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Update - Week 12, 2018
 
Curated by Peter Lansberg,
a Dutch lipidologist and educator, and
reviewed by prof. Philip Barter, Past President of the
International Atherosclerosis Society.
The IAS Statin Newsletter will keep you up-to-date with all recent statin publications, using a curated approach to select relevant articles.

Key publications

Which statin intolerant patients most likely to successfully restart statins?
One of the greatest challenges in managing patients at risk for CVD is ensuring the continued use of their statins. In this retrospective analysis of a primary care registry of two academic medical centers in Boston USA between 2000 and 2012. The authors evaluated patients that reported adverse reactions to statins but ultimately were capable of taking their lipid lowering drugs. They identified actionable patient and treatment characteristics, associated with successful re-treatment. Successful reattempts were defined as having at least 2 statin prescriptions after discontinuation of the culprit statin, and an active EHR, 2 years after the adverse response. The majority of the 6196 participants, 73,5% (4536) were able to reinitiate and tolerate a statin. Characteristics that predicted a successful re-attempt were: history of CAD, stroke or diabetes OR 1.195; p=0.008. Using a different statin for the reattempt OR 1.463; p<0.0001. Patients with adverse reactions in the first year of initiating statins, myalgia or myopathy as well as an history of adverse reactions to nonstatin drugs were less like to successfully re-initiate a statin. OR’s of respectively 0.721; P<0.0001, 0.807; p=0.001 and 0.908; p<0.001). the authors concluded that a patient centered approach to re-initiate statins showed a great likelihood of success.
Zhang H, Plutzky J, Ge W et al. Predictors of a successful statin reattempt after an adverse reaction. J Clin Lipidol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29567104
 
Half of high risk US and UK adults not using statins
Despite the well accepted US and UK guidelines for lipid management, almost half of all high CVD risk US (49.7%) and UK (46%) adults, are not being treated with statins. Data collected in the English Health Survey (2009 -20013) and the US NHANES (2007-2012) registry was used for this analysis. In the US 20.29 million patients would need to start statins as to prevent 616 000 CVD events in the next 10 years. For the UK this would applicable to 1.45 million high risk adults and prevent 101 000 events. If expanded to untreated moderate risk adults, 3.64 million individuals would need to start statins in order to prevent 128 000 CVD events. The authors point out that despite the distinctly different US and UK healthcare systems, these numbers were remarkably comparable. They suggested that many physicians still use cholesterol levels as a trigger to start statins instead of calculating 10-year or lifetime CVD risk. To address this treatment gap, educating physicians as well as implementing simple tools to facilitate risk assessment, e.g. risk charts or computer/mobile applications, would be needed. An impressive potential to significantly reduce CVD complications remains untapped. Initiating simple strategies to improve guideline implementation could have a significant impact on CVD morbidity and mortality in both contries over the next 10 years.
Ueda P, Lung TW, Lu Y et al. Treatment gaps and potential cardiovascular risk reduction from expanded statin use in the US and England. PLoS One 2018; 13:e0190688. http://www.ncbi.nlm.nih.gov/pubmed/?term=29561843
 
Are statins of benefit in advanced liver fibrosis/cirrhosis?
Using statins in patients with elevated transaminases, as frequently observed in NAFLD and NASH, is more and more accepted. The benefits and more importantly the absence of harm in patients with severe liver disease, such as advanced fibrosis and cirrhosis is less robust. In this updated narrative review the authors highlight recent reports and studies that evaluated statins in patients with severe liver dysfunction. Based on their non-lipid lowering, pleiotropic properties improvements have been noted in patients with portal hypertension, hepatocellular carcinoma, cirrhosis and ischemia/reperfusion injury in the context of liver transplantation. Additionally, NAFLD and HCV infections are associated with premature atherosclerosis, independent of traditional cardiovascular risk factors. Based on these observations statins can produce clinical relevant benefit in patients with chronic liver disease; if approved indications, dyslipidemia/increased CVD risk, are present as well. Chronic liver diseases should not be a contraindication for the use of statins, but in patients with decompensated cirrhosis lower dosages and frequent monitoring of CPK levels is advised as to detect serious statin related complications e.g. rhabdomyolysis in a timely fashion.
Moctezuma-Velazquez C, Abraldes JG, Montano-Loza AJ. The Use of Statins in Patients With Chronic Liver Disease and Cirrhosis. Current treatment options in gastroenterology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29572618
 
