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Aldo Lorenzetti M.D, Internal Medicine & Hepatology, Milano - SIMEDET Delegate
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#Statin Safety and Associated Adverse Events: A Scientific Statement From the American #Heart Association

https://www.ahajournals.org/doi/abs/10.1161/ATV.0000000000000073

The risk of statin-induced serious muscle injury, including rhabdomyolysis, is <0.1%, and the risk of serious hepatotoxicity is ≈0.001%. The risk of statin-induced newly diagnosed diabetes mellitus is ≈0.2% per year of treatment, depending on the underlying risk of diabetes mellitus in the population studied.

In patients with cerebrovascular disease, statins possibly increase the risk of hemorrhagic stroke; however, they clearly produce a greater reduction in the risk of atherothrombotic stroke and thus total stroke, as well as other cardiovascular events. There is no convincing evidence for a causal relationship between statins and cancer, cataracts, cognitive dysfunction, peripheral neuropathy, erectile dysfunction, or tendonitis. In US clinical practices, roughly 10% of patients stop taking a statin because of subjective complaints, most commonly muscle symptoms without raised creatine kinase.

In contrast, in randomized clinical trials, the difference in the incidence of muscle symptoms without significantly raised creatinine kinase in statin-treated compared with placebo-treated participants is <1%, and it is even smaller (0.1%) for patients who discontinued treatment because of such muscle symptoms.

This suggests that muscle symptoms are usually not caused by pharmacological effects of the statin. Restarting statin therapy in these patients can be challenging, but it is important, especially in patients at high risk of cardiovascular events, for whom prevention of these events is a priority. Overall, in patients for whom statin treatment is recommended by current guidelines, the benefits greatly outweigh the risks.
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Association of #Statin Therapy With Prevention of Vision-Threatening Diabetic #Retinopathy

https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2720491

Patients in the statin group had a significantly lower rate of diabetic retinopathy nonproliferative diabetic retinopathy (HR, 0.92; 95% CI, 0.86-0.99), proliferative diabetic retinopathy vitreous hemorrhage (HR, 0.62; 95% CI, 0.54-0.71), tractional retinal detachment (HR, 0.61; 95% CI, 0.47-0.79), and macular edema (HR, 0.60; 95% CI, 0.46-0.79) than the nonstatin group, as well as lower rates of interventions such as retinal laser treatment (HR, 0.71; 95% CI, 0.65-0.77), intravitreal injection (HR, 0.74; 95% CI, 0.61-0.89), and vitrectomy (HR, 0.58; 95% CI, 0.48-0.69), along with a smaller number of the interventions (retinal lasers: rate ratio, 0.61; 95% CI, 0.59-0.64; intravitreal injections: rate ratio, 0.68; 95% CI, 0.61-0.76; and vitrectomies: rate ratio, 0.54; 95% CI, 0.46-0.63). Statin therapy was also associated with lower risks of major adverse cardiovascular events (HR, 0.81; 95% CI, 0.77-0.85), new-onset diabetic neuropathy (HR, 0.85; 95% CI, 0.82-0.89), and new-onset diabetic foot ulcers (HR, 0.73; 95% CI, 0.68-0.78).

Conclusions and Relevance Statin therapy was associated with a decreased risk of diabetic retinopathy and need for treatments for vision-threatening diabetic retinopathy in Taiwanese patients with type 2 diabetes and dyslipidemia.
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Efficacy and safety of #statin therapy in #older people: a meta-analysis of individual participant data from 28 randomised controlled trials

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31942-1/fulltext

Statin therapy has been shown to reduce major vascular events and vascular mortality in a wide range of individuals, but there is uncertainty about its efficacy and safety among older people. We undertook a meta-analysis of data from all large statin trials to compare the effects of statin therapy at different ages.

