up-to-date with a click!
Update - Week 51,  2017 
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

Could statins protect the kidneys from radiation damage?
The anti-oxidant and anti-inflammatory properties of statins in general, and atorvastatin persé, are explored to determine if exposed organs can be shielded from these harmful effects. In this rodent study, the authors aimed to find out if atorvastatin could protect the kidneys from oxidative stress caused by radiation for abdominal malignancies. Mice were treated with 10, 20 of 50 mg/kg of atorvastatin for 7 days prior to 2 Gy whole body radiation. Evaluation of biochemical, histological and immune-histological markers showed that atorvastatin was able to reduce renal system damage in the radiated mice. Oxidative markers were reduced and concentrations of urea and creatinine were significantly lower as well. The irradiated mice presented with tubular degeneration, glomerular atrophy, interstitial expansion and fibrosis. In the mice treated with atorvastatin tubular degeneration and glomerular atrophy were diminished. The authors concluded that based on the findings in this animal study, atorvastatin presented as a promising agent, to protect patients, receiving radiation for abdominal malignancies, from irradiation induced nephrotoxicity. The radiation protective effects of atorvastatin seemed to be related to their anti-oxidant and anti-apoptotic effects.
Talebpour Amiri F, Hamzeh M, Naeim RA et al. Radioprotective effect of atorvastatin against ionizing radiation-induced nephrotoxicity in mice. International journal of radiation biology 2017:1-22. http://www.ncbi.nlm.nih.gov/pubmed/?term=29268056
PK and PD of rosuvastatin plus ezetimibe in Korean patients
Asian patients reputedly treated with rosuvastatin are perceived to have a different response in terms of more pronounced LDL-c lowering efficacy and increased risk of harmful effects. Differences in the genetic regulation of proteins involved in the metabolism of such as the SLCO1B1 influx transporter, play a role in the observed altered response. In this study the interaction of rosuvastatin and ezetimibe, was studied in 25 healthy Korean male subjects. The pharmacokinetic and pharmacodynamics of the two drugs were studied in a randomized, open-label, multiple-dose, two-treatment, two-period, two-sequence crossover study with two treatment parts. Rosuvastatin 20 mg and ezetimibe 10 mg were administered for 7 days as mono therapy and combination therapy. No clinical significant interactions or safety issues were observed other than a summation of the LDL-C lowering effects of the individual agents. For rosuvastatin the terminal half-life was determined at 10.4 – 12.2 hrs. and a mean accumulation ratio at steady state of 1.3–1.4. Ezetimibe add on therapy had limited effects on the systemic exposure of rosuvastatin. For ezetimibe, the terminal half-life was determined at 17.2–20.7 h and that the mean accumulation ratio was 1.6–1.8. The addition of Rosuvastatin did increase the systemic exposure of free ezetimibe. However, the 90% CIs of the geometric mean ratio’s for both the Cmax,ss and AUCτ,ss of total ezetimibe were within the range 0.8–1.25 (ie, the bio-equivalence limits). The authors concluded that in this crossover clinical trial, combining rosuvastatin with ezetimibe showed additive lipid-lowering effects and PK bioequivalence.
Kim CH, An H, Kim SH, Shin D. Pharmacokinetic and pharmacodynamic interaction between ezetimibe and rosuvastatin in healthy male subjects. Drug design, development and therapy 2017; 11:3461-3469. http://www.ncbi.nlm.nih.gov/pubmed/?term=29255347
An insulin resistant post AMI patient; start atorvastatin 20 or 40 mg?
Statins share pro diabetogenic effects, dependent on dosage and presence of metabolic syndrome characteristics. For this study, male post AMI patients (N=156) were randomized to atorvastatin 20 or 40 mg, starting 1 day post event. The following biomarkers were monitored at baseline, day 12, 3- and 12 months post event: glucose, insulin, C-peptide, resistin, adiponectin and ghrelin. New onset DM2 was evaluated after 12 months. Immediately after the acute event patients showed moderate insulin resistance, hyperglycemia, hyperinsulinemia, high leptin and resistin levels, and low ghrelin and adiponectin levels. Improvements of these bio-markers were most pronounced in patients that received atorvastatin 20 mg. patients treated with atorvastatin 40 mg presented with Increased levels of glucose, insulin, and C-peptide as well as insulin resistance progression and detection of new T2DM cases. The authors suggested that when prescribing atorvastatin to AMI survivors, dosages should be adjusted in patients at risk for DM reflected by insulin resistance and/or abnormal adipokines.
