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Update - Week 10, 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

Reducing statin dosage by a nutraceutical approach
Reducing statin dosage has been a major issue with patients and some doctor as well. In this study, the authors found a creative approach to select patients that could be adequately treated with half of their original statin dosage + smart food choices. Diabetic Patients (N=53) using statins were given a combination of fish oil (1.7g EPA + DH/day), chocolate containing plant sterols (2.2g/day) and green tea (two sachets per day). After 6 weeks of this pilot protocol the “good responders” where provide with additional supplements for 12 weeks, and their statin dosage was kept during the first 6 weeks but reduced by 50% from week 6 – week12. In the pilot phase using the supplements improved LDL-c (-13.7% ± 3.7, p=0.002) and hsCRP (-35.5% ± 5.9, p=0.03) Based on cholesterol synthesis/absorption markers the LDL-c reduction was related to a decrease in cholesterol absorption. After phase two, and with 50% of the statin dosage, no changes in the above-mentioned markers as well as cholesterol efflux or HDL particles were observed. The authors suggest that their nutraceutical approach to reduce statin dosage in patients unable to tolerate the full doses can be an alternative approach. Strategies to elucidate novel markers that characterize “good responders” will need to be explored.
Scolaro B, Nogueira MS, Paiva A et al. Statin dose reduction with complementary diet therapy: A pilot study of personalized medicine. Molecular metabolism 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29503145
The Janus effect of statins on cognitive function

The effect of statins on neuro-cognitive functions are somewhat contradictory. In this narrative review, the authors explain this Janus type of effect of statins. Reports of reversible cognitive impairment in individual statin users seem to be valid, exposure to increased statin concentrations in plasma puts these patients at risk of adverse effects including cognitive impairment. Lipophilic statins and metabolic syndrome patients are more frequently reporting CNS side effects. In larger observational studies statins were associated with a lower risk of dementia and Alzheimer’s disease and even improved cognitive loss. Starting statins in mid-life as opposed to later in life is associated with reduced cognitive decline and the authors suggest that vascular benefits could be the explanation for these early protective effects. Randomized controlled trials have not been able to provide hard evidence of the benefits that surfaced in observational trials. The authors provide a comprehensive overview of the mechanisms that explain the contradictory findings and that could help health care professionals select the patients that would be more likely to benefit as well avoid statins in patients that have a higher risk of experiencing the harmful effects. The ultimate proof will be to evaluate the appropriate patients in well-designed RCT’s. Patients with hyperlipidemia and starting in mid-life as opposed to later in life would be the appropriate population to evaluate the benefits of statin use on cognitive impairment.
Schultz BG, Patten DK, Berlau DJ. The role of statins in both cognitive impairment and protection against dementia: a tale of two mechanisms. Translational neurodegeneration 2018; 7:5. http://www.ncbi.nlm.nih.gov/pubmed/?term=29507718
Are outcomes different in statin trials with a run in phase compared to no run in phase?
Numerous statin trials have employed run in strategies to ensure proper adherence and tolerance to the study medication. Post hoc, critics have argued that this would provide less reliable information on statin safety because patient intolerant to statins would be filtered out. In this meta-analysis of statins trials with and without a run-in design the authors aimed to evaluate if there were different efficacy and safety outcomes when these compared. Although the 10 trials with a run-in phase included more randomized patients, compared to the 6 no-run in phase trials; N=6 699 vs N=903 respectively; A higher percentage of patients completed the trial when a run-in phase was used, 88% vs 78%, but this difference was not statistically significant. All other evaluated results in the two types of trials were nearly identical. The authors suggest using a run-in phase design wastes scarce clinical trials resources but they acknowledge that replicating the presented results is needed to confirm their findings.
Fralick M, Avorn J, Franklin JM et al. Application and Impact of Run-In Studies for the Evaluation of Statin Efficacy and Safety. Journal of general internal medicine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29520746
Statins have a favorable effect on vulnerable carotid plaque features
The Dutch Rotterdam study is prospective population-based cohort of Participants > 45 years living in Ommoord a district of the city of Rotterdam Between 2007 and 2012 all participants had an ultrasound of the carotid arteries. Patients with an IMT > 2.5 mm (N=2666), were selected for this follow-up protocol and had and MRI examination of their carotid arteries. Ultimately 1740 participants were evaluated for this present analysis.  Mean age 72.9 years and 46% females. The following parameters were studied: presence of calcification, lipid core, and intra-plaque hemorrhage. Statin use, and duration were extracted from pharmacy records. Statin use was associated with calcification OR 1.73(1.22-2.44) and prolonged use re-enforced this association OR 1.82 (1.00-3.33) 10 – 40 months and 1.74 (1.09-2.77) >48 months vs OR 1.65 (0.94-2.89) < 10 months. A reduced Lipid core was associated with current statin use if statins were used for <10 months and only when higher statin dosages were used (DDD> 1.33). Increased calcifications were observed in all statin users. Of note was the observation that statin discontinuation for 3 months or longer was associated with a higher presence of vulnerable components, such as increased lipid core, and intra- plaque hemorrhage, underlining the importance of continuing statins. The authors concluded that active high dose statin use was associated with a reduction of carotid plaque features associated with vulnerable plaques.