The proportional reduction in major vascular events was similar, irrespective of age, among patients with pre-existing vascular disease (ptrend=0·2), but appeared smaller among older than among younger individuals not known to have vascular disease (ptrend=0·05). We found a 12% (RR 0·88, 95% CI 0·85–0·91) proportional reduction in vascular mortality per 1·0 mmol/L reduction in LDL cholesterol, with a trend towards smaller proportional reductions with older age (ptrend=0·004), but this trend did not persist after exclusion of the heart failure or dialysis trials (ptrend=0·2). Statin therapy had no effect at any age on non-vascular mortality, cancer death, or cancer incidence.
Interpretation

Statin therapy produces significant reductions in major vascular events irrespective of age, but there is less direct evidence of benefit among patients older than 75 years who do not already have evidence of occlusive vascular disease. This limitation is now being addressed by further trials
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Low #statin use in nondialysis-dependent chronic #kidney disease in the absence of clinical atherosclerotic cardiovascular disease or diabetes

https://academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfy131/5303222?searchresult=1

Both reduced glomerular filtration rate and increased urine albumin excretion, markers of chronic kidney disease (CKD), are associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). However, CKD is not recognized as an ASCVD risk equivalent by most lipid guidelines. Statin medications, especially when combined with ezetimibe, significantly reduce ASCVD risk in patients with nondialysis-dependent CKD.

Of veterans with CKD, 62.1% used statins in 2012 and 55.4% used statins continuously over 2 years (2012–13). Statin use in 2012 was 76.2 and 75.5% among veterans with CKD and ASCVD or diabetes, respectively, but in the absence of ASCVD, diabetes or a diagnosis of hyperlipidemia, statin use was 21.8% (P < 0.001). The 10-year predicted ASCVD risk was ≥7.5% in 95.1% of veterans with CKD, regardless of diabetes status.

Conclusions
Statin use is low in veterans with nondialysis-dependent CKD in the absence of ASCVD or diabetes despite high-predicted ASCVD risk. Future studies should examine other populations.
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Patient‐Reported Reasons for Declining or Discontinuing #Statin Therapy: Insights From the PALM Registry

https://www.ahajournals.org/doi/full/10.1161/JAHA.118.011765

Of those not on a statin, 894 (59.2%) reported never being offered a statin, 153 (10.1%) declined a statin, and 464 (30.7%) had discontinued therapy. Women (relative risk: 1.22), black adults (relative risk: 1.48), and those without insurance (relative risk: 1.38) were most likely to report never being offered a statin. Fear of side effects and perceived side effects were the most common reasons cited for declining or discontinuing a statin. Compared with statin users, those who declined or discontinued statins were less likely to believe statins are safe (70.4% of current users vs. 36.9% of those who declined and 37.4% of those who discontinued) or effective (86.3%, 67.4%, and 69.1%, respectively). Willingness to take a statin was high; 67.7% of those never offered and 59.7% of patients who discontinued a statin would consider initiating or retrying a statin.

Conclusions
More than half of patients eligible for statin therapy but not on treatment reported never being offered one by their doctor. Concern about side effects was the leading reason for statin refusal or discontinuation. Many patients were willing to reconsider statin therapy if offered
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Association of #Statin Use and High Serum #Cholesterol Levels With Risk of Primary Open-Angle #Glaucoma

https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2732293

The use of statins (hydroxymethylglutaryl coenzyme A inhibitors) has been associated with a lower risk of primary open-angle glaucoma (POAG); however, results have been conflicting, and little is known about the association between high cholesterol levels and POAG

Every 20-mg/dL increase in total serum cholesterol was associated with a 7% increase in risk of POAG (RR, 1.07 [95% CI, 1.02-1.11]; P = .004). Any self-reported history of elevated cholesterol was also associated with a higher risk of POAG (RR, 1.17 [95% CI, 1.00-1.37]). A history of any statin use was associated with a 15% lower risk of POAG (RR, 0.85 [95% CI, 0.73-0.99]). Use of statins for 5 or more years vs never use of statins was associated with a 21% lower risk of POAG (RR, 0.79 [95% CI, 0.65-0.97]; P = .02 for linear trend). The association between use of statins for 5 or more years vs never use of statins and risk of POAG was more inverse in those who were older (≥65 years: RR, 0.70 [95% CI, 0.56-0.87] vs <65 years: RR, 1.05 [95% CI, 0.68-1.63]; P = .01 for interaction).

