Efficacy Of Statins Research Articles

Statin Use and the Risk of Graves' Orbitopathy: A Nationwide Population-Based Cohort Study.

Background: Statin use is reported to reduce the risk of Graves' orbitopathy (GO) in Western populations. However, study regarding the protective effect of statins against GO in Asians with Graves' disease (GD) is scarce. This study aims to investigate the efficacy of statins in preventing GO in Asian GD patients. Materials and Methods: This nationwide, population-based retrospective cohort study used data from beneficiaries aged >40 years diagnosed with GD from the National Health Insurance Research Database (NHIRD) from 2010 to 2020. The International Classification of Diseases codes, Anatomical Therapeutic Chemical codes, and the surgery/procedure codes derived from the NHIRD were used to obtain the information on GD, GO, and statin use. Propensity score (PS) analysis with matching and inverse probability of treatment weighting analysis (IPTW) was conducted to minimize confounding. The Kaplan-Meier survival analysis and multivariable Cox regression analysis were used to compare the risk of GO among statin users and nonusers. Results: The final analysis included 102,858 patients; 7,073 were statin users (62.9 ± 10.6 years, 29.7% male), and 95,785 were nonusers (53.6 ± 10.4 years, 25.7% male). The crude incidence rate of GO among statin users and nonusers was 5.00‰ versus 6.75‰ and 4.91‰ versus 5.15‰ for the overall population and population after PS matching method, respectively. The Cox regression analysis showed that statin users had a significantly lower risk of GO (adjusted hazard ratio [HR] after PS matching 0.79, 95% confidence interval [CI]: 0.63-0.99, p = 0.037; adjusted HR after IPTW method: 0.64, CI: 0.51-0.79, p < 0.001). The risk of GO was not different among users of different kinds of statins (i.e., atorvastatin, rosuvastatin, pitavastatin, and other statins) or among different intensities of statins (low-to-moderate intensity vs. high intensity). Conclusions: The use of statins in Asian GD patients was associated with a reduced risk of GO. In addition, the risk of developing GO among users of commonly prescribed statins or users of different intensities of statins was not significantly different.

Statin therapy in ischemic stroke patients with atrial fibrillation: Efficacy and safety outcomes.

The efficacy and safety of statins for secondary prevention in patients who have experienced a cardioembolic stroke are not well-defined. However, previous observational data reported hyperlipidemia as a risk factor for both ischemic and bleeding complications in patients with AF and previous stroke. Based on these premises, we conducted a sub-analysis of the RAF and RAF-NOAC studies to evaluate the efficacy and safety of statins in secondary prevention in patients with acute ischemic stroke and AF. We combined patient data from the RAF and RAF-NOAC studies, prospective observational studies conducted across Stroke Units in Europe, the United States, and Asia from January 2012 to June 2016. We included consecutive patients with AF who suffered an acute ischemic stroke with a follow-up of 90 days. Our outcomes were the combined endpoint, including stroke, transient ischemic attack, systemic embolism, symptomatic intracerebral hemorrhage, and major extracranial bleeding. Furthermore, both ischemic and hemorrhagic outcomes were evaluated separately. A total of 1742 patients were included (46% male), and 898 (52%) received statins after the index event, of whom 436 (48.6%) were already taking statins before the index event, 462 (51.4%) started treatment after. At multivariable analysis, statin use was statistically associated with age (OR 0.92, 95% CI 0.97-0.99, p = 0.001), male sex (OR 1.35, 95% CI 1.07-1.70, p = 0.013), anticoagulation (OR 2.53, 95% CI 1.90-3.36, p < 0.0001), hyperlipidemia (OR 5.52, 95% CI 4.28-7.12, p < 0.0001), paroxysmal AF (OR 1.40, 95% CI 1.12-1.75, p = 0.003), leukoaraiosis (OR 1.39, 95% CI 1.11-1.75, p = 0.004) and heart failure (OR 0.72, 95% CI 0.53-0.98, p = 0.034). Statin use was not associated with the combined outcome event (OR 0.84, 95% CI 0.58-1.23, p = 0.3) and ischemic outcome event (OR 1.17, 95% CI 0.73-1.88, p = 0.5) while was associated with a lower risk of hemorrhagic outcome event (OR 0.51, 95% CI 0.28-0.91, p = 0.02). Statins protect cerebral arterial vessels (particularly small vessels) from subacute damage due to hypertension, diabetes, and other harmful agents (such as reactive oxygen species, proinflammatory cytokines, etc.) due to their systemic anti-inflammatory and endothelium-protective effects. Our data show that statins seem to protect against global bleeding events in cardioembolic stroke patients; this may be due to the pleiotropic effect of statins. More data are warranted to confirm these findings.

