Dyslipidemia refers to the change in the normal levels of one or more lipid components in the bloodstream, which include triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Dyslipidemia represents a substantial source of danger for cardiovascular disease (CVD). Effectively managing dyslipidemia involves a thorough strategy that includes changing one\'s lifestyle and using medications that are specifically designed to target the complex processes involved in lipid metabolism. Lipid-lowering treatments play a crucial role in this approach, providing a wide range of medications that are developed to specifically target different components of dyslipidemia. Statins are the main drug among these medications. Other drugs that are used with statin or as monotherapy include fibrates, omega-3 fatty acids (OM3FAs), ezetimibe, bile acid sequestrants, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and bempedoic acid. Using the PubMed database, we reviewed the literature about dyslipidemia, drugs used for treating dyslipidemia, their efficacy parameters, and common adverse events. We also reviewed the international guidelines for treating dyslipidemia and discussed the future of lipid-lowering medications. More trials and experiments are still required to verify the effectiveness of many lipid-lowering drugs and to know their common adverse events to be able to manage them properly.

Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease characterized by high circulating low-density lipoprotein (LDL) cholesterol. High circulating LDL cholesterol in FH is due to dysfunctional LDL receptors, and is mainly expressed by hepatocytes. Affected patients rapidly develop atherosclerosis, potentially leading to myocardial infarction and death within the third decade of life if left untreated. Here, we introduce the disease pathogenesis and available treatment options. We highlight different possible targets of therapeutic intervention. We then review different gene therapy strategies currently under development, which may become novel therapeutic options in the future, and discuss their advantages and disadvantages. Finally, we briefly outline the potential applications of some of these strategies for the more common acquired hypercholesterolemia disease.

UNASSIGNED: The relationship between blood lipids, lipid-modifying medications, and cancer risk has been under investigation for some time. Recent studies suggest that lipid-lowering medications might influence melanoma outcomes, though findings remain controversial. Our study aims to clarify the potential causal relationship between lipid-lowering drugs commonly used and melanoma incidence through a comprehensive Mendelian randomization (MR) analysis.
UNASSIGNED: Genetic variations within an LDL-related drug target gene (LDL-cholesterol from a genome-wide association study) served as proxies for exposure to lipid-lowering drugs. We conducted a two-sample Mendelian randomization analysis using inverse variance weighting (IVW), MR-Egger, and weighted median approaches. The MR-PRESSO test and pleiotropy_test were utilized to identify and adjust for horizontal pleiotropy. Stability and reliability of the Mendelian randomization findings were assessed using the leave-one-out method, Cochran\'s Q test, and funnel plot analysis. Odds ratios (OR) were employed to evaluate the causal relationship between genetic proxies of lipid-lowering drugs and melanoma risk.
UNASSIGNED: IVW analysis revealed that HMGCR gene expression is linked to a decreased risk of melanoma [OR: 0.624(0.439-0.888); p = 0.008]. Conversely, PCSK9 gene expression is tied to an elevated risk of melanoma [OR: 1.233(1.026-1.484); p = 0.025]. No significant association was observed between NPC1L1 and melanoma.
UNASSIGNED: HMGCR inhibitors (statins) may increase melanoma risk, while PCSK9 inhibitors (evolocumab, alirocumab) could potentially decrease melanoma risk.

BACKGROUND: Little is known about the benefits of lipid-lowering medications in those age ≥ 75 years. We assessed the effect of lipid-lowering medications on progression to severe atherosclerosis in patients age > 75.
METHODS: Data was retrospectively obtained from the Stroke Prevention & Atherosclerosis Research Centre, Canada. Atherosclerosis burden was measured as carotid total plaque area (TPA), a powerful predictor of cardiovascular risk. Survival time free of severe atherosclerosis (SFSA) was defined as the period when TPA remained <1.19 cm2. Kaplan-Meier, multiple Cox proportional hazard and hierarchical mixed-effect models were used to determine the effects of lipid-lowering medications on progression to severe atherosclerosis.
RESULTS: In total 1404 cases (mean age 81 ± 4 years; women 52%) were included. Those taking lipid-lowering medications were more likely to have a history of diabetes and a higher burden of atherosclerosis at baseline. In Kaplan-Meier analysis, the SFSA was significantly longer in those receiving lipid-lowering therapy. In multivariable-adjusted analyses, those not receiving lipid lowering therapy (irrespective of their vascular disease at baseline) were more likely to have TPA > 1.19 cm2 (hazard ratio (HR) = 1.37, 95% confidence interval (CI): 1.09,0.71). Similar findings were observed in mixed effects models when plaque progression was defined as any change >0.05 cm2 per year (odds ratio (OR):2.17, 95% CI:1.38,3.57).
CONCLUSIONS: Lipid-lowering therapy is effective in controlling the burden of atherosclerosis among older adults with and without vascular disease. The measurement of plaque burden can guide selection and follow-up of those who may benefit from treatment.

