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Background: Despite the advent of new pharmacotherapies, statins remain a cornerstone in the secondary prevention of myocardial infarction (MI). However, the cardiac adverse events (AEs) linked to statins are not well-documented. Aim: This pharmacovigilance study used data from the FDA Adverse Event Reporting System (FAERS) to investigate the association between statin use and cardiac AEs in MI patients. Method: Reports from the FAERS database (2004–2023) identifying statins as the primary suspect in MI patients were analyzed. The study evaluated seven types of statins: atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin. Disproportionality analysis using four major indices, Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma-Poisson Shrinker (MGPS), was conducted to detect signals of statin-related cardiac AEs. Results: Of the 20,346,289 reports reviewed, 150 identified statins as the primary suspect drug in MI patients. The most common cardiac AEs were recurrent MI (50 reports), acute MI (14 reports), followed by tachycardia (10), angina pectoris (8), coronary artery occlusion (6), cardiac failure (6), and arrhythmia (6). The analysis revealed no significant signals of statin-induced cardiac AEs. Conclusion: The findings confirm that statin use in MI patients does not significantly increase the risk of cardiac adverse effects, supporting their safety profile in this context. [ABSTRACT FROM AUTHOR]

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

Purpose of Review: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, characterized by hepatic steatosis with at least one cardiometabolic risk factor. Patients with MASLD are at increased risk for the occurrence of cardiovascular events. Within this review article, we aimed to provide an update on the pathophysiology of MASLD, its interplay with cardiovascular disease, and current treatment strategies. Recent Findings: Given their high burden of cardiovascular comorbidities, patients with MASLD or MASH should undergo regular cardiovascular risk assessment using established risk models. In the absence of liver-specific therapies, therapeutic strategies should focus on improving cardiometabolic risk factors. Patients require a multimodal and multi-stakeholder treatment approach, including optimization of lifestyle, dysglycemia, obesity, and dyslipidemia. Statin treatment represents a safe and effective but often underused therapy in the management of at-risk patients with MASLD and MASH. Novel promising approaches include the use of GLP-1 receptor agonists, especially in, but not limited to, patients with cardiovascular disease and obesity. Summary: Patients with MASLD and MASH are at high cardiovascular risk requiring a multi-modal therapeutic approach including regular cardiovascular risk assessment, as well as lifestyle and pharmacological interventions. Statin therapy represents an inexpensive, safe and effective therapy across the spectrum of non-alcohol related steatotic liver diseases without major safety concerns. More prospective, randomized trials in patients with MASLD and MASH are needed. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine the influence of hyperlipidemia and statin (hydroxyl-methylglutaryl-coenzyme-A reductase inhibitors) use on fatty infiltration (FI) of the rotator cuff muscle after arthroscopic rotator cuff repair (ARCR). The presence or absence of statin use and type of statins used (type 1 naturally derived statins and type 2 synthetic statins) were examined. Methods: This was a retrospective review of 620 cases (620 shoulders) who underwent arthroscopic rotator cuff repair. Total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG) levels, and statin use were reviewed with the medical records. FI of the cuff muscles and repair integrity were assessed by MRI. A generalized linear model was used to analyze the progression of fatty infiltration. Repair integrity was determined according to the Sugaya classification, with types 4 and 5 as retears. Results: The mean age was 66.9 years (272, females). The overall retear rate was 16.1%. There was no significant difference in retears between statin use and non-use with a trend toward higher retear rates in the type 2 statins. FI progressed postoperatively, and multivariate regression showed that type 2 statin use was a significant risk factor (p = 0.006). Other significant risk factor were large-to-massive tear (p = 0.02) and retear (p <.0001). Conclusions: The progression of FI after ARCR was observed. The new generation of strong statins (type 2 statins) was a significant risk factor for the progression of postoperative fatty infiltration, while neither serum lipid level (TC, LDL, and TG) was significant. [ABSTRACT FROM AUTHOR]

Inflammation plays an integral role in the formation, growth, and progression to rupture of unruptured intracranial aneurysms. Aneurysm wall enhancement (AWE) in high-resolution magnetic resonance imaging (HR-MRI) has emerged as a surrogate biomarker of vessel wall inflammation and unruptured intracranial aneurysm instability. We investigated the correlation between anti-inflammatory drug use and three-dimensional AWE of fusiform intracranial aneurysms (FIAs). We retrospectively analyzed consecutive patients with FIAs in our database who underwent 3T HR-MRI at three Chinese centers. FIAs were classified as fusiform-type, dolichoectatic-type, or transitional-type. AWE was objectively defined using the aneurysm-to-pituitary stalk contrast ratio in three-dimensional space by determining the contrast ratio of the average signal intensity in the aneurysmal wall and pituitary stalk on post-contrast T1-weighted images. Data on aneurysm size, morphology, and location, as well as patient demographics and comorbidities, were collected. Univariate and multivariate logistic regression analyses were performed to determine factors independently associated with AWE of FIAs on HR-MRI. In total, 127 FIAs were included. In multivariate analysis, statin use (β = -0.236, P = 0.007) was the only independent factor significantly associated with decreased AWE. In the analysis of three FIA subtypes, the fusiform and transitional types were significantly associated with statin use (rs = -0.230, P = 0.035; and rs = -0.551, P = 0.010; respectively). It establishes an incidental correlation between the use of statins daily for ≥ 6 months and decreased AWE of FIAs. The findings also indicate that the pathophysiology may differ among the three FIA subtypes. [ABSTRACT FROM AUTHOR]

Purpose : While statins and antiplatelet therapies are largely prescribed together worldwide, limited information is available on the safety of their association regarding rhabdomyolysis occurrence. We aimed to assess the reporting of rhabdomyolysis in patients treated with a combination of statin and antiplatelet therapy, compared to statin alone. Methods: We used the World Health Organization pharmacovigilance database (VigiBase®) to compare the rhabdomyolysis reporting between statin (atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin) plus antiplatelet therapy (acetylsalicylic acid, clopidogrel, prasugrel and ticagrelor) groups versus statin alone groups, for each statin and antiplatelet therapy. Study setting was restricted to patients aged 45 or older, including reports up until 1st September, 2021. We computed reporting Odds-Ratio (ROR) and their 95% confidence interval (CI) to quantify the disproportionality between groups, adjusted on age and sex. Results: Among the 11,431,708 reports of adverse reactions, we extracted 9,489 cases of rhabdomyolysis in patients treated with statins, of whom 2,464 (26%) were also treated with antiplatelet therapy. The reporting of rhabdomyolysis was increased when ticagrelor was associated with atorvastatin (ROR 1.30 [1.02–1.65]) or rosuvastatin (ROR 1.90 [1.42–2.54]) compared to the respective statin alone but did not change when aspirin, clopidogrel or prasugrel were considered. Conclusion: Rhabdomyolysis reporting was increased when ticagrelor -but not other antiplatelet agents- was notified with the most prescribed statins in practice. This finding needs to be considered by physicians especially in high-risk patients. [ABSTRACT FROM AUTHOR]

Purpose of Review: The present review aims to summarize current evidence, explore underlying mechanisms, and help guide clinicians regarding statin therapy and diabetes risk in primary prevention. Recent Findings: The observational and genetic epidemiology, as well as evidence from randomized controlled trials and meta-analyses, illustrate a modest, dose-dependent increase in risk of diabetes from statin therapy. Summary: Risk of new onset diabetes from statins appears to be greatest in those near the diagnostic threshold for diabetes or with diabetes risk factors prior to statin initiation. The risk of incident diabetes is vastly offset by the cardiovascular protection offered from statin therapy and should not deter guideline recommended statin initiation in primary prevention. [ABSTRACT FROM AUTHOR]

Hormone therapy, especially androgen deprivation therapy (ADT), is effective against prostate cancer (PC), whereas long-term ADT is a risk for metabolic/cardiovascular disorders including diabetes (DM), hypertension (HT) and dyslipidemia (DL), and might result in progression to castration-resistant prostate cancer (CRPC). We thus conducted a multicenter retrospective cohort study to ask whether CRPC progression would be associated positively with HT, DM or DL and negatively with statins prescribed for treatment of DL. In this study, 1,112 nonmetastatic PC patients undergoing ADT were enrolled. Univariate statistical analyses clearly showed significant association of HT or DM developing after ADT onset, though not preexisting HT or DM, with early CRPC progression. On the other hand, preexisting DL or statin use, but not newly developed DL or started statin prescriptions following ADT, was negatively associated with CRPC progression. Multivariate analysis revealed significant independent association of the newly developed DM or HT, or preexisting statin use with CRPC progression [adjusted hazard ratios (95% confidence intervals): 3.85 (1.65–8.98), p = 0.002; 2.75 (1.36–5.59), p = 0.005; 0.25 (0.09–0.72), p = 0.010, respectively]. Together, ADT-related development of HT or DM and preexisting statin use are considered to have positive and negative impact on CRPC progression, respectively. [ABSTRACT FROM AUTHOR]

