Fibrates In Patients Research Articles

Changing perceptions about the role of combination therapy with statin and fibrate in patients with hypertriglyceridemia

The article discusses the modern therapeutic approach to lowering blood triglyceride levels. The need to consider indications for the use of lipid-lowering therapy in patients with hypertriglyceridemia is caused by the emergence of new evidence-based information. The article describes how elevated blood TG levels are associated with the risk of developing cardiovascular (CV) complications, as well as pancreatitis. The mechanisms of TG metabolism that may regulate the relationship between elevated blood TG levels and the risk of developing CV complications are considered. The findings of large randomized clinical trials, including recent ones, which laid the foundation for the current clinical guidelines for the use of drugs to lower triglycerides levels, are discussed. Indications for fibrate therapy in patients with elevated blood TG levels in various clinical situations are considered. The article emphasizes that the icosapent ethyl ester drug is not currently available in the Russian Federation. According to the latest versions of international guidelines, it is considered a first-line drug to reduce the risk of developing CV complications in patients with an established diagnosis of CVD (i.e. for the purpose of secondary prevention). In this context, the significance of fenofibrate as a drug to lower blood triglyceride levels, specifically in secondary prevention of CV complications, can remain quite high in our country. The appearance of a rosuvastatin and fenofibrate combination drug on the pharmaceutical market of the Russian Federation will increase adherence to the therapy, if a fibrate is required to be added to statin therapy.

Efficacy of fibrates in the treatment of primary biliary cholangitis: a meta-analysis.

Patients with primary biliary cholangitis (PBC) who respond poorly to ursodeoxycholic acid (UDCA) are increasingly being trialed using fibrates, showing promising results. To further investigate, we performed a meta-analysis to evaluate the benefit of administrating fibrates to patients with PBC. PubMed, EMBASE, and Cochrane library databases were searched using the keywords "bezafibrate", "fenofibrate", "fibrate", "primary biliary cholangitis" and clinical studies involving the use of fibrates in patients with PBC were included. The primary outcome of this study was the effect of fibrates administration on biochemical markers related to cholestasis in patients with PBC, and the secondary outcome was the incidence of treatment-related adverse events. A total of 20 studies with 4783 participants were included in this study. The results revealed that adding fibrates could significantly reduce the levels of ALP (fibrates vs. placebo, MD: - 370.14, P = 0.04; fibrates + UDCA vs. UDCA, MD: - 184.15, P < 0.01), total cholesterol (MD: - 2.82, P = 0.04), GGT (fibrates vs. placebo, MD: - 140.88, P < 0.01; fibrates + UDCA vs. UDCA, MD: - 130.73, P = 0.04), alleviate pruritus symptoms (RD: - 0.20, 95% CI: - 0.39 ~ - 0.01, P = 0.04), and did not significantly increase the incidence of treatment-related side effects. Fibrates can significantly improve liver biochemical parameters and alleviate pruritus in PBC patients.

Fibrates for the Treatment of Primary Biliary Cholangitis Unresponsive to Ursodeoxycholic Acid: An Exploratory Study.

Aim: Up to 40% of patients with primary biliary cholangitis (PBC) will have a suboptimal biochemical response to ursodeoxycholic acid (UDCA), which can be improved by the addition of fibrates. This exploratory study aims to evaluate the long-term real-life biochemical response of different fibrates, including ciprofibrate, in subjects with UDCA-unresponsive PBC. Methods: The Brazilian Cholestasis Study Group multicenter database was reviewed to assess the response rates to UDCA plus fibrates in patients with UDCA-unresponsive PBC 1 and 2 years after treatment initiation by different validated criteria. Results: In total, 27 patients (100% women, mean age 48.9 ± 9.2 years) with PBC were included. Overall response rates to fibrates by each validated criterion varied from 39 to 60% and 39–76% at 12 and 24 months after treatment combination, respectively. Combination therapy resulted in a significant decrease in ALT and ALP only after 2 years, while GGT significantly improved in the first year of treatment. Treatment response rates at 1 and 2 years appear to be comparable between ciprofibrate and bezafibrate using all available criteria. Conclusion: Our findings endorse the efficacy of fibrate add-on treatment in PBC patients with suboptimal response to UDCA. Ciprofibrate appears to be at least as effective as bezafibrate and should be assessed in large clinical trials as a possibly new, cheaper, and promising option for treatment of UDCA-unresponsive PBC patients.

