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Update - Week 15, 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

Week 15

Real world data confirms sub-optimal statin use associated with worse outcomes in NSTMI patients
In the UK, 1005 non-STEMI patients, discharged on high potency statins (HPS); atorvastatin 80 mg, rosuvastatin 20 mg, or 40 mg; were prospectively followed for 16 months. Patients who at one month were constant HPS users were compared with patients who were sub-optimal users at that time point. After only 1 month 156 patients (15.5%) did not continue with HPS. Increased sub-optimal use was observed in females OR 1.75 (95% CI 1.14-2.68) and in patients presenting with muscle symptoms OR 4.28 (95% CI 1.30-14.08). Not continuing with HPS resulted in an increased risk for time to MACE HR 2.10 (95% CI 1.25-3.53, p=0.005) and all-cause mortality HR 2.46 (95% CI 1.38-4.39, P=0.003). this prospective analysis in a real-world setting shows the rapid and high rates of statin discontinuation plus the serious consequences related to sub optimal use of high dose, high intensity statins.
Turner RM, Yin P, Hanson A et al. Investigating the prevalence, predictors, and prognosis of suboptimal statin use early after a non-ST elevation acute coronary syndrome. J Clin Lipidol 2017; 11:204-214. http://www.ncbi.nlm.nih.gov/pubmed/?term=28391887
 
Recent ACC/AHA guideline, outperforms ATP III in finding statin eligible patient
STEMI patients (N=1062) who participated in the Minneapolis Heart Institute Level 1 MI program were retrospectively queried for statin use or statin eligibility based on current and previous US guidelines. Majority of patients, 761 (71.7%) did not have any CVD manifestations prior to the STEM. Pre-existing statin use was noted in 72.5% and 19.3% in individuals with and without prior CVD. Based on the older ATP III guideline criteria, 38.7% of the patients, without prior CVD manifestations, would have been eligible for statin treatment. Using the current ACC/AHA November 2013 guidelines, that number would have increased to 79.0 %. Visiting a primary health care provider in the 2 years prior the MI, was observed in 49.2% of the patients with CVD and 41.1% in the ones without. The authors concluded that recent updated guidelines increased statin eligibility significantly in individuals destined to experience a STEMI. However better access and utilization of preventive healthcare services are needed as well in order to provide patients with guideline dictated strategies to prevent CV calamities.  
Miedema MD, Garberich RF, Schnaidt LJ et al. Statin Eligibility and Outpatient Care Prior to ST-Segment Elevation Myocardial Infarction. J Am Heart Assoc 2017; 6. http://www.ncbi.nlm.nih.gov/pubmed/?term=28404560
 
Do patients have benefits of, high intensity – high dose statins after a TAVR?
In this single center retrospective analysis of 294 consecutive patients that had a TAVR procedure between June 2008 and February 2015, statin use and related outcome parameters, such as post-TAVR adverse events, 30-day mortality, and overall survival, were evaluated. High intensity – high dose statins (HIHD) was defined as Atorvastatin 40-80 mg or Rosuvastatin 20-40 mg. Statins considered to be HIHD were used by 41 patients (14%); 173 (59%) used low or moderate intensity statins and 80 (27%) did no use statins. No differences were observed between the three groups for post-TAVR stroke, myocardial infarction, acute kidney injury, in-hospital mortality, or 30-day mortality. But after two years 83% of the patients on HIHD, 70% of the low – moderate intensity statins and 57% of patients that were not using statins were still alive. Patients on HIDHI experience a 64% reduction in all-cause mortality (HR 0.36, 95% CI 0.14 to 0.90, p= 0.029) compared with patients that did not use any statins. The authors suggested that the results of this observational study warrant further prospective testing.
Huded CP, Benck LR, Stone NJ et al. Relation of Intensity of Statin Therapy and Outcomes After Transcatheter Aortic Valve Replacement. Am J Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28395888
 
Statin uses associated with improved limb prognosis in Chinese patients with DM + PAD
Only limited data is available on the effects of statins in patients with peripheral artery disease (PAD). In this retrospective analysis, using the Taiwan National Health Insurance (NHI) registry, 69 332 Taiwanese diabetic patients with PAD were identified. The patients were divided in 3 groups: statin users (N=11 409); non-satin lipid lowering drugs (N=4 430) and no statins users (N=53 493). For all predefined endpoints statin uses showed improved outcome. Lower limb amputations, in-hospital cardiovascular death and all-cause mortality were reduced. With HR’s of 0.75 (95% CI 0.62-0.90); 0.78 (95% CI 0.69-0.87) and 0.73 (95% CI 0.69-0.77) respectively. Based on this analysis statins showed not only CHD protective effects but also had favorable effects on limb prognosis in Chinese DM patients with PAD.
Hsu CY, Chen YT, Su YW et al. Statin therapy reduces future risk of lower limb amputation in patient with diabetes and peripheral artery disease. J Clin Endocrinol Metab 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28398564
 
