Use Of Fibrates Research Articles

Diferencias por edad y sexo en el control y tratamiento de la diabetes mellitus tipo 2 en un centro de salud

Objective. To know the degree of control and treatment of patients with type 2 diabetes (DM2) in our health area, differentiated according to age (< 65 and ≥ 65 years) and gender (male and female). Material and method. Observational, descriptive and cross-sectional study on the medical records of patients with DM2 from the Manzanares II Health Zone. Sociodemographic data, cardiovascular risk factors, vascular repercussions, laboratory values (glucose, lipid) and blood pressure, and drugs for the treatment of diabetes, dyslipidemia, arterial hypertension and with antiplatelet / anticoagulant effect are collected. Results. Data from 342 patients (men: 170; women; 172; 60% with ≤ 7% (no differences between groups) with 40% in the range of ≤ 6.5%. Total cholesterol ≤ 200 mg / dl in 75% of patients: higher percentage in ≥ 65 years and in men (p < 0.01 between age groups and p < 0.05 by gender) with LDL-cholesterol ≤ 100 mg / dl in more than half of the patients: better in ≥ 65 years and in men (with p < 0.01 between age groups and gender). The combination of controlled factors for HbA1C and LDL-cholesterol improved in those ≥ 65 years (p < 0.01). Higher prevalence of CKD in women and in those ≥ 65 years (p < 0.001 for age and p < 0.05 for gender). Higher prevalence of smoking in men and in < 65 years (p < 0.001, in both). ARA II and diuretics are more used in ≥ 65 years (p < 0.05 and p < 0.001) than in < 65 years. There are no differences in antidiabetic treatment by sex, but there are in terms of metformin and iSGLT2 (more frequent in < 65 years, p < 0.01). There are differences in the use of statins (p < 0.01) and fibrates (p < 0.05), higher (64.4%) in ≥ 65 years. There is greater use of anticoagulation (14.9% vs 5.8%, p < 0.05) in ≥ 65 years Conclusions. There are no differences in glucose control, but there are differences in lipid control and in the use of some hypoglycemic, statin and antihypertensive drugs.

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.

Management of dyslipidemia in diabetic nephropathy

Background and Aims: Dyslipidemia in diabetes is associated with higher cardiovascular risk. The CVD risk is higher with diabetic nephropathy. Guidelines focus on lowering the LDL-C level by statins. For the risk modification is substantial to reduce triglycerides levels. Use of fibrates in diabetic nephropathy is controversial. The aim was to reduce LDL and TG levels to target levels without affecting nephropathy degree.

Predisposing factors to acute pancreatitis in patients with severe hypertriglyceridemia

Abstract Severe hypertriglyceridemia (HTG) is a rare condition defined as fasting triglyceride (TG) levels &amp;gt;885 mg/dL. Besides the association between mild-moderate HTG and cardiovascular disease (CVD), severe HTG is a known risk factor for acute pancreatitis (AP). The factors predisposing patients with severe HTG to AP are not completely clear. Purpose Compare patients with severe HTG with and without AP and identify factors predisposing to AP. Methods We performed a retrospective search of patients with severe, refractory HTG in our hospital database over the last 10 years. Inclusion criteria: at least one TG≥2,000mg/dL and the latest on-therapy TG≥1,000mg/dL. Results From 692 patients with at least one TG≥1,000 mg/dL, 27 met the inclusion criteria. Nineteen (70%) were male, mean age 53±14 y-old. The median maximum TG value was 3,384mg/dL and the latest on-therapy TG was 1,791 mg/dL despite fibrate use; 70,4% were diabetics (44% insulin users; 41% had previous CVD). Patients with AP were younger, with higher fasting glucose and lower HDL-C. However, there were no differences between the AP and no AP groups, regarding maximum and latest TG, diagnosis of diabetes and treated HbA1C. Conclusion In this cohort of patients with severe, refractory HTG, those with AP were significantly younger, suggesting a greater genetic role for HTG in this group. There were no other relevant diferences between the AP and no AP groups. Conceivably, other unrecognized factors were at play accounting for the AP events. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Zerbini Foundation, FAPESP (The The São Paulo Research Foundation)