Mujaj B, Bos D, Selwaness M et al. Statin use is associated with carotid plaque composition: The Rotterdam Study. Int J Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29519676
Relevant publications
  1. Park JS, Cha KS, Lee HW et al. Predictive and protective role of high-density lipoprotein cholesterol in acute myocardial infarction. Cardiology journal 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29512093
  2. Cho KI, Sakuma I, Sohn IS et al. Best Treatment Strategies With Statins to Maximize the Cardiometabolic Benefits. Circulation journal : official journal of the Japanese Circulation Society 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29503409
  3. Zaccardi F, Kunutsor SK, Seidu S et al. Is the lower risk of venous thromboembolism with statins related to low-density-lipoprotein reduction? A network meta-analysis and meta-regression of randomised controlled trials. Atherosclerosis 2018; 271:223-231. http://www.ncbi.nlm.nih.gov/pubmed/?term=29524865
  4. Ye X, Zhang G, Righolt C et al. Associations between Statin Use and Risk of Non-Hodgkin Lymphomas by Subtype. International journal of cancer. Journal international du cancer 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29524215
  5. Wiggins BS, Senfield J, Kassahun H et al. Evolocumab: Considerations for the Management of Hyperlipidemia. Curr Atheroscler Rep 2018; 20:17. http://www.ncbi.nlm.nih.gov/pubmed/?term=29511875
  6. Schonmann Y, Bleich O, Matalon A, Yeshua H. Validation of the 2016 USPSTF recommendations for primary cardiovascular prevention in a large contemporary cohort. Eur J Prev Cardiol 2018:2047487318763825. http://www.ncbi.nlm.nih.gov/pubmed/?term=29517367
  7. Sakai K, Koba S, Nakamura Y et al. Small dense low-density lipoprotein cholesterol is a promising biomarker for secondary prevention in older men with stable coronary artery disease. Geriatrics & gerontology international 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29512264
  8. Russell C, Sheth S, Jacoby D. A Clinical Guide to Combination Lipid-Lowering Therapy. Curr Atheroscler Rep 2018; 20:19. http://www.ncbi.nlm.nih.gov/pubmed/?term=29516190
  9. Ponziani MC, Karamouzis I, Mele C et al. Baseline glucose homeostasis predicts the new onset of diabetes during statin therapy: A retrospective study in real life. Hormones (Athens, Greece) 2017; 16:396-404. http://www.ncbi.nlm.nih.gov/pubmed/?term=29518760
  10. Nissen SE. Statin Denial: An Internet-Driven Cult With Deadly Consequences. Annals of internal medicine 2018; 168:381-382. http://www.ncbi.nlm.nih.gov/pubmed/?term=29507960
  11. Miyauchi K, Kimura T, Shimokawa H et al. Rationale and Design of Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) Trial. Int Heart J 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29503404
  12. Korhonen MJ, Tiittanen P, Kastarinen H et al. Statins do not Increase the Rate of Bleeding among Warfarin Users. Basic & clinical pharmacology & toxicology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29504234
  13. Kim CH, Wang S, Park JB et al. Assessing Impact of High-Dose Pitavastatin on Carotid Artery Elasticity with Speckle-Tracking Strain Imaging. J Atheroscler Thromb 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29515050
  14. Erdur H, Polymeris A, Grittner U et al. A Score for Risk of Thrombolysis-Associated Hemorrhage Including Pretreatment with Statins. Frontiers in neurology 2018; 9:74. http://www.ncbi.nlm.nih.gov/pubmed/?term=29503629
  15. Elnaem MH, Nik Mohamed MH, Zaman Huri H, Azarisman SM. Impact of educational outreach intervention on enhancing health care providers' knowledge about statin therapy prescribing in Malaysian patients with type 2 diabetes mellitus. J Eval Clin Pract 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29508492
  16. Davis DS. Statin Denial: An Internet-Driven Cult With Deadly Consequences. Annals of internal medicine 2018; 168:382. http://www.ncbi.nlm.nih.gov/pubmed/?term=29507959
  17. Baum SJ, Cannon CP. PCSK9 inhibitor valuation: A science-based review of the two recent models. Clin Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29512936
  18. Bamji A. Statin Denial: An Internet-Driven Cult With Deadly Consequences. Annals of internal medicine 2018; 168:381-382. http://www.ncbi.nlm.nih.gov/pubmed/?term=29507958
  19. Adams SP, Sekhon SS, Tsang M, Wright JM. Fluvastatin for lowering lipids. The Cochrane database of systematic reviews 2018; 3:Cd012282. http://www.ncbi.nlm.nih.gov/pubmed/?term=29508377