Background: Acute coronary syndrome continues to be a significant cardiovascular issue. Statins are commonly acknowledged as medications that reduce LDL-C levels and stabilize plaques. Nevertheless, their efficacy is limited. Presently, PCSK9 inhibitors are suggested to be advantageous in patients who are already receiving statin treatment. The study seeks to assess the safety and effectiveness of PCSK9 inhibitors in individuals who have been treated with statins after experiencing acute coronary syndrome (ACS), as well as investigate the impact on the characteristics of coronary plaque. Methods: Articles were identified from PubMed, Cochrane Central Register of Controlled Trials, and ProQuest. Our analysis comprised trials and observational studies that compared the plaque phenotype, lipid profile, and safety outcomes between PCSK9 inhibitors and a control group in patients with acute coronary syndrome who were already being treated with statins. The random-effect model was used to measure the pooled effect, which was presented in terms of mean difference, standardized mean difference, and risk ratio. Results: Acquired 12 studies that fulfilled our criteria. The addition of PCSK9 inhibitors ameliorates the plaque phenotype significantly in terms of percent atheroma volume (P = 0.02), total atheroma volume (P < 0.010), fibrous cap thickness (P < 0.00001), lipid arc (P < 0.00001), quantitative flow ratio (P = 0.003), and diameter of stenosis (P = 0.0003) but not in lipid/lesion length (P = 0.17). The administration of PCSK9 inhibitors led to a considerable improvement in all lipid profiles (P < 0.00001). Regarding safety analysis, there is no substantial disparity in the likelihood of non-serious side events (RR 1.21; P = 0.2), however, a significant reduction in the risk of serious adverse effects (RR 0.77; P = 0.04) in the PCSK9 inhibitor group. Conclusions: The addition of PCSK9 inhibitors compared to statin-only treatment led to a majority of patients experiencing significant benefits in terms of safety and efficacy following ACS. [ABSTRACT FROM AUTHOR]

Coronary artery stenosis is often advanced by the time coronary computed tomography angiography (CCTA). Statins are the most important anti-lipidemic medication for improving the prognosis of coronary artery disease (CAD) patients. Although lipid-lowering therapy using statins appears to have been established as a method for preventing CAD, there remains the problem that CAD cannot be completely suppressed. In this study, we investigated whether pre-treatment with statin could significantly inhibit the onset of CAD when patients received CCTA for screening of CAD. The subjects were 1164 patients who underwent CCTA as screening for CAD. CAD was diagnosed when 50% or more coronary stenosis was present in the coronary arteries. Patient backgrounds were investigated by age, gender, body mass index, coronary risk factors [family history of cardiovascular diseases, smoking history, hypertension (HTN), diabetes mellitus (DM), dyslipidemia, chronic kidney disease (CKD) or metabolic sydrome] and medications. Patients were classified into two groups according to the presence or absence of statin pre-administration during CCTA [statin (−) group (n = 804) and (+) group (n = 360)]. Compared with the statin (−) group, the statin (+) group was significantly older and had higher rates of family history, HTN, and DM. The statin (+) group had a significantly higher % CAD than the statin (−) group. Serum levels of low-density lipoprotein cholesterol (LDL-C) were significantly lower in the statin (+) group than in the statin (−) group. There was no significant difference in either high-density lipoprotein cholesterol levels or triglyceride levels between the two groups. Age, male gender, HTN, DM and pre-treatment with statin were all associated with CAD (+) in all patients. In addition, factors that contributed to CAD (+) in the statin (−) group were age, male gender, and DM, and factors that contributed to CAD (+) in the statin (+) group were age, smoking, HTN and % maximum dose of statin. At the time of CCTA, the statin (+) group had a high rate of CAD and coronary artery stenosis progressed despite a reduction of LDL-C levels. To prevent the onset of CAD, in addition to strict control of other coronary risk factors (HTN etc.), further LDL cholesterol-lowering therapy may be necessary. [ABSTRACT FROM AUTHOR]

Pravastatin is a promising medication to treat preeclampsia. However, the appropriate dose of pravastatin for managing preeclampsia has not been established. In this in vitro study, we examined the effects of low concentrations of pravastatin (0.01 to 10 µM) under hypoxic conditions on two types of placental cells and found that pravastatin decreased sFlt-1 levels up to 34% in cytotrophoblast cells isolated from human term placentas. Furthermore, we showed that sFlt-1 levels in HTR-8/SVneo cells, a cell line derived from first trimester trophoblast cells, decreased after exposure to very low concentrations of pravastatin (0.01, 0.1 µM). We also examined the effects of pravastatin on uterine spiral artery remodeling-related events and showed in wound healing and tube formation assays that low concentrations of pravastatin upregulated cell migration and invasion in HTR-8/SVneo cells. These results demonstrated that a low dose of pravastatin has in vitro effects that suggest a potential for anti-preeclamptic effects in vivo. [ABSTRACT FROM AUTHOR]

Dyslipidaemia describes the condition of abnormal lipid levels in a person's bloodstream. Since the 1980s, statin medications have been used to treat dyslipidaemia and other comorbidities, such as stroke risk and atherosclerosis. Statin medications were initially synthesised from fungal metabolites, but many synthetic statin drugs have been manufactured since then. Statin medication is quite effective in reducing total cholesterol levels in the bloodstream, but it has limitations. Due to their poor water solubility, statin drugs possess poor oral bioavailability, which hinders their therapeutic efficacy. Nanoparticle drug delivery technology has been shown to improve the pharmacokinetic profiles of many drug classes, and statins have great potential to benefit from this. This paper reviewed the currently available literature on nanoparticle statin medication and evaluated the possible improvements that can be made to the pharmacokinetic profile and efficacy of conventional statin medication. It was found that the oral bioavailability of nanoparticle medication consistently outperformed conventional medication by up to 400% in some cases. Substantial improvements in time to peak plasma concentration and plasma concentration peaks were also found, and increased periods in circulation before excretion were shown. It was concluded that nanoparticle technology has the potential to completely replace conventional statin medication as it offers more significant benefits with minimal drawbacks. Upon further study and development, the manufacture of nanoparticle statin medication should become feasible enough for large-scale application, which will significantly benefit patients and unburden healthcare systems. [ABSTRACT FROM AUTHOR]

As the most frequent cause of acquired myopathy, toxic myopathies are characterised by clinicopathological features that vary depending on the mode of action of the drugs or toxins involved. Although a large number of substances can induce myotoxicity, the main culprits are statins, alcohol, and corticosteroids. A rigorous, well-organised diagnostic approach is necessary to obtain a rapid diagnosis. For early diagnosis and management, it is important for clinicians to be aware that most toxic myopathies are potentially reversible, and the goal of treatment should be to avoid serious muscle damage. [ABSTRACT FROM AUTHOR]

Background: Statins are widely used in coronary and peripheral arterial disease, but their impact on patency of stents placed for peripheral arterial disease is not well-studied. The purpose of this study was to evaluate femoropopliteal stent primary patency according to statin intensity at the time of stent placement and compare this effect to other covariates that may influence stent patency. Materials and methods: A retrospective review identified 278 discrete femoropopliteal stent constructs placed in 216 patients over a 10-year period; Rutherford categories were 2 (3.6%), 3 (12.9%), 4 (21.2%), 5 (49.6%), and 6 (12.6%). Stent locations were common femoral (1.8%), common femoral/superficial femoral (0.7%), superficial femoral (50.7%), superficial femoral/popliteal (32.7%) and popliteal (14.0%) arteries; 63.3% of stents were paclitaxel-eluting. Primary patency of each stent construct was determined with duplex ultrasound, angiography, or computed tomographic angiography. Greater than 50% restenosis or stent occlusion was considered loss of patency. Cox proportional hazard and Kaplan–Meier modeling were used to assess the effect of statin use and additional covariates on stent patency. Results: Patients on any statin at the time of stent placement were half as likely to undergo loss of primary unassisted patency as patients on no statin therapy (hazard ratio, 0.53; 95% confidence interval, 0.19–0.87; P =.004). Moderate/high intensity statin therapy conferred 17 additional months of median stent patency compared to the no statin group. Antiplatelet therapy, anticoagulant therapy, drug-eluting stents (versus bare metal or covered stents), and Rutherford class were not predictive of stent patency (P = 0.52, 0.85, 0.58, and 0.82, respectively). Conclusion: Use of statin therapy at the time of femoropopliteal stent placement was the most predictive examined variable influencing primary unassisted patency. [ABSTRACT FROM AUTHOR]

Statins were reported to have a potential effect of primary prevention of venous thromboembolism (VTE), although that of secondary prevention remains uncertain. To investigate the association between statins use and recurrent VTE in the current era. The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive VTE patients among 31 centers in Japan between January 2015 and August 2020. We divided the entire cohort into 2 groups according to statins use at the time of discharge; the statins (N = 865) and no statins groups (N = 4332). The statins group was older (72.9 vs. 66.7 years, P < 0.001), and less often had active cancer (22.0% vs. 30.4%, P < 0.001). The cumulative incidence of discontinuation of anticoagulation was significantly lower in the statins group (60.3% vs. 52.6%, Log-rank P < 0.001). The cumulative 5-year incidence of recurrent VTE was significantly lower in the statins group (6.8% vs. 10.1%, Log-rank P = 0.01). Even after adjusting for the confounders, the lower risk of the statins group relative to the no statins group remained significant for recurrent VTE (HR 0.65, 95% CI 0.45–0.91, P = 0.01). The cumulative 5-year incidence of major bleeding was significantly lower in the statins group (12.2% vs. 14.1%, Log-rank P = 0.04), although, after adjusting for the confounders, the risk of the statins group relative to the no statins group turned to be insignificant (HR 0.77, 95% CI 0.59–1.00, P = 0.054). In this large real-world VTE registry, statins use was significantly associated with a lower risk for the recurrent VTE in the current era. [ABSTRACT FROM AUTHOR]