Prevalence of Familial Hypercholesterolaemia in Acute Coronary Syndrome Patients in a Large Regional Coronary Care Unit

Familial hypercholesterolaemia (FH) is an under recognised cause of coronary artery disease, despite the proven reductions in risk with early detection and treatment. Data from 180 consecutive patients presenting to a large regional hospital with acute coronary syndrome were collected. Potential FH was assessed using the Dutch Lipid Clinic Network Criteria (DLCNC), and if patients were on statins, pre-treatment cholesterol was estimated according to a validated algorithm. Ninety per cent (90%) of patients presented with non-ST elevation myocardial infarction (NSTEMI) or ST elevation myocardial infarction (STEMI). A total of 11 patients (6%) were classified as having phenotypic FH. The phenotypic FH cohort was younger (mean age 53.1 vs 62.0, p=0.011); and more likely to have documented ischaemic heart disease (63.6% vs 20.7%, p=0.001). Familial hypercholesterolaemia patients had a higher rate of ezetimibe use (18.2% vs 2.4%, p=0.005), but fibrate use was not significantly different. Phenotypic FH patients also had higher levels of total cholesterol, corrected LDL and triglycerides, but no statistically significant difference in HDL levels compared with non-FH counterparts. The prevalence of FH is relatively high among patients presenting with acute coronary syndromes. This has now been established in a regional Australian population, with similar prevalence to large European registries. This highlights the need for improved access to specialised services in regional and rural areas to reduce adverse cardiovascular (CV) outcomes.

Abstract 104: Mortality Risk Across Chronic Kidney Disease Stages With Fibrate or Niacin Use Compared With No Fibrate or Niacin Therapy in Male US Veterans

Background: Chronic kidney disease (CKD) patients have a higher cardiovascular (CV) disease and mortality risk, elevated triglycerides (TG), and decreased high density lipoproteins (HDL). Post-hoc analysis of trials examining use of fibrate (Fib) or niacin (Nia) therapy in lowering CV outcome risk have failed to show benefit in mild to moderate kidney disease. These analyses were criticized for their study design or small sample size. We sought to examine if Fib or Nia use is associated with lower mortality risk in US veterans across CKD stages. Methods: In a retrospective cohort analysis, we identified male veterans who initiated Fib or Nia, with a high TG ≥150 mg/dL or low HDL ≤40 mg/dL between 2004-2014, and matched them on CKD stage and TG and HDL levels to unexposed men. We examined the association of Fib or Nia use (ref: unexposed) with 12-month all-cause mortality risk across CKD stage strata using an adjusted Cox proportional hazards model. Propensity scores (PS) included baseline demographics, comorbidities and lab measures and high-dimensional propensity scores (HDPS) included over 100 covariates for each drug and stage analysis. PS and HDPS analyses included score adjustment and matching. Results: The cohort had a mean±SD age of 64±12 years, and 30% had CKD stage 3A and higher. There were 69,295 Fib, 87,727 Nia, and 114,411 unexposed patients, respectively. Patient characteristics were similar across drug groups within each CKD stage. With covariate adjustment, both Fib and Nia were associated with a lower death risk compared to unexposed men in lower CKD stages (Figure A and B). Among those with CKD stage 4/5, Fib and Nia were associated with a higher death risk (HR[95%CI]: 1.43[1.15, 1.78] and 1.17[0.97,1.40], respectively). Those on Fib or Nia and in end-stage renal disease had a null association with mortality. Associations were similar for each CKD stage in PS and HDPS analyses, yet Fib and Nia were no longer associated with a lower death risk for CKD stage 3A and 3B patients. Conclusion: Mortality associations of Fib and Nia among male veterans with high TG and low HDL varied across CKD stage, where CKD stage 4/5 patients had a higher mortality risk, even in PS and HDPS analyses. While covariate balance was met, further studies are needed to examine the mechanisms for this higher observed risk in late-stage CKD patients.

