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Update - Week 28,  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

High dose atorvastatin protects kidneys from contrast induced nephropathy
Contrast-induced nephropathy (CIN) is a frequent cause of acute renal dysfunction. Incidence is estimated to be 2% in the general population, but can increase to 20%-30% in patients with chronic kidney disease, DM, congestive heart failure and elderly. The authors evaluated the effects of atorvastatin 80 mg on preventing CIN in patient at high risk for this complication. Patients (N=188) were randomized to N-acetylcysteine (NAC) 1200 mg or atorvastatin 80 mg + 1200 mg NAC, three days before and 2 days after the angiography. Study was completed by 160 patients and CIN developed in 9 patients treated with NAC and in 2 patients that received atorvastatin 80 + NAC. Mean change in serum creatinine was 0.086 ± 0.168 and 0.021 ± 0.083 (P=0.0289); eGFR was reduced by 19.52 vs 13.55 (P=0.003) in patients using only NAC vs NAC + atorvastatin respectively. The authors postulated that the pleiotropic anti-inflammatory and anti-oxidative properties of statins contributed to the observed benefits and emphasized the positive role of statins, along with NAC in CIN prevention.
Syed MH, Khandelwal PN, Thawani VR, Katare SS. Efficacy of Atorvastatin in Prevention of Contrast-induced Nephropathy in High-risk Patients Undergoing Angiography: A Double-blind Randomized Controlled Trial. Journal of pharmacology & pharmacotherapeutics 2017; 8:50-53. http://www.ncbi.nlm.nih.gov/pubmed/?term=28706398
 
Statins and ACE-i associated with improved outcome in patients with chronic liver disease
Liver disease is a significant health care problem and patients affected are increasing partly due to the growing numbers of obesity and diabetes prevalence globally. In this Swedish registry based cohort study the effects of medication for concurrent diseases on liver related morbidity and mortality were analyzed. Data collected from all patients with a first-time diagnosis of chronic liver disease between 2005 and 2012 in Sweden (n=70 546) was linked with the Prescribed Drug Register and the Death Certificate Register. De drugs studies were statins, ACE-i, ARB’s and antibiotics. For statin users (n-11 245) a reduced mortality risk was observed HR 0.57 (0.32-0.99) for auto immune hepatitis and HR 0.84 (0.75-0.94) for alcoholic liver disease. No statistical significant improvements were observed in patients with NAFLD or toxic hepatitis ACE-i use was associated with a reduced risk for alcoholic liver disease related mortality HR 0.85 (0.65-0.96). Antibiotic use showed an increased overall mortality risk; HR: 1.67 (1.55-1.88) for viral hepatitis.  The authors suggest that non-lipid lowering effects of statins such as anti-inflammatory and anti-oxidative effects could explain the reduced risk. Reducing portal hypertension and slowing progression of fibrosis were suggested as an explanation for the benefits of ACE-i. The increased risk of antibiotic use was considered a confounder effect. Bacterial infections can worsen the course of liver disease and antibiotics used for spontaneous bacterial peritonitis are associated with a worse prognosis.
Stokkeland K, Lageborn CT, Ekbom A et al. Statins and ACE Inhibitors are Associated with Reduced Mortality and Morbidity in Chronic Liver Disease. Basic & clinical pharmacology & toxicology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28691216
 
