The effect of fibrates on lowering low-density lipoprotein cholesterol and cardiovascular risk reduction: a systemic review and meta-analysis.

AIMS: The effect of fibrate treatment on cardiovascular risk is inconsistent. This meta-analysis aimed to assess the effect of fibrates on major adverse cardiovascular outcome (MACE) reduction. METHODS AND RESULTS: PubMed, Embase, and Cochrane library databases were searched up to February 2023 for randomized controlled trials comparing fibrate therapy against placebo and reporting cardiovascular outcomes and lipid profile changes. The primary outcome was the clinical outcomes of each trial that most closely corresponding to MACE, a composite of cardiovascular death, acute myocardial infarction, stroke, and coronary revascularization. A pre-specified meta-regression analysis to examine the relationship between the changes in lipid levels after fibrate treatment and the risk of MACE was also performed. Twelve trials were selected for final analysis, with 25 781 patients and 2741 MACEs in the fibrate group and 27 450 patients and 3754 MACEs in the control group. Overall, fibrate therapy was associated with decreased risk of MACE [RR 0.87, 95% confidence interval (CI) 0.81-0.94] with moderate heterogeneity (I2 = 47%). In meta-regression analysis, each 1 mmol/L reduction in low-density lipoprotein cholesterol (LDL-C) after fibrate treatment reduced MACE (RR 0.71, 95% CI 0.49-0.94, P = 0.01), while triglyceride level changes did not show a significant association (RR per 1mmol/L reduction 0.96, 95% CI 0.53-1.40, P = 0.86). A sensitivity analysis with the composite outcome of cardiovascular death or acute myocardial infarction produced similar results. CONCLUSION: Treatment with fibrates was associated with decreased risk of MACE. The reduction in MACE risk with fibrate therapy appears to be attributable to LDL-C reduction rather than a decrease in triglyceride levels.

A systematic review and meta-analysis including 12 trials and 53 231 patients were performed to investigate the effect of fibrates on lowering cardiovascular risk. Overall, fibrate therapy was associated with significantly decreased risk of cardiovascular events. In further analysis, the decrease in cardiovascular risk achieved with fibrate treatment was found to be largely attributable to low-density lipoprotein cholesterol reduction.

Adverse drug reactions of non-statin antihyperlipidaemic drugs in China from 1989 to 2019: a national database analysis.

OBJECTIVE: This study aims to understand the adverse drug reactions (ADRs) for non-statin antihyperlipidaemic drugs included in the China Anti-hyperlipidemic Drug Database. DESIGN: An approach of Chinese national database analysis was employed to screen clinical trials involving non-statin antihyperlipidaemic drugs from 1989 to 2019. SETTING: The database was provided by the China National Medical Products Administration Information Centre. PARTICIPANTS: In total, 117 clinical studies with 8800 patients were selected from 2650 clinical trials of the Anti-hyperlipidemic Drug Database. INTERVENTIONS: The non-statin antihyperlipidaemic drugs were divided into three groups: (1) fibrates (fenofibrate, gemfibrozil, bezafibrate, etofylline clofibrate); (2) nicotinic acid and derivatives (niacin, acipimox) and (3) others (probucol, cholestyramine). RESULTS: The results of this study show that first, gastrointestinal symptoms were the most common reactions (6.975%), which account for approximately 50% of the reported cases with ADRs. Second, cholestyramine (16.418%) and gemfibrozil (13.158%) were the most common gastrointestinal side effect-causing non-statin antihyperlipidaemic drugs, which account for one-third of the population. Third, niacin (7.879%) and gemfibrozil (5.000%) were the most likely cause of liver disease symptoms. Finally, niacin (10.909%) and acipimox (18.847%) were the major non-statin antihyperlipidaemic drugs with skin symptoms. CONCLUSION: This study revealed that gastrointestinal symptoms were the most common ADRs of fibrates, probucol and cholestyramine in the Chinese population. For nicotinic acid and derivatives, the ADRs of skin symptoms were the most common in China.

