Statin Intolerance Research Articles

Statin intolerance and the drucebo effect.

Hypercholesterolemia is a well-described risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins remain the cornerstone of therapy. Statin intolerance (SI) particularly statin associated muscle symptoms (SAMS) and inappropriate stopping of treatment is associated with increased cardiovascular risk. A significant proportion of reported SAMS relates to expectation of side effects and can be termed the 'negative drucebo effect'. Patients should be educated about SI, the negative drucebo effect, in addition to the benefits of adherence to the therapy when first prescribed a statin. The aim of this commentary is to discuss the issue of statin intolerance, the negative drucebo effect and to suggest some interventions that may be used to address this issue.

Therapeutic Monoclonal Antibodies for Metabolic Disorders: Major Advancements and Future Perspectives.

Globally, the prevalence of metabolic disorders is rising. Elevated low-density lipoprotein (LDL) cholesterol is a hallmark of familial hypercholesterolemia, one of the most prevalent hereditary metabolic disorders and another one is Diabetes mellitus (DM) that is more common globally, characterised by hyperglycemia with low insulin-directed glucose by target cells. It is still known that low-density lipoprotein cholesterol (LDL-C) increases the risk of cardiovascular disease (CVD). LDL-C levels are thought to be the main therapeutic objectives. The primary therapy for individuals with elevated cholesterol levels is the use of statins and other lipid lowering drugs like ezetimibe for hypercholesterolemia. Even after taking statin medication to the maximum extent possible, some individuals still have a sizable residual cardiovascular risk. To overcome this proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors-monoclonal antibodies (mAbs) are a novel class of systemic macromolecules that have enhanced LDL-C-lowering efficacy. Along with this other inhibitor are used like Angiopoeitin like 3 inhibitors. Research on both humans and animals has shown that anti-CD3 antibodies can correct autoimmune disorders likediabetes mellitus. Individuals diagnosed with familial hypercholesterolemia (FH) may need additional treatment options beyond statins, especially when facing challenges such as statin tolerance or the inability of even the highest statin doses to reach the desired target cholesterol level. Here is the summary of PCSK9, ANGPTL-3 and CD3 inhibitors and their detailed information. In this review we discuss the details of PCSK9, ANGPTL-3 and CD3 inhibitors and the current therapeutic interventions of using the monoclonal antibodies in case of the metabolic disorder. We further present the present studies and the future prospective of the same.

Interpretation of Chinese Expert Consensus on the Diagnosis and Management Strategy of Patients with Statin Intolerance: A guiding file for helping to lipid management for Chinese population.

It is well-known that elevated low-density lipoprotein cholesterol (LDL-C) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD), statins are cornerstone drugs for the cause-based treatment of ASCVD, which has created a new era for ASCVD therapy. However, statin intolerance is not clinically uncommon, which there are several issues with confusion and misunderstandings. Hence, a file named Chinese Expert Consensus on the Diagnosis and Management Strategy of Patients With Statin Intolerance, like a navigator, has recently been published written by a team of experts from the Cardiovascular Metabolic Medicine Professional Committee, Expert Committee of the National Center for Cardiovascular Diseases aiming to enhance the standardized clinical application of statins and improve the prevention and clinical outcome. In this article, author briefly summarized the key points of above consensus in order to helping to comprehending the content of the consensus suggestions.

