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Update - Week 49, 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

Recalibrating statins benefits vs harms
This recent modeling study, aiming to recalculate statin benefits vs harms, sparked some controversies with experts debating the design of the analysis as well as some of the studies used to generate the conclusions. The aim of the Swiss authors was to come up with a better approach to define the net gains of statins by weighing of harms vs benefits. Using a network meta-analysis of primary prevention studies, as well as a preference survey and selected observational studies they recalculated the 10-year CVD risk at which statins can provide a 60% probability of net benefits, taking into account other relevant variables e.g. harms, preference baseline risk etc. Type of statin, as well as age and gender, weigh in when calculating risk threshold. For men aged 40-44 years, the 10-year risk threshold was 14% vs 21% in men 70-75-year-old. For women, the threshold percentages were 17% and 22%. A distinction was made between high potency statins, atorvastatin, and rosuvastatin vs simvastatin and pravastatin. For the high potency statins, net benefits were calculated to manifest at lower 10-year risk values. Men aged 40-49 years net benefits were observed at a 10-year risk of 15% for atorvastatin, 18% for rosuvastatin, 19% for pravastatin and 21% for simvastatin. Although the approach used by the authors is valid, patients included in this analysis are from a Western geographic, ethnic and genetic background. To extrapolate these observations to different populaces, data from non-Caucasian populations needs to be collected and re-evaluated.
Yebyo HG, Aschmann HE, Puhan MA. Finding the Balance Between Benefits and Harms When Using Statins for Primary Prevention of Cardiovascular Disease: A Modeling Study. Annals of internal medicine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30508425
 
Cardiac rehab essential in post AMI care
The German PATIENT CARE registry was set up to document and improve the care of post-AMI patients. Modifying existing risk factors by improving lifestyle as well as providing the pharmacological therapy to achieve guideline directed targets for LDL-c is the core of rehab competence. This study was conducted in 20 German cardiac rehabilitation centers, including 1408 patients. Over 2/3 were male and the average age was 61 ± 11 years. STEMI’s and NSTEMI’s were equally divided, 48.7% and 45.8% respectively. Previous CABG was reported in 9.9% of the participants. Rehab started 19 ±10 days after hospital admission and lasted for 22 ±4 days. Medication use at discharge were, statins: 96.7%, other add-on lipid-lowering drugs: 13%, antithrombotic’s: 98.5% and anti-diabetic medication: 22.3%. LDL-c targets <70mg/dl (or at least >50% reduction compared to baseline) were observed in 21.4% of the patients at discharge and increased to 41.9% after rehab completion. Most patients (95.2%) successfully completed the rehab program and 88% were able to re-start their previous employment activities. The observed improvements in patients achieving LDL-c targets were substantial, however, the authors did point out that over half of these high-risk patients were unable to do so. The limited duration of cardiac rehab programs was suggested as a possible reason for this observed failure to reach LDL-c goals.  
Schwaab B, Zeymer U, Jannowitz C et al. Improvement of low-density lipoprotein cholesterol target achievement rates through cardiac rehabilitation for patients after ST elevation myocardial infarction or non-ST elevation myocardial infarction in Germany: Results of the PATIENT CARE registry. Eur J Prev Cardiol 2018:2047487318817082. http://www.ncbi.nlm.nih.gov/pubmed/?term=30509144
 
Is NODM risk increased in statin users that report myalgia?
The well-recognized side-effects of statins are myalgia and new-onset diabetes (NOD). Very limited data is available on the interactions of these common side effects; are patients that report muscle-related complaints, also more prone to present with NODM.  The Danish LIFESTAT registry was set up top collect a broad set of data of regular statin users. In a subset of patients, a cross-sectional analysis was performed in statin users. without CVD, that presented with myalgia – M (N-25) and non-myalgic patients – NM (N=39) as well as a control group – C (N=20).  The three cohorts were subjected to an oral glucose tolerance test (OGTT), intravenous glucose tolerance test, euglycemic clamp, and muscle content of GLUT4 + hexokinase. The only parameter that was different was the insulin secretion rate after the OGTT. This was increased in the myalgic group compared with the non-myalgic patients and controls. AUC ISROGTT, C: 1032 (683 - 1500); M: 922 (678 - 1091); NM: 1089 (933 - 1391) pmol·L-1·min (median with 25-75% percentiles). No differences were observed for all other studied parameters. The authors concluded that there seems to be no increased risk of developing NODM in patients that report with myalgic complaints.