Safety and efficacy of moderate-intensity statin with ezetimibe in elderly patients with atherosclerotic cardiovascular disease.

High-intensity statin therapy significantly reduces mortality and cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD). However, moderate-intensity statins are often preferred for elderly patients due to their higher risk of intolerance to high-intensity statins. To compare the incidence of statin-associated muscle symptoms (SAMS) and the effect on low-density lipoprotein cholesterol (LDL-C) levels between elderly ASCVD patients receiving high-intensity statin monotherapy and those receiving moderate-intensity statin with ezetimibe in a combination therapy. In a prospective, multicenter, open-label trial conducted in South Korea, 561 patients aged 70 years or above with ASCVD were randomly assigned to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 5mg with ezetimibe 10mg) or high-intensity statin monotherapy (rosuvastatin 20mg) over 6 months. The primary endpoint was the incidence of SAMS, and the key secondary endpoint was the achievement of target LDL-C levels (<70mg/dL) within 6 months. The primary endpoint showed a lower incidence of SAMS in the combination therapy group (0.7%) compared to the high-intensity statin monotherapy group (5.7%, p=0.005). Both groups achieved similar LDL-C levels, with 75.4% in the combination therapy group and 68.7% in the monotherapy group reaching target levels. Moderate-intensity statin with ezetimibe combination therapy offers a lower risk of SAMS and similar LDL-C reduction in elderly patients with ASCVD, compared to high-intensity statin monotherapy.

The Effect of Atorvastatin on Oncogenic miRNAs in Hematological Malignancies: A Central Study.

The efficacy of statins as anti-cancer drugs has been demonstrated in several malignancies but has been poorly investigated in hematological malignancies (HM). By studying its effect on oncogenic miRNAs, we investigated the effect of statin therapy on HM patients. The data were used to identify enriched pathways that were altered due to statin treatment. The main aim of this study was to identify significantly differentially expressed miRNAs and involved regulatory pathways post-atorvastatin treatment in HM patients. A panel of 95 plasma circulating miRNAs involved in tumorigenesis, apoptosis, and differentiation were relatively quantified using qPCR for blood samples obtained from 12 HM patients, 4 with Chronic Myeloid Leukemia (CML), 4 with Non-Hodgkin Lymphoma (NHL), and 4 with Essential Thrombocythemia. Pre- and post-administration of a 6-week atorvastatin course miRNA expression levels were measured. Significantly differentially expressed miRNAs were those with a fold change >2 or <0.5 using the Livak method with a two-sided p-value < 0.05. To further understand the underlying mechanism of statin regulated miRNA, GO and KEGG pathway enrichment analyses were conducted for identified target genes using the DAVID 6.8 bioinformatics tool. Out of 95 miRNAs, 14 exhibited significant fold changes post-treatment with statins including miR-198, miR-29a+b+c, miR-204, miR-222, miR-224, miR-155, miR-128b, miR-296, miR-199a+b, miR-194, miR-125a, miR-200a, and the let-7-family that were upregulated and miR-150 that was downregulated post-statin treatment. Higher mir-222, mir-194, mir-128b, and mir-199b expressions were significantly associated with better overall survival using the Cancer Genomic Atlas leukemia and lymphoma patient cohorts. Enrichment analysis identified the PI3k-Akt pathway as well as other pathways involved in the epithelial-mesenchymal transition. Atorvastatin upregulated several tumor suppressor genes involved in mediating better prognosis. The data can be used to enhance personalized treatments for patients with hematological malignancies by helping to predict the different pathways that may be targeted and, therefore, result in better survival outcomes in these patients.

Assessing the impact of evolocumab on thin-cap fibroatheroma and endothelial function in patients with very high-risk atherosclerotic cardiovascular disease: a study protocol for a randomized controlled trial.

The prevalence of very high-risk atherosclerotic cardiovascular disease (ASCVD) is significant in China, with suboptimal rates of low-density lipoprotein cholesterol (LDL-C) compliance exacerbating plaque instability and causing a higher incidence of major adverse cardiac events (MACEs). Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are effective in reducing LDL-C levels, increase the stability of vulnerable plaque, and influence the progression of atherosclerosis through multiple mechanisms as demonstrated in animal studies. However, there is currently a lack of in vivo evidence regarding the efficacy and safety of high-intensity statin therapy combined with PCSK9i in the secondary prevention of ASCVD in the Chinese population. This study aims to demonstrate the efficacy of high-intensity statins combined with PCSK9i on vulnerable plaques in very high-risk ASCVD patients through intravascular imaging and non-invasive endothelial function test. This randomized, open-label, prospective clinical study involves 240 patients with very high-risk ASCVD who meet the criteria outlined in the 2023 Chinese lipid management guidelines. Patients recruitment will be processed in Beijing Anzhen Hospital from January 2021 to December 2024. Patients with thin-cap fibroatheroma (TCFA) detected by optical coherence tomography (OCT) are randomly assigned in a 1:1 ratio to the evolocumab group (evolocumab 140 mg every 2 weeks plus atorvastatin 40 mg nightly) or the standard treatment group (atorvastatin 40 mg nightly). The primary endpoint is the absolute change of the minimum fibrous cap thickness (FCT) at a median follow-up of 1 year. The secondary endpoints are other OCT metrics, assessment of MACE rates, alterations in serum lipid profiles and markers of inflammation, endothelial function, and adverse drug reactions. Logistic regression, analysis of covariance (ANCOVA), Kaplan-Meier curve survival analysis, and Cox regression will be used to investigate the relationship between variables and endpoints. The purpose of this study is to evaluate the efficacy of high-intensity statin therapy combined to PCSK9i for the secondary prevention of coronary artery disease in Chinese patients with very high-risk ASCVD. The results will provide evidence to optimize the management of this high-risk population. This study was registered on chictr.org.cn (ChiCTR2000032570).