Worsening of myasthenic symptoms associated with statins

Introduction/AimsThe common presentations of statin intolerance are muscle-specific symptoms. Although statins are one type of drug reported to cause myasthenic worsening, myasthenic worsening has not been recognized as statin intolerance. The purpose of the present study is to investigate in a large cohort the safety profiles of statins in patients with myasthenia gravis (MG). MethodsA total of 1710 consecutive patients with MG who visited sites associated with the Japan MG registry 2021 group between April and October 2021 were reviewed. Statin-associated myasthenic worsening was defined as worsening of any myasthenic symptoms on statin use and improvement of the symptom by stopping the statin or by undertaking additional treatment with patient and doctor confirmation. ResultsAmong the 400 patients who used statins, 8 (2%) patients experienced statin intolerance and 6 (1.5%) patients experienced myasthenic worsening. No patients developed MG on the statin. Ptosis was a main symptom of myasthenic worsening in 4 (67%) patients. Atorvastatin was used in all patients with statin-associated myasthenic worsening. The symptoms of statin intolerance and statin-associated myasthenic worsening were improved within 2 months and 3 months, respectively, in all patients by cessation of statin use. DiscussionRegarding statin-associated myasthenic worsening, prevalence was low, and severity was mild; with cessation of statin use, symptoms improved within a few months, and outcomes were generally good. Although statins can be used in MG patients with little concern, statin-associated myasthenic worsening should be noted in addition to the classical statin intolerance associated with statin use.

Efficacy and Safety of Bempedoic Acid in Patients with High Cardiovascular Risk: An Update.

Statins play a significant role in the prevention of cardiovascular (CV) diseases (CVDs); however, non-adherence with statin treatment or statin intolerance (mainly attributed to muscleassociated side effects) is not uncommon. New agents such as bempedoic acid (BA) can provide more treatment options. BA is administered orally, once daily, at a dose of 180 mg in current clinical practice. It can decrease circulating low-density lipoprotein cholesterol (LDL-C) levels by nearly 30% as monotherapy or by 20% as an add-on to statins. CV outcome studies have shown that BA decreases major adverse CV event risk in patients with established CVD or high CV risk by 13%. When patients with high CV risk were analyzed alone, the risk reduction was 30%. Its side effects include a rise in serum uric acid levels and liver enzyme activity, whereas it does not increase diabetes risk as statins do. BA can be used as adjunctive therapy to statins in patients at high CV risk in whom lipid targets cannot be achieved or as an alternative to statins in patients with statin intolerance.

Early Management of Blood Lipid Levels with Non-Statin Lipid-Lowering Drugs in Acute Coronary Syndrome: A Mini Review.

Acute coronary syndrome (ACS) remains a major cause of morbidity and mortality, despite many improvements in its prevention and management. Lipid management is an important aspect of secondary prevention after ACS. Previous studies indicate that the early use of intensive statin therapy in patients with ACS may alleviate the risk of recurrent cardiovascular events and mortality. However, many patients do not reach the target low-density lipoprotein cholesterol (LDL-C) level of < 55mg/dL with statin monotherapy, and muscle-related adverse effects caused by statins hinder adherence to treatment. Novel non-statin agents are recommended for patients who cannot achieve the target LDL-C levels with high-intensity statin therapy and those with statin intolerance. The combination of statins and non-statins may synergistically affect intensively lowering LDL-C through different mechanisms, which could lead to better cardiovascular outcomes than statin monotherapy. However, it remains uncertain whether the early use of combination lipid-lowering therapy is more beneficial. The present review summarizes the benefits of intensive statin monotherapy and their early combination with non-statin medications including ezetimibe, PCSK9 inhibitors, inclisiran, and bempedoic acid (BDA) in the management of ACS.

PCSK9 inhibitor added to high-intensity statin therapy to prevent cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention: a randomized, double- blind, placebo-controlled, multicenter SHAWN study

BackgroundIt is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. MethodsThis study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1,212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at 1-year follow-up between 2 groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. ConclusionThe SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.