Conclusions and Relevance Among adults aged 40 years or older, higher serum cholesterol levels were associated with higher risk of POAG, while 5 or more years of statin use compared with never use of statins was associated with a lower risk of POAG.
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Association Between #Statin Use and Risk of #dementia After a Concussion

https://jamanetwork.com/journals/jamaneurology/article-abstract/2733673

Concussions are an acute injury that may lead to chronic disability, while statin use might improve neurologic recovery.

This study identified 28 815 patients diagnosed as having a concussion (median age, 76 years; 61.3% female), of whom 7058 (24.5%) received a statin, and 21 757 (75.5%) did not receive a statin. A total of 4727 patients subsequently developed dementia over a mean follow-up of 3.9 years, equal to an incidence of 1 case per 6 patients. Patients who received a statin had a 13% reduced risk of dementia compared with patients who did not receive a statin (relative risk, 0.87; 95% CI, 0.81-0.93; P < .001). The decreased risk of dementia associated with statin use applied to diverse patient groups, remained independent of other cardiovascular medication use, intensified over time, was distinct from the risk of subsequent depression, and was not observed in patients after an ankle sprain.

Conclusions and Relevance In this study, older adults had a substantial long-term risk of dementia after a concussion, which was associated with a modest reduction among patients receiving a statin.
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Benefit of Adding #Ezetimibe to #Statin Therapy on Cardiovascular Outcomes and Safety in Patients With Versus Without Diabetes Mellitus

https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.117.030950

...When stratified by the TIMI (Thrombolysis in Myocardial Infarction) Risk Score for Secondary Prevention, all patients with DM demonstrated benefit with E/S regardless of risk. In contrast, among patients without DM, those with a high risk score experienced a significant (18%) relative reduction in the composite of cardiovascular death, myocardial infarction, and ischemic stroke with E/S compared with placebo/simvastatin, whereas patients without DM at low or moderate risk demonstrated no benefit with the addition of ezetimibe to simvastatin (Pint =0.034).

Conclusions:

In IMPROVE-IT, the benefit of adding ezetimibe to statin was enhanced in patients with DM and in high-risk patients without DM.
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Diagnosis of #osteoporosis in #statin-treated patients is dose-dependent

..There was a highly non-trivial dependence of statin dosage with the ORs of osteoporosis. Osteoporosis was underrepresented in low-dose statin treatment (0–10 mg per day), including lovastatin (OR: 0.39, CI 0.18 to 0.84, p<0.05), pravastatin (OR: 0.68, 95% CI 0.52 to 0.89, p<0.01), simvastatin (OR: 0.70, 95% CI 0.56 to 0.86, p<0.01) and rosuvastatin (OR: 0.69, 95% CI 0.55 to 0.87, p<0.01).

However, the exceeding of the 40 mg threshold for simvastatin (OR: 1.64, 95% CI 1.31 to 2.07, p<0.01), and the exceeding of a 20 mg threshold for atorvastatin (OR: 1.78, 95% CI 1.41 to 2.23, p<0.01) and for rosuvastatin (OR: 2.04, 95% CI 1.31 to 3.18, p<0.01) was related to an overrepresentation of osteoporosis.

Conclusion Our results show that the diagnosis of osteoporosis in statin-treated patients is dose-dependent. Thus, osteoporosis is underrepresented in low-dose and overrepresented in high-dose statin treatment, demonstrating the importance of future studies’ taking dose-dependency into account when investigating the relationship between statins and osteoporosis.

https://ard.bmj.com/content/78/12/1706
#Statin-induced GGPP depletion blocks macropinocytosis and starves cells with oncogenic defects
https://2medical.news/2020/03/18/statin-induced-ggpp-depletion-blocks-macropinocytosis-and-starves-cells-with-oncogenic-defects/