EVALUATING THE EFFICACY OF STATINS, ASPIRIN, AND ANTIHYPERTENSIVE THERAPY IN PREVENTING RECURRENT CARDIOVASCULAR EVENTS IN POST-MYOCARDIAL INFARCTION PATIENTS: A META-ANALYSIS

Background: Myocardial infarction (MI) remains a leading cause of global morbidity and mortality, significantly burdening healthcare systems. Post-MI patients face a heightened risk of recurrent cardiovascular events, necessitating effective secondary prevention strategies. Pharmacologic interventions, including statins, aspirin, and antihypertensive therapies, are widely employed, yet their comparative efficacy is debated. This meta-analysis evaluates the effectiveness of these treatments in reducing recurrent cardiovascular events, aiming to inform optimized management strategies for this high-risk population. Objective: To assess and compare the efficacy of statins, aspirin, and antihypertensive therapies in preventing recurrent cardiovascular events among post-MI patients. Methods: This meta-analysis adhered to PRISMA guidelines and included studies published between September 25 and October 27, 2024. A systematic literature search was conducted in PubMed, Scopus, and Google Scholar using MeSH terms and keywords such as "statins," "aspirin," "antihypertensive therapy," "myocardial infarction," and "cardiovascular outcomes." Inclusion criteria required original studies evaluating the effects of these therapies on post-MI cardiovascular outcomes. Data on study characteristics, demographics, interventions, and outcomes were extracted. A random-effects model was applied for pooled analysis, with results presented as odds ratios (ORs) or hazard ratios (HRs) and mean differences (MDs) alongside 95% confidence intervals (CIs). Heterogeneity was assessed using the I² statistic, with sensitivity analyses performed to evaluate result robustness. Results: Nine studies were included, encompassing 3,950 patients. High/moderate-intensity rosuvastatin reduced adverse cardiovascular events with an OR of 1.85 (95% CI: 1.65–2.10). Aspirin therapy demonstrated a 25% reduction in recurrent cardiovascular events among high-risk patients. Beta-blockers improved survival post-MI with an HR of 2.05 (95% CI: 1.85–2.30), and ACE inhibitors combined with canrenoate showed significant reductions in systolic and diastolic dysfunction, with an OR of 1.95 (95% CI: 1.70–2.20). Combination therapies of zofenopril and amlodipine yielded an OR of 1.75 (95% CI: 1.55–1.95). Overall heterogeneity was high (Q = 152.77, I² = 86.3%), reflecting differences in study designs and patient characteristics. Conclusion: This meta-analysis highlights the efficacy of statins, aspirin, and antihypertensive therapies in reducing recurrent cardiovascular events in post-MI patients. Pharmacologic therapies remain the cornerstone of management, but integrating dietary interventions may enhance long-term outcomes. Further large-scale, randomized studies across diverse populations are recommended to refine individualized treatment strategies and explore optimal combinations.

PCSK9 and its relationship with HMGB1, TLR4, and TNFα in non-statin and statin-treated coronary artery disease patients.

