Fibrates and statins lead worldwide prescriptions of lipid-lowering drugs, whose consumption is increasing considerably due to the growing incidence of dyslipidemias, particularly in high-income areas. Consequently, these chemicals are frequently found in aquatic environments, usually closer to highly urbanized and populated areas, reaching the water systems primarily through waste-water treatment plant (WWTP) effluents. Despite that, the knowledge regarding the effects caused by fibrates and statins in fish, namely in liver lipid metabolism and blood-related parameters, is still very limited. There is yet no standardized fish model for testing the effects of those drugs. However, experimental evidence suggests that the mechanisms of action (MoA) of fibrates and statins are fairly similar to those observed in humans, which makes these aquatic organisms viable alternatives for toxicological and mechanistic studies. This graphical review serves as a state point regarding the potential use of fish as a model for the study of hypolipidemic compounds, addressing (I) the current state of aquatic pollution caused by statins and fibrates, (II) the experimental designs used in the literature to assess effects on fish, (III) the liver metabolism and blood effects caused by exposure to fibrates and statins, as well as (IV) the MoA of both drugs. It further focuses on the current and future benefits of establishing a standardized fish model(s) for testing hypolipidemic drugs.

To evaluate recent clinical trials focusing on patients with hypertriglyceridemia.
Randomized clinical trials have recently been undertaken in hypertriglyceridemic patients to determine whether effective reductions in triglycerides would improve cardiovascular disease (CVD) outcomes. However, the fibric acid derivative, pemafibrate, failed to reduce cardiovascular events despite significant reductions (~ 25-35%) in triglyceride levels and despite background statin therapy. In contrast, icosapent ethyl, a highly purified omega-3 fatty acid was previously shown to reduce CVD events in hypertriglyceridemic patients, despite more modest reductions (~ 20%) in triglyceride levels in statin treated patients. The divergent results obtained in patients with hypertriglyceridemia (HTG), a group at particularly high risk of CVD, especially when coupled with other risk factors, indicates that triglyceride lowering in of itself is insufficient to offset CVD risk. Rather, the effectiveness of therapy in this high-risk cohort may be the result of the suppression of the inherent atherogenic properties associated with HTG.

OBJECTIVE: The purpose of this study is to evaluate the association between lipid-lowering agent use and the risks of diagnosed dry eye disease (DED).
METHODS: This retrospective, case-control study included 780 786 patients who received lipid-lowering agents in 2002-2016, of which 17 409 were newly diagnosed with DED during a ≥2-year follow-up period. These patients were matched 1:4 with control participants for age, sex, and comorbidities. Separate odds ratios (OR) were calculated for DED and each of statin and fibrate use.
RESULTS: Statin users had significantly higher odds of DED (adjusted OR = 1.12; 95% confidence interval (CI) = 1.08-1.16, p < 0.0001) than nonusers. Fibrate users did not show higher odds of DED than nonusers (adjusted OR = 1.04; 95% CI = 0.99-1.10, p = 0.125). The lipophilic statin users did not show higher odds of DED compared with the hydrophilic statin users (adjusted OR = 0.99, 95% CI = 0.93-1.06, p = 0.729). Among statin users, the odds of DED did not differ significantly between patients receiving statin therapy for >180 days vs. ≤90 days or patients receiving statin therapy for 91-180 days vs. ≤90 days (adjusted OR = 1.00, p = 0.922; adjusted OR = 0.94, p = 0.541, respectively). The odds of DED were not statistically different among patients receiving low-intensity, moderate-intensity, and high-intensity of statin therapy.
CONCLUSIONS: Patients receiving statin therapy had a higher DED risk than patients not receiving statin therapy. The type of statin, the duration, and the intensity of statin use were not significantly associated with DED risks. Further studies are required to identify the relevant factors related to DED risks with statin.