Benefits and harms of fibrate therapy in patients with type 2 diabetes: a systematic review and meta-analysis.

PURPOSE: This systematic review aimed to evaluate the benefits and harms of fibrate therapy, alone or in combination with statins, in adult patients with type 2 diabetes (T2D). METHODS: A comprehensive search was conducted in six databases, from inception to January 27, 2022. Clinical trials that compared fibrate therapy with other lipid-lowering interventions or placebo were included. Outcomes of interest comprised cardiovascular (CV) events, complications of T2D, metabolic profile, and adverse events. Random-effects meta-analyses were performed to estimate mean differences (MD) and risk ratios (RR), alongside 95% confidence intervals (CI). RESULTS: A total of 25 studies were included, six comparing fibrates against statins, 11 against placebo, and eight evaluating the combination of fibrates with statins. Overall risk of bias was rated as moderate, and most outcomes rendered low confidence per GRADE approach. Fibrates showed reduction of serum triglycerides (TGs) (MD -17.81, CI -33.92 to -1.69) and a marginal increase of high-density lipoprotein cholesterol (HDL-c) (MD: 1.60, CI 0.29 to 2.90) in adults with T2D, but no differences were found in CV events when compared to statin therapy (RR 0.99, CI 0.76 to 1.09). When used in combination with statins, no major differences were exhibited regarding lipid profile and CV outcomes. Adverse events were comparable between fibrate and statin monotherapies (e.g., RR of 1.03 for rhabdomyolysis, and 0.90 for gastrointestinal events). CONCLUSIONS: Fibrate therapy in patients with T2D results in a marginal improvement of TGs and HDL-c but without reducing the risk of CV events and mortality. Their use should be reserved for very specific scenarios after a deliberative dialogue between patients and clinicians regarding their benefits and harms.

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

ABSTRACT: 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.

Zebrafish as a Model for the Study of Lipid-Lowering Drug-Induced Myopathies.

Drug-induced myopathies are classified as acquired myopathies caused by exogenous factors. These pathological conditions develop in patients without muscle disease and are triggered by a variety of medicaments, including lipid-lowering drugs (LLDs) such as statins, fibrates, and ezetimibe. Here we summarise the current knowledge gained via studies conducted using various models, such as cell lines and mammalian models, and compare them with the results obtained in zebrafish (Danio rerio) studies. Zebrafish have proven to be an excellent research tool for studying dyslipidaemias as a model of these pathological conditions. This system enables in-vivo characterization of drug and gene candidates to further the understanding of disease aetiology and develop new therapeutic strategies. Our review also considers important environmental issues arising from the indiscriminate use of LLDs worldwide. The widespread use and importance of drugs such as statins and fibrates justify the need for the meticulous study of their mechanism of action and the side effects they cause.

[Effects of Fibrates on Risk of Development of Diabetic Retinopathy in Japanese Working Age Patients with Type 2 Diabetes and Dyslipidemia: a Retrospective Cohort Study].

The aims of the present study were to investigate the effects of fenofibrate and bezafibrate on the risk of development of diabetic retinopathy (DR) in patients with type 2 diabetes and dyslipidemia. Japanese working age patients with type 2 diabetes and dyslipidemia were extracted from the Nihon University School of Medicine Clinical Data Warehouse. These patients were divided into three groups: control group (n=2549), fenofibrate group (n=40), and bezafibrate group (n=135). Multivariate logistic regression analysis was performed to assess the association between fibrates and the development of DR. After adjustment for covariates, fenofibrate showed no association with the risk of DR [adjusted odds ratio (OR), 0.160; 95% CI, 0.021-1.209; p=0.0758]. Bezafibrate also showed no association with the risk of DR (adjusted OR, 0.731; 95% CI, 0.411-1.299; p=0.2855). However, poor control of hemoglobin A1c (HbA1c ≥8.0%; adjusted OR, 3.623; 95% CI, 2.649-4.956; p<0.0001) and high low-density lipoprotein cholesterol (LDL-C ≥140 mg/dL; adjusted OR, 1.399; 95% CI, 1.013-1.932; p=0.0415) within the follow-up period of type 2 diabetes and dyslipidemia increased the risk of DR. Our results suggested that to prevent development of DR in patients with type 2 diabetes and dyslipidemia, controlling LDL-C levels as well as HbA1c levels under coexistence type 2 diabetes and dyslipidemia is more important than the selection of fibrate.