Effect of Coenzyme Q10 on Physical Performance in Older Adults with Statin-Associated Asthenia: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

Background: Available evidence from randomized clinical trials is contrasting and definitely inconclusive in determining whether or not CoQ10 dietary supplementation is advisable in patients with statin intolerance or poor statin tolerability. Methods: This randomized, double-blind, placebo-controlled clinical study aimed at investigating the effect of chronic dietary supplementation with coenzyme Q10 (CoQ10) phytosome on physical performance in older adults with a ≥3-month history of statin-associated asthenia. The study's participants were randomized to either a placebo or 300 mg daily CoQ10 phytosome (equivalent to 60 mg CoQ10; Ubiqsome®, Indena SpA, Milan, Italy). Asthenia, handgrip strength (HGs), 2-min step test (2MST), and 1-min sit-to-stand (STS) repetitions were assessed at baseline and at 8-week follow-up. Results: After the first 4 weeks of dietary supplementation, individuals taking CoQ10 phytosome showed a greater improvement in asthenia compared to the placebo group (p < 0.05). Even more significantly, at 8-week follow-up, participants receiving CoQ10 showed substantial improvements in asthenia (-30.0 ± 20.0%), HGS (+29.8 ± 3.6%), 2MST (+11.1 ± 1.8%), and 1-min STS repetitions (+36.4 ± 3.9%) compared to both baseline and placebo (p < 0.05). Conclusions: According to our findings, chronic dietary supplementation with CoQ10 phytosome significantly enhances physical performance in older adults with statin-associated asthenia. This could have relevant implications for improving the compliance of older adults with statin treatment.

Letter by Andreotti et al Regarding Article, “Inflammation and Cholesterol as Predictors of Cardiovascular Events Among 13 970 Contemporary High-Risk Patients With Statin Intolerance”

Letter by Andreotti et al Regarding Article, “Inflammation and Cholesterol as Predictors of Cardiovascular Events Among 13 970 Contemporary High-Risk Patients With Statin Intolerance”

Breaking down statin myopathy: understanding the self-limited and autoimmune subtypes.

Statins are widely used crucial drugs for the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Although generally well tolerated, statin intolerance can unfortunately limit statin use, with statin-associated muscle symptoms (SAMS) being the most common side effect associated with its discontinuation. Statin intolerance is an inability to tolerate a dose of statin required to sufficiently reduce an individual's cardiovascular risk, limiting the effective treatment of patients at risk of or with cardiovascular disease (CVD). Statin myopathy is a broad entity encompassing self-limited/toxic and autoimmune aetiologies. As statins are a mainstay of therapy in those with or at risk for CVD and offer a mortality benefit, it is critical to determine whether one's symptoms are truly statin-associated before discontinuing the drug. This review article aims to provide an update on the epidemiology, pathophysiology, clinical features, diagnosis, evaluation and management of statin myopathy and to elucidate key differences between autoimmune and self-limited types.

A Systematic Review and Meta-Analysis on the Role of Bempedoic Acid in Cardiovascular Outcomes for Patients With Statin Intolerance.

Atherosclerosis, a multifaceted pathogenic process affecting the arteries and aorta, poses a significant threat because of its potential to impede or entirely obstruct blood flow by narrowing blood vessels. This intricate progression involves various factors such as dyslipidemia, immunological responses, inflammation, and endothelial dysfunction. The initial phase manifests as the formation of fatty streaks, considered a pivotal hallmark in the inception of atherosclerotic plaques, a process that can commence as early as childhood. Over time, this process evolves, characterized by the thickening of the arterial inner layer (intima) and accumulation of lipid-laden macrophages, commonly known as foam cells, along with the buildup of the extracellular matrix. Subsequent stages witness the proliferation and aggregation of smooth muscle cells, culminating in the formation of atheroma plaques. As these lesions progress, apoptosis can occur in the deeper layers, further recruiting macrophages, which may undergo calcification and transform into atherosclerotic plaques. Notably, mechanisms such as arterial remodeling and intraplaque hemorrhage also contribute significantly to the progression of atherosclerotic cardiovascular disease, although these facets fall beyond the scope of this article. This study aimed to systematically review and conduct a meta-analysis of randomized controlled trials investigating the efficacy and safety of bempedoic acid in statin-intolerant patients with hyperlipidemia and to provide conclusions and recommendations accordingly. A systematic search of databases, such as PubMed, Web of Science, and Embase, will be performed. Only randomized trials will be included comparing bempedoic acid with placebo in statin-intolerant patients. This study aimed to provide a comprehensive understanding of the role of bempedoic acid in managing hyperlipidemia in statin-intolerant patients. In primary prevention, for patients unable to tolerate recommended statins, bempedoic acid was associated with a significant reduction in major adverse cardiovascular events (MACE) as the primary endpoint.

