up-to-date with a click!
Update - Week 49,  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

Rosuvastatin improved endothelial function in stable CVD patient - but not diabetics!
Statins are the drug of choice for reducing LDL-C levels in patients with elevated CVD risk, their role in improving other risk markers or processes remains controversial. In this study 47 Japanese dyslipidemic, stable CVD patients were treated with rosuvastatin in increasing dosages to reach an LDL-C target of < 80 mg/dl. LDL-C. Statins were not used, prior to the intervention, by 10 patients. The majority of participants (N=37) were switched from other statins. Patients were assessed by endothelial function measurements, using the reactive hyperaemia peripheral artery tonometry (RH-PAT) index of the radial artery, at baseline and after 24 weeks of treatment. RH-PAT index improved significantly from 1.6 ± 0.31 to 1.77±0.57 (p=0.04); a percentage change of 12.8 ±36.9%. LDL-C response did not predict observed improvements. No changes were noted for HDL-C, TG’s and hsCRP. Patients with an elevated TG’s at baseline and/or elevated HbA1C at the end of the study, did not show an improved RH-PAT index. Using rosuvastatin in the dosage range of 5-20 mg not only significantly reduced LDL-C levels but improved endothelial function in patients with normal TG’s at baseline and/or normal HbA1C at the end of the study. This finding supports the notion that restoring endothelial function in diabetic patients remains challenging even when LDL-C is aggressively lowered.
Takayama T, Hiro T, Yoda S et al. Effect of Aggressive lipid-lowering treatment with Rosuvastatin on vascular endoTHelium function: evaluation of vascular endothelium function (EARTH study). Heart Vessels 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29209775
Should we consider combining statins with CoQ10 and L-Carnitine?
Statin adherence is challenging if patients report muscle related symptoms or new onset diabetes (NODM). In this study, the toxic effects of atorvastatin and lovastatin as well as the in vivo protective effects of Co-Q10 and L-Carnitine (LC) were studied in pancreatic mitochondria of male Wistar rats. These supplements can act as free radical scavengers that can protect against statin triggered oxidative damage. Both statins caused increased glucose and decreased insulin plasma levels. Higher rates of pancreas toxicity were also observed; increased reactive oxygen species as well as decreased cytochrome C oxidase activity, collapse of mitochondrial membrane potential and swelling. These factors were significantly diminished when Co-Q10 or LC were co-administered. In addition, Insulin levels and glucose levels improved when supplements were added to their feeding regimen. The data presented shows detrimental effects of lovastatin and atorvastatin on pancreatic mitochondrial function and glycemic parameters. Co-administration of LC or CoQ10 protected mitochondria and improved glycemic parameters. To corroborate that these effects are clinically relevant, properly designed randomized placebo controlled trials have to confirm these findings.
Sadighara M, Joktaji JP, Hajhashemi V, Minaiyan M. Protective effects of coenzyme Q10 and L-carnitine against statin-induced pancreatic mitochondrial toxicity in rats. Research in pharmaceutical sciences 2017; 12:434-443. http://www.ncbi.nlm.nih.gov/pubmed/?term=29204172
Take rosuvastatin before or after a meal?
What can to expect when statins are taken with food or after an overnight fast? To answer this question the authors studied the effects of taking rosuvastatin before or after a (high fat or low-fat) meal.   Study participants were healthy volunteers, patients and rodents. Combining 10 mg rosuvastatin with food resulted in a 40% lower rosuvastatin exposure in the 12 Asian and 11 Caucasian participants. In the Asian participants, higher rosuvastatin concentrations were related to a higher ABCG2 c.421C>A allele frequency. In Caucasians, the Cmax was reduced by 46.7%, the AUC by 34.1%. No significant differences were observed between low- and high -fat meals. In the Chinese participants, the effects were even more pronounced; the Cmax and the AUC decreased >90%! Differences in the test meal and the tablet formulation could perhaps be responsible for this variance. Chinese subjects needed longer a longer time to reach maximum concentrations (Tmax) and a reduced absorption was noted, when rosuvastatin was co-administered with food.  This contrasted with Caucasian participants that showed an increased rosuvastatin clearance and distribution volume when administered with a meal. Increased hepatic uptake after a meal could partly explain the observed differences as well and was confirmed in mice with a 2.1 times greater liver-to-plasma concentration in fed compared to fasting mice. In the 156 patients that were analyzed, no effects on LDL-C or Lathosterol concentrations were observed between those taking their rosuvastatin with or without a meal. The authors concluded that taking rosuvastatin with meals would diminish systemic exposure and related side effects, without compromising LDL-C efficacy. 