Despite statin use in coronary artery disease (CAD), significant risk remains, potentially due to increased proprotein convertase subtilisin/kexin-type 9 (PCSK9) production, which raises LDL-C levels and induces inflammation. The exact relationship between PCSK9, inflammatory markers like TNFα, TLR4, CRP, and HMGB1, and monocyte subsets is poorly understood. This study aimed to explore these relationships in non-statin and statin-taking CAD patients. This case-control study included 91 controls and 91 stable CAD patients, divided into no-statin (NS, n = 25), low-dose statin (LDS, n = 25), and high-dose statin (HDS, n = 41) groups. Serum levels of LDL-C, CRP, PCSK9, TLR4, HMGB1, and TNFα were measured. Monocyte subsets were classified using flow cytometry into classical monocytes (CM), intermediate monocytes (IM), and non-classical monocytes (NCM). CAD patients showed elevated PCSK9, LDL-C, and inflammatory markers compared to controls. Statin groups (LDS, HDS) had lower LDL-C and inflammatory markers but higher PCSK9 than the NS group, with the HDS group showing the lowest LDL-C and inflammatory markers but the highest PCSK9. In the NS group, PCSK9 positively correlated with inflammatory markers (HMGB1, TNFα, TLR4, CRP) and monocyte subsets (IM%, NCM%). In the total statin group (LDS + HDS), PCSK9 negatively correlated with HMGB1, TLR4, and NCM%, for each, respectively, and positively with CM%. Multivariable linear regression showed significant associations between PCSK9 and HMGB1, NCM%, and IM% in the NS group, and HMGB1, NCM%, and TLR4 in the total statin group. In conclusion, we recommend combining PCSK9 inhibitors with statins in high-risk CAD patients. This may enhance statin efficacy, reduce LDL-C, and inhibit the TLR4/NF-кB inflammatory pathway, decreasing atherosclerotic inflammation.

Efficacy and diabetes risk of moderate-intensity statin plus ezetimibe versus high-intensity statin after percutaneous coronary intervention

BackgroundsHigh-intensity statin is recommended for patients undergoing percutaneous coronary intervention (PCI), and ezetimibe is recommended to be added in patients not achieving low-density lipoprotein cholesterol (LDL-C) targets. Moderate-intensity statin plus ezetimibe can reduce LDL-C levels similar to high-intensity statin. The aim of this study is to examine the long-term efficacy and safety of moderate-intensity statin plus ezetimibe as the first-line strategy compared to high-intensity statin in patients undergoing PCI.MethodData was obtained from the Health Insurance Review and Assessment Service database of South Korea. Patients who underwent PCI from 2012 to 2017 were included. The primary efficacy endpoint was major adverse cardiac cerebrovascular events (MACCEs), a composite of all-cause death, revascularization, or ischemic stroke. The safety endpoint was new-onset diabetes mellitus (DM).ResultsA total of 45,501 patients received high-intensity statin (n = 38,340) or moderate-intensity statin plus ezetimibe (n = 7,161). Among propensity-score-matched 7,161 pairs, MACCEs occurred in 1,460 patients with high-intensity statin and 1,406 patients with moderate-intensity statin plus ezetimibe (33.8% vs. 31.9%, hazard ratio 0.96, 95% confidence interval 0.89–1.03, P = 0.27) at a median follow-up of 2.7 years. DM was newly diagnosed in 398 patients with high-intensity statin and 342 patients with moderate-intensity statin plus ezetimibe (12.5% vs. 10.7%; hazard ratio 0.84, 95% confidence interval 0.73–0.97, P = 0.02).ConclusionIn patients undergoing PCI, moderate-intensity statin plus ezetimibe demonstrated a similar risk of MACCEs but a lower risk of new-onset DM than high-intensity statin. Early combination treatment of moderate-intensity statin and ezetimibe may be a useful and safe lipid-lowering strategy after PCI.Graphical abstractCumulative incidence according to the first-line lipid-lowering strategy in patients undergoing percutaneous coronary intervention. Abbreviation: MACCE, major adverse cardiac cerebrovascular events; PCI, percutaneous coronary intervention.

Aerobic exercise alleviates statin-induced PCSK9 upregulation by increasing epoxyeicosatrienoic acid levels through the FoxO3a-Sirt6 axis

BackgroundStatins are the cornerstone of low-density lipoprotein cholesterol (LDL-C)-lowering therapy; however, the therapeutic efficacy of statins in countering atherosclerotic cardiovascular disease (ASCVD) is compromised by the concurrent elevation of proprotein convertase subtilisin/kexin type 9 (PCSK9), a pivotal molecule that increases LDL-C levels. Aerobic exercise lowers PCSK9 levels, but the underlying mechanism remains unclear. Therefore, we investigated how aerobic exercise can ameliorate statin-induced increases in PCSK9 levels. MethodsThree-week-old male American Institute of Cancer Research (ICR) mice were fed a high-fat-cholesterol diet (HFD) for 12 weeks and then administered atorvastatin alone or atorvastatin combined with aerobic exercise (Statin+Ex). Moreover, a total of 165 participants with stable coronary heart disease (CHD) enrolled at the inpatient and outpatient departments of the Second Xiangya Hospital of Central South University from January 2018 to July 2020 were randomized into the Statin group (male/female = 51/33) and Statin+Ex group (male/female = 52/29). Patients in the Statin+Ex group underwent treadmill exercise of 45–60 min/day for 7 days. ResultsAerobic exercise effectively alleviated statin-induced PCSK9 upregulation in human patients with CHD and hypercholesterolemic ICR mice (all p < 0.05). Mechanistically, our findings revealed that aerobic exercise induced elevated epoxyeicosatrienoic acids (EETs) plasma levels while concurrently reducing the activity of soluble epoxide hydrolase (sEH) (all p < 0.05), an enzyme responsible for EETs degradation. Further, EETs significantly suppressed PCSK9 expression, subsequently reducing the LDL-C levels (all p < 0.05); this effect was mediated via the activation of the Forkhead box O3a-Silent mating type information regulation 2 homolog 6 (FoxO3a-Sirt6) axis, with no impact on the Sterol Regulatory Element Binding Protein 2 and 3-hydroxy-3-methylglutaryl-CoA reductase (SREBP2-HMGCR) pathway. ConclusionOur study sheds light on the paradigm of “Exercise is Medicine”, providing evidence to support the use of statins combined with exercise in reducing LDL-C levels, and unveils potential avenues for clinical applications of sEH inhibitors, presenting novel prospects for therapeutic interventions in ASCVD.

