https://www.archivesofmedicalscience.com/pdf-141941-69723?filename=PoLA_CFPiP_PCS_PSLD_PSD_P.pdf

PoLA/CFPiP/PCS/PSLD/PSD/PSH guidelines on diagnosis and therapy of lipid disorders in Poland 2021

Treatment with statins, inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase, has proven beneficial preventive effects on cardiovascular events. However, discontinuation due to intolerance and nonadherence remain two of the major gaps in both primary and secondary prevention. This leads many patients with high-risk of atherosclerotic cardiovascular disease (ASCVD) to be inadequately treated or not to achieve the target lipid level goals, and as consequence they undergo an increased risk of cardiovascular events. The aim of this review is thus to give an overview of the reasons for discontinuation and on the possible mechanisms behind them. Although statins, as a class, are generally safe, they are associated with an increased risk of diabetes mellitus and hepatic transaminase elevations. Incidence of cataracts or cognitive dysfunction and others presented in the literature (e.g., proteinuria and haematuria) have been never confirmed to have a causal link. Conversely, debated remains the effect on myalgia. Muscle side effects are the most commonly reported, although myalgia is still believed by some to be the result of a nocebo/drucebo effect. Concerning mechanisms behind these side effects no clear conclusions have been reached. Thus, if on one side it is important to identify individuals either at higher risk to develop a side effect, or with confirmed risk factors and conditions of statin intolerance, on the other side alternative strategies should be identified to avoid an increased ASCVD risk.

/pdf/side-effects-of-statins-from-pathophysiology-and-1jxpvlgs.pdf

Side effects of statins-from pathophysiology and epidemiology to diagnostic and therapeutic implications.

Statins are competitive inhibitors of hydroxymethylglutaryl-CoA (HMG-CoA) reductase and have been used to treat elevated low-density lipoprotein cholesterol (LDL-C) for almost four decades. Antioxidant and anti-inflammatory properties which are independent of the lipid-lowering effects of statins, i.e., their pleiotropic effects, might be beneficial in the prevention or treatment of many diseases. This review discusses the antioxidant effects of statins achieved by modulating the nuclear factor erythroid 2 related factor 2/ heme oxygenase-1 (Nrf2/HO-1) pathway in different organs and diseases. Nrf2 and other proteins involved in the Nrf2/HO-1 signaling pathway have a crucial role in cellular responses to oxidative stress, which is a risk factor for ASCVD. Statins can significantly increase the DNA-binding activity of Nrf2 and induce the expression of its target genes, such as HO-1 and glutathione peroxidase) GPx, (thus protecting the cells against oxidative stress. Antioxidant and anti-inflammatory properties of statins, which are independent of their lipid-lowering effects, could be partly explained by the modulation of the Nrf2/HO-1 pathway. 

/pdf/antioxidant-effects-of-statins-by-modulating-nrf2-and-nrf2-1rt56qn2.pdf

Antioxidant Effects of Statins by Modulating Nrf2 and Nrf2/HO-1 Signaling in Different Diseases

Statin intolerance is a clinical syndrome whereby adverse effects (AEs) associated with statin therapy [most commonly statin‐associated muscle symptoms (SAMS)] result in the discontinuation of therapy and consequently increase the risk of adverse cardiovascular outcomes. However, complete statin intolerance occurs in only a small minority of treated patients (estimated prevalence of only 3–5%). Many perceived AEs are misattributed (e.g. physical musculoskeletal injury and inflammatory myopathies), and subjective symptoms occur as a result of the fact that patients expect them to do so when taking medicines (the nocebo/drucebo effect)—what might be truth even for over 50% of all patients with muscle weakness/pain. Clear guidance is necessary to enable the optimal management of plasma in real‐world clinical practice in patients who experience subjective AEs. In this Position Paper of the International Lipid Expert Panel (ILEP), we present a step‐by‐step patient‐centred approach to the identification and management of SAMS with a particular focus on strategies to prevent and manage the nocebo/drucebo effect and to improve long‐term compliance with lipid‐lowering therapy.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jcsm.12960

Step‐by‐step diagnosis and management of the nocebo/drucebo effect in statin‐associated muscle symptoms patients: a position paper from the International Lipid Expert Panel (ILEP)

Comparison of statins with steroids and botulinum toxin A in the prevention of benign strictures after esophageal endoscopic submucosal dissection: a retrospective cohort study

Background Conflicting data suggest that statins could cause chronic liver disease in certain group of patients, while improving prognosis in those with chronic viral hepatitis (CVH). Purpose To quantify the potential protective role of statins on some main liver-related health outcomes in clinical studies on CVH patients.Data Sources: The search strategy was explored by a medical librarian using bibliographic databases, from January 2015 to April 2020.Data synthesis: The results showed no significant difference in the risk of mortality between statin users and non-users in the overall analysis. However, the risk of mortality significantly reduced by 39% in statin users who were followed for more than three years. Moreover, the risk of HCC, fibrosis, and cirrhosis in those on statins decreased by 53%, 45% and 41%, respectively. Although ALT and AST reduced slightly following statin therapy, this reduction was not statistically significant. Limitations A significant heterogeneity among studies was observed, resulting from differences in clinical characteristics between statin users and non-users, study designs, population samples, diseases stage, comorbidities, and confounding covariates. Conclusion Not only long-term treatment with statins seems to be safe in patients affected by hepatitis, but also it significantly improves their prognosis.

Statin therapy in chronic viral hepatitis: a systematic review and meta-analysis of nine studies with 195,602 participants.

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Statin therapy in chronic viral hepatitis: a systematic review and meta-analysis of nine studies with 195,602 participants.