Effect of Pemafibrate on Serum Creatinine in Patients with Chronic Kidney Disease.

Introduction: Fibrates are recommended not to be used for the treatment of hypertriglyceridemia in patients with chronic kidney disease (CKD) based on clinical practice guidelines. The major reason for the negative suggestion is the elevation of serum creatinine and rhabdomyolysis by fibrates. This may cause clinical inertia for the treatment of hypertriglyceridemia using fibrate in patients with CKD, who are associated with an increasing risk of cardiovascular disease. Methods: We retrospectively studied the change of serum creatinine via the treatment of pemafibrate. Results: A total of 39 patients with CKD were treated with 0.2 mg of pemafibrate. Serum triglyceride was decreased in 23 fibrate-naïve patients from 380 [308, 455] mg/dL to 180 [152, 215] mg/dL via treatment with pemafibrate (p = 0.00003). Serum creatinine and eGFR were not changed from 1.22 ± 0.29 mg/dL to 1.21 ± 0.28 mg/dL (p = 0.70) and from 45.7 ± 10.9 mL/min/1.73 m2 to 46.2 ± 12.0 mL/min/1.73 m2 (p = 0.67) via treatment with pemafibrate, respectively. In 16 patients, with a change of treatment from fenofibrate or bezafibrate to pemafibrate, serum creatinine was significantly decreased from 1.32 ± 0.36 mg/dL to 1.17 ± 0.24 mg/dL (p = 0.003). eGFR was significantly increased from 45.2 ± 9.9 mL/min/1.73 m2 to 50.1 ± 8.6 mL/min/1.73 m2 (p = 0.001). Conclusions: These results suggest that treatment with pemafibrate does not affect the serum creatinine level and is suitable for use in patients with CKD for the treatment of hypertriglyceridemia.

Prevalence of and Factors Associated With the Prescription of Fibrates Among Patients Receiving Lipid-Lowering Drugs in Germany.

Little recent data are available about the patterns of prescription for fibrates in patients followed in primary care practices. Therefore, the goal of this study was to analyze the prevalence of and the factors associated with the use of fibrates among patients receiving lipid-lowering drugs in Germany. The study included patients aged ≥18 years with at least 1 visit to 1 of 1070 general practices in Germany between January and December 2019. Lipid-lowering drugs included statins (without and with ezetimibe) and fibrates. The prevalence of the prescription of fibrates corresponded to the number of patients with at least 1 prescription for fibrates divided by the total number of patients receiving lipid-lowering drugs. A logistic regression model was used to assess the relationship between several demographic, clinical, and biological factors and the prescription of fibrates. A total of 111,329 patients were included in this study (mean [SD] age 68.8 [11.5] years; 56.0% of patients were men). The prevalence of the prescription of fibrates was 1.5%. Male sex, hypertension, diabetes mellitus, high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, and high triglyceride were positively associated with the use of fibrates. By contrast, there was a negative relationship between the odds of receiving fibrates and coronary heart disease, myocardial infarction, peripheral arterial disease, and stroke including transient ischemic attack. Overall, we found that fibrates were infrequently prescribed in general practices in Germany.

Safety of fibrates in cholestatic liver diseases.