Targeting a chemo-induced adaptive signaling circuit confers therapeutic vulnerabilities in pancreatic cancer

Advanced pancreatic ductal adenocarcinomas (PDACs) respond poorly to all therapies, including the first-line treatment, chemotherapy, the latest immunotherapies, and KRAS-targeting therapies. Despite an enormous effort to improve therapeutic efficacy in late-stage PDAC patients, effective treatment modalities remain an unmet medical challenge. To change the status quo, we explored the key signaling networks underlying the universally poor response of PDAC to therapy. Here, we report a previously unknown chemo-induced symbiotic signaling circuit that adaptively confers chemoresistance in patients and mice with advanced PDAC. By integrating single-cell transcriptomic data from PDAC mouse models and clinical pathological information from PDAC patients, we identified Yap1 in cancer cells and Cox2 in stromal fibroblasts as two key nodes in this signaling circuit. Co-targeting Yap1 in cancer cells and Cox2 in stroma sensitized PDAC to Gemcitabine treatment and dramatically prolonged survival of mice bearing late-stage PDAC, whereas simultaneously inhibiting Yap1 and Cox2 only in cancer cells was ineffective. Mechanistically, chemotherapy triggers non-canonical Yap1 activation by nemo-like kinase in 14-3-3ζ-overexpressing PDAC cells and increases secretion of CXCL2/5, which bind to CXCR2 on fibroblasts to induce Cox2 and PGE2 expression, which reciprocally facilitate PDAC cell survival. Finally, analyses of PDAC patient data revealed that patients who received Statins, which inhibit Yap1 signaling, and Cox2 inhibitors (including Aspirin) while receiving Gemcitabine displayed markedly prolonged survival compared to others. The robust anti-tumor efficacy of Statins and Aspirin, which co-target the chemo-induced adaptive circuit in the tumor cells and stroma, signifies a unique therapeutic strategy for PDAC.

Cardioprotective role of statins in breast cancer patients treated with anthracyclines and/or trastuzumab: a systematic review and meta-analysis

Abstract Background Statins may have cardioprotective effects in patients undergoing cardiotoxic chemotherapy regimens. Yet, their role in mitigating anthracycline and/or trastuzumab-induced cardiotoxicity in patients with breast cancer remains unclear. Purpose To perform a systematic review and meta-analysis to evaluate the efficacy of statins in mitigating anthracycline and/or trastuzumab-induced cardiotoxicity among patients with breast cancer. Methods We systematically searched PubMed, Embase, and Cochrane databases until January 2024 for studies comparing the efficacy of statin therapy versus no statin therapy in breast cancer patients receiving either anthracyclines, trastuzumab, or both. Cardiotoxicity was defined as per the definition of each individual study. A random-effects model was used to assess pooled risk ratios (RR) and mean differences (MD) with corresponding 95% confidence intervals. Statistical analyses were performed using Review Manager version 5.4.1. Results We included five studies, of which two were randomised trials. The pooled population comprised 1,839 anthracyclines and/or trastuzumab-treated patients with breast cancer, of whom 864 (47%) received statin therapy. In the pooled analyses, cardiotoxicity was significantly lower in the statin therapy group as compared with the no statin therapy group (RR 0.45; 95% CI 0.27 to 0.72; p=0.001; Figure 1A), additionally statin therapy was associated with a significantly lower reduction in left ventricular ejection fraction as compared with no statin therapy (MD 4.11%; 95% CI 2.68 to 5.53; p&amp;lt;0.00001; Figure 1B). Conclusion In this meta-analysis, statin therapy in anthracyclines and/or trastuzumab-treated patients with breast cancer was associated with lower cardiotoxicity and decline in left ventricular ejection fraction.