Background: Dyslipidemia is one of the main modifiable risk factors for cardiovascular diseases, which accounts for one third of total deaths worldwide. Statin is considered the cornerstone therapy for treating dyslipidemic patients. H1 Cardiac magnetic resonance spectroscopy (MRS) is a special non-invasive, non-irradiating method for assessing myocardial lipid content in vivo in both health and disease. Aim: To compare dyslipidemic patients and healthy individuals, and to detect the efficacy of statin on the myocardial lipid content in dyslipidemic patients to detect if there will be changes 6 months after starting statin therapy. Methods: Laboratory lipid profile and myocardial lipid content had been measured by H1 MRS in thirty dyslipidemic patients and fifteen healthy matched age and sex individuals as a control group, then dyslipidemic patients were followed up 6 months after statin therapy at Cardiovascular Medicine and Radiology departments; Mansoura University Hospitals, Dakahlia Governorate, Egypt, during the period from January 2020 to October 2022. Results: A total of thirty dyslipidemic patients were screened for lipid profile, myocardial lipid content by H1 MRS; 56.67% were male, with a mean age of 49 ± 9.19 years, and compared with fifteen healthy matched age and sex individuals as a control group. Laboratory lipid profile, and triglyceride lipid concentration by MRS were significantly higher in dyslipidemic group before initiating statin therapy compared to control group (p value, 0.001, 0.019 respectively). Median LDL levels were 161.10 ± 30.28 mg/dl before the start of statin therapy and were 114.27 ± 48.33 mg/dl after statin therapy (p < 0.001). There was a statistically significant reduction in triglyceride lipid concentration in dyslipidemic patients after 6 months of statin therapy: from 0.011 (0.001–0.55 (mmol/l), to 0.0025 (0.001–0.04 mmol/l) with a p value < 0.001. Conclusions: Increased myocardial lipid content as measured by magnetic resonance spectroscopy was demonstrated in dyslipidemic patients in our study that decreased after 6 months of statin therapy. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to clarify the real-world status of lipid management in outpatients with type 2 diabetes (T2DM) following the 2022 revision of the Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases. It also aimed to evaluate characteristics associated with the failure to achieve management targets. Materials and Methods: In this post-hoc analysis of a multicenter, cross-sectional study, we included Japanese outpatients with T2DM undergoing primary prevention of atherosclerotic cardiovascular diseases (ASCVD) who provided fasting blood samples. The frequency and determinants of achieving low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) targets were assessed. Results: Among 223 participants with a mean age of 67 and mean HbA1c of 7.1%, 61 had no history of peripheral arterial disease, microvascular complications, or smoking. Out of the 223 participants, 64.1% (95% CI: 57.6–70.1%) achieved the LDL-C target. In multivariate logistic regression analysis, being female (odds ratio [OR] 3.139, P = 0.0011), having diabetic nephropathy (OR 2.868, P = 0.0021), smoking (OR 2.292, P = 0.0281), and non-use of statins (OR 4.857, P < 0.0001) were independently associated with non-achievement. For non-HDL-C, 65.6% (95% CI: 58.1%–70.6%) of patients met the target. Having diabetic neuropathy (OR 2.428, P = 0.0054), smoking (OR 2.008, P = 0.0478), and non-use of statins (OR 2.277, P = 0.0112) were identified as factors associated with non-achievement. Conclusions: Low achievement rate of revised lipid management targets for ASCVD primary prevention in T2DM was unveiled. Assessing comorbidities, encouraging smoking cessation, and prioritizing statin use are considered. [ABSTRACT FROM AUTHOR]

Purpose: Thyroid eye disease (TED) is the foremost extrathyroidal manifestation of Graves' disease (GD). Currently, available treatments do not entirely prevent the long-term consequences of TED and have distinct disadvantages. Therefore, this systematic review explored available evidence regarding the efficacy of statins in preventing and treating TED. Methods: Relevant studies investigating statin usage in patients with GD or TED were identified by searching Medline (Pubmed and Ovid), Scopus, Web of Science, ProQuest, and Cochrane Library databases (from the database inception to September 2023). The review was done according to the PRISMA statement. Web searching was done independently by two investigators. Two researchers independently extracted the data, and any disagreement was adjudicated by consensus. Based on the study design, the studies' quality appraisal was done using the Newcastle-Ottawa Scale (NOS) and Version 2 of the Cochrane risk-of-bias tool (RoB2). Results: The literature search identified 145 publications, of which four met the inclusion criteria (Three retrospective cohort studies and one randomized clinical trial) and were reviewed in full text. The two retrospective cohort studies demonstrated the beneficial effects of statins on TED in newly diagnosed GD Stein et al. showed that statins, regardless of the type, prevent or delay TED (HR: 0.74 (0.65–0.84)), especially in men or treatment duration of more than one year. Nilsson et al. fascinatingly revealed that at least 60 days of statin usage in the preceding year could decrease the risk of TED development by around 40%. One RCT showed a higher treatment response for active moderate-to-severe TED in patients with hypercholesterolemia who took atorvastatin 20 mg in addition to ivGC for 24 weeks without any increase in serious side effects. The retrospective study revealed that the need for reconstructive surgery was reduced in patients with severe TED who received statin therapy. Conclusion: Statin therapy could be a potential adjunctive modality for preventing and treating TED. Trial registration: PROSPERO registration number: CRD42022315522. [ABSTRACT FROM AUTHOR]

Background: Beyond its ability to decrease cholesterol, statin medication has been proved to have a variety of pleiotropic effects, such as anti-inflammatory and immunomodulatory effects. Statins are an appealing therapeutic option for individuals with infective endocarditis because of these effects, as the condition is linked to a strong inflammatory response. Methods: A comprehensive search was done in Medline/PubMed, Cochrane database (CENTRAL), and Google Scholar to identify relevant studies reporting outcomes of interest (rate of mortality, intensive care unit admission, and embolic events) comparing those who are on statin therapy to nonusers were included. We performed a random effect meta-analysis to pool each study's individual results. Results: Three articles were included in the study. The pooled results regarding our primary endpoint showed there was a significant reduction in mortality among statin users in all time points (1-year mortality: OR 0.69, 95% CI 0.61–0.79, I2: 0%; Chi2 = 0.01; p < 0.0001). Meta-analysis for the secondary outcome showed statin users are less frequently admitted to the intensive care unit (OR 0.73, 95% CI 0.59–0.90, I2: 0%; Chi2 = 0.00; p = 0.0004). The rate of mortality was significantly lower for those with a previous history of cerebrovascular disease who were on statin therapy compared to those without cerebrovascular diseases (CVD). Conclusions: The results of the present study support a significant association with statin therapy as a potential treatment proposed for individuals at risk of infective endocarditis. [ABSTRACT FROM AUTHOR]

Background: Proprotein convertase subtilisin/kexin type-9 (PCSK9), an enzyme produced mainly by hepatocytes and breaks low-density lipoprotein receptor (LDL-R), inflammatory markers [toll like receptor 4 (TLR4), high mobility group box 1 (HMGB1), tumor necrosis factor alpha (TNFα), c-reactive protein (CRP)], and monocyte subtypes are associated with coronary artery disease (CAD) pathogenesis. The circulating microRNA-218 (miR-218) can relieve CAD through the suppression of HMGB1 in monocyte-derived inflammatory cytokines. Herein, we explored the association between circulatory miR-218 expression and serum levels of PCSK9, inflammatory markers, and monocyte subtypes in statin and non-statin CAD patients. This study involved 91 healthy (control) and 91 stable CAD participants which were subdivided into no-statin (NS, n = 25), low-statin (LS, n = 25), and high-statin (HS, n = 41) groups. low-density lipoprotein cholesterol (LDL-C) and CRP serum levels were calorimetrically determined. Serum levels of PCSK9, TLR4, HMGB1, and TNFα were detected by ELISA, while monocyte subsets [classical (CM), intermediate (IM), non-classical (NC)] were calculated by flow cytometry. Circulatory miR-218 expression was detected by real-time PCR. Results: The CAD group had significantly lower miR-218 expression and significantly higher levels of PCSK9, inflammatory markers (HMGB1, CRP, TLR4, and TNFα), and IM% than the control group. Among CAD patients, LS and HS groups had significantly lower miR-218 expression, LDL-C levels, and inflammatory markers and significantly higher levels of PCSK9 than the NS group. The HS group exhibited the lowest miR-218 expression and inflammatory markers and the highest PCSK9 levels. However, there were no significant changes in IM% among statin and non-statin groups. In the three CAD groups, miR-218 showed a significantly negative correlation with PCSK9 and inflammatory markers (HMGB1, CRP, TLR4, and TNFα), while this expression exhibited a significantly negative correlation with CM%, IM%, and NCM% only in the NS group. Results of multivariable linear regression indicated a correlation between miR-218 and five independent variables (PCSK9, HMGB1, CRP, TLR4, and TNFα) in the total statin (LS + HS) group, and eight independent variables (PCSK9, HMGB1, CRP, TLR4, and TNFα, CM%, IM%, NCM%) in the NS group. Provided that all other independent variables are constant, miR-218 expression was significantly correlated to CRP (Beta = 0.234) and PCSK9 (Beta = − 0.875) in the total statin group; TLR4 (Beta = − 0.554) in the LS group; HMGB1 (Beta = − 0.507) in the HS group; and CRP (Beta = − 0.745) in the NS group. Conclusions: Statin-treated CAD patients have a unique negative correlation between miR-218 and PCSK9, HMGB1, and TLR4, and subsequently with CAD progress. Therefore, it could be recommended to combine activators of miR-218 and inhibitors of PCSK9, HMGB1, and TLR4 with statin to efficiently treat CAD. [ABSTRACT FROM AUTHOR]