Overcoming patient reluctance to statin intolerance.

Statin therapy is a cornerstone in the management of dyslipidemia, both in primary and secondary prevention of cardiovascular events. Despite strong guidelines supporting statin use, concerns regarding side effects, particularly musculoskeletal symptoms, contribute to statin intolerance and patient reluctance. While statin intolerance is reported in 5% to 30% of patients, its true prevalence may be overestimated due to the influence of the nocebo effect. Factors associated with higher incidence of statin intolerance include older age, female sex, comorbidities such as diabetes and chronic kidney disease, and concurrent use of medications such as antiarrhythmic agents or calcium channel blockers. Clinical characterization of statin intolerance requires thorough evaluation and exclusion of alternative causes of musculoskeletal symptoms. Strategies to address statin intolerance include reassessing cardiovascular risk, engaging in shared decision-making, statin rechallenge after appropriate washout periods, dosage titration for tolerability, and consideration of alternative therapies when low-density lipoprotein goals cannot be achieved with statins. This review provides an overview of the spectrum of statin intolerance, its clinical assessment, and a systematic approach to caring for a patient with statin intolerance.

A CLASH OF CHOLESTEROL TITANS: STATIN–INTOLERANT VS. STATIN–TOLERANT PATIENTS ON PCSK9 INHIBITORS IN LONG TERM FOLLOW–UP

Abstract Introduction Statin intolerance remains a clinical challenge in the management of dyslipidemia. This study aimed to investigate whether patients with statin intolerance, receiving PCSK9 inhibitors, exhibit lipid profile improvement different from those obtained in those without statin intolerance. Methods In this monocentric outpatient study we enrolled 381 dyslipidemic patients receiving PCSK9 inhibitors. Statin intolerance was defined according to ESC criteria. Patients were divided into two groups, clinical data were collected, and lipid profiles were monitored regularly for a total of 36 months. Results Among the statin–intolerant patients, there was a higher proportion of women compared to those on statin therapy (38.6% vs 27.2% p = 0.051), although among intolerants the majority were men (69% vs 31% p = 0.023). Statin–intolerant patients had higher baseline total cholesterol (242±29.8 mg/dL vs 221±26.3 mg/dL p &amp;lt; 0.001) and LDL cholesterol (161.4±39.7 mg/dL vs 147±37.1 mg/dL p = 0.010). Interestingly, lipid reduction in both groups became comparable as early as 6 months (LDL 67±37 mg/dL vs 63±39 mg/dL p = 0.42) and continued to be similar at 12 and 36 months of follow–up (LDL 74±44 mg/dL vs 69±29 mg/dL p = 0.62). Conclusion PCSK9 inhibitors effectively lower lipid levels in both statin–intolerant and statin–tolerant dyslipidemic patients. Statin–intolerant patients seem to have similar management and can achieve cholesterol levels comparable to patients on statin therapy.