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

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. 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. 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. 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.

Fibrate Use and Patients with Chronic Kidney Disease

Fibrate Use and Patients with Chronic Kidney Disease

16 - Low Prevalence of Fibrate Use in Established Diabetic Retinopathy at a Tertiary Care Centre: A Cross-Sectional Study

Diabetic retinopathy (DR) is the leading cause of blindness in adults in Canada. Effective treatments to prevent/delay DR-related vision loss include glycemic and blood pressure control, laser photocoagulation and fenofibrate. Current guidelines recommend considering fenofibrate (in addition to statins) to delay DR progression in those with type 2 diabetes and established DR. Despite this, fenofibrate is not widely used. This study’s goal was to determine the prevalence of fibrate use and factors predictive of fibrate use in patients with known DR.

P651Prevalence of hypertriglyceridemia in statin treated high risk patients who might benefit from treatment with icosapent ethyl for secondary prevention in clinical practice - Results of DYSIS

Abstract Background Patients with elevated triglyceride (TG) levels are at increased risk for ischemic events. In the recently published REDUCE-IT-Study among patients with elevated triglyceride levels who were receiving statin therapy, the risk of major ischemic events, including cardiovascular death, was significantly lower with 2 g of icosapent ethyl twice daily than with placebo. Little is known about how many patients in clinical practice might benefit from this additional treatment. Methods The cross sectional, observational Dyslipidemia International Study (DYSIS) examined lipid goal attainment among statin-treated very high cardiovascular risk patients (defined as per 2011 EAS/ESC guidelines, including patients suffering from coronary heart disease, diabetes, chronic kidney disease or peripheral atherosclerotic disease) in Canada, Europe, Middle East countries and China. Data were collected under real life conditions in physicians' offices and hospital outpatient wards between 2008–2012. We examined the prevalence of mixed dyslipidemia with TG &gt;135 mg/dl in high statin treated high risk patients in clinical practice. Results Of a total of 44,593 patients on very high cardiovascular risk, all on chronic statin treatment, 21,312 (47.8%) had mixed dyslipidemia with TG values &gt;135mg/dl. Patients with elevated TG also had higher levels of total and LDL-cholesterol. The overall use of additional fibrates on top of statins was low (4.0%), but more frequent in patients with TG &gt;135 mg/dl. CVD patients with TG&gt;135 mg/dl Pts with TG &gt;135 mg/dl Pts with TG ≤135 mg/dl p-value OR (95% CI) n=21,312 (47.8%) n=23,281 (52.2%) Age (years) 65.4±10.1, 68.1±10.2 &lt;0.0001 Females 42.2% 38.6% &lt;0.0001 1.16 (1.12–1.21) Sedentary lifestyle 43.0% 37.6% &lt;0.0001 1.25 (1.20–1.30) Risk factors/CV-disease Hypertension 79.0% 74.9% &lt;0.0001 1.26 (1.21–1.32) Diabetes mellitus 56.3% 45.3% &lt;0.0001 1.55 (1.50–1.61) Ischemic heart disease 50.6% 54.4% &lt;0.0001 0.86 (0.83–0.89) Cerebrovascular disease 16.1% 17.7% &lt;0.0001 0.90 (0.85–0.94) Peripheral artery disease 8.1% 6.9% &lt;0.0001 1.18 (1.10–1.27) Lipid lowering therapy Rosuvastatin 11.3% 11.8% 0.13 0.95 (0.90–1.01) Atorvastatin 38.2% 40.9% &lt;0.0001 0.89 (0.86–0.93) Simvastatin 41.9% 38.9% &lt;0.0001 1.13 (1.09–1.18) Other statins 8.6% 8.4% 0.12 0.96 (0.88–1.05) Fibrates 5.5% 1.5% &lt;0.0001 3.86 (3.40–4.37) Lipid Profile Total Cholesterol (mg/dl) 185.6 159.0 &lt;0.0001 LDL-Cholesterol (mg/dl) 102.1 88.9 &lt;0.0001 Triglyderides (mg/dl) 189.5 95.7 &lt;0.0001 Conclusion Almost half of consecutive patients with cardiovascular disease treated with statins for secondary prevention in clinical practice suffer from TG levels &gt;135 mg/dl and might benefit from additional treatment with icosapent ethyl with further reduction in subsequent major ischemic events, including cardiovascular death. Acknowledgement/Funding MSD