Objective: Statin treatment compliance and achieving target levels differ between populations. This study aimed to determine the status of achieving the lipid targets and evaluate patients' compliance to statin treatment in type 2 diabetic patients with dyslipidemia. Method: This cross-sectional study included type 2 diabetes mellitus (T2DM) patients with dyslipidemia who applied for treatment at our polyclinics. Statin compliance was evaluated using the Modified Morisky Adherence Scale (MMAS-8) through a face-to-face interview. Cardiovascular (CV) risk was calculated according to the 2019 ESC (European Society of Cardiology) criteria by evaluating the patients' individual risk factors. LDL targets were determined according to risk categories with the same criteria. Results: A total of 504 patients (F/M: 274/230) were included. The serum LDL levels were 102.6 ± 39.2 mg/dL. Of the patients, 56.1% were under statin treatment. CV risk was very high in 73.6% of patients. LDL levels were significantly lower in users than in non-users (91.2 ± 26.0, 117.3 ± 38.4, p < 0.0001). The rate of reaching the LDL target was 14.8% in statin users. Treatment compliance was low for 40.6% of statin users. Discontinuation of statin treatment due to side effects was 15.7% (n = 14). N = 49 patients willingly discontinued statin treatment. They reported that 40.8% considered the treatment unnecessary. Conclusion: It was observed that 56.1% of type 2 diabetic patients were on statin therapy. A small percentage of them 14.8% (n = 42) reached the LDL target. Statin non-compliance and a lack of awareness of the statin treatment are the main reasons for high LDL levels in type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Low-density lipoprotein cholesterol (LDL-C) levels are recommended according to the patient's risk factors based on guidelines. In patients achieving low LDL-C levels, the need for statins is uncertain, and the plaque characteristics of patients not treated with statins are unclear. In addition, the difference in plaque characteristics with and without statins is unclear in similarly high LDL levels. We evaluate the impact of statins on plaque characteristics on optical coherence tomography (OCT) in patients with very low LDL-C levels and high LDL-C levels. A total of 173 stable angina pectoris patients with 173 lesions undergoing OCT before percutaneous coronary intervention were evaluated. We divided the LDL-C levels into three groups: < 70 mg/dL (n = 48), 70 mg/dL ≤ LDL-C < 100 mg/dL (n = 71), and ≥ 100 mg/dL (n = 54). Among patients with LDL-C < 70 mg/dL, patients not treated with statins showed a significantly higher C-reactive protein level (0.27 ± 0.22 mg/dL vs. 0.15 ± 0.19 mg/dL, p = 0.049), and higher incidence of thin-cap fibroatheromas (TCFAs; 44% [7/16] vs. 13% [4/32], p = 0.021) than those treated with statins. Among patients with LDL-C level ≥ 100 mg/dL, patients treated with statins showed a significantly higher prevalence of familial hypercholesterolemia (FH) (38% [6/16] vs. 5% [2/38], p = 0.004), lower incidence of TCFAs (6% [1/16] vs. 39% [15/38], p = 0.013), healed plaques (13% [2/16] vs. 47% [18/38], p = 0.015), and higher incidence of fibrous plaques (75% [12/16] vs. 42% [16/38], p = 0.027) than patients not treated with statins. While patients achieved a low LDL-C, patients not treated with statins had high plaque vulnerability and high systemic inflammation. While patients had a high LDL-C level with a high prevalence of FH, patients treated with statins had stable plaque characteristics. [ABSTRACT FROM AUTHOR]

Background and aims: Whether statin treatment is effective in retarding the progression of radiation-induced carotid stenosis (RICS) in head and neck cancer (HNC) survivors has not been well studied. The purpose of this study was to assess the association of statin treatment with RICS progression rate in HNC survivors after radiotherapy. Methods: We conducted a retrospective cohort study at Sun Yat-sen Memorial Hospital, Sun Yat-sen University in Guangzhou, China. Between January 2010 and December 2021, we screened HNC survivors whose carotid ultrasound scans had shown stenosis of the common and/or internal carotid arteries. The primary outcome was the RICS progression rate. We compared eligible patients treated with statins with those who did not in multivariable Cox regression models. Results: A total of 200 patients were included in this study, of whom 108 received statin treatment and 92 did not. Over a mean follow-up time of 1.5 years, 56 (28.0%) patients showed RICS progression, 24 (42.9%) and 32 (57.1%) in the statin and control groups, respectively. The statin group showed less RICS progression than the control group (adjusted-HR 0.49, 95% CI 0.30–0.80, P = 0.005). In the subgroup analysis, there was no significant interaction in the effect of statins on lowering RICS progression rate in the subgroups stratified by baseline low-density lipoprotein cholesterol (LDL-C) levels (P for interaction = 0.53) or baseline degrees of stenosis (P for interaction = 0.50). Conclusions: Statin treatment was associated with a lower risk of RICS progression in patients with HNC after radiotherapy, regardless of baseline LDL-C level and baseline stenosis degrees. [ABSTRACT FROM AUTHOR]

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Objective: To assess whether changes in MRI-based measures of thigh muscle quality associated with statin use in participants with and without/at-risk of knee osteoarthritis. Methods: This retrospective cohort study used data from the Osteoarthritis Initiative study. Statin users and non-users were matched for relevant covariates using 1:1 propensity-score matching. Participants were further stratified according to baseline radiographic knee osteoarthritis status. We used a validated deep-learning method for thigh muscle MRI segmentation and calculation of muscle quality biomarkers at baseline, 2nd, and 4th visits. Mean difference and 95% confidence intervals (CI) in longitudinal 4-year measurements of muscle quality biomarkers, including cross-sectional area, intramuscular adipose tissue, contractile percent, and knee extensors and flexors maximum and specific contractile force (force/muscle area) were the outcomes of interest. Results: After matching, 3772 thighs of 1910 participants were included (1886 thighs of statin-users: 1886 of non-users; age: 62 ± 9 years (average ± standard deviation), range: 45–79; female/male: 1). During 4 years, statin use was associated with a slight decrease in muscle quality, indicated by decreased knee extension maximum (mean-difference, 95% CI: − 1.85 N/year, − 3.23 to − 0.47) and specific contractile force (− 0.04 N/cm2/year, − 0.07 to − 0.01), decreased thigh muscle contractile percent (− 0.03%/year, − 0.06 to − 0.01), and increased thigh intramuscular adipose tissue (3.06 mm2/year, 0.53 to 5.59). Stratified analyses showed decreased muscle quality only in participants without/at-risk of knee osteoarthritis but not those with established knee osteoarthritis. Conclusions: Statin use is associated with a slight decrease in MRI-based measures of thigh muscle quality over 4 years. However, considering statins' substantial cardiovascular benefits, these slight muscle changes may be relatively less important in overall patient care. [ABSTRACT FROM AUTHOR]

Background: Bariatric surgery has been shown to improve hyperlipidemia, decreasing the need for statin medications. Although maintaining statin therapy post-surgery for those with a history of atherosclerotic cardiovascular disease (ASCVD) is advised, it is uncertain if discontinuation risks differ between those with and without ASCVD history. Aim: The study aims to analyze the rate and reasons for statin cessation post-bariatric surgery in the US using real-world data. Methods: Using the TriNetX electronic medical records network from 2012 to 2021, the study involved patients aged 18 or older on statins at the time of bariatric surgery. They were categorized into primary and secondary prevention groups based on prior ASCVD. Statin discontinuation was defined as a 90-day gap post the last statin dosage. The Cox model assessed factors influencing statin cessation. Results: Seven hundred and thirty-three statin users undergoing bariatric surgery were identified, with 564 (77%) in primary prevention. Six months post-surgery, 48% of primary prevention patients and 34.5% of secondary ones stopped statins. Primary prevention patients had a 30% higher likelihood of cessation compared to secondary prevention (hazard ratio, 1.30; 95% CI, 1.06–1.60) as shown by multivariable analysis. Conclusions: Post-bariatric surgery, primary prevention patients are more likely to discontinue statins than secondary prevention patients. [ABSTRACT FROM AUTHOR]