Our studies establish a connection between two isolated observations that 1) statins, taken by millions to lower cholesterol, have antitumor activity and 2) Ras-induced macropinocytosis is important in tumorigenesis. We discover that by depleting GGPP required for pseudopod extension and macropinocytosis, statins selectively kill cells with oncogenic defects by limiting nutrient uptake. https://bit.ly/2wT1ypw
Association between #statin use and incidence or progression of #osteoarthritis: Meta-analysis of observational studies
https://2medical.news/2020/05/04/association-between-statin-use-and-incidence-or-progression-of-osteoarthritis-meta-analysis-of-observational-studies/

..A total of 11 studies (679807 participants) were identified from the systematic literature search. No significant association between statin use and incidence (OR = 1.010; 95% CI: 0.968 to 1.055; P = 0.638) or progression (OR = 1.076; 95% CI: 0.824 to 1.405; P = 0.589) of OA was found in our meta-analysis. The meta-analysis according to the symptomatic or radiological OA also found no …
Interventions to Improve #Statin Tolerance and Adherence in Patients at Risk for #Cardiovascular Disease
https://2medical.news/2020/09/25/interventions-to-improve-statin-tolerance-and-adherence-in-patients-at-risk-for-cardiovascular-disease/

Strategies to improve patients’ tolerance of and adherence to statins may enhance the effectiveness of dyslipidemia treatment in those at risk for cardiovascular disease (CVD).. ..One SR, 1 RCT, and 4 cohort studies were included. The SR found that intensified patient care improved adherence and decreased levels of total serum cholesterol and low-density lipoprotein cholesterol (LDL-C) at 6 months or more of follow-up. Compared with …
#Statin treatment and #muscle symptoms: series of randomised, placebo controlled n-of-1 trials
https://2medical.news/2021/02/26/statin-treatment-and-muscle-symptoms-series-of-randomised-placebo-controlled-n-of-1-trials/

To establish the effect of statins on muscle symptoms in people who had previously reported muscle symptoms when taking statins. Design Series of randomised, placebo controlled n-of-1 trials. Setting Primary care across 50 sites in the United Kingdom, December 2016 to April 2018. Participants 200 participants who had recently stopped or were considering stopping treatment with statins because of muscle symptoms. Interventions Participants were randomised …
Association between antecedent #statin use and decreased mortality in hospitalized patients with #COVID-19
https://2medical.news/2021/03/07/association-between-antecedent-statin-use-and-decreased-mortality-in-hospitalized-patients-with-covid-19/

The coronavirus disease 2019 (COVID-19) can result in a hyperinflammatory state, leading to acute respiratory distress syndrome (ARDS), myocardial injury, and thrombotic complications, among other sequelae. Statins, which are known to have anti-inflammatory and antithrombotic properties, have been studied in the setting of other viral infections, but their benefit has not been assessed in COVID-19. This is a retrospective analysis of patients admitted with COVID-19 …
#Statin use is associated with lower prevalence of advanced liver #fibrosis in patients with type 2 diabetes
https://2medical.news/2021/03/14/statin-use-is-associated-with-lower-prevalence-of-advanced-liver-fibrosis-in-patients-with-type-2-diabetes/

Patients with type 2 diabetes (T2D) are at increased risk of both cardiovascular disease (CVD) and advanced liver fibrosis related to non-alcoholic fatty liver disease (NAFLD). Statin use is known to reduce the incidence of CVD while evidence on an effect on NAFLD severity is limited. Methods This is a cross-sectional study performed with data from the 2017–2018 cycle of the National Health and Nutrition Examination …
Effects of double-dose #statin therapy for the prevention of post- #stroke #epilepsy: A prospective clinical study
https://2medical.news/2021/04/19/effects-of-double-dose-statin-therapy-for-the-prevention-of-post-stroke-epilepsy-a-prospective-clinical-study/

To determine treatment effects on the incidence of post-stroke epilepsy (PSE) using different doses of statin, a prospective hospital-based cohort study was designed to explore whether a double-dose statin treatment can better prevent the occurrence of PSE. Methods :A total of 1152 patients with newly diagnosed ischemic stroke admitted to our hospital from March to August 2017 were selected, 1033 of whom were followed-up. Patients …