UNASSIGNED: Previous research has yielded conflicting results on the link between epilepsy risk and lipid-lowering medications. The aim of this study is to determine whether the risk of epilepsy outcomes is causally related to lipid-lowering medications predicted by genetics.
UNASSIGNED: We used genetic instruments as proxies to the exposure of lipid-lowering drugs, employing variants within or near genes targeted by these drugs and associated with low-density lipoprotein cholesterol (LDL cholesterol) from a genome-wide association study. These variants served as controlling factors. Through drug target Mendelian randomization, we systematically assessed the impact of lipid-lowering medications, including HMG-CoA reductase (HMGCR) inhibitors, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and Niemann-Pick C1-like 1 (NPC1L1) inhibitors, on epilepsy.
UNASSIGNED: The analysis demonstrated that a higher expression of HMGCR was associated with an elevated risk of various types of epilepsy, including all types (OR = 1.17, 95% CI:1.03 to 1.32, p = 0.01), focal epilepsy (OR = 1.24, 95% CI:1.08 to 1.43, p = 0.003), and focal epilepsy documented with lesions other than hippocampal sclerosis (OR = 1.05, 95% CI: 1.01 to 1.10, p = 0.02). The risk of juvenile absence epilepsy (JAE) was also associated with higher expression of PCSK9 (OR = 1.06, 95% CI: 1.02 to 1.09, p = 0.002). For other relationships, there was no reliable supporting data available.
UNASSIGNED: The drug target MR investigation suggests a possible link between reduced epilepsy vulnerability and HMGCR and PCSK9 inhibition.

BACKGROUND: We aimed to estimate the trends in dispensing rate and the spectrum of all state-funded lipid-lowering medications (LLMs) in Latvia over a decade.
METHODS: Using data from the National Health Service of the Republic of Latvia, we retrospectively analyzed all dispensed LLM-containing drug units in a ten-year period from 2012 to 2021.
RESULTS: In Latvia, 318.2 million oral and 994 subcutaneous units of LLMs were dispensed over a decade. Statins were the most dispensed LLMs (94.5%), and their use doubled from 19.7 to 43.5 million units. The proportion of high-intensity statins increased from 31.3% to 45.2%. The dispensing rate of ezetimibe increased from 184.7 thousand to 4.8 million. The share of fixed-dose statin combinations with ezetimibe grew from 0.2% to 10.0% among all statins and from 22.2% to 90.9% among all ezetimibe units. Statin use for primary and secondary prevention increased from 7.0 to 19.9 million and from 12.8 to 23.6 million units, respectively.
CONCLUSIONS: The dispensing rate of statins doubled, and the use of ezetimibe increased more than 25 times in Latvia over a decade. The proportion of high-intensity statins increased from one third to almost half of all statins. Fixed-dose statin combinations with ezetimibe became frequently used.

BACKGROUND: Phramongkutklao Hospital is one of the largest military hospitals in Thailand. Beginning in 2016, an institutional policy was implemented in which medication prescription length was increased from 30 to 90 days. However, there have been no formal investigations into how this policy has impacted medication adherence among patients in hospitals. As such, this study evaluated how prescription length impacted medication adherence among dyslipidemia and type-2 diabetes patients who were treated at Phramongkutklao Hospital.
METHODS: This pre-post implementation study compared patients who received prescription lengths of 30 and 90 days based on information recorded in the hospital database between 2014 and 2017. Therein, we used the medication possession ratio (MPR) to estimate patient adherence. Focusing on patients with universal coverage insurance, we employed the difference-in-difference method to examine changes in adherence from before and after policy implementation, then conducted a logistic regression to test for associations between the predictors and adherence.
RESULTS: We analyzed data from a total of 2,046 patients, with equal amounts of 1,023 placed into the control group (no change to 90-day prescription length) and intervention group (change from 30 to 90-day prescription length). First, we found that increased prescription length was associated with 4% and 5% higher MPRs among dyslipidemia and diabetes patients in the intervention group, respectively. Second, we found that medication adherence was correlated with sex, comorbidities, history of hospitalization, and the number of prescribed medications.
CONCLUSIONS: Increasing the prescription length from 30 to 90 days improved medication adherence in both the dyslipidemia and type-2 diabetes patients. This shows that the policy change was successful for patients in the hospital considered for this study.

