Accenture, Chennai, INDIA. Abstract:Aim: To compare the effects of Atorvastatin and Rosuvastatin in combination with fenofibrate in patients with mixed Hyperlipidemia. Materials and Methods: It was an open label, randomized, parallel group, comparative, prospective clinical study. A total of 70 subjects diagnosed with mixed hyperlipidemia were screened and were randomly allocated into two groups of thirty each. Initial readings of lipid levels like TC, TG, HDL, LDL and VLDL for both the groups were taken as baseline values. Then, Group I received Tab Atorvastatin 10 mg + Fenofibrate 160 mg and Group II received Tab Rosuvastatin 10 mg+ Fenofibrate 160 mg once a day at night for 12 weeks. Patients were assessed after 12 weeks and their Lipid profile was done. Results: Patients who received a combination of atorvastatin with fenofibrate had a reduction of Total cholesterol by 39%, Triglycerides by 47%, LDL-C by 50% and VLDL-C by 35% respectively. In group treated with combination of rosuvastatin with fenofibrate there was a decrease in TC by 54%, TGs by 58%, LDL-C by 52% and VLDL-C by 56% respectively. At the same time, HDL-C levels were increased by 14% in the group treated with rosuvastatin with fenofibrate as compared to atorvastatin with fenofibrate treated group which increased the HDL-C levels by 6%. Conclusion: Both the treatment regimens significantly decreased TC, TG, LDL‑C, VLDL‑C, but the reduction was more and statistically significant in Rosuvastatin and fenofibrate combination group when compared with atorvastatin and fenofibrate treated group at the end of 12 weeks. Keywords:Atherosclerosis, Cholesterol, Heart, Lipoprotein, StatinsView:PDF (464.7 KB) PDFClick here to download the PDF file. Images Study design

Comparison of the effects of hypolipidemic treatment on monocyte proinflammatory cytokine release in men and women with type 2 diabetes and atherogenic dyslipidemia.

Statins and fibrates reduce monocyte release of proinflammatory cytokines, but it remains unknown whether this effect is sex dependent. We retrospectively analysed age-, weight-, and lipid-matched populations of type 2 diabetic patients of both sexes, who, because of atherogenic dyslipidaemia, were treated with simvastatin (40 mg daily), fenofibrate (200 mg daily), or simvastatin plus fenofibrate. Monocyte release of tumour necrosis factor α (TNF-α), inteleukin-1β, interleukin-6, and monocyte chemoattractant protein-1 (MCP-1), as well as circulating levels of high-sensitivity C-reactive protein (hsCRP) and free fatty acids (FFA) were assessed separately for men and women before and after 12 weeks of treatment. Baseline monocyte release of TNF-α, interleukin-1β, interleukin-6, and MCP-1, as well as plasma hsCRP and FFA levels were comparable in both sexes. Simvastatin, fenofibrate, and simvastatin/fenofibrate combination therapy reduced monocyte release of TNF-α, inteleukin-1β, interleukin-6, and MCP-1, with no difference between the treatment groups. The impact of simvastatin and fenofibrate administered alone on monocyte cytokine release and systemic inflammation did not differ between the men and women. The effect of simvastatin/fenofibrate combination therapy on monocyte release of interleukin-6 and MCP-1 was more pronounced in the male population. The impact of simvastatin administered together with fenofibrate on TNF-α, interleukin-1β, and hsCRP was also stronger in the men than in the women, but the difference did not reach the level of significance. The obtained results suggest that sex differences determine the strength of the monocyte-suppressing effect of simvastatin/ /fenofibrate combination therapy in type 2 diabetic patients with atherogenic dyslipidaemia.

Atorvastatin and fenofibrate combination induces the predominance of the large HDL subclasses and increased apo AI fractional catabolic rates in New Zealand white rabbits with exogenous hypercholesterolemia.

