OBJECTIVE: Previous studies implied that different types of statins may pose divergent impacts on the risk of glaucoma onset. This study aimed to comprehensively evaluate the effects of various statins on the risk of glaucoma occurrence.
METHODS: PubMed, Cochrane CENTRAL, Embase, and Web of Science were searched from February 1994 to February 2024. We included studies that investigated the effects of various types of statins, fibrates, ezetimibe, cholestyramine, niacin, PCSK9 inhibitors, omega-3 fatty acids, and any cholesterol-lowering medications on glaucoma onset or progression. The revised Cochrane risk-of-bias tool for randomized trials (RoB 2.0) and the Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-1) tool were used to assess the quality of randomized controlled trials (RCTs) and non-RCTs, respectively. The frequentist network meta-analysis framework was utilized to evaluate the comparative effectiveness, with the random effects model applied.
RESULTS: This network meta-analysis comprised 12 studies, encompassing 262,217 individuals and including cholesterol-lowering medications such as statins, fibrates, ezetimibe, cholestyramine, niacin, and omega-3 fatty acids. Our findings demonstrate that comparing to the placebo, rosuvastatin (risk ratio [RR], 1.23; 95% confidence interval [CI], 1.03 to 1.46), simvastatin (RR, 1.21; 95% CI, 1.02 to 1.43), and pravastatin (RR, 1.20; 95% CI, 1.01 to 1.43) increased the risk of glaucoma onset with statistical significance.
CONCLUSIONS: Rosuvastatin, simvastatin, and pravastatin were each associated with a significantly increased risk of glaucoma onset. We advise medical practitioners to exercise caution when prescribing these specific statins for patients who are at risk of developing glaucoma.
CONCLUSIONS: What is known Previous studies have suggested a link between statins and the risk of developing glaucoma. However, there is still ongoing debate regarding the specific effects of each type of statin on the onset of glaucoma. What is new This network meta-analysis comprehensively evaluated the effects of various statins on the risk of glaucoma onset. Rosuvastatin, simvastatin, and pravastatin were associated with a significantly increased risk of glaucoma onset.

OBJECTIVE: 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.
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.
CONCLUSIONS: 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.

BACKGROUND: Statins and fibrates are two lipid-lowering drugs used in patients with dyslipidemia. This systematic review and meta-analysis were conducted to determine the magnitude of the effect of statin and fibrate therapy on serum homocysteine levels.
METHODS: A search was undertaken of the PubMed, Scopus, Web of Science, Embase, and Google Scholar electronic databases up to 15 July 2022. Primary endpoints focused on plasma homocysteine levels. Data were quantitatively analyzed using fixed or random- effect models, as appropriate. Subgroup analyses were conducted based on the drugs and hydrophilic-lipophilic balance of statins.
RESULTS: After screening 1134 papers, 52 studies with a total of 20651 participants were included in the meta-analysis. The analysis showed a significant decrease in plasma homocysteine levels after statin therapy (WMD: -1.388 μmol/L, 95% CI: [-2.184, -0.592], p = 0.001; I2 = 95%). However, fibrate therapy significantly increased plasma homocysteine levels (WMD: 3.459 μmol/L, 95% CI: [2.849, 4.069], p < 0.001; I2 = 98%). The effect of atorvastatin and simvastatin depended on the dose and duration of treatment (atorvastatin [coefficient: 0.075 [0.0132, 0.137]; p = 0.017, coefficient: 0.103 [0.004, 0.202]; p = 0.040, respectively] and simvastatin [coefficient: -0.047 [-0.063, -0.031]; p < 0.001, coefficient: 0.046 [0.016, 0.078]; p = 0.004]), whereas the effect of fenofibrate persisted over time (coefficient: 0.007 [-0.011, 0.026]; p = 0.442) and was not altered by a change in dosage (coefficient: -0.004 [-0.031, 0.024]; p = 0.798). In addition, the greater homocysteine- lowering effect of statins was associated with higher baseline plasma homocysteine concentrations (coefficient: -0.224 [-0.340, -0.109]; p < 0.001).
CONCLUSIONS: Fibrates significantly increased homocysteine levels, whereas statins significantly decreased them.

Coronavirus disease-2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multiorgan manifestations. Lipid-modulating agents may be useful in treating patients with COVID-19. These agents may inhibit viral entry by lipid raft disruption or ameliorate the inflammatory response and endothelial activation. In addition, dyslipidemia with lower high-density lipoprotein cholesterol and higher triglyceride levels portend worse outcomes in patients with COVID-19. Upon a systematic search, 40 randomized controlled trials (RCTs) with lipid-modulating agents were identified, including 17 statin trials, 14 omega-3 fatty acids RCTs, 3 fibrate RCTs, 5 niacin RCTs, and 1 dalcetrapib RCT for the management or prevention of COVID-19. From these 40 RCTs, only 2 have reported preliminary results, and most others are ongoing. This paper summarizes the ongoing or completed RCTs of lipid-modulating agents in COVID-19 and the implications of these trials for patient management.