Statin intolerance is associated with higher costs and increased risk for non-fatal CVD events
Using patient data collected the Geisinger Health System (GHS) electronic health record (EHR), from January 1, 2008, through September 30, 2014, the authors extracted data from 5190 patients with statin intolerance (SI) and based on a propensity matching score, compared outcomes with 15 570 controls. Based on 6 pre-defined CV risk categories, patients with SI incurred higher medical costs, were less likely to reach their LDL-C target, were at higher risk for revascularization, for 5 of the 6 CV risk categories (not in ACS patients). Patients in the diabetes CV risk category had a significant higher risk to develop CVD events. Although most of the patients experiencing SI could tolerate at least a non-daily dose of statin, they were at increased risk for a non-fatal CV event, incurred higher health care costs and were less likely to reach their LDL-C targets. All risk categories showed a lower total mortality in the SI group compared to the controls. The authors suggest that more careful monitoring of SI patients and resulting in earlier interventions for potentially fatal events. High dose – high intensity was used by only 25% of the high CV-risk patients in the non-SI cohort, as compared to 15% in the SI group.
Graham JH, Sanchez RJ, Saseen JJ et al. Clinical and economic consequences of statin intolerance in the United States: Results from an integrated health system. J Clin Lipidol 2017; 11:70-79.e71. http://www.ncbi.nlm.nih.gov/pubmed/?term=28391913
 
How to manage muscle related symptoms in statin intolerant patients
Updated review with recent studies that evaluated statin intolerance and a practical framework addressing several, tried and proven successful, approaches how to support and guide patients experiencing muscle related complaints. The review discusses recent clinical trials, available (on-line) resources, the typical manifestations of statin related myalgia’s; how to identify true intolerance; reviewing concomitant medications; the different supplements that allegedly alleviate muscle symptoms; dietary factors that are related to fatigue and muscle pain; the role of Ezetimibe; alternative non-statin lipid lowering drugs and alternative regimens that could lower LDL-cholesterol but not cause muscle symptoms 
Backes JM, Ruisinger JF, Gibson CA; Moriarty PM. Statin-associated muscle symptoms-Managing the highly intolerant. J Clin Lipidol 2017; 11:24-33. http://www.ncbi.nlm.nih.gov/pubmed/?term=28391891
 