Another approach to the Kan\u2013Quillen model structure

By careful analysis of the embedding of a simplicial set into its image under Kan’s mathop {mathop {mathsf {Ex}}^infty } functor we obtain a new and combinatorial proof that it is a weak homotopy equivalence. Moreover, we obtain a presentation of it as a strong anodyne extension. From this description we can quickly deduce some basic facts about mathop {mathop {mathsf {Ex}}^infty } and hence provide a new construction of the Kan–Quillen model structure on simplicial sets, one which avoids the use of topological spaces or minimal fibrations.

Positioning of darunavir/cobicistat-containing antiretroviral regimens in real life: results from a large multicentre observational prospective cohort (SCOLTA)

BackgroundStudy aim was to evaluate the safety and durability of darunavir/cobicistat (DRV/c) in a real life setting.MethodsMulticentre prospective cohort study performed in the context of SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals). Patients were evaluated at baseline, week 24 and 48. Changes were evaluated using the paired t test or signed rank test. The multivariable analysis was performed using a general linear model, after ranking of not normally distributed variables.ResultsA total of 249 patients were included, 72 (29%) were in DRV/c-based dual therapies (DT). Hypercholesterolemia, HC, (total cholesterol (TC) ≥ 200 mg/dL or low density-C (LDL-C) ≥ 130 or statin use) was present in 121 (48.6%) and hypertriglyceridemia, (triglycerides (TG) ≥ 200 mg/dl or fibrate use) in 41 (16.5%) patients. Blood lipid profile did not change significantly in either the global population or patients with HC. After a median observation of 17 months (IQR 13–20), 59 (25.3%) patients discontinued DRV/c, of which 13 were in DT. The durability DT resulted higher than that of triple therapy (log-rank test p = 0.01). Main reasons for stopping DRV/c were simplification (15 patients), adverse events (13 patients), planned discontinuation for treatment initiation with DAA (4 patients), treatment failure (2 patients); death (2 patients), other causes (10 patients). Twenty-six were lost to follow-up.ConclusionsDRV/c was safe and well tolerated. Dual therapies showed a better profile of tolerability and a longer durability compared to triple therapies.

Treatment with fibrates is associated with higher LAL activity in dyslipidemic patients

Lysosomal acid lipase (LAL) is responsible for the hydrolysis of cholesteryl esters (CE) and triglycerides (TG) within the lysosomes; generated cholesterol and free fatty acids (FFA) are released in the cytosol where they can regulate their own synthesis and metabolism. When LAL is not active, as in case of genetic mutations, CE and TG accumulate in the lysosomal compartment, while the lack of release of cholesterol and FFA in the cytosol leads to an upregulation of their synthesis. Thus, LAL plays a central role in the intracellular homeostasis of lipids. Since there are no indications about the effect of different lipid-lowering agents on LAL activity, aim of the study was to address the relationship between LAL activity and the type of lipid-lowering therapy in a cohort of dyslipidemic patients.LAL activity was measured on dried blood spot from 120 patients with hypercholesterolemia or mixed dyslipidemia and was negatively correlated to LDL-cholesterol levels. Among enrolled patients, ninety-one were taking one or more lipid-lowering drugs, as statins, fibrates, ezetimibe and omega-3 polyunsaturated fatty acids. When patients were stratified according to the type of lipid-lowering treatment, i.e. untreated, taking statins or taking fibrates, LAL activity was significantly higher in those with fibrates, even after adjustment for sex, age, BMI, lipid parameters, liver function, metabolic syndrome, diabetes and statin use. In a subset of patients tested after 3 months of treatment with micronized fenofibrate, LAL activity raised by 21%; the increase was negatively correlated with baseline LAL activity.Thus, the use of fibrates is independently associated with higher LAL activity in dyslipidemic patients, suggesting that the positive effects of PPAR-α activation on cellular and systemic lipid homeostasis can also include an improved LAL activity.