Gruzdeva O, Uchasova E, Dyleva Y et al. Effect of different doses of statins on the development of type 2 diabetes mellitus in patients with myocardial infarction. Diabetes, metabolic syndrome and obesity : targets and therapy 2017; 10:481-489. http://www.ncbi.nlm.nih.gov/pubmed/?term=29255368
Diabetic post ACS patients showed enhanced benefit in IMPROVE-IT
The IMPROVE-IT study was designed to evaluate the added protective effects of ezetimibe 10 mg on top of simvastatin 40 mg in post ACS patients baseline LDL-C, 50-125 mgdl. This pre-specified sub-analysis explored the effects of the E+S combination S monotherapy in diabetic participants. Diabetic patients (N=4 933 [27%]) were more frequently older, female, a history of a previous MI, revascularization and a Non-STEMI presentation (P<0.001). At baseline LDL-C was significantly lower in diabetic’s vs non-diabetics; 89 vs 97 mg/dl (p<0.001). Diabetic post ACS patients, using E+S achieved a 5.5% absolute risk reduction; HR 0.85 (0.78-0.94); In the non-DM patients the absolute event rates were reduced by 0.7%; HR 0.98 (0.91-1.04); Pinteraction=0.02. ACS Patients with DM2 experienced greater benefit using S+E relative to patients without DM2. This enhanced benefit was driven by reduced acute ischemic events including strokes. The non-diabetic patients <75 years or with a low risk-score did not exhibit any added protection from the addition of ezetimibe to simvastatin 40 mg. this is in line with the hypothesis that patients at highest risk for cardiovascular events benefit most, from adding ezetimibe. The authors speculated that the increased benefits could not be explained by the 3 mg/dl, median time average, lower LDL-C levels in patients allocated to E+S vs S. No incremental benefits in triglycerides, HDL-C, or hsCRP were observed either and achieving the dual targets of LDL-C <70 mg/dL and hsCRP < 2 mg/dL were more frequently found among patients without DM than in patients with DM. Perhaps the favorable effects of ezetimibe on glucose metabolism, including reductions in fasting plasma glucose, insulin levels, and insulin resistance, may have contributed to the enhanced benefit observed in diabetic patients. Other pleiotropic effects of ezetimibe on e.g. platelet activation, cholesterol absorption, oxidative stress/inflammation could theoretically contribute to the enhanced treatment benefits observed in diabetic as well. The authors concluded that adding ezetimibe to simvastatin was safe and benefitted diabetics as well as high-risk non-diabetic ACS patients only.
Giugliano RP, Cannon CP, Blazing MA et al. Benefit of Adding Ezetimibe to Statin Therapy on Cardiovascular Outcomes and Safety in Patients With vs. Without Diabetes: Results from IMPROVE-IT. Circulation 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29263150
A 30-day evaluation of atorvastatin 80 mg vs 20 mg in primary PTCA STEMI patients
The benefits of high dose, 80 mg atorvastatin vs an intermediate dose, 20 mg atorvastatin were evaluated in this small cohort of 52 Italian primary PCI, STEMI patients. Treatment was initiated <24 hr. after initial contact and patients were re-valuated for treatment targets after 1 month of follow-up. Primary end points, endothelium-dependent vasodilation (measured with the reactive hyperemia index [RHI]) and changes in plasma levels of HS-CRP, IL6, TNFα, and LDL-OX. Flow mediated dilatation showed better outcomes in patients using 80 mg atorvastatin vs the ones that used 20 mg atorvastatin; RH-PAT index 1.96±0.16 vs 1.72±0.19, (P=0.002). CRP and IL6 levels showed similar trends:  0.04±0.02 mg/dL vs 0.36±0.3 mg/dL, (P=0.001) and 1.12±0.93 pg/mL vs 3.13±2.84 pg/mL, (P=0.03) respectively. No significant difference between baseline and 30-days values of TNFα and LDLOX, in patients randomized to atorvastatin 20 mg, in contrast with the 80-mg group where these markers improved. The Improved RH-PAT index showed an inverse association with hs-CRP levels. The authors concluded that using a high atorvastatin dosage of 80 mg proved to have superior vasculo-protective effects, compared to atorvastatin 20 mg, in primary PTCA STEMI patients.