UNASSIGNED: Although a recent study reported that fibrates are associated with a low risk of cardiovascular (CV) death and can postpone the need for long-term hemodialysis in patients with advanced chronic kidney disease (CKD), little is known regarding whether the CV protective effects of fibrates extend to patients with end-stage renal disease (ESRD). The present study compared CV outcomes and mortality among patients with ESRD treated with fibrates, statins, neither, or their combination.
UNASSIGNED: This cohort study extracted data from Taiwan\'s National Health Insurance Research Database (NHIRD). Adult patients with ESRD and hyperlipidemia were identified and categorized into four groups (fibrate, statin, combination, and non-user groups) according to their use of different lipid-lowering therapies within 3 months prior to the commencement of permanent dialysis. Inverse probability of treatment weighting was used to balance the baseline characteristics of the groups. The follow-up outcomes were all-cause mortality, CV death, and major adverse cardiac and cerebrovascular events (MACCEs).
UNASSIGNED: Compared with the non-user and statin groups, the fibrate group did not exhibit significantly lower risks of all-cause mortality [fibrate vs. non-user: hazard ratio (HR), 0.97; 95% confidence interval (CI), 0.92-1.03; statin vs. fibrate: HR, 0.95; 95% CI, 0.90-1.01], CV death (fibrate vs. non-user: HR, 0.97; 95% CI, 0.90-1.05; statin vs. fibrate: HR, 0.97; 95% CI, 0.90-1.06), and MACCEs (fibrate vs. non-user: HR, 1.03; 95% CI, 0.96-1.10; statin vs. fibrate: HR, 0.94; 95% CI, 0.87-1.004). The combination of fibrates and statins (specifically moderate- to high-potency statins) did not result in lower risks of all-cause mortality, CV death, or MACCEs compared with statins alone.
UNASSIGNED: In patients with ESRD, the use of fibrates might be not associated with reduced mortality or CV risks, regardless of whether they are used alone or in combination with statins.

Hypertriglyceridemia (HTG) is known as the third most common cause of acute pancreatitis (AP).
To study the prevalence and outcomes of HTG-AP as well as the quality of the follow-up post HTG-AP hospitalization in Canada.
This retrospective multicenter study was performed in patients admitted with AP (ICD 10 code K85) in quaternary care hospitals between 2012 and 2018. For every case of HTG-AP (TG ≥ 5.6 mmol/L on admission), two controls of biliary-AP were selected and matched for sex and age at the time of admission.
Out of 1490 admitted AP patients, 40 (3%) had HTG-AP. The average TG concentration was higher in patients admitted to the ICU compared to those who were not (27.34 mmol/L vs 13.02 mmol/L). Compared to biliary-AP group, the HTG-AP patients had more frequent severe Balthazar grade (45% vs 25%) with longer duration of hospitalisation (nine versus five days) and more frequent ICU admission (38% vs 8%). Furthermore, only 35% of HTG-AP patients were referred to specialized clinics and 42.5% were left with no follow-up. Only 17% of newly discovered HTG-AP patients were started on fibrate at discharge.
In comparison to biliary-AP, HTG-AP patients had a worse clinical course of pancreatitis. Furthermore, the quality of the follow-up post HTG-AP hospitalization was suboptimal. This could be explained by of the lack of knowledge of health care providers concerning the proper diagnosis and management of chylomicronemia syndromes, leading to this condition to be frequently missed or underdiagnosed.

BACKGROUND: The incidence of severe (S-HTG) and very severe hypertriglyceridemia (VS-HTG) among Canadians is unknown. This study aimed to determine the incidence, characteristics, predictors and care patterns for individuals with VS-HTG.
METHODS: Using linked administrative healthcare databases, a population-based cohort study of Ontario adults was conducted to determine incidence of new onset S-HTG (serum triglycerides (TG) > 10-20 mmol/L) and VS-HTG (TG > 20 mmol/L) between 2010 and 2015. Socio-demographic and clinical characteristics of those with VS-HTG were compared to those who had no measured TG value > 3 mmol/L. Univariable and multivariable logistic regression were used to determine predictors for VS-HTG. Healthcare patterns were evaluated for 2 years following first incidence of TG > 20 mmol/L.
RESULTS: Incidence of S-HTG and VS-HTG in Ontario was 0.16 and 0.027% among 10,766,770 adults ≥18 years and 0.25 and 0.041% among 7,040,865 adults with at least one measured TG, respectively. Predictors of VS-HTG included younger age [odds ratios (OR) 0.64/decade, 95% confidence intervals (CI) 0.62-0.66], male sex (OR 3.83; 95% CI 3.5-4.1), diabetes (OR 5.38; 95% CI 4.93-5.88), hypertension (OR 1.69; 95% CI 1.54-1.86), chronic liver disease (OR 1.71; 95% CI 1.48-1.97), alcohol abuse (OR 2.47; 95% CI 1.90-3.19), obesity (OR 1.49; 95% CI 1.13-1.98), and chronic kidney disease (OR 1.39; 95% CI 1.19-1.63).
CONCLUSIONS: The 5-year incidence of S-HTG and VS-HTG in Canadian adults was 1 in 400 and 1 in 2500, respectively. Males, those with diabetes, obese individuals and those with alcohol abuse are at highest risk for VS-HTG and may benefit from increased surveillance.