 
Could statins become a therapeutic option for women at risk for pre-eclampsia?
Pre-eclampsia (PE) is serious systemic vascular complication affecting 3-5% of all pregnancies Although underlying pathophysiology and causes of pre-eclampsia remain elusive, abnormal implantation and placentation are the key underling mechanisms that trigger the serious and frequently fatal complications in mother and child. In this review the authors highlight recent developments in preventing and managing PE patients using statins during the final two trimesters of pregnancy. Statins possess therapeutic benefits beyond their LDL-c lowering properties that potentially address factors associated with the physiological processes of PE. Because of its pharmaco-kinetic profile, a hydrophilic statin, like pravastatin, is less likely to cross the placental barrier and in most studies have this statin was selected. Starting in the 2nd trimester reduces the chances of teratogenic effects and no serious birth defects effects have been noted thus far. The preliminary results with pravastatin confirm the potential preventive and even therapeutic effects of PE related pregnancy complications. However, data from larger properly designed randomized clinical trials are needed as to determine efficacy and safety in pregnant women and their offspring. Exploratory studies are being conducted, examining if pravastatin can correct the angiogenic imbalance and endothelial dysfunction. If these trials confirm the results from earlier studies, statins could become of significant importance for the prevention and management of PE.
Gajzlerska-Majewska W, Bomba-Opon DA, Wielgos M. Is pravastatin a milestone in the prevention and treatment of preeclampsia? Journal of perinatal medicine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29570452

Review discussing the potential of statins to prevent Alzheimer disease
The effects of statins in Alzheimer’s disease (AD) have been controversial. The so-called neurocognitive adverse effects have been reported in case reports and observational studies, but meta-analyses of RCT’s showed no harms and even benefits in preventing dementia related symptoms were observed in large epidemiological studies. In this review the authors discuss the evidence pointing towards a relationship between the disruption of cholesterol homeostasis and Alzheimer disease. Mediated by influencing amyloid precursor protein cleavage an increase of amyloid β (Aβ) is observed, this is considered one of the most important risk factors for Alzheimer disease. Aβ has also been implicated in triggering neuronal insulin resistance, and by this pathway inducing neurotoxicity an AD. Statins could have beneficial effects in reducing Aβ-induced neurotoxicity, however the exact underlying molecular effects have not been completely elucidated, activation AMP activated protein kinase in neuronal cells has been implicated as one of the main statin triggered protective effects. The authors aimed to provide insights on the effects of statins and lipid homeostasis on Aβ-induced neurotoxicity. Reducing neurodegenerative effects by targeting neuronal insulin resistance, my point towards novel diagnostic and therapeutic pathways for the prevention and/or treatment of AD patients in the future.
Li HH, Lin CL, Huang CN. Neuroprotective effects of statins against amyloid beta-induced neurotoxicity. Neural regeneration research 2018; 13:198-206. http://www.ncbi.nlm.nih.gov/pubmed/?term=29557360
 