SUN-071 Unexpected Paradoxical Extremely Low of HDL-Cholesterol Level in a Non-Diabetes, Non-CKD Patient after Treatment with Specific Fibrate and Statin and Specific Fibrate Alone

Background: Fibrates are the class of the lipid-modifying agents to treat hypertriglyceridemia with usually increasing HDL that generally reflected by increased plasma levels of apoA-I and apoA-II. Paradoxical decrease in serum HDL level has been rarely reported. This presents a specific use of fibrates and statins therapy lead to markedly low of serum HDL level, in a non-diabetes and non-kidney disease patient. Clinical case: A 50-year-old man, underlying NAFLD, hypertension and dyslipidemia, has been followed up for 11 years. He was a non-smoker, non-drinker and denied to use any herbal supplement. His BMI and renal function were normal. He had a family history of cardiovascular death, including his grandmother (at 63 years old), his father (at 59 years old) and his mother (at 65 years old). Eleven years ago, he was started with simvastatin 10 mg when his presentation fasting serum lipids values were LDL 130 mg/dL, triglyceride 137 mg/dL and HDL 34 mg/dL. Three years later, his lipids showed severe hypertriglyceridemia; 795 mg/dL, LDL 75 mg/dL and HDL 28 mg/dL, he was added gemfibrozil 600 mg and up titrate dose to 900 mg during next two years of follow-up without any adverse event. After that, FDA warning drugs interaction between statins and gemfibrozil, simvastatin 10 mg was changed to ezetimibe 10 mg when his serum lipids were LDL 85 mg/dL, triglyceride 339 mg/dL and HDL 41 mg/dL for the next 3 years. Because his lipids values showed increase LDL to 150 mg/dL, he was changed his medications to ezetimibe/ simvastatin 10/20 with lifestyle modification to maintain normal triglyceride level. One year following, he complained myalgia with mildly elevated of CPK (298 U/L; < 190) together with ALT (86 U/L; < 41). At that time, his serum lipids were LDL 67 mg/dL, triglyceride 318 mg/dL and HDL 32 mg/dL. Ezetimibe/ simvastatin 10/20 was stopped and changed to pravastatin 40 mg due to the lesser side effects on the muscles and liver. In the next six months, his CPK level turned to normal however triglyceride level elevated to 533 mg/dL then fenofibrate 300 mg was added. Four months later, his serum lipids revealed triglyceride 190 mg/dL, LDL 86 mg/dL and HDL 3 mg/dL which pravastatin was stopped alone. During next several visits, serum HDL slightly elevated from 3 to 9 to 11 mg/dL every two months until fenofibrate was decided to stop as the serum HDL level was 8 mg/dL, LDL 126 mg/dL and triglyceride 241 mg/dL. Four months later, his serum HDL returned to 31 mg/dL with ezetimibe 10 mg alone. Concussion: This case presents the paradoxical severe decrease in serum HDL-cholesterol after treatment with specific combination of pravastatin and fenofibrate and fenofibrate alone which did not happen in the longer period use of simvastatin and gemfibrozil or gemfibrozil alone without abnormal renal function or diabetes. Awareness of decline in HDL during treatment with fenofibrate alone or combination with statins should be considered.

Inverse Association of Fibrates and Liver Cancer: A Population-Based Case-Control Study in Taiwan.