Safety of fibrates in cholestatic liver diseases.

BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Comparative efficacy and safety of statin and fibrate monotherapy: A systematic review and meta-analysis of head-to-head randomized controlled trials.

OBJECTIVE: To assess whether in adults with dyslipidemia, statins reduce cardiovascular events, mortality, and adverse effects when compared to fibrates. METHODS: Systematic review and meta-analysis of head-to-head randomized trials of statin and fibrate monotherapy. MEDLINE, EMBASE, Cochrane, WHO International Controlled Trials Registry Platform, and ClinicalTrials.gov were searched through October 30, 2019. Trials that had a follow-up of at least 28 days, and reported mortality or a cardiovascular outcome of interest were eligible for inclusion. Efficacy outcomes were cardiovascular mortality and major cardiovascular events. Safety outcomes included myalgia, serious adverse effects, elevated serum creatinine, and elevated serum alanine aminotransferase. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using the Mantel-Haenszel fixed-effect model, and heterogeneity was assessed using the I2 statistic. RESULTS: We included 19 eligible trials that directly compared statin and fibrate monotherapy and reported mortality or a cardiovascular event. Studies had a limited duration of follow-up (range 10 weeks to 2 years). We did not find any evidence of a difference between statins and fibrates for cardiovascular mortality (OR 2.35, 95% CI 0.94-5.86, I2 = 0%; ten studies, n = 2657; low certainty), major cardiovascular events (OR 1.15, 95% CI 0.80-1.65, I2 = 13%; 19 studies, n = 7619; low certainty), and myalgia (OR 1.32, 95% CI 0.95-1.83, I2 = 0%; ten studies, n = 6090; low certainty). Statins had less serious adverse effects (OR 0.57, 95% CI 0.36-0.91, I2 = 0%; nine studies, n = 3749; moderate certainty), less elevations in serum creatinine (OR 0.17, 95% CI 0.08-0.36, I2 = 0%; six studies, n = 2553; high certainty), and more elevations in alanine aminotransferase (OR 1.43, 95% CI 1.03-1.99, I2 = 44%; seven studies, n = 5225; low certainty). CONCLUSIONS: The eligible randomized trials of statins versus fibrates were designed to assess short-term lipid outcomes, making it difficult to have certainty about the direct comparative effect on cardiovascular outcomes and mortality. With the exception of myalgia, use of a statin appeared to have a lower incidence of adverse effects compared to use of a fibrate.

Association between lipid-lowering agents and severe hyponatremia: a population-based case-control study.

PURPOSE: Drug-induced hyponatremia is common, with medications from many drug-classes implicated. Lipid-lowering agents are among the most prescribed drugs. Limited evidence suggests an inverse association between statins and hyponatremia, while data on other lipid-lowering agents is absent. The objective of this investigation was to study the association between lipid-lowering drugs and hospitalization due to hyponatremia. METHODS: This was a register-based case-control study of the general Swedish population. Those hospitalized with a main diagnosis of hyponatremia (n = 11,213) were compared with matched controls (n = 44,801). Multivariable logistic regression adjusting for co-medication, diseases, previous hospitalizations, and socioeconomic factors was used to explore the association between severe hyponatremia and the use of lipid-lowering drugs. RESULTS: Unadjusted ORs (95% CI) for hospitalization due to hyponatremia were 1.28 (1.22-1.35) for statins, 1.09 (0.79-1.47) for ezetimibe, 1.38 (0.88-2.12) for fibrates, and 2.12 (1.31-3.35) for resins. After adjustment for confounding factors the adjusted odds ratios (95% CI) compared with controls were 0.69 (0.64-0.74) for statins, 0.60 (0.41-0.86) for ezetimibe, 0.87 (0.51-1.42) for fibrates, and 1.21 (0.69-2.06) for resins. CONCLUSIONS: Use of statins and ezetimibe was inversely correlated with severe hyponatremia. Consequently, these drugs are unlikely culprits in patients with hyponatremia, and they appear safe to initiate in hyponatremic patients. A potential protective effect warrants further studies on how statins and other lipid-lowering drugs are linked to dysnatremias.