The anti-atherogenic properties of high-density lipoproteins (HDLs) may be related to their structure and metabolism. The HDL physicochemical characteristics that determine their plasma clearance during treatment with statins and fibrates are not well understood. In this study, we analyzed HDL-apo AI fractional catabolic rates (FCRs), size distributions, and the lipid composition of the HDL subclasses in New Zealand white rabbits with exogenous dyslipidemia that received low doses of atorvastatin and fenofibrate. Hypercholesterolemia decreased only partially with the combination of both drugs. HDL size distribution shifted toward larger particles among the groups of rabbits that received atorvastatin, fenofibrate, or their combination, compared with both the control group and the dyslipidemic group. The HDL subclasses were significantly rich in cholesterol in each of the groups compared with controls. The structural changes noted in the HDL subclasses were not associated with impaired plasma paraoxonase-1 (PON1) activity. The groups receiving monotherapy and the drug combination group were all associated with a higher apo AI FCR value compared with both the dyslipidemic rabbits and the control group. In conclusion, the combination of atorvastatin and fenofibrate induced a more favorable HDL subclass profile than did the individual use of these drugs. Similarly, the apo AI FCR values were augmented in every group receiving drug treatment (either monotherapy or combination therapy) in the setting of hypercholesterolemia. The anti-atherogenic properties of HDLs, excluding their capacity to bind PON1, may be enhanced by the structural and metabolic modifications induced by the combination of atorvastatin and fenofibrate.

Comparative Study of Atorvastatin plus Fenofibrate versus Atorvastatin alone for its safety and efficacy in Hyperlipidemic patients

The aim of this study is to compare the efficacy and safety of combination containing Atorvastatin plus Fenofibrate (ATO+FENO) and to determine whether combination of Fenofibrate had clinically significant benefit over Atorvastatin alone (ATO) in patients with Hyperlipidemia. This is a single centric, open labelled, prospective study, involving 50 Hyperlipidemic patients of 18 years and older. Data of only Hyperlipidemic patients with Low Density Lipoprotein (LDL –C) ≥ 140 - 60 mg/dl, Total Cholesterol (TC): 200-240 mg/dl and Triglyceride (TG): ≥ 165- < 400 mg/dl and who were prescribed either Atorvastatin 10 mg and Atorvastatin plus Fenofibrate 160 mg were included in the study. Efficacy end points included the change in LDL-C, HDL-C, TC and TG at week 12 and the safety of the treatment was also evaluated based on adverse events. Total of 50 patients were enrolled in the study but 1 patient lost follow up in ATO Group and 2 patients in ATO + FENO Group. Therefore 24 patients in ATO and 23 patients in ATO + FENO group completed study. A statistically significant reduction in LDL-C, TG and TC was seen in both the groups (Atorvastatin 10 mg and Atorvastatin plus Fenofibrate 160 mg). Similarly a statistically significant increase in HDL-C levels was observed in both the groups. ATO + FENO treatment showed a statistically significant reduction in TG at week 12 as compared to ATO alone. Decrease in LDL-C, TC, and TG were 24.86%, 24.81%, and 30.13% respectively and increasing HDL-C 42.37% in ATO + FENO group while the reduction was 21.1%, 21.31%, and 22.84% respectively and increasing HDL-C 38.2% in ATO alone group. The most common adverse events were headache, myalgia and nausea. ATO + FENO treatment showed a greater reduction in lipid parameters as compared to ATO alone (percentage change). Both treatments were well tolerated with similar incidence of adverse events. Study demonstrated that combination treatment was more effective than Atorvastatin alone in reducing LDL-C, Total Cholesterol and Triglyceride. It was also better in increasing HDL-C as compared to Atorvastatin. Statin in combination of fenofibrate may have lesser adverse effects. Thus Combination therapy seems to be a better treatment in patients having Hyperlipidemia.

Enhancement of radiosensitivity in human esophageal carcinoma cells by fenofibrate and its potential mechanism.