Gavazzoni M, Gorga E, Derosa G et al. High-dose atorvastatin versus moderate dose on early vascular protection after ST-elevation myocardial infarction. Drug design, development and therapy 2017; 11:3425-3434. http://www.ncbi.nlm.nih.gov/pubmed/?term=29270001
Can a high LDL-c level at admission protect ICH patients
The effects of LDL-c plasma concentrations, in patients presenting with acute intracerebral hemorrhages (ICH), is discussed in the retrospective observational analysis. Data collected from patients admitted for an ICH, in a single US tertiary-care stroke center, between 2011 - 2016 were evaluated. Outcome data (hematoma volume, hematoma expansion, in-hospital functional outcome, and in-hospital mortality) as well as demographic characteristics, clinical severity (NIHSS-score and ICH-score), neuroimaging parameters, pre-hospital statin use and doses, LDL-C and HDL-C levels were collected and analyzed. The average age of the 672 included patients was 61.6 ± 14.0 years; 43.6% were female. The median ICH score 1 (IQR: 0-2). LDL-C levels showed an independent negative association with hematoma volume (linear regression coefficient -0.021 (-0.042 - -0.001; p=0.049). Higher LDL-C concentrations were associated with a decreased hematoma expansion and lower risk of in-hospital mortality; OR 0.88 (0.77-0.99; p=0.048) and OR 0.68 (per 10 mg/dl LDL-c increase [0.57-0.80; p<0.001])>
This suggests that in patients, presenting with acute ICH, higher LDL-c levels at admission were an independent predictor of reduced hematoma expansion as well as in-hospital mortality risk. Statin pre-treatment and pre-hospital intensive statin use showed no associations with clinical or imaging outcomes. A statistical, but not statistical significant trend was observed for improved functional independence at hospital discharge with statin use. The authors suggested that the association of LDL-C with reduced cerebral micro-bleeds could possibly be one of the potential unifying mechanism to explain the observed outcomes. They emphasized the need for larger prospective outcome studies to independently confirm their findings.
Chang JJ, Katsanos AH, Khorchid Y et al. Higher low-density lipoprotein cholesterol levels are associated with decreased mortality in patients with intracerebral hemorrhage. Atherosclerosis 2017; 269:14-20. http://www.ncbi.nlm.nih.gov/pubmed/?term=29253643
Relevant publications
  1. Vassilieva EV, Wang S, Li S et al. Skin immunization by microneedle patch overcomes statin-induced suppression of immune responses to influenza vaccine. Scientific reports 2017; 7:17855. http://www.ncbi.nlm.nih.gov/pubmed/?term=29259264
  2. Stoekenbroek RM, Hartgers ML, Rutte R et al. PCSK9 inhibitors in clinical practice: Delivering on the promise? Atherosclerosis 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29254691
  3. Dyrbus K, Osadnik T, Desperak P et al. Evaluation of dyslipidaemia and the impact of hypolipidemic therapy on prognosis in high and very high risk patients through the Hyperlipidaemia Therapy in tERtiary Cardiological cEnTer (TERCET) Registry. Pharmacol Res 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29258913
  4. Seyam E, Al Gelany S, Abd Al Ghaney A et al. Evaluation of prolonged use of statins on the clinical and biochemical abnormalities and ovulation dysfunction in single young women with polycystic ovary syndrome. Gynecological endocrinology: the official journal of the International Society of Gynecological Endocrinology 2017:1-8. http://www.ncbi.nlm.nih.gov/pubmed/?term=29258367
  5. Scicali R, Di Pino A, Ferrara V et al. New treatment options for lipid-lowering therapy in subjects with type 2 diabetes. Acta diabetologica 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29260404