Cumulative non-HDL-cholesterol burden in patients with hypertriglyceridemia receiving long-term fibrate therapy: Real life data from a lipid clinic cohort.

OBJECTIVE: Though epidemiological data suggest that an elevated triglyceride (TG) level may be a risk factor for coronary artery disease (CAD), there is still insufficient clinical evidence. This study was designed to evaluate the real-life efficacy and side effects of fibrate treatment for hypertriglyceridemia seen in a lipid clinic, as well as cardiovascular and diabetic outcomes. METHODS: This retrospective study evaluated patients who were followed-up for a diagnosis of hypertriglyceridemia at the lipid outpatient clinic of the Ege University Cardiology Department between 1997 and 2018. Data of demographic and clinical characteristics were obtained from hospital records. All patients (n=240) with at least 1 year of follow-up were included in the analysis. During follow-up, patients were treated with fenofibrate, and less frequently, gemfibrozile (14 patients), at different doses according to the TG level and disease severity. RESULTS: Of the study population, 23% had CAD, 21% were diabetic, and 52% were obese. On admission, 20% were using fibrates and 17% were on statins. The mean admission lipid levels were TG: 281±194 mg/dL, low-density lipoprotein cholesterol: 115±37 mg/dL, high-density lipoprotein (HDL) cholesterol: 43±13 mg/dL, and non-HDL cholesterol: 166±42 mg/dL. The mean length of follow-up was 5.3±4.7 years (range: 1-16 years). A total of 8 (4.3%) patients had adverse effects during follow-up (1 on statin combination and 7 on fibrates alone). The side effects observed were an elevation of liver enzymes in 3, myalgia in 2, insomnia in 1, malaise in 1, and a skin rash in 1 patient. No rhabdomyolysis or myopathy was seen. During follow-up, diabetes developed in 14 and cardiovascular disease (CVD) in 14 patients. The cumulative non-HDL cholesterol level was significantly high in patients who developed diabetes or CVD. Receiver operating curve analysis indicated that a cumulative non-HDL cholesterol value of 1016 mg/dL was predictive of the development of diabetes mellitus or CVD with 85% sensitivity and 70% specificity. CONCLUSION: In real life, long-term fibrate use is effective and safe. The cumulative non-HDL cholesterol burden can be used to assess the efficacy of treatment as a simple and easily calculated method. Large studies are needed to further clarify the value of this parameter in predicting the development of both diabetes and CVD.

DPP-4 Inhibitors in Combination with Lipid-Lowering Agents and Risk of Serious Muscular Injury: A Nested Case-Control Study in a Nationwide Cohort of Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: After a safety warning was issued for a risk of muscular injury associated with dipeptidyl peptidase-4 (DPP-4) inhibitor use, especially when co-prescribed with statins, spontaneous reporting analyses provided conflicting results. OBJECTIVE: The aim of this study was to investigate the association between DPP-4 inhibitor use and the risk of muscular injury in individuals with type 2 diabetes mellitus using statins or fibrates. METHODS: We conducted a nested case-control study amongst a cohort of individuals with type 2 diabetes using statins or fibrates, identified from a nationwide French health insurance database (2009-2014). Cases of serious muscular injury were defined as subjects hospitalized for rhabdomyolysis or myopathy, or for whom testing for myoglobin or creatine phosphokinase followed by a change in statin or fibrate prescription (dose decrease, treatment switch, or stop) was identified. Up to ten controls were matched to each case according to sex, age, and type of lipid-lowering agent. Associations between DPP-4 inhibitor use and serious muscular injury were estimated using a multivariate conditional logistic regression model, providing odds ratios (ORs) adjusted for alcoholism, chronic renal failure, hypothyroidism, and number of concomitant drugs. RESULTS: Within the 35,117 individuals with type 2 diabetes mellitus constituting the source cohort, 437 statin-user cases were identified who were matched to 4358 statin-user controls. Similarly, 54 fibrate-user cases were identified who were matched to 540 fibrate-user controls. The adjusted OR for DPP-4 inhibitor use and serious muscular injury was estimated at 1.0 (95% confidence interval [CI] 0.7-1.2) in statin users and 0.8 (95% CI 0.4-1.9) in fibrate users. CONCLUSION: In this study, DPP-4 inhibitor use was not associated with an increased risk of serious muscular injury among patients with type 2 diabetes mellitus using statins or fibrates.