NON–RESPONSE TO INCLISIRAN THERAPY IN THREE PATIENTS WITH STATIN INTOLERANCE: A CASE SERIES

Abstract Background Inclisiran is the first silencing–RNA therapy used to reduce LDL–C. It is also recommended in patients with statin intolerance. We describe a case series of three no–responder patients to inclisiran. Case Series 64–year–old man with medical history of type II diabetes mellitus, obesity, hypertension, chronic kidney disease (eGFR 38 ml/min/1.73 m^2), dyslipidemia and statin intolerance. In 2022 the coronary angiography showed diffuse atherosclerosis without significant stenosis. His LDL–c was 115 mg/dl. Rosuvatatin 10 mg was prescribed however it was withdrawn due myalgia. Inclisiran and ezetimibe were prescribed, however one, three and four months later his LDL–C was 96 mg/dl, 114 mg/dl, and 115 mg/dl respectively (Fig 1). Due to the lack of effect, lovastatin 20 mg was added after the third dose of inclisiran, reaching LDL–C levels of 100 mg/dl one month after the initiation of lovastatin. Inclisiran was withdraw (as well as statin due to myalgia) and evolocumab 140 mg was administrated three months later the last dose of inclisiran. Ten days after evolocumab, LDL value was 66 mg/dl. 60–year–old man with hypertension, obesity, and dyslipidemia (LDL 152 mg/dl) with a moderate cardiovascular risk (target LDL–C &amp;lt;70 mg/dl). Patient refused statin therapy because he was scared about myalgia. In October 2021 (first Italian patient out of clinical trial) inclisiran was administrated. However, LDL–C did not change one month after the first and the second dose (147 mg/dl and 134 mg/dl respectively, Fig1). Due to the inefficacy, inclisiran was withdraw and the combination rosuvastatin and ezetimibe 10/10 mg was started with a reduction in LDL–cholesterol levels (51 mg/dl) four months later. However, this treatment was withdrawn due to myalgia in favor of bempedoic acid. One month later LDL–C level was 79 mg/dl. 79–year–old woman with history of coronary revascularization. She was statin and ezetimibe–intolerant, so she was treated with alirocumab 150 mg (LDL–C 89 mg/dl). Since the treatment was ineffective to reach the LDL target values, alirocumab was stopped in favor to inclisiran. However, LDL values increased over the time reaching 103 mg/dl one month after the first dose and 120 mg/dl two months later the second dose (Fig1). Conclusion some patients may be no–responder to inclisiran. A polymorphism of the asialoglycoprotein receptors might be a possible reason. Statin intolerance may also affect inclisiran efficacy.

Vegetables Spices Fermentation Extract Inhibit NAFLD Development by Attenuation of Steatosis through Suppression of C/EBPα and TNFα mRNA Expression

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), characterized by inflammation and steatosis, is one of the metabolic problems that trigger serious complications. Statin is usually used for NAFLD therapy, however, statin intolerance and resistance reduce the effectiveness of NAFLD treatment. Therefore, this study was conducted to develop the phytopharmaca against NAFLD by elucidating the anti-inflammatory and steatosis suppression of vegetable spices fermentation extract (VSFE) in rabbits induced with high-fat diet (HFD).METHODS: Twenty New Zealand White rabbits were determined into 4 groups; which were groups receiving standard diet (SD), HFD, HFD and 100 mg/kgBW VSFE, as well as HFD and 200 mg/kgBW VSFE. mRNA expressions of tumor necrosis factor alpha (TNFα) and CCAAT/enhancer-binding protein alpha (C/EBPα) were evaluated. The TNFα concentration was quantified after protein and RNA isolation. Inflammation and steatosis were observed in liver hematoxylin-eosin-stained preparate using microscope.RESULTS: Macrophage cells and hepatic steatosis showed significant decrease in a drug dependent manner. An effective dose of 200 mg/kgBW decreased C/EBPα and TNFα expression to 0.45±0.32 and 0.72±0.29 (p=0.013 and p=0.002, compared to the HFD group), respectively. TNFα inflammatory cytokine concentrations also responded to the administration of 100 mg/kgBW and 200 mg/kgBW doses, with the value of 31.72±10.40 mg/dL and 48.35±7.15 mg/dL (p=0.009 and p=0.002, compared to the HFD group), respectively.CONCLUSION: VSFE might prevent NAFLD by inhibit steatosis and inflammation through suppression of C/EBPα expression and TNFα expression.KEYWORDS: C/EBPα, TNFα, fermentation, steatosis, NAFLD