Background: Coronary computed tomography angiography (CCTA) enables improved diagnosis of subclinical, coronary artery disease (CAD). This retrospective cohort study investigated the association between different treatment modalities guided by CCTA and the prevention of major adverse cardiovascular events (MACEs) in patients with stable CAD. Methods: From 2005 to 2013, a total of 9338 patients, including both asymptomatic individuals with risk factors and symptomatic patients with suspected CAD, who underwent CCTA were analyzed. The patients were categorized into one of three groups based on results of CCTA: obstructive CAD (≥ 50% stenosis in at least one vessel), non-obstructive CAD (1–49% stenosis in at least one vessel), and no observed CAD (0% stenosis). They were subsequently followed up to assess the treatment they received and the occurrence of MACEs (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or late revascularization). Results: During an average follow-up period of 9.9 ± 2.4 years, patients with obstructive CAD had the highest incidence of MACEs (19.8%), followed by those with non-obstructive CAD and no coronary artery stenosis (10.3 and 5.5%, respectively). After adjusting for confounding variables, it was found that patients treated with statins alone were the least likely to develop MACEs in all three groups, compared to those receiving no treatment, with hazard ratios (95% CI) of 0.43 (0.32, 0.58), 0.47 (0.34, 0.64), and 0.46 (0.31, 0.69), respectively. In patients with obstructive CAD, treatment with a combination of statin and aspirin, or early revascularization was associated with a lower likelihood of experiencing MACEs compared to no treatment with hazard ratios of 0.43 (0.33, 0.58) and 0.64 (0.43, 0.97), respectively. Conclusion: CCTA offers useful guidance for the treatment of patients with stable CAD and shows potential for prevention of CV events. However, the full validation of a given strategy utilizing CCTA will require a prospective longitudinal study, utilizing a randomized clinical trial design. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of using statins and ascorbic acid for the prevention of post-contrast acute kidney injury (PC-AKI) in patients undergoing urologic diagnostic elective contrast-enhanced computed tomography (CECT). Methods: This registered trial (NCT03391830) was for statin naïve patients underwent elective CECT. Patients were randomized allocated to two groups: the first group received atorvastatin 80-mg the day before the study and atorvastatin 40-mg two hours before the CECT and for continue on atorvastatin 40-mg two days after CECT; plus ascorbic acid 500 mg with atorvastatin. The other group received two tablets of placebo once/daily before the procedure and for another 3 days. The primary outcome was to assess the incidence PC-AKI. Results: The baseline parameters were comparable between both groups. The final median (interquartile range "IQR") serum creatinine were 0.80 (0.60, 1.00) and 0.80 (0.60, 1.00), respectively, with insignificant p-value (p = 0.8). The median (IQR) final estimated GFR were 95.2 (72.8, 108.1) and 88.6 (71.9, 111.0) mL/min in placebo and statin plus ascorbic acid groups, respectively (p = 0.48). The eGFR difference median (IQR) were − 6.46 (− 11.72, − 4.18) and − 6.57 (− 13.38, − 3.82) ml/min in placebo and statin plus ascorbic acid groups, respectively (p = 0.58). PC-AKI occurred in 11 patients (9.8%) in placebo group and in 3 patients (3%) in statin plus ascorbic acid group (p = 0.04). Conclusions: Statin and ascorbic acid did not statistically improve neither serum creatinine nor eGFR values in patient underwent CECT. However, it can decrease the incidence of the clinically insignificant PC-AKI. [ABSTRACT FROM AUTHOR]

Background: Statin use before hospitalization or after discharge increased the survival rates of patients with dialysis-requiring acute kidney injury. This study aimed to investigate whether statin use during hospitalization period after renal replacement therapy is associated with reduced mortality in patients with dialysis-requiring acute kidney injury. Methods: This retrospective cohort study was conducted using the Medical Information Mart for Intensive Care IV database between 2008 and 2019. We compared 1-year mortality in patients with dialysis-requiring acute kidney injury with and without exposure to statin during hospitalization period after renal replacement therapy. The secondary outcome was in-hospital mortality. Results: Among 1035 patients with dialysis-requiring acute kidney injury, only 24.9% of the participants received statin therapy during hospitalization after renal replacement therapy. During the 1-year follow-up, 127 of 258 statin users (49.2%) and 541 of 777 statin nonusers (69.6%) died. The risk of 1-year mortality and in-hospital mortality of statin users was 54% lower [hazard ratio (HR) = 0.46; 95% confidence interval (CI) = 0.37 to 0.56, P < 0.001] and 59% lower HR = 0.41, 95% CI = 0.32 to 0.53, P < 0.001), respectively. Conclusion: For patients with dialysis-requiring acute kidney injury, statin therapy during hospitalization period after renal replacement therapy was associated with decreased 1-year mortality and in-hospital mortality. [ABSTRACT FROM AUTHOR]

Identification of high-risk carotid plaques in asymptomatic patients remains a challenging but crucial step in stroke prevention. The challenge is to accurately monitor the development of high-risk carotid plaques and promptly identify patients, who are unresponsive to best medical therapy, and hence targeted for carotid surgical interventions to prevent stroke. Inflammation is a key operator in destabilisation of plaques prior to clinical sequelae. Currently, there is a lack of imaging tool in routine clinical practice, which allows assessment of inflammatory activity within the atherosclerotic plaque. Herein, we have used a periarterial cuff to generate a progressive carotid atherosclerosis model in apolipoprotein E–deficient mice. This model produced clinically relevant plaques with different levels of risk, fulfilling American Heart Association (AHA) classification, at specific timepoints and locations, along the same carotid artery. Exploiting this platform, we have developed smart molecular magnetic resonance imaging (MRI) probes consisting of dual-targeted microparticles of iron oxide (DT-MPIO) against VCAM-1 and P-selectin, to evaluate the anti-inflammatory effect of statin therapy on progressive carotid atherosclerosis. We demonstrated that in vivo DT-MPIO-enhanced MRI can (i) quantitatively track plaque inflammation from early to advanced stage; (ii) identify and characterise high-risk inflamed, vulnerable plaques; and (iii) monitor the response to statin therapy longitudinally. Moreover, this molecular imaging–defined therapeutic response was validated using AHA classification of human plaques, a clinically relevant parameter, approximating the clinical translation of this tool. Further development and translation of this molecular imaging tool into the clinical arena may potentially facilitate more accurate risk stratification, permitting timely identification of the high-risk patients for prophylactic carotid intervention, affording early opportunities for stroke prevention in the future. [ABSTRACT FROM AUTHOR]

Purpose of Review: To review recent data describing the challenges and innovations in therapeutic research focused on the prevention and treatment of preeclampsia. Recent Findings: Pregnant individuals have traditionally been excluded from therapeutic research, resulting in a paucity of innovation in therapeutics for pregnancy-specific medical conditions, especially preeclampsia. With the increased awareness of maternal morbidity and mortality, there is significant interest among researchers to expand therapeutic research in pregnancy. Several medications, including aspirin, pravastatin, metformin, and esomeprazole, which are commonly used in non-pregnant populations, are now being investigated for preeclampsia prevention. However, given the historic precedent of exclusion, along with the regulatory, ethical, and feasibility concerns that accompany this population, the study of these and novel medications has been complicated by numerous challenges. Summary: While complex, and laden with challenges, there is great ongoing need for therapeutic research to address preeclampsia. Aspirin, pravastatin, metformin, and esomeprazole have all shown promise as potential therapeutic agents; however, their use remains to be optimized, and innovative therapeutics need to be developed. [ABSTRACT FROM AUTHOR]

Purpose: To study the effects of a perindopril-based regimen on cardiovascular (CV) outcomes in patients with vascular disease in relation to background statin therapy. Methods: A pooled analysis of the randomized ADVANCE, EUROPA, and PROGRESS trials was performed to evaluate CV outcomes in 29,463 patients with vascular disease treated with perindopril-based regimens versus placebo. The primary endpoint was a composite of CV mortality, nonfatal myocardial infarction, and stroke. Multivariable Cox regression analyses were performed to assess the effects of a perindopril-based regimen versus placebo in relation to statin use. Results: At randomization, 39.5% of the overall combined study population used statins. After a mean follow-up of 4.0 years (SD 1.0), the cumulative event-free survival was highest in the statin/perindopril group and lowest in the no statin/placebo group (91.2% vs. 85.6%, respectively, log-rank p < 0.001). In statin users (adjusted hazard ratio [aHR] 0.87, 95% confidence interval [CI] 0.77–0.98) and non-statin users (aHR 0.80, 95% CI 0.74–0.87), a perindopril-based regimen was associated with a significantly lower risk of the primary endpoint when compared to placebo. The additional treatment effect appeared numerically greater in non-statin users, but the observed difference was statistically nonsignificant. Conclusion: Our data suggest that the treatment benefits of a perindopril-based regimen in patients with vascular disease are independent of statin use. [ABSTRACT FROM AUTHOR]