Relevant publications
Week 15
  1. Yu EJ, Graber JM, Lu SE et al. Effect of Metformin and Statin Use on Survival in Pancreatic Cancer Patients: a Systematic Literature Review and Meta-analysis. Curr Med Chem 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28403788
  2. Xu Y, Wang Y, Zhi J et al. Impact of matrix metalloproteinase 9 rs3918242 genetic variant on lipid-lowering efficacy of simvastatin therapy in Chinese patients with coronary heart disease. BMC pharmacology & toxicology 2017; 18:28. http://www.ncbi.nlm.nih.gov/pubmed/?term=28390432
  3. Umemoto T, Yasu T, Arao K et al. Pravastatin improves postprandial endothelial dysfunction and hemorheological deterioration in patients with effort angina pectoris. Heart Vessels 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28396938
  4. Thongtang N, Diffenderfer MR, Ooi EM et al. Metabolism and proteomics of large and small dense LDL in combined hyperlipidemia. Effects of rosuvastatin. Journal of lipid research 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28392500
  5. Scherer DJ, Nelson A, Psaltis PJ, Nicholls SJ. Targeting LDL Cholesterol with PCSK9 Inhibitors. Internal medicine journal 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28401639
  6. Pearlman M, Covin Y, Schmidt R et al. Statins and Lower Gastrointestinal Conditions: A Retrospective Cohort Study. Journal of clinical pharmacology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28398604
  7. Kastelein JJ, Hovingh GK, Langslet G et al. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 monoclonal antibody alirocumab vs placebo in patients with heterozygous familial hypercholesterolemia. J Clin Lipidol 2017; 11:195-203.e194. http://www.ncbi.nlm.nih.gov/pubmed/?term=28391886
  8. Kaplon-Cieslicka A, Michalak M, Koltowski L, Filipiak KJ. How has the treatment of hypercholesterolemia in Poland changed over the last 6 years? Cardiology journal 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28394011
  9. Eccleston D, Horrigan M, Rafter T et al. Improving Guideline Compliance in Australia With a National Percutaneous Coronary Intervention Outcomes Registry. Heart, lung & circulation 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28389196
  10. Atkins ER, Du X, Wu Y et al. Use of cardiovascular prevention treatments after acute coronary syndrome in China and associated factors. Int J Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28389125
  11. Wiggers JK, van Golen RF, Verheij J et al. Atorvastatin does not protect against ischemia-reperfusion damage in cholestatic rat livers. BMC surgery 2017; 17:35. http://www.ncbi.nlm.nih.gov/pubmed/?term=28399849
  12. Rafeeq MM, Habib HS, Murad H et al. Effect of rosuvastatin on dyslipidemia and other parameters associated with metabolic syndrome in Saudi patients. Nigerian journal of clinical practice 2017; 20:445-453. http://www.ncbi.nlm.nih.gov/pubmed/?term=28406125
  13. Poinsot P, Collardeau Frachon S, Restier L et al. Childhood/adult-onset lysosomal acid lipase deficiency: A serious metabolic and vascular phenotype beyond liver disease-four new pediatric cases. J Clin Lipidol 2017; 11:167-177.e163. http://www.ncbi.nlm.nih.gov/pubmed/?term=28391883
  14. Oda T, Sawada Y, Yamaguchi T et al. Drug Eruption Caused by Rosuvastatin. J Investig Allergol Clin Immunol 2017; 27:140-141. http://www.ncbi.nlm.nih.gov/pubmed/?term=28398205
  15. Nixon DE, Bosch RJ, Chan ES et al. Effects of atorvastatin on biomarkers of immune activation, inflammation, and lipids in virologically suppressed, human immunodeficiency virus-1-infected individuals with low-density lipoprotein cholesterol <130 mg/dL (AIDS Clinical Trials Group Study A5275). J Clin Lipidol 2017; 11:61-69. http://www.ncbi.nlm.nih.gov/pubmed/?term=28391912
  16. Miedema MD, Sidebottom AC, Sillah A et al. Clinical implications of the American College of Cardiology/American Heart Association guidelines for the treatment of blood cholesterol for a rural community: Data from the Heart of New Ulm Project. J Clin Lipidol 2017; 11:94-101. http://www.ncbi.nlm.nih.gov/pubmed/?term=28391916
  17. Md KF, Grunfeld C. Triglyceride Lowering Drugs. In: Endotext. Edited by: De Groot LJ, Chrousos G, Dungan K et al. South Dartmouth (MA): MDText.com, Inc.; 2000.
  18. Maraqa AD. Effect of atorvastatin on interleukins and prostaglandin E2 in the kidney of type 1 diabetic rats. European cytokine network 2016; 27:97-101. http://www.ncbi.nlm.nih.gov/pubmed/?term=28396300
  19. Madonna R, Renna FV, Lanuti P et al. The acute impact of high-dose lipid-lowering treatment on endothelial progenitor cells in patients with coronary artery disease-The REMEDY-EPC early substudy. PLoS One 2017; 12:e0172800. http://www.ncbi.nlm.nih.gov/pubmed/?term=28394933
  20. Izuka NJ, Alexander MA, Balasooriya-Smeekens C et al. How do stroke survivors and their carers use practitioners' advice on secondary prevention medications? Qualitative study of an online forum. Family practice 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28398553
  21. Hersi A, Giannoccaro JP, Howarth A et al. Statin Induced Regression of Cardiomyopathy Trial: A Randomized, Placebo-controlled Double-blind Trial. Heart views : the official journal of the Gulf Heart Association 2016; 17:129-135. http://www.ncbi.nlm.nih.gov/pubmed/?term=28400935
  22. Della Pepa G, Bozzetto L, Annuzzi G, Rivellese AA. Alirocumab for the treatment of hypercholesterolaemia. Expert Rev Clin Pharmacol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28395555
  23. Albright KC, Zhao H, Blackburn J et al. Racial differences in statin adherence following hospital discharge for ischemic stroke. Neurology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28404800

Miscellaneous publications
Week 15
  1. Yu L, Da XW, Wu XL et al. Simvastatin prevents lipopolysaccharide-induced septic shock in rats. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 2017; 37:226-230. http://www.ncbi.nlm.nih.gov/pubmed/?term=28397043
  2. Santos BF, Souza EQ, Brigagao MR et al. Local application of statins in the treatment of experimental periodontal disease in rats. Journal of applied oral science : revista FOB 2017; 25:168-176. http://www.ncbi.nlm.nih.gov/pubmed/?term=28403357
  3. Li M, Zhang ZJ, Kong XD et al. Engineering Streptomyces coelicolor carbonyl reductase for efficient synthesis of atorvastatin precursor. Applied and environmental microbiology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28389544
  4. El-Sayed AS, Abdel-Ghany SE, Ali GS. Genome editing approaches: manipulating of lovastatin and taxol synthesis of filamentous fungi by CRISPR/Cas9 system. Applied microbiology and biotechnology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28389711

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