Morville T, Dohlmann T, Kuhlman AB et al. Glucose homeostasis in statin users - the LIFESTAT study. Diabetes/metabolism research and reviews 2018:e3110. http://www.ncbi.nlm.nih.gov/pubmed/?term=30517978
 
Is statin-induced hyperglycemia a class effect?
Comparing the pro diabetogenic effects of different statin in Korean participants of the National Health Screening Cohort was the aim of this recent analysis. From the NHSC cohort 379 865 individuals with ≥2 health screening visits and in whom fasting blood glucose was measured. (2001-2013). Then exposure to statins was calculated by using the prescription records of the database and estimated the proportion of days covered (PDC) as well as the average number of defined daily doses per day (DDD) for statins. Using a multivariate linear mixed statistical model, they examined the effects of different statins on changes in fasting glucose (∆glu). Glucose level responded positively to PDC increases, coefficient for PDC: 0.093 mmol/L ± 0.007 (p < 0.001). Similar trend was observed for DDD, coefficient: 0.119 mmol/L, ± 0.009 (p < 0.001.) No effects on ∆glu for ezetimibe, fibrates and for the statin time interval. When comparing different statins, atorvastatin, rosuvastatin, simvastatin, and pitavastatin showed a significant association with increases in Δglu. This was also observed for pravastatin, lovastatin, and fluvastatin but changes were not statistically significant. The findings of this prospective Korean registry confirm the pro diabetogenic effects of statins and that adherence and higher potency contributed to worse NODM outcomes. Statistically significant differences were observed for all higher potency statins, including pitavastatin. The lower potency statins, lovastatin, pravastatin, and fluvastatin showed non-significant trends of worsening glycemic control, confirming the class effect of statin-induced hyperglycemia.
Kim J, Lee HS, Lee KY. Effect of statins on fasting glucose in non-diabetic individuals: nationwide population-based health examination in Korea. Cardiovascular diabetology 2018; 17:155. http://www.ncbi.nlm.nih.gov/pubmed/?term=30518364
 
Are statins safe in patients with systemic autoimmune myopathies?
Dyslipidemia is frequently observed in patients with immune-mediated myopathies (SAM) such as dermatomyositis, polymyositis, and anti-synthetase syndrome. Limited information on statin safety is available on SAM patients. To explore the effects of statins the authors conducted a retrospective cohort study (2004-2018) collecting data on 250 SAM patients. Evaluated were 24 stable dyslipidemic SAM patients that used statins. Patients with amyopathic dermatomyositis, immune-mediated necrotizing myopathy, dermatomyositis, or polymyositis induced by statins were excluded. Most of the patients were females, mean age 50.6 years, and they have been diagnosed for a median period of 5.0 years. Statins used were simvastatin (10-60 mg), 11 patients; 12 were using atorvastatin (20-40 mg) and 1 patient started with atorvastatin 20 mg but was switched to simvastatin 20 mg. Exposure time to statins was 22.5 months. Information collected at follow up visits showed improvements of plasma lipids and no recurrences or exacerbations of their underlying myopathy. Although this was a relatively small study, no safety issues emerged in SAM patients that used statins. New studies with larger number of patients and with different disease activities are needed to corroborate these findings.