Relevant publications
  1. He SJ, Liu Q, Li HQ et al. Role of statins in preventing cardiac surgery-associated acute kidney injury: an updated meta-analysis of randomized controlled trials. Therapeutics and clinical risk management 2018; 14:475-482. http://www.ncbi.nlm.nih.gov/pubmed/?term=29551897
  2. Watts GF, Chan DC, Somaratne R et al. Controlled study of the effect of proprotein convertase subtilisin-kexin type 9 inhibition with evolocumab on lipoprotein(a) particle kinetics. Eur Heart J 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29566128
  3. Waters DD, Vogt L. Lipids, inflammation, and chronic kidney disease: a SHARP perspective. Kidney international 2018; 93:784-786. http://www.ncbi.nlm.nih.gov/pubmed/?term=29571452
  4. Lee HY, Jun DW, Kim HJ et al. Ezetimibe decreased nonalcoholic fatty liver disease activity score but not hepatic steatosis. The Korean journal of internal medicine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29551054
  5. Khan SU, Talluri S, Riaz H et al. A Bayesian network meta-analysis of PCSK9 inhibitors, statins and ezetimibe with or without statins for cardiovascular outcomes. Eur J Prev Cardiol 2018:2047487318766612. http://www.ncbi.nlm.nih.gov/pubmed/?term=29569492
  6. Karalis DG, Mallya UG, Ghannam AF et al. Prescribing Patterns of Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors in Eligible Patients With Clinical Atherosclerotic Cardiovascular Disease or Heterozygous Familial Hypercholesterolemia. Am J Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29548678
  7. Huang Q, Yang H, Lin Q et al. Effect of Statin Therapy on Survival After Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-analysis. World journal of surgery 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29564515
  8. Dezsi CA. Treatment with triple combination of atorvastatin, perindopril, and amlodipine in patients with stable coronary artery disease: A subgroup analysis from the PAPA-CAD study. J Int Med Res 2018:300060518760158. http://www.ncbi.nlm.nih.gov/pubmed/?term=29557300
  9. Ciccarelli G, D'Elia S, De Paulis M et al. Lipid Target in Very High-Risk Cardiovascular Patients: Lesson from PCSK9 Monoclonal Antibodies. Diseases (Basel, Switzerland) 2018; 6. http://www.ncbi.nlm.nih.gov/pubmed/?term=29562587
  10. Tariq R, Mukhija D, Gupta A et al. Statin use and the risk of Clostridium difficile infection: a systematic review with meta-analysis. Infection and drug resistance 2018; 11:405-416. http://www.ncbi.nlm.nih.gov/pubmed/?term=29559802
  11. Packer M. Are the effects of drugs to prevent and to treat heart failure always concordant? The statin paradox and its implications for understanding the actions of antidiabetic medications. European journal of heart failure 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29566300
  12. Mark L, Nagy M, Dani G et al. [Lipid-lowering therapy of patients suffering from acute coronary syndrome in a Hungarian county hospital in 2015]. Orvosi hetilap 2018; 159:478-484. http://www.ncbi.nlm.nih.gov/pubmed/?term=29552926
  13. Levy ME, Greenberg AE, Magnus M et al. Evaluation of Statin Eligibility, Prescribing Practices, and Therapeutic Responses Using ATP III, ACC/AHA, and NLA Dyslipidemia Treatment Guidelines in a Large Urban Cohort of HIV-Infected Outpatients. AIDS patient care and STDs 2018; 32:58-69. http://www.ncbi.nlm.nih.gov/pubmed/?term=29561173
  14. Lee DS, Lee MY, Park CM et al. Preoperative statins are associated with a reduced risk of postoperative delirium following vascular surgery. PLoS One 2018; 13:e0192841. http://www.ncbi.nlm.nih.gov/pubmed/?term=29570715
  15. Kim DD, Barr AM, Thornton AE et al. Statin add-on therapy for schizophrenia: Is the effect the same for clozapine? Psychiatry research 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29566972
  16. Han X, Zhang Y, Yin L et al. Statin in the treatment of patients with myocardial infarction: A meta-analysis. Medicine (Baltimore) 2018; 97:e0167. http://www.ncbi.nlm.nih.gov/pubmed/?term=29561426
  17. Asgari S, Abdi H, Hezaveh AM et al. The Burden of Statin Therapy based on ACC/AHA and NCEP ATP-III Guidelines: An Iranian Survey of Non-Communicable Diseases Risk Factors. Scientific reports 2018; 8:4928. http://www.ncbi.nlm.nih.gov/pubmed/?term=29563602
Miscellaneous publications
  1. Yu Y, Jin L, Zhuang Y et al. Cardioprotective effect of rosuvastatin against isoproterenol-induced myocardial infarction injury in rats. International journal of molecular medicine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29568858
  2. Yang C, Zhao D, Liu G et al. Atorvastatin Attenuates Metabolic Remodeling in Ischemic Myocardium through the Downregulation of UCP2 Expression. International journal of medical sciences 2018; 15:517-527. http://www.ncbi.nlm.nih.gov/pubmed/?term=29559841
  3. Song KH, Kim YH, Im AR, Kim YH. Black Raspberry Extract Enhances LDL Uptake in HepG2 Cells by Suppressing PCSK9 Expression to Upregulate LDLR Expression. Journal of medicinal food 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29569973
  4. Melo AC, Cattani-Cavalieri I, Barroso MV et al. Atorvastatin dose-dependently promotes mouse lung repair after emphysema induced by elastase. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2018; 102:160-168. http://www.ncbi.nlm.nih.gov/pubmed/?term=29554594
  5. Kowalska K, Habrowska-Gorczynska DE, Neumayer C et al. Lower levels of Caveolin-1 and higher levels of endothelial nitric oxide synthase are observed in abdominal aortic aneurysm patients treated with simvastatin. Acta biochimica Polonica 2018; 65:111-118. http://www.ncbi.nlm.nih.gov/pubmed/?term=29549671
  6. Kotyla PJ. Short course of simvastatin has no effect on markers of endothelial activation in normolipidemic patients with systemic sclerosis. J Int Med Res 2018:300060518762681. http://www.ncbi.nlm.nih.gov/pubmed/?term=29557229
  7. Ko HHT, Lareu RR, Dix BR, Hughes JD. In vitro antibacterial effects of statins against bacterial pathogens causing skin infections. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29569046
  8. Kassner F, Sauer T, Penke M et al. Simvastatin induces apoptosis in PTENhaploinsufficient lipoma cells. International journal of molecular medicine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29568880
  9. Machairas G, Panderi I, Geballa-Koukoula A et al. Development and validation of a hydrophilic interaction liquid chromatography method for the quantitation of impurities in fixed-dose combination tablets containing rosuvastatin and metformin. Talanta 2018; 183:131-141. http://www.ncbi.nlm.nih.gov/pubmed/?term=29567155
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