Off-label use of fibrates in patients with cholestatic liver diseases results in improved biochemical parameters and pruritus; however, their safety in this population has been a concern. This study summarizes safety data for fibrates when used for treatment of cholestatic liver diseases. A systematic review of published studies evaluating the use of fibrates for treatment of primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) was performed. Electronic databases were searched up to December 2019 for published studies evaluating treatment outcomes associated to fibrates for these 2 diseases. A total of 37 studies were identified, including 31 for PBC and 6 for PSC, with a total of 1107 unique patients treated with fibrates±ursodeoxycholic acid (UDCA). Most studies evaluated fenofibrate and bezafibrate, and only 1 study evaluated pemafibrate. There were no studies evaluating gemfibrozil or clofibrate. The most commonly reported adverse events (AEs) were gastrointestinal and musculoskeletal. Elevations of aminotransferases and serum creatinine were reported more commonly in patients treated with UDCA plus fibrates versus UDCA monotherapy. Fibrates appear to be safe and well tolerated in patients with PBC, with a low frequency of AEs. There are scarce data about the safety of these agents for treatment of PSC.

Clinical and economic aspects of fibrates

Today statins are considered as first-line drugs for treating dyslipidemia. Fibrates also have a place in the treatment of dyslipidemia. Taking the above into account it is relevant to highlight the evidence of the effectiveness of these drugs in reducing unfavorable outcomes of cardiovascular diseases (CVD) and feasibility of using them in the complex therapy of dyslipidemia, as well as the study of the pharmacoeconomic characteristics of fibrates presented at the Ukrainian pharmaceutical market. Aim. To analyze the clinical efficacy of fibrates in reducing the consequences of CVD, as well as to study the range, price characteristics, availability and consumption of fibrates at the Ukrainian pharmaceutical market from 2017 to 2019.Materials and methods. The analysis of the evidence of the clinical efficacy of fibrates in patients with CVD and dyslipidemia was performed in accordance to systematic reviews from the international Pubmed database. The retrospective analysis of the assortment, prices, affordability and consumption of fibrates in Ukraine was conducted according to the data from the “PharmXplorer” analytical system of the “Morion” information retrieval company and the Compendium system. The economic affordability was assessed by the value of adequacy of paying capacity (Ca.s.), the consumption volumes – by DDDs (the number of average daily doses) and the number of packages sold during 2017-2019.Results. The evidence of the clinical efficacy of fibrates in reducing cardiovascular events in patients with CVD and DM type 2 with dyslipidemia were summarized in systematic reviews. Within 2017-2019, only 3 trade names (TNs) of foreign fenofibrate, which prices did not fluctuate significantly, were registered at the Ukrainian pharmaceutical market. Fenofibrate drug – Lipofen NS (Nobel, Turkey), caps., 250 mg, blister No. 30, was highly available for the Ukrainian consumer (Ca.s. less than 5.0 %), and Traikor® (Abbot Products GmbH, Germany), film coated tablets, 145 mg, blister No. 20 and No. 30 (Ca.s. more than 5.0 %), were moderately available. The dynamics of the sales growth (2.4 times) of fenofibrate packages in 2019 compared to 2017 was determined due to the growth in sales of Traikor® (film coated tablets, 145 mg, blister No. 20). The dynamics of the increase in consumption of fibrates by the value of DDDs was found. It generally corresponded to the dynamics of sales in the number of packages, but the consumption volumes were insignificant.Conclusions. The use of fibrates in patients with CVD and dyslipidemia for the primary or secondary prevention of risks of adverse cardiovascular events leads to their decrease; moreover, in patients with DM type 2 it helps to reduce the risk of nonfatal myocardial infarction (MI) development. The consumption of fibrates at the Ukrainian pharmaceutical market is insignificant, and is determined by their clinical efficacy and the place in the antihyperlipidemic therapy of CVD where statins prevail today.