Borges IBP, Shinjo SK. Safety of statin drugs in patients with dyslipidemia and stable systemic autoimmune myopathies. Rheumatology international 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30519709
Relevant publications
  1. Teramoto T, Kiyosue A, Ishigaki Y et al. Efficacy and safety of alirocumab 150mg every 4 weeks in hypercholesterolemic patients on non-statin lipid-lowering therapy or lowest strength dose of statin: ODYSSEY NIPPON. J Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30509509
  2. Kocyigit D, Tokgozoglu L, Kayikcioglu M et al. Is there a gender gap in secondary prevention of coronary artery disease in Turkey? Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir 2018; 46:683-691. http://www.ncbi.nlm.nih.gov/pubmed/?term=30516526
  3. Giannopoulos G, Vrachatis D, Kossyvakis C et al. Effect of Postablation Statin Treatment on Arrhythmia Recurrence in Patients With Paroxysmal Atrial Fibrillation. Journal of cardiovascular pharmacology 2018; 72:285-290. http://www.ncbi.nlm.nih.gov/pubmed/?term=30520854
  4. Ennezat PV, Le Jemtel T, Cosgrove S et al. Outcome postponement as a potential patient centred measure of therapeutic benefit: examples in cardiovascular medicine. Acta Cardiol 2018:1-10. http://www.ncbi.nlm.nih.gov/pubmed/?term=30513258
  5. Alshaikh HN, Bohsali F, Gani F et al. Statin intensity and postoperative mortality following open repair of intact abdominal aortic aneurysm. BJS open 2018; 2:411-418. http://www.ncbi.nlm.nih.gov/pubmed/?term=30511041
  6. Vuorio A, Kovanen PT. Decreasing the Cholesterol Burden in Heterozygous Familial Hypercholesterolemia Children by Dietary Plant Stanol Esters. Nutrients 2018; 10. http://www.ncbi.nlm.nih.gov/pubmed/?term=30513705
  7. Sisa I. Gender differences in cardiovascular risk assessment in elderly adults in Ecuador: evidence from a national survey. Journal of investigative medicine : the official publication of the American Federation for Clinical Research 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30518558
  8. Lecerf JM. Should we prescribe statins for primary prevention of cardiovascular risk? Rather no. Rev Prat 2016; 66:334-337. http://www.ncbi.nlm.nih.gov/pubmed/?term=30512651
  9. Kutner JS, Abernethy AP. Coding Error Resulting in Change in Secondary Outcome Scores in Trial of Safety and Benefit of Discontinuing Statin Therapy Among Terminally Ill Patients. JAMA Intern Med 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30508023
  10. Kandzia I, Kowar M, Frackowiak M, Jacobs AH. [Simvastatin-Induced Myopathy after Dose Increase]. Deutsche medizinische Wochenschrift (1946) 2018; 143:1791-1794. http://www.ncbi.nlm.nih.gov/pubmed/?term=30508862
  11. Jialal I, Chaudhuri A. Targeting inflammation to reduce ASCVD in type 2 diabetes. Journal of diabetes and its complications 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30514609
  12. Feldman MD, Cabe AG, Milner TE. IVOCT Has a Bright Future in the Identification of Vulnerable Plaques. JACC. Cardiovascular imaging 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30503625
  13. Caussy C, Charriere S, Moulin P. Statins in secondary prevention of cardiovascular risk. Rev Prat 2016; 66:322-326. http://www.ncbi.nlm.nih.gov/pubmed/?term=30512646
  14. Cariou B, Smati S. LDL-cholesterol hypothesis:the lower is trully better. Rev Prat 2016; 66:317-321. http://www.ncbi.nlm.nih.gov/pubmed/?term=30512645
  15. Beliard-Lasserre S. Should we prescribe statins for primary prevention of cardiovascular risk? Rather yes. Rev Prat 2016; 66:332-334. http://www.ncbi.nlm.nih.gov/pubmed/?term=30512650
Miscellaneous publications
 
 
  1. Zhang Y, Fang Q, Niu K et al. Time-dependently slow-released multiple-drug eluting external sheath for efficient long-term inhibition of saphenous vein graft failure. J Control Release 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30521829
