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Update - Week 27,  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

Cochrane meta-analysis to assess the efficacy and safety of statin in FH children
Only randomized and controlled clinical studies, including participants up to 18 years old, comparing a statin to placebo or to diet alone, were used for this meta-analysis. Of the 26 potential, eligible studies only 9 trials with 1177 participants were included. The median follow-up time was 26 weeks ranging from 6 weeks to 2 years. The age ranges from 6 -17 years. Statin therapy was effective in lowering LDL-C in children with FH and no short-term safety issues surfaced, although the quality of the evidence was low to moderate. Changes in AST, ALT, CPK did not differ between the treatment group vs controls. Myopathy and clinical adverse events were low and no difference between the two groups was observed. No hard clinical endpoints could be studied due to the young age of the participants. In one study using simvastatin flow mediated dilatation improved and in a children using pravastatin for 2 years, carotid intima media thickness regressed significantly in the treatment group. Based on this meta-analysis there was a significant LDL-C lowering effect observed and no issues regarding short term safety surfaced. Long term safety remains an unanswered question that needs to be addressed by long term randomized controlled trials or by collecting data from national of regional FH registries.
Vuorio A, Kuoppala J, Kovanen PT et al. Statins for children with familial hypercholesterolemia. The Cochrane database of systematic reviews 2017; 7:Cd006401. http://www.ncbi.nlm.nih.gov/pubmed/?term=28685504
 
Metformin potentially increases rosuvastatin plasma concentrations
In this pharmacokinetic study, the effects of metformin and furosemide, in increasing dosages, on rosuvastatin plasma concentrations were studied. Eighteen male volunteers were given rosuvastatin 10 mg, subsequently they received, 10, 50 and 500 mg of metformin and 1 or 5 mg of furosemide in a six-treatment, six –period and six-sequence crossover trial. With Metformin in the 10 -50 mg dosage range the bio-availability of rosuvastatin remained unchanged, but with the 500-mg dosage the AUC increased to 154% (135-171%) and the Cmax increased 154% (132-180%). Co-administration with furosemide 1 mg did not show any plasma increases of rosuvastatin but with 5 mg this increased slightly to 116% for AUC (102-132%) and 118% for Cmax (98-142%). Although this protocol was part of a probe drug cocktail study, aiming to reduce the number of clinical studies when investigate drug-drug interactions, the observed changes are clinically relevant. An increased risk of rosuvastatin related side effects in diabetic patients using metformin in dosages equal or exceeding 500 mg/day cannot be ruled out.
Stopfer P, Giessmann T, Hohl K et al. Effects of Metformin and Furosemide on Rosuvastatin Pharmacokinetics in Healthy Volunteers: Implications for Their Use as Probe Drugs in a Transporter Cocktail. European journal of drug metabolism and pharmacokinetics 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28685495
 
Prolonged use of high intensity statins not associated with DM in FH and FCH patients
In this Greek study, age matched elderly patients with familial hypercholesterolemia (n=90), familial combined dyslipidemia (N=112) both treated with statins and a control group (N=78) were retrospectively followed for 10 years. The incidence of DM was significantly lower in the FH (2%) compared to the FCH patients (20%) and the reference group (17%). Independent predictors of developing DM were impaired fasting glucose at entry (P<0.001) and central obesity (p=0.02). Despite prolonged use of high intensity statins, the incidence of DM in the FH patients was very low. The 10-year incidence of DM in the FCH group, although much higher compared to the FH group, was not significantly different from the control group, despite the prolonged use of high dose, high intensity statins. This suggest that long term use of high intensity statins do not increase the risk of DM in FCH patients, but that metabolic factors such as waist circumference and impaired glucose tolerance play a more important role.