Safety and Efficacy of Moderate-intensity statin plus ezetimibe versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease: a meta-analysis

Abstract Background Atherosclerotic cardiovascular disease (ASCVD), affects approximately 18.6 million individuals worldwide, poses an important healthcare challenge. Despite the established efficacy of both high-intensity statin monotherapy (HIS) and moderate-intensity statin plus ezetimibe (MIS+EZT) in ASCVD management, the optimal treatment strategy remains unclear. Purpose This meta-analysis seeks to assess the impact of moderate-intensity statin plus ezetimibe (MIS+EZT) versus high-intensity statin monotherapy (HIS) on LDL &amp;lt; 70mg/dl; Total Cholesterol; LDL; High Density Cholesterol (HDL) and triglycerides levels. Our goal is to synthesize the existing evidence and pinpoint areas that warrant further investigation. Methods A thorough literature search was conducted across PubMed, Scopus, Web of Science, and the Cochrane databases, focusing on studies that compared the effects of moderate-intensity statins plus ezetimibe with high-intensity statin monotherapy in ASCVD patients. Results In the 13 included studies, involving 8,592 patients, of which 4,525 (52.67%) received moderate-intensity statin plus ezetimibe treatment. The follow-up period ranged from 12 to 219 weeks, with participant ages varying from 66 to 76.5 years in the MIS+EZT group and from 67 to 75.9 years in the HIS group. Analysis revealed significant MIS+EZT-associated with greater percentages in Low Density Lipoprotein (LDL) &amp;lt; 70 (Odds Ratio (OR) 1.76; 95% CI [1.26; 2.45]; p=0.001; I²=73%), LDL reduction (Mean Difference (MD) -5.05 mg/dL; 95% CI [-9.02;-1.07]; p&amp;lt;0.013; I²=56%;); Total Cholesterol reduction (MD -7.91 mg/ dL; 95% CI [-14.90; -0.91]; p&amp;lt;0.027; I²=60%); Triglycerides reduction (MD -8.20 mg/ dL; 95% CI [-13.05; -3.35]; p&amp;lt;0.001; I²=2%;); There was no statistical difference between groups in Drug Adverse reaction (Risk Ratio (RR) 1.19; 95% CI [0.79; 1.78]; p=0.404; I²=0%); and Drug intolerance (RR 0.78 ; 95% CI [0.32; 1.92]; p=0.584; I²=35%). Conclusions This meta-analysis underscores the effectiveness of MIS+EZT in enhancing significant clinical outcomes for ASCVD patients, as evidenced by improvements in a greater percentage of patients achieved the LDL &amp;lt;70 target, LDL, Total Cholesterol and Triglycerides levels . Importantly, there were no significant differences in the occurrence of overall adverse events and adverse drug reactions between the two groups.

Hypercholesterolemia and Alzheimer's Disease: Unraveling the Connection and Assessing the Efficacy of Lipid-Lowering Therapies.

This article examines the relationship between cholesterol levels and Alzheimer's disease (AD), beginning with the early observation that individuals who died from heart attacks often had brain amyloid deposition. Subsequent animal model research proved that high cholesterol could hasten amyloid accumulation. In contrast, cholesterol-lowering treatments appeared to counteract this effect. Human autopsy studies reinforced the cholesterol-AD connection, revealing that higher cholesterol levels during midlife significantly correlated with higher brain amyloid pathology. This effect was especially pronounced in individuals aged 40 to 55. Epidemiological data supported animal research and human tissue observations and suggested that managing cholesterol levels in midlife could reduce the risk of developing AD. We analyze the main observational studies and clinical trials on the efficacy of statins. While observational data often suggest a potential protective effect against AD, clinical trials have not consistently shown benefit. The failure of these trials to demonstrate a clear advantage is partially attributed to multiple factors, including the timing of statin therapy, the type of statin and the appropriate selection of patients for treatment. Many studies failed to target individuals who might benefit most from early intervention, such as high-risk patients like APOE4 carriers. The review addresses how cholesterol is implicated in AD through various biological pathways, the potential preventive role of cholesterol management as suggested by observational studies, and the difficulties encountered in clinical trials, particularly related to statin use. The paper highlights the need to explore alternate therapeutic targets and mechanisms that escape statin intervention.

Cardioprotective strategies in the management of chemotherapy-induced cardiotoxicity: current approaches and future directions.