Reporting quality and adherence of randomized controlled trials about statins and/or fibrates for diabetic retinopathy to the CONSORT checklist.

BACKGROUND: A considerable amount of randomized controlled trials (RCTs) have been published on statins and/or fibrates for diabetic retinopathy, a clinical condition associated with high social and economic burden. Adherence to the CONSORT statement items is imperative to ensure transparency and reproducibility in clinical research. The aim of this study is to assess the reporting quality and the adherence to CONSORT of RCTs assessing statins and/or fibrates for diabetic retinopathy. METHODS: We conducted a critical appraisal study at Discipline of Evidence-based Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp). A sensitive literature search was performed to identify all relevant RCTs, with no time or language limits. Two authors independently evaluated the reporting quality of the selected RCTs using the CONSORT statement as a standard. RESULTS: Thirteen reports of RCTs were included in this study. The adherence of the reports to CONSORT items ranged from 24% to 68%. The median score was 11 (interquartile range (IQR) 8 to 13). When analyzed separately, the methods sections of the reports had a median of three items (IQR 2 to 4) judged adherent to the methods items of CONSORT (items 3 to 12). The most underreported items were those related to trial design, title and abstract, allocation concealment, implementation of the randomization sequence, and blinding. Other important items, such as the one related to the description of the inclusion criteria, also had low adherence. CONCLUSIONS: The overall adherence to the CONSORT checklist items was poor, especially in the items related to the methods section. RCT reports on statins and/or fibrates for diabetic retinopathy must be optimized to avoid reporting biases and to improve transparency and reproducibility.

Curbing Lipids: Impacts ON Cancer and Viral Infection.

Lipids play a fundamental role in maintaining normal function in healthy cells. Their functions include signaling, storing energy, and acting as the central structural component of cell membranes. Alteration of lipid metabolism is a prominent feature of cancer, as cancer cells must modify their metabolism to fulfill the demands of their accelerated proliferation rate. This aberrant lipid metabolism can affect cellular processes such as cell growth, survival, and migration. Besides the gene mutations, environmental factors, and inheritance, several infectious pathogens are also linked with human cancers worldwide. Tumor viruses are top on the list of infectious pathogens to cause human cancers. These viruses insert their own DNA (or RNA) into that of the host cell and affect host cellular processes such as cell growth, survival, and migration. Several of these cancer-causing viruses are reported to be reprogramming host cell lipid metabolism. The reliance of cancer cells and viruses on lipid metabolism suggests enzymes that can be used as therapeutic targets to exploit the addiction of infected diseased cells on lipids and abrogate tumor growth. This review focuses on normal lipid metabolism, lipid metabolic pathways and their reprogramming in human cancers and viral infection linked cancers and the potential anticancer drugs that target specific lipid metabolic enzymes. Here, we discuss statins and fibrates as drugs to intervene in disordered lipid pathways in cancer cells. Further insight into the dysregulated pathways in lipid metabolism can help create more effective anticancer therapies.

Use of Lipid-Lowering Drugs and the Risk of Cataract: A Population-Based Nested Case-Control Study.