Using a meta-analysis of randomized controlled trials (RCTs), this study aimed to investigate the efficacy and safety of pemafibrate, a novel selective peroxisome proliferator-activated receptor α modulator, in patients with dyslipidemia.
A search was performed using the MEDLINE, Cochrane Controlled Trials Registry, and ClinicalTrials.gov databases. We decided to employ RCTs to evaluate the effects of pemafibrate on lipid and glucose metabolism-related parameters in patients with dyslipidemia. For statistical analysis, standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CIs) were calculated using the random effect model.
Our search yielded seven RCTs (with a total of 1623 patients) that satisfied the eligibility criteria of this study; hence, those studies were incorporated into this meta-analysis. The triglyceride concentration significantly decreased in the pemafibrate group (SMD, - 1.38; 95% CI, - 1.63 to - 1.12; P < 0.001) than in the placebo group, with a reduction effect similar to that exhibited by fenofibrate. Compared with the placebo group, the pemafibrate group also showed improvements in high-density and non-high-density lipoprotein cholesterol levels as well as in homeostasis model assessment for insulin resistance. Furthermore, the pemafibrate group showed a significant decrease in hepatobiliary enzyme activity compared with the placebo and fenofibrate groups; and, total adverse events (AEs) were significantly lower in the pemafibrate group than in the fenofibrate group (OR, 0.60; 95% CI, 0.49-0.73; P < 0.001). In contrast, the low-density lipoprotein cholesterol level was significantly higher in the pemafibrate group than in the placebo (P = 0.006) and fenofibrate (P < 0.001) groups.
The lipid profile significantly improved in the pemafibrate group than in the placebo group. In addition to the pemafibrate group having an improved lipid profile, which was comparable with that of the fenofibrate group, the AEs were significantly lower than in the fenofibrate group and an improvement in hepatobiliary enzyme activity was also recognized. However, we believe that actual clinical data as well as long-term efficacy and safety need to be investigated in the future.

This meta-analysis of randomised placebo-controlled clinical trials aimed to assess the effect of fenofibrate on apolipoprotein C-III (apo C-III), a key regulator of triglyceride metabolism.
Randomised placebo-controlled trials investigating the impact of fenofibrate treatment on apo C-III levels were searched in PubMed-Medline, Scopus, Web of Science and Google Scholar databases from inception to 18 August 2017. Quantitative data synthesis was determined by a random-effects model and generic inverse variance method. Sensitivity analysis was conducted using the leave-one-out method. A weighted random-effects meta-regression was performed to evaluate glycaemic parameter confounders.
Meta-analysis of 10 clinical trials involving 477 subjects showed fenofibrate therapy decreased apo C-III levels (weighted mean difference (WMD) -4.78 mg/dL, 95% CI -6.95 to -2.61, p<0.001; I266.87%). Subgroup analysis showed that fenofibrate reduced plasma apo C-III concentrations in subgroups of trials with treatment durations of either <12 weeks (WMD -4.50 mg/dL, p=0.001) or ≥12 weeks (WMD: -4.73 mg/dL, p=0.009) and doses of fenofibrate <200 mg/day (WMD -6.33 mg/dL, p<0.001) and >200 mg/day (p=0.006), with no significant difference between the subgroups.
This meta-analysis found that fenofibrate therapy significantly decreases apo C-III levels, an effect evident with both short-term treatment and doses less than 200 mg/day.

Cardiovascular disease is the leading cause of death and morbidity in people with chronic kidney disease (CKD) making measures to modify cardiovascular risk a clinical priority. The relationship between risk factors and cardiovascular outcomes is often substantially different in people with CKD compared with the general population, leading to uncertainty around pathophysiological mechanisms and the validity of generalizations from the general population. Furthermore, published reports of subgroup analyses from clinical trials have suggested that a range of interventions may have different effects in people with kidney disease compared with those with normal kidney function. There is a relative scarcity of randomized controlled trials (RCTs) conducted in CKD populations, and most such trials are small and underpowered. As a result, evidence to support cardiovascular risk modification measures for people with CKD is largely derived from small trials and post hoc analyses of RCTs conducted in the general population. In this review, we examine the available RCT evidence on interventions aimed at preventing cardiovascular events in people with kidney disease to identify beneficial treatments as well as current gaps in knowledge that should be a priority for future research.