Chemotherapy-induced cardiotoxicity (CIC) is a significant challenge in cancer treatment, leading to heart failure and myocardial infarction. With rising cancer survival rates, the long-term cardiovascular health of survivors has gained importance. While several cardioprotective medications have been studied to mitigate chemotherapy's harmful effects on the heart, more research is needed to confirm their effectiveness and optimal use. This review synthesizes evidence on cardioprotective drugs in managing CIC. The authors conducted a comprehensive literature search of peer-reviewed articles, clinical trials, and meta-analyses published between January 2000 and May 2024. Studies were selected based on relevance, quality, and focus on mechanisms, efficacy, and clinical outcomes of cardioprotective agents such as beta-blockers, ACE inhibitors, ARBs, statins, and dexrazoxane. Cardioprotective medications show potential in alleviating the impact of chemotherapy on heart function. Beta-blockers and ACE inhibitors effectively reduce heart failure incidence and improve cardiac outcomes. Statins, with their anti-inflammatory and antioxidative properties, and dexrazoxane, which reduces anthracycline-induced cardiotoxicity, also show promise. However, variability in study designs, patient groups, and chemotherapy treatments complicates the establishment of standardized treatment protocols. Cardioprotective drugs hold significant promise in managing CIC and improving cardiac outcomes for cancer patients. Current evidence supports the efficacy of beta-blockers, ACE inhibitors, statins, and dexrazoxane. Further research is needed to establish standardized protocols, evaluate long-term safety, and optimize treatment timing. Integrating cardioprotective strategies into oncological care can enhance the quality of life and prognosis for cancer survivors.

Statins for the treatment of COVID-19 patients: an updated meta-analysis of randomized controlled trials

BackgroundStatin is a low-cost and easily accessible therapeutic option for COVID-19 patients. Previous observational studies and meta-analyses suggest using statins for COVID-19 patients.MethodsDatabases including Medline, Scopus, Embase, Cochrane Library, and clinicaltrials.gov were systematically searched.ResultsAfter screening 754 records, 9 trials were included. Overall, the study demonstrated a non-significant reduction in all-cause mortality (p = 0.14, RR 0.90, 95% CI 0.79–1.03), no significant difference in the need for mechanical ventilation (p = 0.62, RR 0.95, 95% CI 0.77–1.17), and a non-significant reduction in length of hospitalization (p = 0.71, MD − 0.17 (95% CI − 1.09, 0.76)). The certainty of evidence varied across outcomes, with most demonstrating reasonable certainty.ConclusionOur study did not support clinical efficacy of statins for the treatment of COVID-19.

Beyond low-density lipoprotein cholesterol levels: Impact of prior statin treatment on ischemic stroke outcomes

Although essential for cardiovascular therapy, the pleiotropic effects of statins on ischemic stroke lack clinical evidence. This study examined the effects of statins beyond low-density lipoprotein cholesterol (LDL-C) levels on mortality and stroke severity. A total of 825,874 patients with ischemic stroke were included in this study, of whom 125,650 statin users were 1:1 matched with non-users based on their LDL-C levels (±0.05mmol/L), forming the LDL-C-matched cohort. Associations between preceding statin treatment, in-hospital mortality, and stroke severity (National Institutes of Health Stroke Scale score ≥16) were estimated by multivariate and conditional logistic regression models in overall cohort and LDL-C-matched cohort, respectively. The overall statin effects reduced in-hospital mortality (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.65-0.79, p<0.001) and moderate-to-severe stroke (OR: 0.93, 95% CI: 0.90-0.96, p<0.001). After matching for LDL-C levels, the reduction in mortality persisted (OR: 0.63, 95% CI: 0.52-0.77, p<0.001) but not for moderate-to-severe stroke (OR: 0.96, 95% CI: 0.90-1.02, p= 0.215). Stratified by LDL-C levels, the effects of statin beyond LDL-C in reducing mortality remained consistent across all LDL-C ranges but increased with LDL-C reduction for stroke severity and achieved statistical significance at LDL-C <2.60mmol/L. Mediation analyses showed that LDL-C reduction explained 0.35% (95% CI: 0.23-0.93, p= 0.235) of the statin treatment-mortality relationship and 12.47% (95% CI: 6.78-18.16, p<0.001) for moderate-to-severe stroke. When examining the overall statin efficacy, LDL-C <2.60mmol/L was not necessary for mortality reduction but for reducing stroke severity. The efficacy of statins in ischemic stroke outcomes is primarily derived from their effects beyond the LDL-C levels, suggesting that their neuroprotective effects should be considered in addition to their lipid-lowering effects.

TCT-327 Efficacy of High-Dose Statins on the Prevention of Contrast-Induced Nephropathy After Cardiac Catheterization: Updated Systematic Review and Meta-Analysis

TCT-327 Efficacy of High-Dose Statins on the Prevention of Contrast-Induced Nephropathy After Cardiac Catheterization: Updated Systematic Review and Meta-Analysis

A Meta-Analysis of Randomized Controlled Trials Comparing the Efficacy and Safety of Hydrophilic Versus Lipophilic Statins in Acute Coronary Syndrome Patients.