This large-scale case-control study in Taiwan elucidated the potential connection between fibrate use and liver cancer by using the Longitudinal Health Insurance Database 2005 with a propensity-score-matching design. In total, 4173 patients diagnosed as having liver cancer were included as cases, and 4173 propensity-score-matched patients without liver cancer were identified as controls. The association between previous fibrate use and liver cancer occurrence was demonstrated using conditional logistic regression. Fibrate use was noted in 371 (8.89%) cases and 481 (11.53%) controls. After adjustments, the cases had significantly lower odds of previous fibrate use than did the controls (adjusted odds ratio 0.70, 95%CI 0.60-0.82); moreover, regardless of the patients' sex, age group, and comorbidities, the cases were less likely to have used fibrates than were the controls. Dose-dependent analysis revealed that 1-695 cumulative defined daily doses of fibrates may significantly induce a protective effect for liver cancer. Although other fibrate dose intervals did not reach statistical significance, the dose-response curve presented the trend of a protective effect for liver cancer among the fibrate users. In summary, fibrate use had a significant protective effect against liver cancer in this Asian population.

Risk of diabetes associated with statins and fibrates and their association: A disproportionality analysis using the WHO spontaneous reporting database, Vigibase®

Relations between hypolipidemic drugs and diabetes are discussed. The aim of our study was to assess the association between diabetes and use of statins or fibrates or their association using the World Health Organization (WHO) global individual case safety reports database, VigiBase®, which records reports from over 130 countries worldwide. We performed a disproportionality analysis including all reports until the 31st December 2017 to measure the risk of reporting “new onset of diabetes” compared with all other reports [as a reporting odds ratio (ROR 95% CI)] for statins, fibrates and their association. The likelihood that diabetes resulted from statin-fibrate pharmacodynamic 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 excluding reports with drugs known to induce hyperglycaemia or diabetes. We identified 7633 cases of diabetes (mainly with atorvastatin) and 169,690 non-cases among reports with statins alone, 189 cases (mainly with fenofibrate) and 18,960 non-cases among reports with fibrates alone with 60 cases and 3,187 among reports with the combination statin-fibrates. Statin use alone was associated with an increase in the ROR of diabetes (ROR = 1.75 [1.72–1.78]), but not with fibrate use alone (ROR = 0.76 [0.71–0.82]). The combination of statin + fibrate was associated with an increase in the ROR of diabetes (ROR = 1.46 [1.28–1.67]) but was not significant to support a DDI. Similar results were found in sensitivity analyses. Using the WHO pharmacovigilance database, our study confirmed the signal of diabetes with statins but failed to find any potential signal with fibrates alone and did not suggest a pharmacodynamic DDI with the use of statin + fibrate.

Effects of high-density lipoprotein targeting treatments on cardiovascular outcomes: A systematic review and meta-analysis.

The effects of increasing high-density lipoprotein cholesterol on cardiovascular outcomes remain uncertain. We conducted a meta-analysis to investigate the effects of high-density lipoprotein cholesterol modifiers (niacin, fibrates and cholesteryl ester transfer protein inhibitors) on cardiovascular outcomes. Thirty-one randomized controlled trials (154,601 patients) with a follow-up of 6 months or more and a sample size of 100 or more patients were selected using MEDLINE, EMBASE and CENTRAL database (inception January 2018). High-density lipoprotein cholesterol modifiers had no statistically significant effect on cardiovascular mortality in terms of relative risk (RR) (RR 0.94, 95% confidence interval (CI) 0.89-1.00, P = 0.05, I2 = 13%) or absolute risk (risk difference -0.0001, 95% CI -0.0014, 0.0011, P = 0.84, I2 = 28%). High-density lipoprotein cholesterol modifiers reduced the RR of myocardial infarction (RR 0.87, 95% CI 0.82-0.93, P < 0.001, I2 = 37%). This significant effect was derived by the use of fibrates (RR 0.80, 95% CI 0.73-0.87, P < 0.001, I2 = 22%) and meta-regression analysis showed that this benefit was consistent with an absolute reduction in low-density lipoprotein cholesterol. High-density lipoprotein cholesterol modifiers had no effect on stroke (RR 1.00, 95% CI 0.93-1.09, P = 0.94, I2 = 25%) or all-cause mortality (RR 1.02, 95% CI 0.97-1.08, P = 0.48, I2 = 49%). Meta-regression analyses failed to demonstrate a significant association of pharmacologically increased high-density lipoprotein cholesterol with key endpoints. In studies with background statin therapy, high-density lipoprotein cholesterol modifiers had no statistically significant impact on cardiovascular mortality, myocardial infarction, stroke or all-cause mortality ( P > 0.05). The use of high-density lipoprotein cholesterol modifying treatments had no significant effect on cardiovascular mortality, stroke or all-cause mortality. The beneficial effect on myocardial infarction was lost when drugs were used with statin therapy.