 McLean CC, Teft WA, Morse BL et al. Food Effect on Rosuvastatin Disposition and Low-Density Lipoprotein Cholesterol. Clinical pharmacology and therapeutics 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29218707
Sharing Facts and addressing fears are equally important when discussing statin use
Strategies on how to address long term statin adherence have been partly neglected by healthcare professionals, caring for high CVD risk patients. The biggest challenges is to explore what triggers patients to stop taking their statins and how to predict which patients is more likely to be unconvinced of statin benefits and how to prevent this. The authors of this article used a population survey conducted in 2 015 Danish residents (45-65 years). Previous statin users were studied to discover their motivation to stop. Different ways of finding information as well processing this knowledge was analyzed using a multivariate logistical regression model. Important discontinuation determinants were personal experiences of side effect as well as fear of side effects. Uncertainty and confusion regarding information on harms and beneftis of statins were also powerful predictors of withdrawal as well. Information that was provided by mass media or primary care physicians contributed equally, no distinct pattern of information seeking and statin stopping could be discerned.
The authors suggest that in congruence providing with factual information on the expected effects of statin use, health care providers should pay more attention to emotional aspects of information dissemination, perception and understanding.
Kriegbaum M, Lau SR. Medication non-adherence and uncertainty: Information-seeking and processing in the Danish LIFESTAT survey. Research in social & administrative pharmacy : RSAP 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29203408
Safety of statins in a large UK pediatric FH cohort
The first UK pediatric FH registry was used to explore the safety of statins in children. The LDL-C lowering drugs are started at the age of 10 years. Markers of muscle and liver cell damage as well as growth rate and obesity indices were analyzed after 1 year of statin treatment. The mean levels of untreated, baseline LDL-C level was 5.48 (1.49) mmol/L. Statins were used by (stratified by age categories): <5 years = 0%; 5-10 years = 16.7%;  10-15 years = 57.1% and >15 years = 73.2% of the  FH children. Statins were well tolerated and reduced LDL-C by 31% (1.84 [1.43] mmol/L). No raised markers of liver toxicity and/or muscle cell damage were observed. At baseline 16.9% of the FH children were overweight (>85th percentile) and 11.1% were obese (>95th percentile). In the UK 21.2% of non-FH children a were reported to be obese. Annual growth rate in statin vs no statin users was not significantly different; age adjusted weight increase 3.58 vs 3.53 kg (P=0.91). Height increase 4.45 vs 4.60 cm (P=0.73). The authors concluded that prescribing statins to a pediatric FH population seems to have no detrimental effects on growth and muscle/liver metabolism. The Long-term benefits are expected to show an impressive decrease of CHD risk in adulthood; if statin therapy is not stopped prematurely.