Fenofibrate is a specific agonist of PPARα, and is characterized by relatively low systemic toxicity. Recent studies have revealed that fenofibrate suppresses the growth of several cancer lines in vitro, but the exact relation between fenofibrate and irradiation has not been explored. The purpose of this study was to investigate the radiosensitivity enhancement effects of fenofibrate combined with radiation on the human esophageal carcinoma cell lines Eca-109 and TE1, and the potential mechanism underlying these effects. The Eca-109 and TE1 cell lines were tested by the CCK-8 assay for cell proliferation. The multitarget click model was used to delineate the survival curve and radiosensitivity was determined after cells were treated with fenofibrate and/or x-ray radiation. Flow cytometry was used to examine the effect of fenofibrate and radiation on the cell cycle. The expression of vascular endothelial growth factor (VEGF) protein was detected by Western blot analysis. When given alone, fenofibrate had a time- and concentration-dependent cytotoxic effect on cells. The dose-enhancement ratio for combined fenofibrate and radiation increased markedly compared with fenofibrate alone. Further, the ratio of cells in the G2/M phase after fenofibrate and radiation was higher than that after fenofibrate or irradiation alone. The expression of VEGF protein was suppressed after treatment with fenofibrate alone or fenofibrate plus radiation. Fenofibrate can enhance the radiosensitivity of human esophageal carcinoma cells by increasing G2/M phase arrest. Modulation of VEGF expression could contribute in vivo to a favorable interaction.

Simvastatin/fenofibrate combination in the treatment of dyslipidemia: current evidence

Simvastatin/fenofibrate combination in the treatment of dyslipidemia: current evidence Jose G Jimenez-Montero,1 Gregory Haft2 1Post Graduate Studies, University of Medical Sciences, San Jos&eacute;, Costa Rica; 2Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA Background: It has been demonstrated that statins can reduce major cardiovascular complications throughout a broad range of patients with dyslipidemia and multiple cardiovascular risk. Despite the impact of statin therapy on cardiovascular morbidity and mortality, a residual cardiovascular risk remains following lowering of low-density lipoprotein cholesterol. In many patients, optimization of the lipid profile cannot be achieved with statin therapy. Therefore, pharmacologic interventions with non-statin therapy can be used. Aims: The objective of this review was to analyze current clinical evidence of the effects of simvastatin/fenofibrate combination therapy. Methods: We searched and analyzed the evidence up to June 2014, regarding the effects of statin/fibrate combination therapy for reducing cardiovascular complications. Results: Forty-nine studies reporting the efficacy and safety of statin/fibrate combination therapy were analyzed. Of the forty-nine, 19 analyzed the simvastatin/fenofibrate combination therapy. This therapy was demonstrated to be safe and superior to the statin monotherapy in modifying atherogenic dyslipidemia, including lipoprotein subclasses. Nevertheless, in randomized clinical trials cardiovascular endpoints were not significantly different when fenofibrate was added to a standard low-density lipoprotein cholesterol reducing therapy. Of note, in the subgroup analysis, positive results were observed in patients with high triglycerides and low high-density lipoproteins. The inclusion of heterogeneous populations in these studies may explain the mixed results of cardiovascular outcomes seen in randomized clinical trials. Conclusion: Future clinical studies that rigorously address the effects of simvastatin/fenofibrate in patients with triglycerides &gt;2.25 mmol/L and high density lipoprotein cholesterol &lt;0.90 mmol/L, will provide a more accurate conclusion regarding the use of simvastatin/fenofibrate combination therapy. For now, emphasis must be put on non-pharmacological interventions that effectively induce weight loss and strict glycemic control in diabetics. The initiation of simvastatin/fenofibrate combination therapy among patients with residual cardiovascular risk should be employed at the physician&#39;s discretion, as this strategy lacks hard cardiovascular end points. Keywords: dyslipidemia, atherosclerotic cardiovascular disease, residual risk, simvastatin fenofibrate combination therapy

Combinations of oseltamivir and fibrates prolong the mean survival time of mice infected with the lethal H7N9 influenza virus.

The outbreak of human infections caused by the novel avian-origin H7N9 influenza viruses in China since March 2013 underscores the urgent need to find an effective treatment strategy against H7N9 infection in humans. In this study, we assessed the effectiveness of combinations of oseltamivir and two immunomodulators (simvastatin and fenofibrate) against H7N9 infection in a mouse model. Mice treated with oseltamivir plus fenofibrate exhibited the longest mean survival time, the largest reduction of viral titre in lung tissue, the highest levels of CD4(+) and CD8(+) T-lymphocytes, and the greatest decrease in pulmonary inflammation. Thus, the combination of oseltamivir plus fenofibrate improved the outcomes of mice infected with H7N9 virus by simultaneously reducing viral replication and normalizing the aberrant immune response. This drug combination should be considered in randomized controlled trials of treatments for H7N9 patients.

