Bempedoic acid 180mg / Ezetimibe 10mg tablets

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are significant health concerns affecting a large segment of the population and are known to be associated with adverse cardiovascular outcomes. As a result, various lipid-lowering medications are commonly employed in clinical practice to address the elevated cardiovascular risk in these patients. This systematic review summarizes the current evidence on emerging non-statin lipid-lowering therapies-ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, eicosapentaenoic acid (EPA), and bempedoic acid-and their effects on hepatic outcomes in patients with MASLD or MASH. A total of 18 studies involving 933 participants were deemed eligible for inclusion, along with 1 ongoing study included for descriptive analysis. Ezetimibe had the most extensive supporting evidence: 4 of 5 non-randomized studies reported improvements in hepatic enzyme levels, whereas 5 of 8 randomized controlled trials found no significant changes. Imaging results were mixed, with some studies demonstrating reduced hepatic fat content by magnetic resonance imaging or ultrasound, while others found no effect. Histological improvements were observed in non-randomized studies, but randomized trials showed no significant histopathological changes. Only 3 studies on PCSK9 inhibitors were included, of which 2 reported imaging-based improvements in hepatic steatosis. Two studies assessed EPA, but yielded conflicting results, and only 1 ongoing study has examined bempedoic acid. Although preclinical data suggest potential hepatic benefits of these therapies in MASLD, current clinical evidence remains limited and inconsistent, highlighting the need for larger, high-quality trials to establish definitive conclusions.

Abstract licence: CC BY-NC

Background and aimsAlthough the safety profile of lipid-lowering therapies (LLTs) is known, there are no comprehensive comparative assessments. We aimed to compare the risk of muscle-related events, diabetes, liver dysfunction, and cognitive disorders among LLTs through a network meta-analysis.Methods and resultsDatabases were searched from inception to May 2025. Eligible studies included adult patients, using statins, ezetimibe, PCSK9 monoclonal antibodies (PCSK9mAbs), inclisiran, bempedoic acid, or their combinations as intervention, reporting the information about any of the selected adverse events, a total sample size of ≥200 subjects, and had ≥1 month of intervention. Pooled estimates were assessed by fixed effects model within a frequentist setting. Pooled relative risks (RR) and their 95% confidence interval were estimated. A total of 303,397 subjects from 153 RCTs were included. Bempedoic acid ranked the lowest risk of myalgia (vs PCSK9mAbs, RR 0.80 [0.69, 0.93]). PCSK9mAbs were associated with lower incidence of creatine kinase (CK) elevation, diabetes, and liver dysfunction comparing to statins (statins vs PCSK9mAbs, RR 1.44 [1.14, 1.81], RR 1.13 [1.05, 1.22], and RR 1.38 [1.17, 1.62], respectively). In terms of muscle-related events and cognitive disorders, no significant risk differences were found among treatments and their combinations.ConclusionsPCSK9mAbs appear to have a more favourable safety profile regarding the risk of CK elevation, diabetes, and liver dysfunction. Bempedoic acid seem to be a better choice for subjects with high risk of myalgia. This information can be valuable when selecting therapy for specific patient subgroups at higher risk of certain adverse events.

Abstract licence: CC BY

AbstractHypercholesterolemia is associated with atherosclerotic cardiovascular disease (ASCVD), a leading cause of morbidity and mortality. Nonstatin lipid-lowering therapies (LLTs) such as ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs), bempedoic acid, and inclisiran have been recommended in clinical guidelines to treat patients with ASCVD and/or high cardiovascular (CV) risk having elevated low-density lipoprotein cholesterol (LDL-C) despite being treated with maximally tolerated doses (MTD) of statins. Our previously published network meta-analysis (NMA) 1 was updated in this study to evaluate comparative efficacy of nonstatin LLTs in reducing LDL-C among patients with ASCVD and/or high CV risk receiving MTD statins. The systematic literature review previously conducted to inform our NMA was updated through January 2023, wherein more recent clinical trials of nonstatin LLTs (ORION-15, ORION-18, and HUA TUO) and additional data on monthly dosing regimens for PCSK9 mAbs were included. The outcome of interest was percentage change in LDL-C at week 24. Random-effects Bayesian NMA was performed. Comparative efficacy was estimated as mean difference (MD) with 95% credible intervals (CrIs). A total of 20 trials were deemed relevant for the NMA. Consistent with the previous findings from our NMA, this study demonstrated that inclisiran provided superior efficacy in LDL-C lowering compared with ezetimibe and bempedoic acid (MD: -44.24 [95% CrI: -51.84 to -36.70]). This NMA further reaffirmed that inclisiran provided comparable LDL-C reduction versus alirocumab (MD: -1.93% [95% CrI: -8.56 to 4.20]) and evolocumab (MD: 2.00% [95% CrI: -4.58 to 8.60]) among patients with ASCVD and/or high CV risk on MTD statins.

Abstract licence: CC BY-NC-ND

BackgroundAnalyses of statin trials by the Cholesterol Treatment Trialists' Collaboration have suggested larger relative risk reduction (RRR) for major adverse cardiovascular events (MACE) per 1 mmol/L (38.7 mg/dL) low-density lipoprotein cholesterol (LDL-C) lowering in primary prevention than in secondary prevention. However, controversy remains about the value of LDL-C lowering in primary prevention.ObjectiveThis meta-analysis examined the relationship between LDL-C reduction and MACE risk in primary prevention with statin and nonstatin LDL-C-lowering therapies in cardiovascular outcomes trials (CVOTs).MethodsPubMed and Cochrane Central Register of Controlled Trials were searched from inception through August 26, 2025. The primary endpoint was the pooled RRR vs controls for 4-point composite MACE (coronary heart disease death, nonfatal myocardial infarction, fatal and nonfatal stroke, and coronary revascularization) per 1 mmol/L LDL-C lowering.ResultsEleven CVOTs of solely primary prevention participants (n = 74,466) and 3 in which >80% of participants were primary prevention (n = 24,071) were identified (11 statin, 1 bempedoic acid, 1 ezetimibe, 1 statin+ezetimibe). In 13 trials, the pooled mean difference between groups in LDL-C reduction was 1.00 mmol/L (95% CI: 0.82-1.18 mmol/L) with a pooled estimate of 30% (relative risk: 0.70; 95% CI: 0.67-0.74) RRR for 4-point MACE per 1 mmol/L LDL-C reduction vs control.ConclusionIn CVOTs of solely or predominantly primary prevention participants, each 1 mmol/L reduction in LDL-C was associated with a 30% RRR in 4-point MACE. These results strengthen the evidence and rationale for the benefits of LDL-C lowering in primary prevention.

Abstract licence: CC BY