Objective: While the cardioprotective benefits of statins for rheumatoid arthritis (RA) patients are well-established, there might be a hesitation in recommending them for dermatomyositis/polymyositis (DM/PM) patients with hyperlipidemia (HLD), particularly with myopathy. We sought to contrast statin prescription patterns between DM/PM-HLD and RA-HLD patients and delve into the mortality variations among DM/PM-HLD statin users and non-users. Methods: We examined a decade's worth of anonymized US health data from the TriNetX database. Inclusion criteria were a subsequent HLD diagnosis after an initial DM/PM or RA diagnosis. We compared statin initiation rates and mortality outcomes, adjusting for demographics and cardiovascular risks through propensity score matching. Results: The analysis comprised 33,000 RA-HLD and 1079 DM/PM-HLD patients. RA-HLD patients exhibited higher statin initiation (27.4%) than DM/PM-HLD patients (17.91%, p < 0.0001). Notably, DM/PM-HLD statin users (n = 311) presented a reduced mortality rate (75 deaths/1000/year) compared to non-users (n = 661) with 147 deaths/1000/year (p = 0.0273, HR = 0.515, CI 0.28–0.93). Conclusion: There is a marked disparity in statin initiation between DM/PM-HLD and RA-HLD patients, accompanied by elevated mortality in DM/PM-HLD non-users. It is imperative for further research to elucidate this discrepancy and formulate patient-centric cardiovascular guidelines for DM/PM-HLD patients. Key Points • Statin initiation among patients with DM/PM-HLD is significantly lower than that with RA-HLD. • Mortality rates within the statin initiator DM/PM-HLD were significantly lower compared to non-statin DM/PM-HLD initiators, spanning multiple time intervals. [ABSTRACT FROM AUTHOR]

There is limited and inconsistent evidence for the association of statin therapy and statin treatment patterns with the risk of recurrent intracerebral hemorrhage (ICH) in patients with prior ICH. To assess the association of statin therapy and its intensity, type, initiation time, and discontinuation with the risk of recurrent ICH and mortality in Chinese patients with ICH. Patients with newly diagnosed ICH in the Beijing Employee Medical Claims Data database from 2010 to 2017 were included. Post-ICH statin users (post-diagnosis only) and nonusers (never), statin discontinuers (pre-diagnosis only) and continuers (pre- and post-diagnosis) were matched on a 1:1 propensity score, respectively. Adjusted Cox proportional risk models were used to estimate the risk ratios for ICH readmission and mortality under various statin patterns. A total of 2668 post-ICH statin users and 2668 nonusers without a history of statin use were enrolled. Post-ICH statin users had a lower risk of ICH readmission (HR, 0.57; 95% CI 0.48, 0.69) and all-cause death (0.56: 0.49, 0.63) than nonusers. Low/moderate-intensity treatment was associated with a 63% lower risk of recurrent ICH compared with nonusers (0.37: 0.29, 0.46), whereas high-intensity treatment did not reduce the risk (0.93: 0.74, 1.16). Both low/moderate-intensity (0.42: 0.36, 0.48) and high-intensity statins (0.57: 0.48, 0.69) were associated with a lower risk of all-cause mortality. The risk of ICH readmission was 53% (0.47: 0.30, 0.74) lower with adherence to rosuvastatin than with atorvastatin. Only starting medication within 30 days of the first diagnosis of ICH reduced the risk of ICH readmission (0.49: 0.40, 0.60). Among patients with a history of statin use, 1807 discontinuing and 1,807 continuing users of statins were included. The risk of ICH readmission (4.00: 3.32, 4.80) and the risk of all-cause death (4.01: 3.57, 4.50) were substantially increased in statin discontinuation compared with continued statin use. Statin therapy after ICH was associated with lower risks for ICH readmission and all-cause mortality compared with non-statin therapy, especially at low/moderate intensity and early initiation of statins after ICH. Adherence to rosuvastatin was associated with a lower risk of recurrence of ICH than atorvastatin. Among patients with a statin history prior to ICH, discontinuation of statins after ICH was associated with increased risk of ICH recurrence and death. [ABSTRACT FROM AUTHOR]

There is increasing interest in drug therapy for preventing aneurysmal subarachnoid hemorrhage (aSAH). We aimed to comprehensively evaluate the association between drug use and the risk of aSAH. We searched PubMed and Scopus from the databases' inception until December 2021. Observational studies reporting the association between any drug therapy and aSAH were included. The odds ratios (ORs) for each drug used in aSAH were meta-analyzed with a random-effect model. According to the systematic review, 25 observational studies were eligible for the present study. Four therapeutic purpose-based classes (e.g., lipid-lowering agents) and 14 mechanism-based classes (e.g., statins) were meta-analyzed. Anti-hypertensive agents (OR, 0.50; 95% confidence interval [95% CI], 0.33–0.74), statins (OR, 0.55; 95% CI, 0.35–0.85), biguanides (OR, 0.57; 95% CI, 0.34–0.96), and acetylsalicylic acid (ASA) (OR, 0.62; 95% CI, 0.41–0.94) were inversely associated with the risk of aSAH. Non-ASA non-steroidal anti-inflammatory drugs (OR, 1.73; 95% CI, 1.07–2.79), selective cyclooxygenase-2 inhibitors (OR, 2.04; 95% CI, 1.24–3.35), vitamin K antagonists (OR, 1.50; 95% CI, 1.18–1.91), and dipyridamole (OR, 1.77; 95% CI, 1.23–2.54) were positively associated with the incidence of aSAH. There was also a trend toward a positive association between glucocorticoids (OR, 1.38; 95% CI, 0.97–1.94) and aSAH. The present study suggests that anti-hypertensive agents, statins, biguanides, and ASA are candidate drugs for preventing aSAH. By contrast, several drugs (e.g., anti-thrombotic drugs) may increase the risk of aSAH. Thus, the indications of these drugs in patients with intracranial aneurysms should be carefully determined. [ABSTRACT FROM AUTHOR]

Derangements of body composition affect surgical outcomes. Chronic statin use may induce muscle wasting and impair muscle tissue quality. Aim of this study was to evaluate the association of chronic statin use, skeletal muscle area (SMA), myosteatosis and major postoperative morbidity. Between 2011 and 2021, patients undergoing pancreatoduodenectomy or total gastrectomy for cancer, and using statins since at least 1 year, were retrospective studied. SMA and myosteatosis were measured at CT scan. The cut-off for SMA and myosteatosis were determined using ROC curve and considering severe complications as the binary outcome. The presence of myopenia was defined when SMA was lower that the cut-off. A multivariable logistic regression was applied to assess the association between several factors and severe complications. After a matching procedure (1:1) for key baseline risk factors (ASA; age; Charlson comorbidity index; tumor site; intraoperative blood loss), a final sample of 104 patients, of which 52 treated and 52 not treated with statins, was obtained. The median age was 75 years, with an ASA score ≥ 3 in 63% of the cases. SMA (OR 5.119, 95% CI 1.053–24.865) and myosteatosis (OR 4.234, 95% CI 1.511–11.866) below the cut-off values were significantly associated with major morbidity. Statin use was predictive of major complication only in patients with preoperative myopenia (OR 5.449, 95% CI 1.054–28.158). Myopenia and myosteatosis were independently associated with an increased risk of severe complications. Statin use was associated with a higher risk of having major morbidity only in the subgroup of patients with myopenia. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Inflammation is a core component of residual cardiovascular risk in type 2 diabetes. With new anti-inflammatory therapeutics entering the field, accurate markers to evaluate their effectiveness in reducing cardiovascular disease are paramount. Gallium-68-labelled DOTATATE (68Ga-DOTATATE) has recently been proposed as a more specific marker of arterial wall inflammation than 18F-fluorodeoxyglucose (18F-FDG). This study set out to investigate whether 68Ga-DOTATATE uptake is amenable to therapeutic intervention in individuals with type 2 diabetes. Methods: Individuals aged >50 years with type 2 diabetes underwent 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) at baseline and after 3 months treatment with atorvastatin 40 mg once daily. Primary outcome was the difference in coronary 68Ga-DOTATATE uptake, expressed as target-to-background ratio (TBR). The secondary outcome was difference in bone marrow and splenic uptake, expressed as the standardised uptake value (SUV). Results: Twenty-two individuals with type 2 diabetes (mean age 63.2±6.4 years, 82% male, LDL-cholesterol 3.42±0.81 mmol/l, HbA1c 55±12 mmol/mol [7.2%±3.2%]) completed both 68Ga-DOTATATE PET/CT scans. The maximum TBR was −31% (95% CI −50, −12) lower in the coronary arteries, and bone marrow and splenic 68Ga-DOTATATE uptake was also significantly lower post statin treatment, with a mean percentage reduction of −15% (95% CI −27, −4) and −17% (95% CI −32, −2), respectively. Conclusions/interpretation: 68Ga-DOTATATE uptake across the cardio–haematopoietic axis was lower after statin therapy in individuals with type 2 diabetes. Therefore, 68Ga-DOTATATE is promising as a metric for vascular and haematopoietic inflammation in intervention studies using anti-inflammatory therapeutics in individuals with type 2 diabetes. Trial registration: ClinicalTrials.gov NCT05730634 [ABSTRACT FROM AUTHOR]