  20. Xu D, Hu J, Wu Q et al. Efficacy and safety of Zhibitai in combination with atorvastatin for lipid lowering in patients with coronary heart disease. Oncotarget 2018; 9:9489-9497. http://www.ncbi.nlm.nih.gov/pubmed/?term=29507705
  21. Wang H, Yin J, Guo Y. Atorvastatin might resist tobacco smoking-induced endothelial inflammation through the inhibition of NF-kappaB signal pathway. Clinical and experimental hypertension (New York, N.Y. : 1993) 2018:1-4. http://www.ncbi.nlm.nih.gov/pubmed/?term=29509049
  22. Silverman JM, Schmeidler J. Outcome age-based prediction of successful cognitive aging by total cholesterol. Alzheimer's & dementia : the journal of the Alzheimer's Association 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29514768
  23. Perng CH, Chang YC, Tzang RF. The treatment of cognitive dysfunction in dementia: a multiple treatments meta-analysis. Psychopharmacology (Berl) 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29502274
  24. Park IS, Lee SB, Song SH et al. Ticagrelor-induced acute kidney injury can increase serum concentration of statin and lead to concurrence of rhabdomyolysis. Anatol J Cardiol 2018; 19:225-226. http://www.ncbi.nlm.nih.gov/pubmed/?term=29521318
  25. Keihani S, Martin C, Craig JR et al. Semen parameters are unaffected by statin use in men evaluated for infertility. Andrologia 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29512172
  26. Iarrobino NA, Gill B, Bernard ME et al. Targeting Tumor Metabolism With Statins During Treatment for Advanced-stage Pancreatic Cancer. American journal of clinical oncology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29509593
  27. Demirci D, Ersan Demirci D. Lack of accurate evidence on non-statin medication in patients receiving highintensity statin therapy: Re-evaluation of recommendations is needed. Anatol J Cardiol 2018; 19:230. http://www.ncbi.nlm.nih.gov/pubmed/?term=29521324
  28. Bruckert E, Gallo A. [Statin treatment must be personalized]. La Revue de medecine interne / fondee ... par la Societe nationale francaise de medecine interne 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29510859
  29. Bin Abdulhak AA, Vaughan-Sarrzin M, Kaboli P et al. Temporal Trends of High-Intensity Statin Therapy Among Veterans Treated With Percutaneous Coronary Intervention. J Am Heart Assoc 2018; 7. http://www.ncbi.nlm.nih.gov/pubmed/?term=29503265
  30. Agus A, Phair G, Page VJ, McAuley DF. Simvastatin for the prevention and treatment of delirium in critically ill, mechanically ventilated patients (MoDUS): a cost-effectiveness analysis. The lancet. Respiratory medicine 2018; 6:e9-e10. http://www.ncbi.nlm.nih.gov/pubmed/?term=29508709
Miscellaneous publications
  1. Zhou F, Tan Y, Chen XH et al. Atorvastatin improves plaque stability in diabetic atherosclerosis through the RAGE pathway. Eur Rev Med Pharmacol Sci 2018; 22:1142-1149. http://www.ncbi.nlm.nih.gov/pubmed/?term=29509268
  2. Wang CY, Shui HA, Chang TC. Dual effects for lovastatin in anaplastic thyroid cancer: the pivotal effect of transketolase (TKT) on lovastatin and tumor proliferation. Journal of investigative medicine : the official publication of the American Federation for Clinical Research 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29502067
  3. Shen Z, Li S, Sheng B et al. The role of atorvastatin in suppressing tumor growth of uterine fibroids. Journal of translational medicine 2018; 16:53. http://www.ncbi.nlm.nih.gov/pubmed/?term=29523174
  4. Oi M, Donner D, Peart J et al. Pravastatin improves risk factors but not ischaemic tolerance in obese rats. Eur J Pharmacol 2018; 826:148-157. http://www.ncbi.nlm.nih.gov/pubmed/?term=29501869
  5. McFarland AJ, Davey AK, McDermott CM et al. Differences in statin associated neuroprotection corresponds with either decreased production of IL-1beta or TNF-alpha in an in vitro model of neuroinflammation-induced neurodegeneration. Toxicology and applied pharmacology 2018; 344:56-73. http://www.ncbi.nlm.nih.gov/pubmed/?term=29522792
  6. Hwang AR, Nam JO, Kang YJ. Fluvastatin inhibits advanced glycation end products-induced proliferation, migration, and extracellular matrix accumulation in vascular smooth muscle cells by targeting connective tissue growth factor. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 2018; 22:193-201. http://www.ncbi.nlm.nih.gov/pubmed/?term=29520172
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