THE EFFECTS OF LOW-DOSE ROSUVASTATIN ALONE OR IN COMBINATION WITH FENOFIBRATE OR OMEGA 3 FATTY ACIDS IN MIXED DYSLIPIDEMIA

Objective Mixed dyslipidemia is characterized by elevated cholesterol and triglycerides. Indians have high prevalence of this pattern. The aim of present study was to evaluate the effects of rosuvastatin and in combination with fenofibrate or omega-3-FAs on lipids and hsCRP. Methods This was an open-label randomized study. Patients were allocated to low-dose rosuvastatin(R), rosuvastatin plus fenofibrate (RF) or rosuvastatin plus omega-3-FA(RO). At 6-weeks and 12-weeks follow-up, lipid lowering effect and change in hsCRP was studied. Results The study involved 105 participants (M/F=68/37) with a mean age of 57±13 years. At end of 6 and 12-weeks, there was significant reduction in TC, LDL-C, TG and hsCRP in all treatment groups, but increase in HDL-C became significant at 12-weeks. Percentage reduction in TC was 21%vs17%vs23% at 6-weeks and 31%vs37%vs35% at 12-weeks in group R, RF and RO, respectively. At 12-weeks, reduction in LDL-C was 22% in R vs 45% in RF vs 18% in RO and increase in HDL-C was 3.8% in R vs 7.6% in RF vs 15.8% in RO. Percentage reduction in triglycerides was 18%vs31% vs30% at 6 weeks and 23%vs52%vs51% at 12-weeks. Conclusion The mixed dyslipidemic patients responded well in terms of significant reduction in TC, LDL-C, and improving HDL-C and inflammation across all study groups. However, combination of low-dose-rosuvastatin plus fenofibrate or omega-3-FAs had more potent effect in reducing triglycerides and also in percentage increase in HDL-C, when compared with rosuvastatin alone. Omega-3 FAs, therefore, seem to be an attractive alternative to fibrates in patients with mixed dyslipidemia.

The long-term safety and efficacy of fibrates in patients with hypertriglyceridemia: Real-life data from a lipid clinic cohort.

The long-term safety and efficacy of fibrates in patients with hypertriglyceridemia: Real-life data from a lipid clinic cohort.

Comparative study of efficacy and safety of omega 3 fatty acids and fenofibrate with background atorvastatin therapy in patients of atherogenic dyslipidaemia

Background: Trials of atorvastatin combined either with fenofibrate or with omega-3 fatty acids (O3FA) have shown promising results in atherogenic dyslipidemia but there are very few studies where both these TGs lowering agents have been compared with each other. This study was conducted to compare efficacy and safety of these two agents on lipid profile of patients of atherogenic dyslipidaemia on background statin therapy and also to monitor effects of these interventions on serum uric acid (SUA) levels.Methods: About 90 patients of dyslipidemia were randomised to 3 groups and received O3FA (2000 mg), fenofibrate (80 mg) or dietary restrictions, each with atorvastatin (20 mg) in background for a period of 90 days. Total cholesterol (TC), HDL-C,TGs, LDL-C, SGOT and SGPT levels were done at baseline, 6 weeks and 12 weeks. Other parameters (SUA and BMI) were done at baseline and 12 weeks.Results: Both group 1 (O3FA) and group 2 (fenofibrate) showed highly significant fall in TG levels (p &lt;0.001) in comparison to group 3 (dietary restrictions) whereas comparative TG reduction between groups 1 and group 2 was not significant. Group 2 also showed significant fall in LDL-C levels (p &lt;0.01) in comparison to group 3. LDL-C reduction, TG reduction and SUA reduction was more in group 2 compared to group 1 followed by group 3. No significant difference was observed in the incidence of adverse effects in three study groups.Conclusions: Combination of fenofibrate and atorvastatin was more effective than that of omega-3 fatty acid and atorvastatin, in lowering serum TG and LDL-C levels. There was a significant reduction in SUA levels in all three groups, but combination of fenofibrate and atorvastatin again showed better outcomes. With respect to the safety, all the 3 groups were comparable. O3FA, however, may be a good alternative to fibrates in patients not tolerating latter.

Use of fibrates in the metabolic syndrome: A review.