Aging is a major risk factor for many chronic diseases. This study aimed to examine the effects of antihypertensive, lipid-lowering, and antidiabetic drugs on biological aging. We included 672 participants and 2746 repeated measurements from the Swedish Adoption/Twin Study of Aging. Self-reported medicine uses were categorized into antidiabetic, antihypertensive, and lipid-lowering drugs. A total of 12 biomarkers for biological aging (BA biomarkers) were included as outcomes. Conditional generalized estimating equations were applied conditioning on individuals to estimate the drug effect on BA biomarker level within the same person when using or not using the drug. Chronological age, body mass index, smoking status, number of multiple medication uses, blood pressure, blood glucose level, and apoB/apoA ratio were adjusted for as covariates in the model. Overall, using antihypertensive drugs was associated with a decrease in one DNA-methylation age (PCGrimAge: beta = - 0.39, 95%CI = - 0.67 to - 0.12). When looking into drug subcategories, calcium channel blockers (CCBs) were associated with a decrease in several DNA-methylation ages (PCHorvathAge beta = - 1.28, 95%CI = - 2.34 to - 0.21; PCSkin&bloodAge beta = - 1.34, 95%CI = - 2.61 to - 0.07; PCPhenoAge beta = - 1.74, 95%CI = - 2.58 to - 0.89; PCGrimAge beta = - 0.57, 95%CI = - 0.96 to - 0.17) and in functional biological ages (functional age index beta = - 2.18, 95%CI = - 3.65 to - 0.71; frailty index beta = - 1.31, 95%CI = - 2.43 to - 0.18). However, the results within other drug subcategories were inconsistent. Calcium channel blockers may decrease biological aging captured by the BA biomarkers measured at epigenetic and functional level. Future studies are warranted to confirm these effects and understand the underlying biological mechanisms.

MK-0616 is an oral macrocyclic peptide inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) in development for the treatment of hypercholesterolemia.
This Phase 2b, randomized, double-blind, placebo-controlled, multicenter trial aimed to evaluate the efficacy and safety of MK-0616 in participants with hypercholesterolemia.
This trial was planned to include 375 adult participants with a wide range of atherosclerotic cardiovascular disease risk. Participants were assigned randomly (1:1:1:1:1 ratio) to MK-0616 (6, 12, 18, or 30 mg once daily) or matching placebo. The primary endpoints included percentage change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 8 and the proportion of participants with adverse events (AEs) and study intervention discontinuations due to AEs; participants were monitored for AEs for an additional 8 weeks after the 8-week treatment period.
Of the 381 participants randomized, 49% were female, and the median age was 62 years. Among 380 treated participants, all doses of MK-0616 demonstrated statistically significant (P < 0.001) differences in least squares mean percentage change in LDL-C from baseline to Week 8 vs placebo: -41.2% (6 mg), -55.7% (12 mg), -59.1% (18 mg), and -60.9% (30 mg). AEs occurred in a similar proportion of participants in the MK-0616 arms (39.5% to 43.4%) as placebo (44.0%). Discontinuations due to AEs occurred in 2 or fewer participants in any treatment group.
MK-0616 demonstrated statistically significant and robust, dose-dependent placebo-adjusted reductions in LDL-C at Week 8 of up to 60.9% from baseline and was well tolerated during 8 weeks of treatment and an additional 8 weeks of follow-up. (A Study of the Efficacy and Safety of MK-0616 [Oral PCSK9 Inhibitor] in Adults With Hypercholesterolemia [MK-0616-008]; NCT05261126).

OBJECTIVE: Patients with familial hypercholesterolemia (FH) are known to have higher exposure to coronary risk than those without FH with similar low-density lipoprotein cholesterol (LDL-C) level. Lipid-lowering medications (LLMs) are the mainstay treatments to lower the risk of premature coronary artery disease in patients with hypercholesterolemia. However, the LLM prescription pattern and its effectiveness among Malaysian patients with FH are not yet reported. The aim of this study was to report the LLM prescribing pattern and its effectiveness in lowering LDL-C level among Malaysian patients with FH treated in specialist hospitals.
METHODS: Subjects were recruited from lipid and cardiac specialist hospitals. FH was clinically diagnosed using the Dutch Lipid Clinic Network Criteria. Patients\' medical history was recorded using a standardized questionnaire. LLM prescription history and baseline LDL-C were acquired from the hospitals\' database. Blood samples were acquired for the latest lipid profile assay.
RESULTS: A total of 206 patients with FH were recruited. Almost all of them were on LLMs (97.6%). Only 2.9% and 7.8% of the patients achieved the target LDL-C of ＜1.4 and ＜1.8 mmol/L, respectively. The majority of patients who achieved the target LDL-C were prescribed with statin-ezetimibe combination medications and high-intensity or moderate-intensity statins. All patients who were prescribed with ezetimibe monotherapy did not achieve the target LDL-C.
CONCLUSIONS: The majority of Malaysian patients with FH received LLMs, but only a small fraction achieved the therapeutic target LDL-C level. Further investigation has to be conducted to identify the cause of the suboptimal treatment target attainment, be it the factors of patients or the prescription practice.