Humphries SE, Cooper J, Dale P, Ramaswami U. The UK Paediatric Familial Hypercholesterolaemia Register: Statin-related safety and 1-year growth data. J Clin Lipidol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29208363
Surprising IVUS outcomes in ACS patients using Ezetimibe on top of pitavastatin
Comparing the effects of statin + ezetimibe vs statin only in 128 Japanese ACS patients that underwent an IVUS guided PTCA. Patients were randomized to receive 2 mg pitavastatin(P) or 2 mg pitavastatin + 10 mg ezetimibe (P/E) for 10 months. Baseline and follow-up evaluable IVUS imaging data of the non-culprit coronary lesion were available for 103 patients. Primary endpoints were: % change of non-culprit coronary plaque volume (PV) and lipid PV. LDL-C was reduced from 123 mg/dl to 64 mg/dl in the P/E group vs 126 mg/dl to 87 mg in the P cohort. This resulted in a between group difference of 16.9% (P<0.0001). IN the P/E group the change in PV was -5.1% and -6.2% in the patients using P. The lipid PV was not statistically different between the two groups (4.3% vs -3.0%; P=0.37). Both groups showed a significant PV reduction from baseline (P<0.01 for both groups). The authors concluded that in statin naïve Japanese ACS patients the addition of ezetimibe 10 mg did not result in a significant plaque regression compared to pitavastatin monotherapy, despite a statistically significant 16% lower plasma LDL-C in the patients that used ptivastatin plus ezetimibe. Despite the limitatations of the study design and relatively small number of patients, the discrepency between LDL-C reduction and IVUS outcome data is intruiging and deserves further follow-up.  Hibi K, Sonoda S, Kawasaki M et al. Effects of Ezetimibe-Statin Combination Therapy on Coronary Atherosclerosis in Acute Coronary Syndrome. Circulation journal : official journal of the Japanese Circulation Society 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29212965
Relevant publications
  1. Zhang QH, Yin RX, Chen WX et al. Association between the TIMD4-HAVCR1 variants and serum lipid levels, coronary heart disease and ischemic stroke risk and atorvastatin lipid-lowering efficacy. Bioscience reports 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29208769
  2. Ren Y, Zhu H, Fan Z et al. Comparison of the effect of rosuvastatin versus rosuvastatin/ezetimibe on markers of inflammation in patients with acute myocardial infarction. Experimental and therapeutic medicine 2017; 14:4942-4950. http://www.ncbi.nlm.nih.gov/pubmed/?term=29201198
  3. Wolffenbuttel BHR, Slagter SN, van Waateringe RP et al. Unfavourable blood pressure and LDL-cholesterol levels in obese non-diabetic individuals. The Netherlands journal of medicine 2017; 75:399-411. http://www.ncbi.nlm.nih.gov/pubmed/?term=29219813
  4. Naiqiong W, Liansheng W, Zhanying H et al. A Multicenter and Randomized Controlled Trial of Bicyclol in the Treatment of Statin-Induced Liver Injury. Medical science monitor : international medical journal of experimental and clinical research 2017; 23:5760-5766. http://www.ncbi.nlm.nih.gov/pubmed/?term=29200411
  5. Kovarnik T, Chen Z, Mintz GS et al. Plaque volume and plaque risk profile in diabetic vs. non-diabetic patients undergoing lipid-lowering therapy: a study based on 3D intravascular ultrasound and virtual histology. Cardiovascular diabetology 2017; 16:156. http://www.ncbi.nlm.nih.gov/pubmed/?term=29212544
  6. Herrett E, Williamson E, Beaumont D et al. Study protocol for statin web-based investigation of side effects (StatinWISE): a series of randomised controlled N-of-1 trials comparing atorvastatin and placebo in UK primary care. BMJ Open 2017; 7:e016604. http://www.ncbi.nlm.nih.gov/pubmed/?term=29197834
  7. Han N, Han SH, Song YK et al. Statin therapy for preventing cardiovascular diseases in patients treated with tacrolimus after kidney transplantation. Therapeutics and clinical risk management 2017; 13:1513-1520. http://www.ncbi.nlm.nih.gov/pubmed/?term=29200861
  8. Danaei G, Garcia Rodriguez LA, Cantero OF et al. Electronic medical records can be used to emulate target trials of sustained treatment strategies. J Clin Epidemiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29203418
  9. Bauters C, Tricot O, Lemesle G et al. Reaching low-density lipoprotein cholesterol treatment targets in stable coronary artery disease: Determinants and prognostic impact. Arch Cardiovasc Dis 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29198936
  10. Zhang C. Does Statin Reloading Before Cardiac Surgery Improve Postoperative Outcomes? Journal of cardiothoracic and vascular anesthesia 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29203297