Statins improve survival in patients previously treated with nivolumab for advanced non-small cell lung cancer: An observational study.

There are a number of suggested predictive factors of nivolumab for non-small cell lung cancer (NSCLC), however, there is not enough evidence to determine a single factor that can predict the efficacy of nivolumab. As the progress of biomarkers for cancer treatment is improving, it has been speculated that certain clinical factors serve an important role when predicting the outcome of chemotherapy. A total of 67 patients treated with nivolumab for NSCLC from 2016-2017 were prospectively investigated. Age, sex, the Eastern Cooperative Oncology Group Performance Status, histology, epidermal growth factor receptor (EGFR) mutation, history of chemotherapy, smoking status, use of statins, use of fibrates, use of dipeptidyl peptidase-4 (DPP-4) inhibitors, and use of metformin were examined as clinical factors. Statistical analyses were performed using the Kaplan-Meier method and Cox regression adjusted for risk factors and the tumor response of 67 patients was assessed. The patients had a median age of 67 years (range, 36-87 years), and 46 males and 21 females were enrolled; performance status 0/1 was 59. Cases were categorized as adenocarcinoma (n=41), squamous cell carcinoma (n=17) and other (n=9). A total of 13 patients (19.4%) had EGFR mutations. These clinical factors were not statistically significant in overall survival (OS). Clinical laboratory findings, complications and use of medical agents including antidiabetes mellitus or lipidemia were also analyzed. Statins exhibited statistical significance for response (P=0.02). Time-to-treatment failure (TTF) in statin-use group was not reached [95% confidence interval (CI): 1.9-not reached] and was 4.0 months (95% CI: 2.0-5.4) in the non-statin group (P=0.039). The median OS in statin-use group was not reached (95% CI: 8.7-not reached) and was 16.5 months (95% CI: 7.5-not reached) in the non-statin group (P=0.058). NSCLC patients previously treated with nivolumab who were administered statins exhibited an increased response rate and longer TTF. This response was not statistically significant in OS.

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 45years 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 5years (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.

Nonfunctioning adrenal incidentaloma: A novel predictive factor for metabolic syndrome.

Although metabolic syndrome has been studied in patients with autonomous cortisol secretion, there are limited data for those with nonfunctioning adrenal incidentaloma (NFAI). To assess metabolic syndrome frequency in NFAI patients and controls without adrenal adenoma according to World Health Organization (WHO), National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III), American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) and International Diabetes Federation (IDF) criteria. Retrospective and transversal study. Seventy-four NFAI and 90 controls were evaluated. NFAI diagnosis was established according to current guidelines. The control group was selected based on normal adrenal imaging examinations. Subjects were categorized by metabolic syndrome presence according to WHO, NCEP-ATP III, AACE/ACE and IDF. Age, gender, ethnicity, body mass index, smoking, menopause, statin and fibrate use were comparable between patients and controls. The frequency of prediabetes, dyslipidaemia and hypertension as well as waist circumference were significantly higher in the NFAI patients compared to the controls. The metabolic syndrome frequency in the NFAI group was significantly higher compared to the normal adrenal group: WHO: 69.2%×31.0% (P<0.001); NCEP-ATP III: 81.7%×44.9% (P<0.001); AACE/ACE: 77.1%×31.9% (P<0.001); IDF: 78.6%×45.5% (P<0.001). Logistic regression analysis showed that NFAI was a predictor of metabolic syndrome according to WHO (P=0.001), NCEP-ATP III (P=0.005) and AACE/ACE (P=0.007). Metabolic syndrome is frequently found in patients with NFAI, and this frequency is higher in NFAI patients than in those with normal adrenal imaging.