Skoumas I, Ioakeimidis N, Vlachopoulos C et al. Statin Therapy and Risk of Diabetes Mellitus in Aging Patients With Heterozygous Familial Hypercholesterolemia or Familial Combined Hyperlipidemia: A 10-Year Follow-Up. Angiology 2017:3319717718331. http://www.ncbi.nlm.nih.gov/pubmed/?term=28681648
 
Plaque stabilization related to anti-inflammatory effects of statins
This study was a post hoc analysis of the STABLE trial (Statin and Atheroma Vulnerability Evaluation), which was a prospective, single-centre, randomized double-blinded trial conducted to determine the effect of rosuvastatin 10 versus 40 mg (1:2 randomization) in modifying plaque composition. Participants (N=312) were followed for 12 months and required coronary angiography or PTCA, aged 18-75 years). Patients were evaluated using virtual histology (VH)-intravascular ultrasound to determine plaque characteristics. Patients were stratified into quartiles of hsCRP concentrations. Patients where hsCRP decreased the most showed a greater decline in % necrotic core volume and absence of thin cap fibro-atheroma (TCFA) at 12 months follow-up. This relationship was not observed for LDL-C reduction.  In the accompanying editorial Paul Rider points out that this trial might be underpowered and that IVUS-VH might not be sensitive enough to capture the change in biomarkers and subtle alterations of plaque composition, especially if TCFA thickness <65
Relevant publications
  1. Wang Y, Geng Y, Shi Z et al. Good recovery of subarachnoid haemorrhage concomitant with ischemia due to anterior cerebral artery dissection by conservative treatment: A case report. Experimental and therapeutic medicine 2017; 14:155-158. http://www.ncbi.nlm.nih.gov/pubmed/?term=28672907
  2. Wander GS, Jadhav UM, Chemburkar A et al. Lipid management in India: a nationwide, cross-sectional physician survey. Lipids Health Dis 2017; 16:130. http://www.ncbi.nlm.nih.gov/pubmed/?term=28673294
  3. Vlachopoulos C, Andrikopoulos G, Terentes-Printzios D et al. Patients with acute coronary syndrome are at high risk prior to the event and lipid management is underachieved pre- and post-hospitalization. Current vascular pharmacology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28676022
  4. Athyros VG, Boutari C, Stavropoulos K et al. Statins: an under-appreciated asset for the prevention and the treatment of NAFLD or NASH and the related cardiovascular risk. Current vascular pharmacology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28676019
  5. Papademetriou M, Athyros VG, Geladari E et al. The co-existence of NASH and chronic kidney disease boosts cardiovascular risk: are there any common therapeutic options? Current vascular pharmacology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28676027
  6. Ooba N, Setoguchi S, Sato T, Kubota K. Lipid-lowering drugs and risk of new-onset diabetes: a cohort study using Japanese healthcare data linked to clinical data for health screening. BMJ Open 2017; 7:e015935. http://www.ncbi.nlm.nih.gov/pubmed/?term=28667223
  7. Mitsiou E, Boutari C, Kotsis V et al. Effect of low (5 mg) vs high (20-40 mg) rosuvastatin dose on 24h arterial stiffness, central haemodynamics, and non-alcoholic fatty liver disease in patients with optimally controlled arterial hypertension. Current vascular pharmacology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28669329
  8. Maxwell WD, Ramsey LB, Johnson SG et al. Impact of Pharmacogenetics on Efficacy and Safety of Statin Therapy for Dyslipidemia. Pharmacotherapy 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28672099
  9. Liang M, Yang S, Fu N. Efficacy of short-term moderate or high-dose rosuvastatin in preventing contrast-induced nephropathy: A meta-analysis of 15 randomized controlled trials. Medicine (Baltimore) 2017; 96:e7384. http://www.ncbi.nlm.nih.gov/pubmed/?term=28682890
  10. Bazoukis G, Papadatos SS, Letsas KP et al. Impact of statin therapy on all-cause mortality and ICD interventions in heart failure patients - a systematic review. Acta Cardiol 2017:1-6. http://www.ncbi.nlm.nih.gov/pubmed/?term=28685653
  11. Zhang X, Sun Y, Xie H et al. The effect of simvastatin on periprosthetic bone mineral density in the hypercholesterolaemic patients after total hip arthroplasty. Int Orthop 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28681228
  12. Wilbek TE, Jansen RB, Jorgensen B, Svendsen OL. Risk Factors for Premature Death in Diabetes Patients who Undergo Amputations below Ankle Level. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28675915
  13. Watts GF, Chan DC, Somaratne R et al. Response by Watts et al to Letter Regarding Article, "Factorial Effects of Evolocumab and Atorvastatin on Lipoprotein Metabolism". Circulation 2017; 136:120-121. http://www.ncbi.nlm.nih.gov/pubmed/?term=28674100
  14. Shehab A, Al-Rasadi K, Arafah M et al. The management of dyslipidaemia in patients with type 2 diabetes mellitus receiving lipid-lowering drugs: a sub-analysis of the CEPHEUS findings. Current vascular pharmacology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28677510
  15. Park CH, Kang EW, Park JT et al. Association of serum lipid levels over time with survival in incident peritoneal dialysis patients. J Clin Lipidol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28669685