Lipid clinic experience with bempedoic acid in three UK centres

Objective Novel lipid-lowering therapies are being introduced. Few studies exist of the real-world effectiveness of adenosine-tri-phosphate citrate lyase inhibition with bempedoic acid. Methods This study audited bempedoic acid therapy in 216 consecutive patients from three hospital centres – a university hospital (n = 77) and two district general hospitals (n = 106 and 33). Cardiovascular disease (CVD) risk factors, prescription qualification criteria, efficacy and adverse effects were assessed. Results The population was aged 65.9 ± 11.0 years, 42% were male, 25% had type 2 diabetes, and 31% had familial hypercholesterolaemia. CVD was present in 19% and multibed vascular disease in 8%. Statin intolerance was reported in 92%. Bempedoic acid reduced total cholesterol by 1.58 ± 1.44 mmol/L (20%), LDL-C by 1.37 ± 1.31 mmol/L (27%), triglycerides by 0.22 mmol/L (2%) with an 0.06 mmol/L (1%) increase in HDL-C after 22 ± 9 months follow-up. An LDL-C <2.5 mmol/L was achieved in 40% and <2 mmol/L in 20%. Efficacy (r2 = .33) was predicted by baseline LDL-C (β = .54; p <.001). No significant changes were seen in transaminases, creatinine, creatine kinase, urate or HbA1c. Treatment was discontinued by 33% of patients and occurred due to myalgia (43%), lack of efficacy (16%) and gastrointestinal adverse effects (15%). No cases of gout were observed. In a logistic regression only the number of previous drug classes not tolerated (β = 1.60; p = .009) was a contributing factor to discontinuation. Conclusion This audit suggests that bempedoic acid therapy is effective but that adverse effects and discontinuation are common. This suggests nocebo effects might be generalizable to all lipid-lowering drug therapies in susceptible individuals.

Lipid-lowering approaches to manage statin-intolerant patients.

Statins have improved the potential to prevent cardiovascular disease events and to prolong the lives of patients. Statins, among the most widely used drugs worldwide, reduce the levels of low-density lipoprotein cholesterol (LDL-C) by an average of 30-50%. However, non-adherence to statin therapy, due to statin intolerance, might be as high as 60% after 24 months of treatment and is associated with a 70% increase in the risk of cardiovascular disease events. Statin intolerance can be classified as a complete inability to tolerate any dose of a statin or a partial intolerance with the inability to tolerate the dose necessary to achieve the patient-specific therapeutic objective. Reasons for discontinuation are many, with statin-associated muscle symptoms being cited as the most frequent reason for stopping therapy and the incidence of muscle symptoms increasing with treatment intensity. Considering the causal effect of LDL-C in the atherosclerotic process, clinicians should consider that regardless of the lipid-lowering drugs patients are willing to take, any reduction in LDL-C they achieve will afford them some benefit in reducing cardiovascular risk. Besides statins, the current therapeutic armamentarium offers different strategies to reach LDL-C targets in statin-intolerant patients (i.e. a fixed combination between a lower dose of statin plus ezetimibe, bempedoic acid, or proprotein convertase subtilisin/kexin type 9 inhibition).

Lipid-Lowering Therapy after Acute Coronary Syndrome.