  11. Skeldon SC, Cheng L, Morgan SG et al. Erectile Dysfunction Medications and Treatment for Cardiometabolic Risk Factors: A Pharmacoepidemiologic Study. The journal of sexual medicine 2017; 14:1597-1605. http://www.ncbi.nlm.nih.gov/pubmed/?term=29198514
  12. MA VW, Kaleta EJ, Bryant SC et al. Genetic variation in statin intolerance and a possible protective role for UGT1A1. Pharmacogenomics 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29210320
  13. Llobet Vila L, Manresa Dominguez JM, Carmona Segado JM et al. [Facing a dilemma in elderly complex and vulnerable patients: to stop or not to stop prevention?]. Atencion primaria / Sociedad Espanola de Medicina de Familia y Comunitaria 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29221946
  14. Lin BM, Li WQ, Cho E et al. Statin Use and Risk of Skin Cancer. Journal of the American Academy of Dermatology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29208416
  15. Hasegawa Y, Hori M, Nakagami T et al. Glucagon-like peptide-1 receptor agonists reduced the low-density lipoprotein cholesterol in Japanese patients with type II diabetes mellitus treated with statins. J Clin Lipidol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29217412
  16. Denisov IG, Baylon JL, Grinkova YV et al. Drug-drug interactions between Atorvastatin and Dronedarone mediated by monomeric CYP3A4. Biochemistry 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29200287
  17. Bertl K, Steiner I, Pandis N et al. Statins in nonsurgical and surgical periodontal therapy. A systematic review and meta-analysis of preclinical in vivo trials. Journal of periodontal research 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29211309
Miscellaneous publications
  1. Zhang W, Yang X, Chen Y et al. Activation of hepatic Nogo-B receptor expression-A new anti-liver steatosis mechanism of statins. Biochim Biophys Acta 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29217477
  2. Temiz MZ, Yuruk E, Ertas K et al. Effects of statin treatment with atorvastatin on urolithiasis-associated urinary metabolic risk factors: an experimental study. International urology and nephrology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29197934
  3. Tahta A, Izgi N, Onder TB et al. Assessment of the MRI and Behavioral Test Results in Focal Cerebral Ischemia Reperfusion Model in Rat after Separate and Combined Use of Mouse-Derived Neural Progenitor Cells, Human-Derived Neural Progenitor Cells and Atorvastatin. Turkish neurosurgery 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29204982
  4. Raffoul-Orozco AK, Avila-Gonzalez AE, Rodriguez-Razon CM et al. Combination effect naringin and pravastatin in lipid profile and glucose in obese rats. Life sciences 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29197498
  5. Jin Y, Xu K, Chen Q et al. Simvastatin inhibits the development of radioresistant esophageal cancer cells by increasing the radiosensitivity and reversing EMT process via the PTEN-PI3K/AKT pathway. Experimental cell research 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29208461
  6. Fong Soe Khioe R, Skedgel C, Hart A et al. Adjuvant Statin Therapy for Esophageal Adenocarcinoma: A Cost-Utility Analysis. PharmacoEconomics 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29210031
  7. Fang D, He Y, Luan Z. Simvastatin augments activation of liver regeneration through attenuating transforming growth factor-beta1 induced-apoptosis in obstructive jaundice rats. Experimental and therapeutic medicine 2017; 14:4839-4845. http://www.ncbi.nlm.nih.gov/pubmed/?term=29201188
  8. Choi HW, Shin PG, Lee JH et al. Anti-inflammatory effect of lovastatin is mediated via the modulation of NF-kappaB and inhibition of HDAC1 and the PI3K/Akt/mTOR pathway in RAW264.7 macrophages. International journal of molecular medicine 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29207042
  9. Broniarek I, Jarmuszkiewicz W. Atorvastatin affects negatively respiratory function of isolated endothelial mitochondria. Archives of biochemistry and biophysics 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29217137
  10. Lv ZH, Phuong TA, Jin SJ et al. Protection by simvastatin on hyperglycemia-induced endothelial dysfunction through inhibiting NLRP3 inflammasomes. Oncotarget 2017; 8:91291-91305. http://www.ncbi.nlm.nih.gov/pubmed/?term=29207644
  11. Fathi HA, Allam A, Elsabahy M et al. Nanostructured lipid carriers for improved oral delivery and prolonged antihyperlipidemic effect of simvastatin. Colloids and surfaces. B, Biointerfaces 2017; 162:236-245. http://www.ncbi.nlm.nih.gov/pubmed/?term=29197789
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