  16. Nakamura M, Uno K, Hirayama A et al. Exploration into lipid management and persistent risk in patients hospitalised for acute coronary syndrome in Japan (EXPLORE-J): protocol for a prospective observational study. BMJ Open 2017; 7:e014427. http://www.ncbi.nlm.nih.gov/pubmed/?term=28674132
  17. Mukai Y, Narita M, Akiyama E et al. Co-administration of Fluvastatin and CYP3A4 and CYP2C8 Inhibitors May Increase the Exposure to Fluvastatin in Carriers of CYP2C9 Genetic Variants. Biological & pharmaceutical bulletin 2017; 40:1078-1085. http://www.ncbi.nlm.nih.gov/pubmed/?term=28674251
  18. Manoj K, Jain N, Madhu SV. Myopathy in Patients Taking Atorvastatin: A Pilot Study. Indian journal of endocrinology and metabolism 2017; 21:504-509. http://www.ncbi.nlm.nih.gov/pubmed/?term=28670530
  19. Koh KK. Letter by Koh Regarding Article, "Factorial Effects of Evolocumab and Atorvastatin on Lipoprotein Metabolism". Circulation 2017; 136:118-119. http://www.ncbi.nlm.nih.gov/pubmed/?term=28674099
  20. Fracassi A, Marangoni M, Rosso P et al. Statins and the brain: more than lipid lowering agents? Curr Neuropharmacol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28676012
  21. Eilenberg W, Stojkovic S, Kaider A et al. NGAL and MMP-9/NGAL as biomarkers of plaque vulnerability and targets of statins in patients with carotid atherosclerosis. Clin Chem Lab Med 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28672747
  22. De Jong HJI, van Staa TP, Lalmohamed A et al. Pattern of risks of systemic lupus erythematosus among statin users: a population-based cohort study. Ann Rheum Dis 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28684558
  23. Capogrosso Sansone A, Convertino I, Galiulo MT et al. Muscular Adverse Drug Reactions Associated with Proton Pump Inhibitors: A Disproportionality Analysis Using the Italian National Network of Pharmacovigilance Database. Drug Saf 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28681266
  24. Calza L, Magistrelli E, Colangeli V et al. Substitution of nevirapine or raltegravir for protease inhibitor vs. rosuvastatin treatment for the management of dyslipidaemia in HIV-infected patients on stable antiretroviral therapy (Nevrast study). Infectious diseases (London, England) 2017:1-11. http://www.ncbi.nlm.nih.gov/pubmed/?term=28683645
  25. Briguori C, Quintavalle C, D'Alessio F et al. Impact of statin therapy intensity on endothelial progenitor cells after percutaneous coronary intervention in diabetic patients. The REMEDY-EPC late study. Int J Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28668399
  26. Akhabue E, Rittner SS, Carroll JE et al. Implications of American College of Cardiology/American Heart Association (ACC/AHA) Cholesterol Guidelines on Statin Underutilization for Prevention of Cardiovascular Disease in Diabetes Mellitus Among Several US Networks of Community Health Centers. J Am Heart Assoc 2017; 6. http://www.ncbi.nlm.nih.gov/pubmed/?term=28673901
Miscellaneous publications
  1. Yang H, Huang F, Tao Y et al. Simvastatin ameliorates ionizing radiation-induced apoptosis in the thymus by activating the AKT/sirtuin 1 pathway in mice. International journal of molecular medicine 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28677744
  2. Sun X, Mathew B, Sammani S et al. Simvastatin-induced sphingosine 1-phosphate receptor 1 expression is KLF2-dependent in human lung endothelial cells. Pulmonary circulation 2017; 7:117-125. http://www.ncbi.nlm.nih.gov/pubmed/?term=28680571
  3. Selim A, Khalaf MM, Gad AM, Abd El-Raouf OM. Evaluation of the possible nephroprotective effects of vitamin E and rosuvastatin in amikacin-induced renal injury in rats. Journal of biochemical and molecular toxicology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28683192
  4. Naeimi RA, Amiri FT, Khalatbary AR et al. Atorvastatin mitigates testicular injuries induced by ionizing radiation in mice. Reproductive toxicology (Elmsford, N.Y.) 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28668617
  5. Cunha V, Santos MM, Moradas-Ferreira P et al. Simvastatin modulates gene expression of key receptors in zebrafish embryos. Journal of toxicology and environmental health. Part A 2017:1-12. http://www.ncbi.nlm.nih.gov/pubmed/?term=28682217
  6. Chen L, Cai P, Cheng Z et al. Pharmacological postconditioning with atorvastatin calcium attenuates myocardial ischemia/reperfusion injury in diabetic rats by phosphorylating GSK3beta. Experimental and therapeutic medicine 2017; 14:25-34. http://www.ncbi.nlm.nih.gov/pubmed/?term=28672889
  7. Qiao F, Zhang J, Wang J et al. Silk fibroin-coated PLGA dimpled microspheres for retarded release of simvastatin. Colloids and surfaces. B, Biointerfaces 2017; 158:112-118. http://www.ncbi.nlm.nih.gov/pubmed/?term=28686902
  8. Mauro M, Lepera JS, Borsari B et al. Effect of inhalation exposure to toluene on the activity of organic anion transporting polypeptide (Oatp) using pravastatin as a probe drug in rats. Xenobiotica 2017:1-15. http://www.ncbi.nlm.nih.gov/pubmed/?term=28686078
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