The use of fibrates in the treatment of dyslipidaemia has changed significantly over recent years. Their role appeared clear at the start of this century. The Helsinki Heart Study and Veterans Affairs High-Density Cholesterol Intervention Trial suggested significant benefit, especially in patients with atherogenic dyslipidaemia. However, this clarity disintegrated following the negative outcomes reported by the Bezafibrate Infarction Prevention, Fenofibrate Intervention and Event Lowering in Diabetes and Action to Control Cardiovascular Risk in Diabetes randomised controlled trials. In this review we discuss these and other relevant trials and consider patient subgroups such as those with the metabolic syndrome and those needing treatment to prevent the microvascular complications associated with diabetes in whom fibrates may be useful. We also discuss observations from our group that may provide some explanation for the varying outcomes reported in large trials. The actions of fibrates in patients who are also on statins are interesting and appear to differ from those in patients not on statins. Understanding this is key as statins are the primary lipid lowering agents and likely to occupy that position for the foreseeable future. We also present other features of fibrate treatment we have observed in our clinical practice; changes in creatinine, liver function tests and the paradoxical high density lipoprotein reduction. Our purpose is to provide enough data for the reader to make objective decisions in their own clinical practice regarding fibrate use.

Therapy of Primary Biliary Cirrhosis: Novel Approaches for Patients with Suboptimal Response to Ursodeoxycholic Acid

Primary biliary cirrhosis (PBC) is a chronic cholestatic disease of presumed autoimmune pathogenesis, characterized by the inflammation and damage of the intrahepatic intermediate and small bile ducts, which eventually results in cirrhosis. A number of randomized and observational and pilot studies using several agents were carried out in the 80s, but no clear results or even harmful effects were reported. Over the past 2 decades, increasing evidence indicates that ursodeoxycholic acid (UDCA) - 13 to 16 mg/kg/day - is the treatment of choice for patients with PBC. Biochemical response to UDCA, assessed at 1 year, clearly predicts the long-term outcome, since in UDCA, responders survival is similar to that estimated for the matched control population. However, about 40% of patients have incomplete biochemical response and increased risk of progression and decreased survival free of transplantation. Patients with suboptimal biochemical response to UDCA outline the group in whom further single or combined treatments with UDCA are needed. Accordingly, data on the effect of fibrates alone or in combination with UDCA, and budesonide in combination with UDCA have been reported. The combined treatment of UDCA and fibrates in patients without optimal biochemical response to UDCA improves the degree of cholestasis and may minimize the long-term management of these patients. The results of the combined therapy of UDCA with budesonide are appealing but they should be established in large randomized trials. The effect of new agents such obeticholic acid are promising, since the addition of this farnesoide-X-receptor agonist bile acid in patients with stable UDCA dosage and increased alkaline phosphatase levels results in an improvement of cholestasis as compared to placebo, with a parallel decrease of aminotransferases and immunoglobulin M, as well as one surrogate marker of bile acid synthesis. New molecular therapies are currently being investigated.

Safety and efficacy of statin treatment alone and in combination with fibrates in patients with dyslipidemia: a meta-analysis

Background:Dyslipidemia is a major risk factor for cardiovascular disease and is treated with many effective lipid-lowering agents. Statins are often used alone or in combination with fibrates. Combination therapy is more effective due to their comparative actions, but the increased incidence of side effects should be considered carefully.Research design and methods:A meta-analysis of published data was conducted to compare the safety and efficacy of statins alone versus statins plus fibrates in patients with dyslipidemia. In total, nine articles were assessed for efficacy analysis and ten articles were assessed for safety analysis.Results:In the efficacy analysis, a combination of statins and fibrates provided significantly greater reductions in total cholesterol (SE = 0.430; 95% CI 0.315–0.545), LDL cholesterol (SE = 0.438; 95% CI 0.321–0.555) and triglycerides (SE = 0.747; 95% CI 0.618–0.876), and a significantly greater increase in HDL cholesterol (SE = 0.594; 95% CI 0.473–0.715) than treatment with statins alone. In the safety analysis, treatment with statins alone was associated with a significant reduction in the numbers of total adverse events (RR = 0.665; 95% CI 0.539–0.819), liver-related adverse events (RR = 0.396; 95% CI 0.206–0.760) and kidney-related adverse events (RR = 0.146; 95% CI 0.075–0.285).Conclusion:We suggest that treatment with statins plus fibrates provides clinical benefits over treatment with statins alone but increased risks, especially of hepatic or renal side effects, should be monitored carefully.