Aims/hypothesis: We aimed to examine whether individuals with initial omission of glucose-lowering drug treatment (GLDT), including those achieving initial remission of type 2 diabetes, may experience a higher risk of major adverse cardiovascular events (MACE) compared with well-controlled individuals on GLDT after a new type 2 diabetes diagnosis in real-world clinical practice. Furthermore, we examined whether a higher risk could be related to lower initiation of statins and renin–angiotensin system inhibitors (RASi). Methods: In this cohort study, we used Danish registers to identify individuals with a first measured HbA1c between 48 and 57 mmol/mol (6.5–7.4%) from 2014 to 2020. Six months later, we divided participants into four groups according to GLDT and achieved HbA1c (<48 vs ≥48 mmol/mol [6.5%]): well-controlled and poorly controlled on GLDT; remission and persistent type 2 diabetes not on GLDT. We reported how much the standardised 5 year risk of MACE could be reduced for each group if initiation of statins and RASi was the same as in the well-controlled group on GLDT. Results: We included 14,221 individuals. Compared with well-controlled participants on GLDT, the 5 year standardised risk of MACE was higher in the three other exposure groups: by 3.3% (95% CI 1.6, 5.1) in the persistent type 2 diabetes group not on GLDT; 2.0% (95% CI 0.4, 3.7) in the remission group not on GLDT; and 3.5% (95% CI 1.3, 5.7) in the poorly controlled group on GLDT. Fewer individuals not on GLDT initiated statins and RASi compared with individuals on GLDT. If initiation of statins and RASi had been the same as in the well-controlled group on GLDT, participants not on GLDT could have reduced their risk of MACE by 2.1% (95% CI 1.2, 2.9) in the persistent type 2 diabetes group and by 1.1% (95% CI 0.4, 1.9) in the remission group. Conclusions/interpretation: Compared with well-controlled individuals on GLDT, individuals not on initial GLDT had a higher 5 year risk of MACE, even among those achieving remission of type 2 diabetes. This may be related to lower use of statins and RASi. [ABSTRACT FROM AUTHOR]

Statin-associated diabetes (SAD) is an issue that has come to light after a series of recent clinical trials that has led to the issue of a black box warning for statins by the US FDA. However, the benefit of statin outweighs its risk. Nevertheless, experiments have been conducted to identify the mechanism by which statins aggravate the risk of diabetes only in a select population who bear the risk factors of obesity, sedentary lifestyle, hypertension, and other associated risk factors of lifestyle disorders. In this study, the possibility of utilization of a phyto-molecule, sesamol, for its ability to combat statin-associated diabetes using atorvastatin as the agent of choice has been explored. MMP assay and western blot was conducted to investigate the effects of atorvastatin on apoptotic cascade with sesamol as a protective agent was conducted in MIN-6 cells. Effect of the combination was tested in L6 cells with 2-NBDG uptake assay and as well as western blot for GLUT-4. A diet-induced hypercholesterolemia model was developed in an in vivo model animals and treated with atorvastatin and sesamol with histopathological analysis being carried out to evaluate the apoptotic markers and GLUT-4 presence. It was found that sesamol can combat pancreatic beta cell apoptosis via the internal apoptotic pathway activated by atorvastatin. With regards to muscle cells, sesamol could improve the GLUT-4 vesical production, but not improve glucose uptake which is inhibited by atorvastatin. These findings are further confirmed by animal studies. These findings indicate that sesamol can serve as a prototype molecule for further development and investigation of similar compounds to tackle SAD. [ABSTRACT FROM AUTHOR]

Chronic subdural hematoma (cSDH) is common among the elderly, with surgical evacuation as a prevalent treatment, facing recurrence rates up to 30%. Recently, middle meningeal artery embolization (MMAE) has emerged as a promising approach, offering reduced treatment failures and recurrence rates. Additionally, statins, known for their anti-inflammatory properties, have been considered as a potential adjunctive or sole treatment for cSDH. However, the combination of MMAE with statins remains understudied. This systematic review and meta-analysis aims to evaluate the comparative outcomes of MMAE with statins versus MMAE alone in the treatment of cSDH. A comprehensive systematic search of the PubMed, Web of Science, and SCOPUS databases was conducted. Inclusion criteria were: studies published in English between the dates of inception of each database and August 2023, studies comparing the treatment of cSDH with either MMAE + statin or MMAE alone were included. Main outcome measures were complete resolution of the hematoma at follow-up and the recurrence rates. Two studies comprising 715 patients were included; 408 patients underwent MMAE + statin; and 307 underwent MMAE alone. MMAE + statin was not significantly superior to MMAE alone in achieving complete resolution of the hematoma at follow-up (RR: 0.99; CI: 0.91 to 1.07, P = 0.84), nor was it a significant difference in rates of recurrence (RR: 1.35; CI: 0.83 to 2.17, P = 0.21) between the two groups. MMAE + statin did not demonstrate significant superiority over MMAE alone for achieving complete resolution and decreasing the recurrence rates in cSDH patients. Further research with larger, randomized studies may be required to fully elucidate the potential synergistic effects of MMAE and statins in this patient population. [ABSTRACT FROM AUTHOR]

Rosuvastatin calcium (RST) is a medication used to lower cholesterol levels by increasing the number of low-density lipoprotein receptors on the cell surface. RST undergoes different degradation processes under different conditions (Thermal, light, acidity...etc.) leading to the formation of different degradation products; 5-oxo isomer, anti-isomer, and lactone form of RST. Lactone form of RST is the major degradation product. Chromatographic techniques were used to identify and quantitatively determine the concentration of RST and its degradation products, where the aqueous aprotic solvent mixture (acetonitrile (25): water (75)) is used as an extraction medium to release RST and its degradation product RST-Lactone from the dosage form. Unfortunately, the presence of water in the extraction mixture or mobile phase could enhance the acid hydrolysis of lactone (i.e., conversion of RST-Lactone into RST) during the analysis time giving an underestimated result of the actual content of the degradation product. The type of solvent matrix used in sample extraction was found to control the direction of RST ⇌ RST-lactone equilibrium. It is found that: (a) In aprotic solvents, the forward reaction (i.e., the conversion of RST to its lactone form is the only reaction that occurs. (b) When RST extracted in the acidic aqueous mobile phase, the reverse reaction was observed, and RST-Lactone was converted into RST. (c) When organic protic solvents such as methanol was used for the extraction, both RST and RST-Lactone were stable, and no reaction was observed. Kinetics helps to distinguish and control the type of and sources of degradation impurities. The rates of both reactions were found to follow the first-order kinetics with rate constants directly related to the ageing temperature, the rate constant for the reverse reaction (RST-Lactone → RST) was 20 times greater than the forward reaction. The formation of RST-Lactone form from RST occurs via intramolecular esterification mechanisms followed by proton transfer to the solvent. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Hyper-reflective crystalline deposits found in retinal lesions have been suggested to predict the progression of diabetic retinopathy, but the nature of these structures remains unknown. Methods: Scanning electron microscopy and immunohistochemistry were used to identify cholesterol crystals (CCs) in human donor, pig and mouse tissue. The effects of CCs were analysed in bovine retinal endothelial cells in vitro and in db/db mice in vivo using quantitative RT-PCR, bulk RNA sequencing, and cell death and permeability assays. Cholesterol homeostasis was determined using 2H2O and 2H7-cholesterol. Results: We identified hyper-reflective crystalline deposits in human diabetic retina as CCs. Similarly, CCs were found in the retina of a diabetic mouse model and a high-cholesterol diet-fed pig model. Cell culture studies demonstrated that treatment of retinal cells with CCs can recapitulate all major pathogenic mechanisms leading to diabetic retinopathy, including inflammation, cell death and breakdown of the blood–retinal barrier. Fibrates, statins and α-cyclodextrin effectively dissolved CCs present in in vitro models of diabetic retinopathy, and prevented CC-induced endothelial pathology. Treatment of a diabetic mouse model with α-cyclodextrin reduced cholesterol levels and CC formation in the retina, and prevented diabetic retinopathy. Conclusions/interpretation: We established that cholesterol accumulation and CC formation are a unifying pathogenic mechanism in the development of diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Hereditary spastic paraplegias (HSP) are rare, inherited neurodegenerative or neurodevelopmental disorders that mainly present with lower limb spasticity and muscle weakness due to motor neuron dysfunction. Whole genome sequencing identified bi-allelic truncating variants in AMFR, encoding a RING-H2 finger E3 ubiquitin ligase anchored at the membrane of the endoplasmic reticulum (ER), in two previously genetically unexplained HSP-affected siblings. Subsequently, international collaboration recognized additional HSP-affected individuals with similar bi-allelic truncating AMFR variants, resulting in a cohort of 20 individuals from 8 unrelated, consanguineous families. Variants segregated with a phenotype of mainly pure but also complex HSP consisting of global developmental delay, mild intellectual disability, motor dysfunction, and progressive spasticity. Patient-derived fibroblasts, neural stem cells (NSCs), and in vivo zebrafish modeling were used to investigate pathomechanisms, including initial preclinical therapy assessment. The absence of AMFR disturbs lipid homeostasis, causing lipid droplet accumulation in NSCs and patient-derived fibroblasts which is rescued upon AMFR re-expression. Electron microscopy indicates ER morphology alterations in the absence of AMFR. Similar findings are seen in amfra-/- zebrafish larvae, in addition to altered touch-evoked escape response and defects in motor neuron branching, phenocopying the HSP observed in patients. Interestingly, administration of FDA-approved statins improves touch-evoked escape response and motor neuron branching defects in amfra-/- zebrafish larvae, suggesting potential therapeutic implications. Our genetic and functional studies identify bi-allelic truncating variants in AMFR as a cause of a novel autosomal recessive HSP by altering lipid metabolism, which may potentially be therapeutically modulated using precision medicine with statins. [ABSTRACT FROM AUTHOR]