  6. Lewis SJ, Olufade T, Anzalone DA et al. LDL cholesterol levels after switch from atorvastatin to rosuvastatin. Current medical research and opinion 2017:1-16. http://www.ncbi.nlm.nih.gov/pubmed/?term=29271267
  7. Hua P, Liu J, Tao J et al. Efficacy and Mechanism of Preoperative Simvastatin Therapy on Myocardial Protection after Extracorporeal Circulation. BioMed research international 2017; 2017:6082430. http://www.ncbi.nlm.nih.gov/pubmed/?term=29250545
  8. Gbelcova H, Rimpelova S, Knejzlik Z et al. Isoprenoids responsible for protein prenylation modulate the biological effects of statins on pancreatic cancer cells. Lipids Health Dis 2017; 16:250. http://www.ncbi.nlm.nih.gov/pubmed/?term=29262834
  9. Faggiano P, Pirillo A, Griffo R et al. Prevalence and management of familial hypercholesterolemia in patients with coronary artery disease: The heredity survey. Int J Cardiol 2018; 252:193-198. http://www.ncbi.nlm.nih.gov/pubmed/?term=29249427
  10. Couttenier A, Lacroix O, Vaes E et al. Statin use is associated with improved survival in ovarian cancer: A retrospective population-based study. PLoS One 2017; 12:e0189233. http://www.ncbi.nlm.nih.gov/pubmed/?term=29261726
  11. Chen JH, Wu T, Yang LK et al. Protective effects of atorvastatin on cerebral vessel autoregulation in an experimental rabbit model of subarachnoid hemorrhage. Mol Med Rep 2018; 17:1651-1659. http://www.ncbi.nlm.nih.gov/pubmed/?term=29257200
  12. Sisson EM, Pamulapati L, Bucheit JD et al. Evolving Role of Non-Statin Therapy for the Management of Dyslipidemia and Cardiovascular Risk Reduction: Past, Present, and Future. Pharmacotherapy 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29266309
  13. Rossignol M, Labrecque M, Cauchon M et al. Number of patients needed to prescribe statins in primary cardiovascular prevention: mirage and reality. Family practice 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29267889
  14. Morival C, Westerlynck R, Bouzille G et al. Prevalence and nature of statin drug-drug interactions in a university hospital by electronic health record mining. Eur J Clin Pharmacol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29255993
  15. Leonard CE, Brensinger CM, Bilker WB et al. Thromboembolic and neurologic sequelae of discontinuation of an antihyperlipidemic drug during ongoing warfarin therapy. Scientific reports 2017; 7:18037. http://www.ncbi.nlm.nih.gov/pubmed/?term=29269848
  16. Hubacek JA, Adamkova V, Zlatohlavek L et al. COQ2 polymorphisms are not associated with increased risk of statin-induced myalgia/myopathy in the Czech population. Drug Metab Pers Ther 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29257754
  17. Huang BT, Huang FY, Pu XB et al. No modifying effect of nutritional status on statins therapy in relation to all-cause death in older patients with coronary artery disease. Aging clinical and experimental research 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29260400
  18. Herrera-Gonzalez S, Martinez-Trevino DA, Aguirre-Garza M et al. Effect of AGTR1 and BDKRB2 gene polymorphisms on atorvastatin metabolism in a Mexican population. Biomedical reports 2017; 7:579-584. http://www.ncbi.nlm.nih.gov/pubmed/?term=29250329
  19. Gurgle HE, Schauerhamer MB, Rodriguez SA, McAdam-Marx C. Impact of statin guidelines on statin utilization and costs in an employer-based primary care clinic. The American journal of managed care 2017; 23:e387-e393. http://www.ncbi.nlm.nih.gov/pubmed/?term=29261246
  20. Fransgaard T, Thygesen LC, Gogenur I. Statin use is not associated with improved 30-day survival in patients undergoing surgery for colorectal cancer. International journal of colorectal disease 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29270783