Eye lens membrane cells require high cholesterol concentrations that might be counteracted by lipid-lowering drugs. Using a nationwide database, we conducted a nested case-control study to evaluate the risk of cataract development associated with the use of lipid-lowering drugs. Patients aged 45 years and over with first cataract surgery in 2014 (cases) and up to four controls matched on age, gender, diabetes, hypothyroidism, glucocorticoid use, cardiovascular risk, and area of residence were included in the study. Among the 2,811 cases and 11,106 matched controls included, analyses showed a significantly increased risk of cataract surgery for a cumulative exposure to fibrates exceeding 5 years (adjusted odds ratio (aOR) 1.58; 95% confidence interval (CI): 1.17-2.15), unlike cumulative exposure to statins, whatever the dose or duration of treatment (aORs from 1.00-1.08, none being significant). This study highlighted an increased risk of cataract surgery with prolonged use of fibrates but not of statins.

Risk of diabetes with fibrates and statins: a pharmacoepidemiological study in VigiBase®.

In contrast to statins, the risk of diabetes with fibrates was not clearly studied. This study investigates a putative signal of diabetes associated with the use of fibrates using the World Health Organization (WHO) global individual case safety reports database, VigiBase® . We included all reports registered until the 31st December 2017 in VigiBase® to measure the risk of reporting 'hyperglycemia or new onset of diabetes' (SMQ term) compared with all other reports [as a reporting odds ratio (ROR 95% CI)] for fibrates, statins, and the combination fibrates + statins. The likelihood that diabetes resulted from statin-fibrate interaction was also estimated. According to the interaction additive model, a ROR value for coexposure exceeding the sum of the RORs estimated for each individual class of drug supports a potential drug-drug interaction (DDI). To assess the stability of our results, we performed several sensitivity analyses, according to outcome definition and after exclusion of putative competitive (hyperglycemic) drugs. We included 19 149 patients exposed to fibrates (without statins), 177 323 to statins (without fibrates) and 3 247 to statins plus fibrates. In contrast to statins (ROR = 1.75, 95% CI 1.72-1.78), no association was found for fibrates (ROR = 0.76, 95% CI 0.71-0.82). The ROR value was lower for the combination statins plus fibrates (ROR = 1.46, 95% CI 1.28-1.67). Similar trends were found in sensitivity analyses. This study, performed in the real conditions of use, failed to find a signal of diabetes with fibrates. It strengths the association previously described with statin without any evidence for a statin-fibrate DDI.

Association between venous thromboembolism events and fibrates: A comparative study.

AIM: Previous studies highlighted a significant association between fibrates and venous thromboembolism (VTE) events in dyslipidemia diabetic patients. Studies in non-diabetic patients are divergent. The present study investigated the association between VTE events and fibrates in diabetic and non-diabetic patients. METHODS: Two approaches were used: (1) a disproportionality analysis using the World health organization pharmacovigilance database VigiBase® was used to evaluate the reporting odds-ratio (ROR) of fibrates for VTE events. Clinical and demographic characterizations of patients with fibrates-related VTE reports are described; (2) a case control-study was performed using the Caen university hospital medical information database between January 2008 and December 2012. Cases were dyslipidemia patients who were hospitalized for VTE without an evident provoking factor. Up to four controls per case were selected in dyslipidemia patients hospitalized for a non-VTE event. Controls were matched to cases by age, gender, date of hospitalization, diabetes, chronic kidney disease and hospitalization department. A multivariate conditional logistic regression was performed. RESULTS: Disproportionality analysis: a total of 946 notifications were identified in VigiBase® (32.9% of diabetic patients). Fibrates were significantly associated with an increased report of VTE (ROR 1.14, CI 1.07-1.22). Case-control study: a total of 163 cases (21.5% of diabetic patients) and 514 matched controls were recruited. Fibrates were significantly associated with a higher risk of VTE events that required hospitalization in multivariate analysis (odds-ratio (OR) 3.67, CI 1.82-7.37, P=0.0003). The association was only significant for fenofibrate in both approaches. CONCLUSION: Fenofibrate was associated with a higher incidence of VTE events in diabetic and non-diabetic patients.