Purpose: Novel pharmaceutical treatments reducing cardiovascular events in dyslipidaemia patients must demonstrate clinical efficacy and cost-effectiveness to promote long-term adoption by patients, physicians, and insurers. Objective: To assess the cost-effectiveness of statin monotherapy compared to additive lipid-lowering therapies for primary and secondary cardiovascular prevention from the perspective of Germany's healthcare system. Methods: Transition probabilities and hazard ratios were derived from cardiovascular outcome trials for statin combinations with icosapent ethyl (REDUCE-IT), evolocumab (FOURIER), alirocumab (ODYSSEY), ezetimibe (IMPROVE-IT), and fibrate (ACCORD). Costs and utilities were retrieved from previous literature. The incidence of major adverse cardiovascular events was simulated with a Markov cohort model. The main outcomes were the incremental cost-effectiveness ratios (ICER) per quality adjusted life year (QALY) gained. Results: For primary prevention, the addition of icosapent ethyl to statin generated 0.81 QALY and €14,732 costs (ICER: 18,133), whereas fibrates yielded 0.63 QALY and € − 10,516 costs (ICER: − 16,632). For secondary prevention, the addition of ezetimibe to statin provided 0.61 QALY at savings of € − 5,796 (ICER: − 9,555) and icosapent ethyl yielded 0.99 QALY and €14,333 costs (ICER: 14,485). PCSK9 inhibitors offered 0.55 and 0.87 QALY at costs of €62,722 and €87,002 for evolocumab (ICER: 114,639) and alirocumab (ICER: 100,532), respectively. A 95% probability of cost-effectiveness was surpassed at €20,000 for icosapent ethyl (primary and secondary prevention), €119,000 for alirocumab, and €149,000 for evolocumab. Conclusions: For primary cardiovascular prevention, a combination therapy of icosapent ethyl plus statin is a cost-effective use of resources compared to statin monotherapy. For secondary prevention, icosapent ethyl, ezetimibe, evolocumab, and alirocumab increase patient benefit at different economic costs. [ABSTRACT FROM AUTHOR]

Purpose of Review: To review recent international and domestic definitions, considerations, and treatment algorithms for statin intolerance, and specifically, statin-associated muscle symptoms (SAMS). Recent Findings: Multiple organizations around the world have produced guidance documents to aid clinicians on managing statin intolerance. A common theme resides among all the guidance documents that most patients can tolerate statins. For those patients who cannot, healthcare teams need to evaluate, rechallenge, educate, and ensure adequate reduction of atherogenic lipoproteins. Summary: Statin therapy remains the cornerstone of lipid-lowering therapies to reduce atherosclerotic cardiovascular disease (ASCVD) and reduce mortality and morbidity. The common theme throughout all these guidance documents is the importance of statin therapy to reduce ASCVD and continual adherence to treatment. Because adverse events occur and inhibit patients from achieving adequate lowering of their atherogenic lipoproteins, trial and rechallenge of statin therapy, as well as addition of non-statin therapies, especially in high-risk patients, is also undisputed. The main differences stem from laboratory monitoring and the classification of the severity of the adverse effect. Future research should focus on consistently diagnosing SAMS so that these patients can be easily identified in the electronic health records. [ABSTRACT FROM AUTHOR]

Purpose: While some work has been done on Health-Related Quality of Life (HRQoL) in statin users, none has focused specifically on statin-associated muscle symptoms (SAMS) sufferers. The objective was to assess self-reported HRQoL, before and after statin withdrawal, in patients reporting SAMS. We hypothesized that the presence of SAMS associated with decreased self-reported physical and mental well-being. Methods: Patients (50 men/28 women [M/W], aged 49 ± 9 years [Mean ± SD]) in primary cardiovascular prevention were recruited into three cohorts: statin users with (SAMS, 29 M/18W) or without symptoms (No SAMS, 10 M/5W) and controls (11 M/5W). The Short Form 36 Health Survey (SF-36) was used to assess HRQoL. All variables were measured before and after 2 months of statin withdrawal, and repeated measures analyses were used to verify withdrawal and group effects as well as their interaction. Results: SF-36 physical and mental component scores (respectively, PCS and MCS) were lower in the SAMS group compared with other groups (both p < 0.01). Statin withdrawal led to an increase in LDL cholesterol for statin users (+69.0%, p < 0.01) and an improvement in well-being in the SAMS group, other groups showing no change. A time x category interaction (p = 0.02) was seen for PCS and post hoc analyses showed that statin withdrawal improved PCS and MCS (respectively, +12.5% [ES 0.77] and +5.1% [ES 0.27], both p < 0.05) in the SAMS group. Conclusion: Patients self-reporting SAMS showed improved HRQoL following drug withdrawal, but this was mirrored by a rise in LDL cholesterol. These findings should be considered by clinicians in the evaluation and follow-up of treatment with statins. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) is a major cause of morbidity and mortality among patients with type 2 diabetes. Statin reduces CVD risk. The ACC/AHA 2018 guideline on dyslipidemia recommends all patients with type 2 diabetes mellitus to be given moderate-intensity statin. We aimed to determine the prescription practices of statins among patients with type 2 diabetes mellitus. Methods: A cross-sectional study was conducted from February to April 2021. Patients with type 2 diabetes mellitus between 40 and 75 years were recruited from the University Medical Clinic and Endocrine Clinic at Colombo South Teaching Hospital, Sri Lanka. Results: Four hundred seventy-one patients were enrolled with a mean age of 59.05 (± 9.139) years. The mean duration of diabetes was 10.97 (± 9.57) years. Four hundred forty-one (93.6%) patients were on statin and 30 (6.4%) patients were not on statin therapy. Those not on statins were not prescribed statins. Conclusions: There were 163 (34.61%) patients who required high intensity. Though only 3 (1.73%) were on high-strength statin, the rest were on moderate (152, 93.25%), low (4, 2.45%), and none (4, 2.45%). Among patients with prior history of atherosclerotic cardiovascular disease (ASCVD) and the high-risk category according to the 10-year ASCVD risk estimation (155, 32.91%), only 17 (10.97%) have achieved optimal LDL therapeutic targets (55mg/dL). A large proportion of the study population received statin therapy for primary and secondary prophylaxis. However, the majority were on suboptimal doses of statin and have not achieved therapeutic targets with regard to LDL-C levels. The findings highlight the importance of improving statin therapy and optimizing lipid management according to evidence-based guideline recommendations. [ABSTRACT FROM AUTHOR]

Statins represent the cornerstone of pharmacotherapy for the prevention of atherosclerotic cardiovascular disease. These medications not only reduce low-density lipoprotein cholesterol (LDL-C) via inhibition of 3-hydroxy-3-methylglutarate attached to CoA reductase, the key rate-limiting step in the cholesterol biosynthetic pathway, but also upregulate expression of the low-density lipoprotein receptor, improving serum clearance. Given LDL-C is a causal risk factor for the development of atherosclerosis, these complementary mechanisms largely explain why statin therapy leads to reductions in major adverse cardiovascular events. However, decades of basic and clinical research have suggested that statins may exert other effects independent of LDL-C lowering, termed pleiotropic effects, which have become a topic of debate among the scientific community. While some literature suggests statins may improve plaque stability, reduce inflammation and thrombosis, decrease oxidative stress, and improve endothelial function and vascular tone, other studies have suggested potential harmful pleiotropic effects related to increased risk of muscle-related side effects, diabetes, hemorrhagic stroke, and cognitive decline. Furthermore, the introduction of newer, non-statin LDL-C lowering therapies, including ezetimibe, proprotein convertase subtilisin/Kexin Type 9, and bempedoic acid, have challenged the statin pleiotropy theory. This review aims to provide a historical background on the development of statins, explore the mechanistic underpinnings of statin pleiotropy, review the available literature, and provide up to date examples that suggest statins may exert effects outside of LDL-C lowering and the cardiovascular system. [ABSTRACT FROM AUTHOR]

Background: We sought to determine whether statin treatment has a protective effect on the outcome of critically ill patients on mechanical ventilation. Methods: Patients who underwent mechanical ventilation were selected from the MIMIC-III database. Patients with statin usage were allocated into the statin cohort. Patients without any statin use were matched to the statin cohort in a 1:1 ratio by propensity score. To ensure the robustness of the findings, we utilized the gradient boosted model, propensity score analysis, doubly robust estimation and an inverse probability‐weighting model in the statistical procedure. Results: Before matching, 17,452 patients were enrolled in the non-statin group and 3,999 in the statin group. After matching, 3,363 patients were enrolled in each group. Compared with nonusers, the use of statins was associated with improved 28-day survival in the unmatched cohort (HR 0.85 95% CI 0.80–0.90, p < 0.01) and matched cohort (HR 0.79 95% CI 0.73–0.85, p < 0.01). Statin use was associated with longer ventilator-free days (VFD, 14.93 ± 13.11 vs 12.06 ± 13.26, p < 0.01) and longer ICU-free days (IFD, 13.41 ± 12.14 vs 10.86 ± 12.19, p < 0.01) in the matched cohort. Different types of statins were all associated with significantly improved 28-day survival. Conclusions: In a population of mechanically ventilated patients, the use of statins may be associated with improved survival, longer VFDs and longer IFDs. [ABSTRACT FROM AUTHOR]