In patients with asymptomatic carotid stenosis optimal risk factor control associated with impressive improved outcomes
To evaluate the benefits of optimal risk management in patients with asymptomatic car0tid artery stenosis (ACAS) the authors executed a retrospective analysis of patients that underwent a carotid duplex ultrasound from 2001- 2014 in a single institute the University of Kansas Medical Center, department of Cardiovascular Medicine. The factors evaluated to determine their benefits on outcome: smoking, SBP<140 mmHg, DBP ,90 mgHg, LDL-C< 100mg/dl and moderate to high intensity statins. Progression of severity of carotid stenosis (PSCS) and transient ischemic attack (TIA), ischemic stroke (IA), carotid revascularization (CRV) were the designated endpoints. There were 864 patients included in the analysis with a median follow-up time of 79 ± 36 months. Overall IS/TIA occurred in 12.9% of the patients and PCSS was observed in 21.5% of the vessels. When comparing the extreme spectra of the groups patients with all RF optimal only the annual rate of suffered a IA/TIA/CRV was 0.64% vs 3.6% in the group were all RF targets were not achieved.  For PCSC these numbers were 9.3% vs 28.2% respectively. The authors concluded that there was a significant incremental benefit of multiple risk factor control on outcome measures in patients with asymptomatic carotid artery stenosis.
Shah Z, Masoomi R, Thapa R et al. Optimal Medical Management Reduces Risk of Disease Progression and Ischemic Events in Asymptomatic Carotid Stenosis Patients: A Long-Term Follow-Up Study. Cerebrovasc Dis 2017; 44:150-159. Cancer mortiality occurred in 4.2% vs 0.4% http://www.ncbi.nlm.nih.gov/pubmed/?term=28689200
 
Statin eligibility accurately identifies patients at increased risk for cancer
Cancer and CVD have numerous risk factors in common. In this sub analysis of the Framingham Heart study patients deemed eligible for statin treatment, based on the ACC/AHA 2013 guidelines, found to be at high risk for developing cancer. There were 2 196 participants (50.5 ± 8.1 years; 55% female) included in this analysis. None of them had used statins and they were all free of cancer at baseline. The primary outcome was incident cancer at a median follow up time of 10.0 years (interquartile range, 9.1-10.6 years). Secondary outcomes were cancer mortality and non-cardiovascular mortality. In 11.2% of the participants a diagnosis of cancer was established and there were 58 non-cardiovascular deaths, including 39 cancer related deaths (1.8%). Overall, 37% of the patients were statin eligible. When comparing statin eligible patients with the non-eligible patients, cancer occurred in 15% vs 8.8%; HR 1.8(1.4-2.3) P<0.001. Deaths due to cancer were observed in 4.2% vs 0.4%; HR 12.1 (4.7-31) P<0.001. For non-cardiovascular mortality, the numbers amounted to 6.0% vs 0.7% HR 10.1 (5.0-21) P<0.001. These findings were independent of any individual risk factor such as body mass index, age, or smoking status. The authors concluded that in a primary prevention cohort statin eligibility accurately identified patients at much high risk for developing cancer or cancer related death. They also suggested that the shared risk profiles and potential benefits of statins on cancer and cardiovascular outcomes potentially provides a unique opportunity to improve population health.
Pursnani A, Massaro JM, D'Agostino RB, Sr. et al. Guideline-Based Statin Eligibility, Cancer Events, and Noncardiovascular Mortality in the Framingham Heart Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2017:Jco2016713594. http://www.ncbi.nlm.nih.gov/pubmed/?term=28700275
 
Statin use in patients with Ankylosing Spondylitis associated with improved survival
Patients with ankylosing spondylitis (AS) have an increased CV risk. The Health Improvement Network (THIN), a computerized medical record database created by general practitioners in the UK, contains information on 11 million patients (approximately 6.2% of the UK population). Data analysis was based on a time stratified propensity score matching and patients had their information added between January 1st 2000and December 31st, 2014. The variables used to create the propensity score model included disease duration, body mass index, lifestyle factors, comorbidities and medication use. The analysis comprised 1430 statin users and 1430 patients not using statins; Before propensity score matching statin use was associated with a 43% increased mortality risk, HR 1.43 (1.12-1.84). After matching 96 deaths were observed in AS patients using statins vs 134 in the group not using statins, after a mean follow up period of 5.3 and 5.1 years respectively. The corresponding mortality rates were 16.5 vs 23.8/1000 person-years (PY) respectively. This translated in a HR 0.63 (0.46-0.86) and an absolute mortality rate difference of 7.3/1000 PY (2.1-12.5). The authors were unable to examine cause-specific mortality due to incomplete data within THIN. In order to generate higher quality evidence additional appropriately designed studies in AS patients need to be initiated.   Oza A, Lu N, Schoenfeld SR et al. Survival benefit of statin use in ankylosing spondylitis: a general population-based cohort study. Ann Rheum Dis 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28698231
 