Asociación de pravastatina y fenofibrato (Pravafenix®). Estudios de seguridad

Although LDL cholesterol is the primary treatment objective for reducing cardiovascular risk, the increase in triglyceride levels and the reduction of HDL cholesterol levels constitute the so-called residual cardiovascular risk. Treatment with statins combined with fibrates is an actual possibility for the treatment of overall cardiovascular risk. However, this combination is often associated with adverse eff ects, especially muscular and hepatic.Due to its pharmacological characteristics, the combination of pravastatin and fenofibrate can be eff ective and safe, with few adverse eff ects. In this review, we analyze the available safety studies and conclude that Pravafenix® (the combination of 40-mg pravastatin and 160-mg fenofibrate) achieves complementary benefits on the overall atherogenic lipid profile, is well tolerated and has few adverse eff ects, which is similar to the monotherapy of each of its components. It remains to be seen whether this combination confers additional long-term benefits for patients treated with statins.

Efficacy and Safety of Alternate Day Therapy With Atorvastatin and Fenofibrate Combination in Mixed Dyslipidemia

The long half-life of atorvastatin and fenofibrate makes them suitable for alternate day therapy. Hence, we aimed to study the efficacy, safety, and cost-effectiveness of alternate day therapy with atorvastatin and fenofibrate combination in mixed dyslipidemia. Eligible patients with mixed dyslipidemia were randomly allotted into 2 equal parallel groups-alternate day therapy group (group 1) and daily therapy group (group 2). Patients in groups 1 and 2 received fixed dose combination of atorvastatin 10 mg and fenofibrate 160 mg on alternate days and daily, respectively, for 12 weeks. Mean percentage change from baseline in triglycerides (TGLs), non-high-density lipoprotein cholesterol (non-HDL-C), HDL-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and TC-HDL ratio, incidence of adverse effects, and cost-effectiveness were compared in both the groups. Among 110 patients randomized, 99 completed the study till 12 weeks treatment duration. The TGLs, non-HDL-C, TC, and LDL-C decreased by 56.4%, 49.7%, 36.5%, and 39.2%, respectively, in alternate day therapy group and by 57.5%, 51.2%, 37.5%, and 39.4%, respectively, in daily therapy group. The HDL-C levels increased by 20.1% in alternate day therapy group compared to 21.8% in daily therapy group. No statistically significant difference was seen between both the groups in mean percentage change in lipid parameters from baseline to end of 12 weeks. Incidence of adverse events was reasonably less in alternate day therapy group. Alternate day therapy with atorvastatin-fenofibrate combination is an effective and safe alternative to daily therapy in mixed dyslipidemia. Apart from significant cost savings, reasonable reduction in the incidence of adverse events is seen with alternate day regimen. However, larger studies are needed to more reliably confirm our interesting but preliminary results.

Akut Böbrek Yetmezliğinin Nadir Bir Sebebi: Fenofibrata Bağlı Rabdomiyoliz

Fibrates are derivative of fibric acid and broad spectrum drugs which are commonly used in the treatment of dyslipidemia and hypertriglyceridemia. Side effects are often related with striated muscles, kidney and liver. Rhabdomyolysis developing with striated muscle destruction is potentially the most lethal of these side effects. Although several case reports of rhabdomyolysis have been reported due to the combination of statin and fenofibrate, fenofibrate alone rarely causes rhabdomyolysis. The purposes of this paper are to present a patient whom we diagnosed with acute renal injury due to use of fenofibrate in order to emphasize the importance of questioning drugs which have been used, and to review management of rhabdomyolysis due to fenofibrate use.

GW24-e0076 Safety of fenofibrate-statin therapy versus statin alone: a meta-analysis

ObjectivesAlthough fenofibrate-statin combination therapy could improve the lipid parameters in patients with mixed dyslipidemia, the coadministration is still underutilised because of safety of the combination therapy.MethodsRandomised, controlled trials were searched...