The Need for Combination Drug Therapies in Patients with Complex Dyslipidemia

Statins are first line therapy for the prevention of cardiovascular disease (CVD). Only 30 %-70 % of high risk patients will attain standard low-density lipoprotein cholesterol targets. Patients with familial hypercholesterolemia and genetic mixed hyperlipidemias do not meet goals with standard therapy. Patients with mixed hyperlipidemia secondary to the metabolic syndrome, diabetes, renal, or HIV infection are at high residual risk due to low HDL-cholesterol or high triglycerides. Newer therapies can be added to statins. The use of ezetimibe has CVD outcomes evidence in chronic renal disease. Adding omega-3 fatty acids, fibrates, or niacin to statins has failed to show any benefit except possibly with fibrates in patients with diabetes and low HDL-C/high triglycerides. Additional benefits on lipid profiles have been shown with pro-protein convertase subtilisin/kexin-9 (PCSK9), mipomersen, lomitapide, and cholesterol ester transfer protein inhibitors (CETPIs). Two CETPIs have failed to show benefit in hard outcomes trials but others remain under investigation. It remains unclear whether additional therapies add to statins for the prevention of CVD in most patients. They may have some added benefit in patients with complex dyslipidemias.

Niacin: Does It affect 8-hydroxy-2-deoxyguanosine levels of the patients having low HDL cholesterol levels?

We aimed to determine whether niacin improve plasma HDL-cholesterol levels by decreasing 8-Hydroxydeoxyguanosine (8-OHdG) as a biomarker of oxidative DNA damage or not. Patients (n=32) with low HDL-cholesterol levels (40 mg/dl) were included in the study. Lipoprotein profiles (total cholesterol, HDL-C, and total triglycerides) were measured in all patients. LDL-C was calculated as described by Friedewald et al. Before and after 16 week of niacin therapy serum 8-OHdG was measured. There were significant difference between pre and post treatment plasma HDL-C and 8-OHdG levels. We concluded that niacin may raise HDL-C levels. The improvement of plasma HDL-C levels may have a protective effect on endothelial dysfunction. By reducing the level of 8-OHdG, niacin may decrease DNA damage. Thus, niacin therapy may be consider as an alternative to statins or fibrates in patients in whom fail to sufficiently correct low HDL-C levels.

Efficacy and safety of the combination therapy of ezetimibe and fibrate in patients with mixed dyslipidemia who had an inadequate response to statin were recruited

Efficacy and safety of the combination therapy of ezetimibe and fibrate in patients with mixed dyslipidemia who had an inadequate response to statin were recruited

Should we use fibrates in patients with diabetes and mild CKD?

Recent analyses from the FIELD randomized trial of fenofibrate in type 2 diabetes mellitus suggests that fibrates have beneficial effects and are safe in patients with moderate renal impairment. However, too few participants with chronic kidney disease were included in the study to provide reliable information.