  21. Fonseca FAH, Izar MC, Maugeri IML et al. Effects of four antiplatelet/statin combined strategies on immune and inflammatory responses in patients with acute myocardial infarction undergoing pharmacoinvasive strategy: Design and rationale of the B and T Types of Lymphocytes Evaluation in Acute Myocardial Infarction (BATTLE-AMI) study: study protocol for a randomized controlled trial. Trials 2017; 18:601. http://www.ncbi.nlm.nih.gov/pubmed/?term=29258572
  22. Flannery LD, Fahed AC, DeFaria Yeh D et al. Frequency of Guideline-Based Statin Therapy in Adults With Congenital Heart Disease. Am J Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29268935
  23. Dawe DE, Mahmud S. Biologic and epidemiologic evidence assessing if statins prevent prostate cancer. The Canadian journal of urology 2017; 24:9081-9088. http://www.ncbi.nlm.nih.gov/pubmed/?term=29260632
  24. Chemello RML, Benvegnu AM, Dallazem LND, Chemello D. Aggressive and fatal statin-induced dermatomyositis: a case report. Oxford medical case reports 2017; 2017:omx063. http://www.ncbi.nlm.nih.gov/pubmed/?term=29255614
  25. Abbasalizadeh F, Saleh P, Dousti R et al. Effects of atorvastatin on proteinuria of type 2 diabetic nephropathy in patients with history of gestational diabetes mellitus: A clinical study. Nigerian medical journal : journal of the Nigeria Medical Association 2017; 58:63-67. http://www.ncbi.nlm.nih.gov/pubmed/?term=29269983
Miscellaneous publications
  1. Zhang JJ, Zhang YZ, Peng JJ et al. Atorvastatin exerts inhibitory effect on endothelial senescence in hyperlipidemic rats through a mechanism involving down-regulation of miR-21-5p/203a-3p. Mechanisms of ageing and development 2017; 169:10-18. http://www.ncbi.nlm.nih.gov/pubmed/?term=29248491
  2. Tripathi CB, Gupta N, Kumar P et al. omega-3 Fatty Acid Synergized Novel Nanoemulsifying System for Rosuvastatin Delivery: In Vitro and In Vivo Evaluation. AAPS PharmSciTech 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29260378
  3. Liu W, Zhao Y, Zhang X, Ji J. Simvastatin ameliorates cognitive impairments via inhibition of oxidative stressinduced apoptosis of hippocampal cells through the ERK/AKT signaling pathway in a rat model of senile dementia. Mol Med Rep 2018; 17:1885-1892. http://www.ncbi.nlm.nih.gov/pubmed/?term=29257256
  4. Leite M, Soares DG, Basso FG et al. Biostimulatory effects of simvastatin on MDPC-23 odontoblast-like cells. Brazilian oral research 2017; 31:e104. http://www.ncbi.nlm.nih.gov/pubmed/?term=29267665
  5. Hao J, Chou J, Kuroda S et al. Injectable simvastatin gel for minimally invasive periosteal distraction: In vitro and in vivo studies in rat. Clinical oral implants research 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29250831
  6. Liu Y, Tu X, Xu Q et al. Engineered monoculture and co-culture of methylotrophic yeast for de novo production of monacolin J and lovastatin from methanol. Metabolic engineering 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29258964
  7. Itoh H, Miura A, Matsui M et al. Knockout of the SREBP system increases production of the polyketide FR901512 in filamentous fungal sp. No. 14919 and lovastatin in Aspergillus terreus ATCC20542. Applied microbiology and biotechnology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29270733
  8. Cong L, Fu S, Zhang J et al. Effects of atorvastatin on porcine aqueous humour outflow and trabecular meshwork cells. Experimental and therapeutic medicine 2018; 15:210-216. http://www.ncbi.nlm.nih.gov/pubmed/?term=29250149
  9. Alhazmi HA, Alnami AM, Arishi MAA et al. A Fast and Validated Reversed-Phase HPLC Method for Simultaneous Determination of Simvastatin, Atorvastatin, Telmisartan and Irbesartan in Bulk Drugs and Tablet Formulations. Scientia pharmaceutica 2017; 86. http://www.ncbi.nlm.nih.gov/pubmed/?term=29257120
IAS Website
For information
You are now on the editors mailing list of the IAS Statin Newsletter.
The IAS Statin Newsletter is part of the IAS News and Literature update service.
This activity is supported by an educational grant from Pfizer.