Effect of the combination of metformin and fenofibrate on glucose homeostasis in diabetic Goto-Kakizaki rats

Metformin has been reported to increase the expression of the glucagon-like peptide-1 (GLP-1) receptor in pancreatic beta cells in a peroxisome proliferator-activated receptor (PPAR)-α-dependent manner. We investigated whether a PPARα agonist, fenofibrate, exhibits an additive or synergistic effect on glucose metabolism, independent of its lipid-lowering effect, when added to metformin. Non-obese diabetic Goto-Kakizaki (GK) rats were divided into four groups and treated for 28 days with metformin, fenofibrate, metformin plus fenofibrate or vehicle. The random blood glucose levels, body weights, food intake and serum lipid profiles were not significantly different among the groups. After 4 weeks, metformin, but not fenofibrate, markedly reduced the blood glucose levels during oral glucose tolerance tests, and this effect was attenuated by adding fenofibrate. Metformin increased the expression of the GLP-1 receptor in pancreatic islets, whereas fenofibrate did not. During the intraperitoneal glucose tolerance tests with the injection of a GLP-1 analog, metformin and/or fenofibrate did not alter the insulin secretory responses. In conclusion, fenofibrate did not confer any beneficial effect on glucose homeostasis but reduced metformin's glucose-lowering activity in GK rats, thus discouraging the addition of fenofibrate to metformin to improve glycemic control.

Differential effects on lung cancer cell proliferation by agonists of glucocorticoid and PPARα receptors

Glucocorticoids (GCs) are well-known anti-inflammatory compounds, but they also inhibit cell proliferation depending on cell type. Similarly, peroxisome proliferator-activated receptors (PPARα, PPARδ, and PPARγ) also possess anti-proliferation properties beyond their canonical roles as metabolic mediators. In the present study, we investigated the potential additive or synergistic inhibitory effects on cancer cell proliferation by simultaneous application of fenofibrate and budesonide, agonists for PPARα and glucocorticoid receptor, respectively. We observed differential effects on cell proliferation in A549 and SK-MES-1 lung cancer cells by budesonide and fenofibrate. Fenofibrate inhibited cell proliferation in both TP53 wild type and deficient lung cancer cells. The anti-proliferation effect of budesonide in TP53 wild type A549 cells was abolished in SK-MES-1 cells that do not have wild type TP53 protein. An additive effect against cell proliferation by budesonide and fenofibrate combination was observed only in TP53 wild type A549 cancer cells. Analysis of cell cycle distribution and cyclin profile indicated that the inhibition of cell proliferation was associated with G1 cell cycle arrest. The suppression of NF-κB activity and ERK signaling may contribute to the inhibition of cell proliferation by budesonide and or fenofibrate. The additive inhibitory effect on cell proliferation by budesonide and fenofibrate combination suggests that the same or greater therapeutic effect could be achieved with reduced dosage and side effects when the two compounds are applied simultaneously.

Adverse events following statin–fenofibrate therapy versus statin alone: A meta‐analysis of randomized controlled trials

The combination of fenofibrate with statins is a beneficial therapeutic option for patients with mixed dyslipidaemia, but concerns about adverse events (AEs) make physicians reluctant to use this combination therapy. Medline, Embase and the Cochrane Library were searched to identify 13 randomized controlled trials, involving 7712 patients, of statin-fenofibrate therapy versus statin alone for review. There were significant decreases in low-density lipoprotein-cholesterol, triglycerides and total cholesterol and increases in high-density lipoprotein-cholesterol in patients receiving combination therapy compared with statin therapy alone. The incidence of aminotransferase elevations in the fenofibrate-statin therapy group was significantly higher than in the statin monotherapy group (odds ratio (OR), 1.66; 95% confidence interval (CI) 1.17-2.37; P < 0.05). The incidence of elevated creatine kinase levels (OR 0.88; 95% CI 0.63-1.23; P > 0.05), muscle-associated AEs (OR 0.98; 95% CI 0.88-1.09; P > 0.05) and withdrawals attributed to liver and muscle dysfunction did not differ significantly between the two groups. The efficacy of fenofibrate + standard-dose statin and incidence of AEs in the fenofibrate + standard-dose statin group were almost identical to those in the fenofibrate-statin group. In conclusion, combination therapy improves the blood lipid profile of patients. Fenofibrate-statin combination therapy appears to be as well tolerated as statin monotherapy. Physicians should consider fenofibrate-statin combination therapy in patients but monitor aminotransferase levels to avoid hepatic complications.