BACKGROUND: Statins are a potential treatment for venous thromboembolism (VTE) prophylaxis complementary to conventional anticoagulants without associated bleeding complications. This study aimed to compare pro-thrombotic activities of different classes of lipid-lowering drugs in an active comparator design and determine whether there is a relation between statin versus fibrate/niacin use and pro-coagulant factor outcomes.
METHODS: This is a cross-sectional analysis of participants from the Netherlands Epidemiology of Obesity study using any class of lipid-lowering drugs, including any types of statins, niacin, and fibrates. We performed linear regression analyses to determine fibrinogen, factor (F) VIII, FIX, and FXI activity in statins versus fibrate/niacin users and adjusted for age, sex, tobacco smoking, body mass index (BMI), hypertension, diabetes, and prevalent cardiovascular disease.
RESULTS: Among 1043 participants, the mean age was 58.4 ± 5.2 years, 61% were men, and the mean BMI was 31.3 ± 4.5 kg/m2. Clinical characteristics were balanced between statin and fibrate/niacin users. Statin users had lower mean FXI (18.3 IU/dL, 95% confidence interval (CI) 9.4 to 27.3) levels compared to fibrate/niacin users. The level of FVIII (15.8 IU/dL, 95% CI - 0.003 to 31.6), and FIX (11.3 IU/dL, 95% CI - 0.4 to 23.2) were lower in statin users than fibrate/niacin users with marginal statistical significance.
CONCLUSIONS: Current statin use was associated with lower plasma levels of FXI than fibrate/niacin use. The effects on coagulation factors may, in part, explain the benefit of statin therapy rendered in primary and secondary prevention of VTE.

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.

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.

Our aim was to assess whether long-term adherence to a Mediterranean diet (MedDiet) and leisure-time physical activity (LTPA) were associated with a lower initiation of cardiovascular drug use. We studied the association between cumulative average of MedDiet adherence and LTPA and the risk of cardiovascular drug initiation in older adults at high cardiovascular risk (PREvención con DIeta MEDiterránea trial participants) non-medicated at baseline: glucose-lowering drugs (n = 4437), antihypertensives (n = 2145), statins (n = 3977), fibrates (n = 6391), antiplatelets (n = 5760), vitamin K antagonists (n = 6877), antianginal drugs (n = 6837), and cardiac glycosides (n = 6954). One-point increases in MedDiet adherence were linearly associated with a decreased initiation of glucose-lowering (HR: 0.76 [0.71-0.80]), antihypertensive (HR: 0.79 [0.75-0.82]), statin (HR: 0.82 [0.78-0.85]), fibrate (HR: 0.78 [0.68-0.89]), antiplatelet (HR: 0.79 [0.75-0.83]), vitamin K antagonist (HR: 0.83 [0.74; 0.93]), antianginal (HR: 0.84 [0.74-0.96]), and cardiac glycoside therapy (HR: 0.69 [0.56-0.84]). LTPA was non-linearly related to a delayed initiation of glucose-lowering, antihypertensive, statin, fibrate, antiplatelet, antianginal, and cardiac glycoside therapy (minimum risk: 180-360 metabolic equivalents of task-min/day). Both combined were synergistically associated with a decreased onset of glucose-lowering drugs (p-interaction = 0.04), antihypertensive drugs (p-interaction < 0.001), vitamin K antagonists (p-interaction = 0.04), and cardiac glycosides (p-interaction = 0.01). Summarizing, sustained adherence to a MedDiet and LTPA were associated with lower risk of initiating cardiovascular-related medications.