Achieving guideline-recommended low-density lipoprotein cholesterol (LDL-C) targets remains a significant challenge in clinical practice. This review assesses the barriers to reaching LDL-C goals and explores the potential solutions to these issues. When aiming for the recommended LDL-C goal, strategies like "lower is better" and "strike early and strong" should be used. The evidence supports the safety and efficacy of intensive lipid-lowering therapy post-acute coronary syndrome (ACS), leading to improved long-term cardiovascular health and atherosclerotic plaque stabilization. Despite the availability of effective lipid-lowering therapies, such as high-intensity statins, ezetimibe, the combination of both, bempedoic acid, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a substantial proportion of patients do not meet their LDL-C targets. Contributing factors include systemic healthcare barriers, healthcare provider inertia, patient non-adherence, and statin intolerance. Statin intolerance, often rather statin reluctance, is a notable obstacle due to perceived or expected side effects, which can lead to discontinuation of therapy. In conclusion, while there are obstacles to achieving optimal LDL-C levels post-ACS, these can be overcome with a combination of patient-centric approaches, clinical vigilance, and the judicious use of available therapies. The safety and necessity of reaching lower LDL-C goals to improve outcomes in patients post-ACS are well-supported by current evidence.

Abstract 5873: ERα coordinates with squalene synthase to confer statin resistance in lung cancer

Abstract Statins are widely used to treat hypercholesterolemia by inhibiting hydroxymethylglutaryl coenzyme A reductase (HMGCR). Accumulating evidence suggests that statins also have protective effects against cancer recurrence. However, the role of statins in preventing lung cancer and biomarkers for predicting statin treatment response remains lacking. This study analyzes molecular features that dictate statin sensitivity in lung cancer by correlating large-scale statin sensitivity data and basal gene expression in a collection of 125 lung cancer patients. We identified a gene signature associated with lovastatin sensitivity and showed that gene expression in mesenchymal molecular features, the cholesterol biosynthesis pathway, and estrogen receptor alpha (ERα) signaling were key determinants of lovastatin sensitivity in lung cancer cells. To this end, we further discovered that overexpression of a committed step enzyme in cholesterol biosynthesis farnesyl-diphosphate farnesyltransferase 1 (FDFT1), also known as squalene synthase (SQS), is capable of activating ERα and is associated with increased statin tolerance. In clinical specimens, overexpression of SQS positively correlated with nuclear expression of ERα in lung cancer patients, and the combination of SQS and ERα is a powerful prognostic predictor for lung cancer. Activation of the SQS-ERα signaling axis and epithelial-to-mesenchymal transition (EMT) status represents two important features in determining statin sensitivity in lung cancer. Keywords: Statin, cholesterol biosynthesis, squalene synthase, estrogen receptor α, Epithelial-mesenchymal transition Citation Format: Yi-Fang Yang. ERα coordinates with squalene synthase to confer statin resistance in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5873.

Real-world data on treatment patterns in at least high cardiovascular risk patients on dual and triple lipid lowering therapy in a Hellenic nationwide e-prescription database

BackgroundDespite recent guidelines appropriate lipid-lowering treatment (LLT) remains suboptimal in everyday clinical practice. AimsWe aimed to describe clinical practice of use of LLT for at least high CV risk populations in a Hellenic real-world setting and assess how this relates to the European Society of Cardiology treatment guidelines. MethodsWe analyzed data from a retrospective cohort study of the National Registry of patients with dyslipidemia between 1/7/2017 and 30/6/2019 who were at least of high CV risk and filled a dual or triple lipid-lowering treatment (dLLT, tLLT) prescription. The primary outcomes of interest of this analysis were to report on the patterns of LLT use in at least high CV risk patients. ResultsA total of 994,255 (45.4% of Greeks on LLT) were of at least high CV risk and 120,490 (5.5%) were on dLLT or tLLT. The percentage of patients with reported statin intolerance ranged from 2 to 10%. While persistence was reported to be satisfactory (>85% for both dLLT or tLLT), adherence was low (ranging between 14 and 34% for dLLT). In 6-month intervals, the percentage of patients achieving a low-density lipoprotein cholesterol (LDL-C) target below 100 md/dL ranged from 20% to 23% for dLLT and 34%–37% for tLLT. ConclusionsThe prevalence of at least high CV risk patients among patients receiving LLT in Greece is substantial. Despite the high persistence and probably due to the low adherence to treatment, LDL-C remains above targets in more than two thirds of patients.