Benefits and risks of the treatment with fibrates--a comprehensive summary.

INTRODUCTION: The need to reduce residual cardiovascular risk led to the development of novel therapeutic strategies to improve patients' outcomes. The residual risk in people with atherogenic dyslipidemia, despite LDL reduction obtained mainly by statins, remains high. Fibrates in those patients lead to significant clinical improvements. Those include reduction in the progression of atherosclerosis, which translates into decrease in cardiovascular events and improvements in microvascular diabetic complications. Furthermore, there are other clinical and biochemical benefits connected with fibrate therapy (e.g. improved insulin sensitivity). Nevertheless, similar to all effective therapeutic modalities, fibrates are associated with unfavorable effects that may lead to complications or treatment discontinuation. Here, we provide up-to-date review of benefits and potential risks associated with the therapy with fibrates. Area covered: A review of available data from clinical trials, meta-analyses and case-reports on the efficacy of fibrate treatment was performed. A specific attention was given to clinical and biochemical benefits as well as adverse events that were reported. Expert commentary: Fibrates are performing well as drugs that reduce residual risk in patients with atherogenic dyslipidemia and hypertriglyceridemia. The adverse events rate is not negligible, but definitely manageable by selection of proper target population and supervision of treated patients.

Los fibratos en la prevención primaria de la enfermedad cardiovascular. Comentarios a los resultados de una revisión sistemática de la Colaboración Cochrane / Fibrates in primary prevention of cardiovascular disease. Comments on the results of a systematic review of the Cochrane Collaboration

Los fibratos son un grupo de hipolipidemiantes que reducen los triglicéridos, elevan las lipoproteínas de alta densidad y disminuyen la fracción de partículas de LDL pequeñas y densas. Recientemente, se han publicado los resultados de un estudio de la Colaboración Cochrane sobre su eficacia y seguridad en la prevención primaria de la enfermedad cardiovascular. Este estudio incluye una revisión sistemática y un metaanálisis de 6 estudios (16.135 pacientes) que evalúan, en personas en prevención primaria, los beneficios clínicos de los fibratos comparados con el uso de un placebo o de otros hipolipidemiantes. Concluyen que, comparados con placebo, los fibratos son útiles para reducir en un 16% el combinado muerte por enfermedad cardiovascular, infarto de miocardio no fatal o accidente cerebrovascular no fatal (NNT: 112) y que disminuyen la morbimortalidad coronaria un 21% (NNT: 125). Complementariamente, los fibratos podrían reducir la retinopatía diabética previamente establecida. Sin embargo, no influyen en la mortalidad total ni en la de origen no cardiovascular. Tampoco su empleo conjunto con estatinas beneficia a pacientes sin enfermedad cardiovascular establecida, comparado con el uso de estatinas en monoterapia. Los fibratos son seguros, aunque pueden elevar los niveles séricos de creatinina

Fibrates are drugs that reduce triglycerides, elevate high-density lipoproteins, as well as decrease small, dense LDL particles. The results of a study have recently been published by the Cochrane Collaboration on fibrates efficacy and safety in the primary prevention of cardiovascular disease. This study includes a systematic review and a meta-analysis of 6 studies (16,135 patients) that evaluated the clinical benefits of fibrates compared to placebo use or other lipid-lowering drugs. This review showed evidence of a protective effect of the fibrates compared with placebo as regards a reduction 16% of a compound objective of death due to cardiovascular disease, non-fatal myocardial infarction, or non-fatal cerebrovascular accident (NNT: 112), and that reduce coronary morbidity and mortality by 21% (NNT: 125). In addition, fibrates could reduce previously established diabetic retinopathy. However, fibrates do not influence total mortality, or non-cardiovascular mortality. Its joint use with statins does not benefit patients without established cardiovascular disease, compared to the use of statins in monotherapy. Fibrates are safe, although they can elevate serum creatinine levels