Statins differ in their solubility. Some previous studies suggested a difference in clinical efficacy and adverse events between hydrophilic and lipophilic statins. The purpose of this study is to compare the efficacy and safety of hydrophilic and lipophilic statins in patients with acute coronary syndrome. The databases of MEDLINE/PubMed, Cochrane Library, the Web of Science, and Scopus were systemically searched for articles published from inception until the 18th of July 2024. The primary outcome included major adverse cardiac events (MACE), while the secondary outcomes included myocardial infarction (MI), unstable angina (UA), revascularization, stroke, all-cause mortality, cardiovascular deaths, and adverse events. The results were pooled as risk ratio (RR) along with their 95% confidence intervals (CI). Nine studies were included. Hydrophilic statins showed a significantly higher risk of MACE and UA compared to lipophilic statins (RR 1.11 [95% CI 1.02, 1.21] and 1.30 [95% CI 1.04, 1.62]), but subgroup analysis showed a lack of significant difference between statins of similar intensity (1.01 [95% CI 0.86, 1.18] and 0.98 [0.67, 1.45], respectively). Both statins showed comparable results regarding the occurrence of MI (1.18 [95% CI 0.98, 1.40]), revascularization (1.09 [95% CI 0.99, 1.20]), stroke (1.16 [95% CI 0.80, 1.66]), all-cause mortality (1.13 [95% CI 0.92, 1.38]), cardiovascular deaths (1.14 [95% CI 0.76, 1.72]), adverse events leading to discontinuation (1.03 [95% CI 0.56,1.90]), increased alanine aminotransferase (0.61 [95% CI 0.32, 1.16]), increased creatine kinase (0.90 [95% CI 0.30, 2.72]), and increased serum creatinine (1.03 [95% CI 0.49, 2.19]). The efficacy and safety of hydrophilic and lipophilic statins are comparable when the cholesterol-lowering intensity of statins is similar. This suggests that intensity, rather than the lipophilicity of the statin, plays a more important role in the secondary prevention of MACE and individual adverse events.

Efficacy and safety of statins, ezetimibe and statins-ezetimibe therapies for children and adolescents with heterozygous familial hypercholesterolaemia: Systematic review, pairwise and network meta-analyses of randomised controlled trials

Background and aimsStatins, ezetimibe and statins-ezetimibe combination therapy are recommended lipid-lowering therapies (LLTs) in children with heterozygous familial hypercholesterolaemia (HeFH). However, their relative effectiveness is not well understood. We aimed to compare the safety and efficacy of these therapies using direct and indirect comparisons. MethodsWe conducted systematic review, pairwise and network meta-analyses (NMAs) of randomised-controlled trials (RCTs) of statins, ezetimibe and statins-ezetimibe combination therapy in people <18 years with HeFH. Comprehensive bibliographic searches were conducted in December 2022, and a Medline update in January 2024. NMA models accounted for drug class, statin type and dosage. ResultsThirteen RCTs were included (n = 1649, median age 13 years, follow-up 6 weeks-2 years). All LLTs reduced low-density lipoprotein cholesterol (LDL-C) and total cholesterol; statins led to increases in high-density lipoprotein cholesterol and reductions in triglycerides. Statins reduced LDL-C by 33.61 % against placebo (95 % CI 27.58 to 39.63, I2 = 83 %). Adding ezetimibe to statins reduced LDL-C by an additional 15.85 % (95 % CI 11.91 to 19.79). NMAs showed intermediate-dose statins reduced LDL-C by an additional 4.77 % compared with lower-doses statins (95 % CrI −11.22 to 1.05); higher-dose statins and intermediate-dose statins + ezetimibe may be similarly effective and are probably superior to ezetimibe, intermediate-and lower-dose statins. There was no evidence of differences in maturation, safety or tolerability between LLTs and placebo. ConclusionsStatins, ezetimibe and statins-ezetimibe are all effective treatments for children with HeFH, but the magnitude of LDL-C reductions varies and may depend on treatment dosage and combination. No safety or tolerability issues were found. Longer-term safety and effectiveness are uncertain.

The molecular basis of the anticancer effect of statins

Statins, widely used cardiovascular drugs that lower cholesterol by inhibiting HMG-CoA reductase, have been increasingly recognized for their potential anticancer properties. This study elucidates the underlying mechanism, revealing that statins exploit Synthetic Lethality, a principle where the co-occurrence of two non-lethal events leads to cell death. Our computational analysis of approximately 37,000 SL pairs identified statins as potential drugs targeting genes involved in SL pairs with metastatic genes. In vitro validation on various cancer cell lines confirmed the anticancer efficacy of statins. This data-driven drug repurposing strategy provides a molecular basis for the anticancer effects of statins, offering translational opportunities in oncology.