  2. Zamani M, Shirinzadeh A, Aghajanzadeh M et al. In Vivo Study of mPEG-PCL as a Nanocarriers for Anti-Inflammatory Drug Delivery of Simvastatin. Pharmaceutical development and technology 2018:1-25. http://www.ncbi.nlm.nih.gov/pubmed/?term=30516412
  3. Yan J, Qiao L, Wu J et al. Simvastatin Protects Dopaminergic Neurons Against MPP+-Induced Oxidative Stress and Regulates the Endogenous Anti-Oxidant System Through ERK. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2018; 51:1957-1968. http://www.ncbi.nlm.nih.gov/pubmed/?term=30513525
  4. Singh F, Zoll J, Duthaler U et al. PGC-1beta modulates statin-associated myotoxicity in mice. Archives of toxicology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30511338
  5. Seliger C, Schaertl J, Gerken M et al. Use of statins or NSAIDs and survival of patients with high-grade glioma. PLoS One 2018; 13:e0207858. http://www.ncbi.nlm.nih.gov/pubmed/?term=30507932
  6. Ritter P, Yousefi K, Ramirez J et al. LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring. Journal of visualized experiments : JoVE 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30507918
  7. Otrocka-Domagala I, Pazdzior-Czapula K, Maslanka T. Simvastatin Impairs the Inflammatory and Repair Phases of the Postinjury Skeletal Muscle Regeneration. BioMed research international 2018; 2018:7617312. http://www.ncbi.nlm.nih.gov/pubmed/?term=30519583
  8. Mamdooh N, Kasabri V, Al-Hiari Y et al. Evaluation of selected commercial pharmacotherapeutic drugs as potential pancreatic lipase inhibitors and antiproliferative compounds. Drug development research 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30511444
  9. Malik M, Britten J, Borahay M et al. Simvastatin, at clinically relevant concentrations, affects human uterine leiomyoma growth and extracellular matrix production. Fertility and sterility 2018; 110:1398-1407.e1391. http://www.ncbi.nlm.nih.gov/pubmed/?term=30503138
  10. Kaminska M, Aliko A, Hellvard A et al. Effects of statins on multispecies oral biofilm identify simvastatin as a drug candidate targeting Porphyromonas Gingivalis. Journal of periodontology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30506795
  11. Jiang SY, Li H, Tang JJ et al. Discovery of a potent HMG-CoA reductase degrader that eliminates statin-induced reductase accumulation and lowers cholesterol. Nature communications 2018; 9:5138. http://www.ncbi.nlm.nih.gov/pubmed/?term=30510211
  12. Hasanvand A, Ahmadizar F, Abbaszadeh A et al. The Antinociceptive Effects of Rosuvastatin in Chronic Constriction Injury Model of Male Rats. Basic and clinical neuroscience 2018; 9:251-260. http://www.ncbi.nlm.nih.gov/pubmed/?term=30519383
  13. Gurzeler E, Aavik E, Laine A et al. Therapeutic effects of rosuvastatin in hypercholesterolemic prediabetic mice in the absence of low density lipoprotein receptor. Biochimica et biophysica acta. General subjects 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30508567
  14. Cheng WP, Lo HM, Wang BW et al. Effect of atorvastatin on cardiomyocyte hypertrophy through suppressing MURC induced by volume overload and cyclic stretch. Journal of cellular and molecular medicine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30511410
  15. Ali M, Jackson-Bey T, Al-Hendy A. Simvastatin and uterine fibroids: opportunity for a novel therapeutic option. Fertility and sterility 2018; 110:1272-1273. http://www.ncbi.nlm.nih.gov/pubmed/?term=30503124
  16. Anzilaggo D, O'Reilly Beringhs A, Pezzini BR et al. Liquisolid systems: Understanding the impact of drug state (solution or dispersion), nonvolatile solvent and coating material on simvastatin apparent aqueous solubility and flowability. Colloids and surfaces. B, Biointerfaces 2018; 175:36-43. http://www.ncbi.nlm.nih.gov/pubmed/?term=30517903
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