Combination therapy with statin and fibrate in patients with dyslipidemia associated with insulin resistance, metabolic syndrome and type 2 diabetes mellitus

Introduction: People with insulin resistance/metabolic syndrome (IR/MS) and/or type 2 diabetes mellitus (T2DM) have increased rates of cardiovascular disease (CVD) even when low-density lipoprotein cholesterol levels are at or near target levels. Contributors to this problem are the high triglyceride (TG) levels and low levels of high-density lipoprotein cholesterol (HDLC) that are commonly present in this population, even with statin therapy.Areas covered: This review focuses on the use of a combination of statins with fibrates, which lower TG and raise HDLC concentrations and, therefore, have the potential to further lower rates of CVD more in people with IR/MS and/or T2DM. Treatment with this combination is uncommon because doctors and patients are fearful of muscle, liver and renal complications and because the evidence that the combination will actually reduce risk has been lacking. In this review, the authors examine the efficacy and safety of the statin–fibrate combination, particularly fenofibrate and simvastatin, the combination used in the ACCORD trial.Expert opinion: The authors' opinion is that this combination of fenofibrate and statin is as safe as either drug alone and, in patients with significant dyslipidemia, is likely to reduce CVD. Concerns remain concerning fenofibrate-associated increases in serum creatinine levels and the significant heterogeneity in the reduction in CVD by the combination in women. A trial of statin + fenofibrate in people with IR/MS and/or T2DM who also have significant dyslipidemia is needed.

Combination lipid therapy in type 2 diabetes mellitus

Introduction: A significant drop in cardiovascular risk has been seen in patients with type 2 diabetes treated with statins. However, this cardiovascular risk remains high, compared with nondiabetic individuals. This is partly due to the typical abnormalities of diabetic dyslipidemia – hypertriglyceridemia and decreased high-density lipoprotein cholesterol (HDL-C) – that are uncontrolled by statins. For this reason, combination lipid therapy may be considered in patients with type 2 diabetes.Areas covered: This review presents the main reasons for a combination lipid therapy in type 2 diabetes and the effects of several drugs, including fibrates, pioglitazone, niacin and omega 3, on diabetic dyslipidemia and the prevention of cardiovascular events. The real cardiovascular benefit of fibrates in patients with type 2 diabetes is not totally clear, but they may produce a significant benefit in patients with type 2 diabetes and diabetic dyslipidemia (hypertriglyceridemia, low HDL-C). Pioglitazone, which reduces triglycerides and increases HDL-C, has been shown to reduce the risk for major cardiovascular events in type 2 diabetes. Niacin and omega 3 fatty acids have a positive effect on diabetic dyslipidemia, but warrants clinical trials to demonstrate a clear cardiovascular benefit in type 2 diabetes.Expert opinion: Although combination lipid therapy seems to be useful to control diabetic dyslipidemia, the efficacy of such combined therapies on significantly reducing cardiovascular risk has still to be confirmed by additional clinical trials.

Fibrates in the prevention of cardiovascular disease in patients with type 2 diabetes mellitus – A pooled meta-analysis of randomized placebo-controlled clinical trials

Objective Fibrates are thought to be useful anti-dyslipidemic agents particularly in patients with diabetes mellitus and dyslipidemia characterized by high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels. We conducted a systematic review and meta-analysis of long-term randomized controlled trials to evaluate the role of fibrates in the prevention of cardiovascular events in patients with type 2 diabetes mellitus. Data sources English-language journals indexed in Index Medicus/MEDLINE and the Cochrane Collaboration databases (through December 2007), unpublished data from selected clinical trials. Data extraction and analysis A total of 11,590 patients from 6 published randomized placebo-controlled trials were analyzed using pooled meta-analysis techniques. Relative risks were computed for various cardiovascular outcomes and mortality, and statistical significance was tested using the z-test statistic (two-sided alpha error < 0.05). Results The use of fibrates did not significantly affect the risk of all-cause mortality or cardiac mortality, and also did not affect the risk of stroke, unstable angina, or invasive coronary revascularization. However, the relative risk of non-fatal myocardial infarction was significantly reduced by about 21% (pooled relative risk 0.79, p = 0.006) with the use of fibrates. Conclusions Long-term use of fibrates in patients with type 2 diabetes mellitus significantly reduces the risk of non-fatal myocardial infarction, but has no significant effect on mortality or on other adverse cardiovascular outcomes.