Statins in the in the drinking water for primary prevention?
Cost effectiveness of statins for primary prevention was calculated for 3 different risk scoring approaches:  the ATPIII guidelines, the ACC/AHA 2013 recommendations and universal statin use for all men age 45-74 years and women age 55-74 years, over a 10 year period from 2016 -2025. Primary outcomes were incremental cost-effectiveness ratios (ICER) and numbers needed to treat for 10 years per quality adjusted life-year gained. (NNT/QUALY). Full adherence to ATPIII, ACC-AHA guidelines and moderate intensity statins in all men (45-74 years) and women (55-74 years) would result in 8.8 million (compared to status quo) , 12.1 million (compared to ATP III) and 28.9 million (compared to ACC-AHA guideline) additional statin users. This would result in an NNT/QUALY change of 35, 68 and 108 respectively. Men would get more benefit compared to women. All strategies were actually cost saving, except for women using the ACC-AHA guideline. The costs amounted to $ 3 400/QALY (ICER). Projected benefits did depend greatly on the patients preference for taking a daily pill. This is the most important factor (and not treatment thresholds!) to assess if statins should be initiated in a primary prevention setting or not.
Heller DJ, Coxson PG, Penko J et al. Evaluating the Impact and Cost-Effectiveness of Statin Use Guidelines for Primary Prevention of Coronary Heart Disease and Stroke. Circulation 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28687710
Relevant publications
  1. Zhang L, Wahle A, Chen Z et al. Predicting Locations of High-Risk Plaques in Coronary Arteries in Patients Receiving Statin Therapy. IEEE transactions on medical imaging 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28708548
  2. Zafrir B, Jubran A, Lavie G et al. Clinical Features and Gaps in the Management of Probable Familial Hypercholesterolemia and Cardiovascular Disease. Circulation journal : official journal of the Japanese Circulation Society 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28701632
  3. Raghow R. Statins redux: A re-assessment of how statins lower plasma cholesterol. World J Diabetes 2017; 8:230-234. http://www.ncbi.nlm.nih.gov/pubmed/?term=28694924
  4. Nunley KA, Orchard TJ, Ryan CM et al. Statin use and cognitive function in middle-aged adults with type 1 diabetes. World J Diabetes 2017; 8:286-296. http://www.ncbi.nlm.nih.gov/pubmed/?term=28694929
  5. Mortensen MB, Falk E, Schmidt M. Twenty-Year Nationwide Trends in Statin Utilization and Expenditure in Denmark. Circ Cardiovasc Qual Outcomes 2017; 10. http://www.ncbi.nlm.nih.gov/pubmed/?term=28698192
  6. Farzanegan GR, Derakhshan N, Khalili H et al. Effects of atorvastatin on brain contusion volume and functional outcome of patients with moderate and severe traumatic brain injury; a randomized double-blind placebo-controlled clinical trial. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28688622
  7. Farnier M, Colhoun HM, Sasiela WJ et al. Long-term treatment adherence to the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab in 6 ODYSSEY Phase III clinical studies with treatment duration of 1 to 2 years. J Clin Lipidol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28693998
  8. Alaarg A, Senders ML, Varela-Moreira A et al. A systematic comparison of clinically viable nanomedicines targeting HMG-CoA reductase in inflammatory atherosclerosis. J Control Release 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28700897
  9. Zhao W, Zheng XL, Jiang ZN et al. Risk factors associated with atherogenic dyslipidemia in the presence of optimal statin therapy. Int J Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28689987
  10. Thomas T, Loke Y, Beales ILP. Systematic Review and Meta-analysis: Use of Statins Is Associated with a Reduced Incidence of Oesophageal Adenocarcinoma. Journal of gastrointestinal cancer 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28691139
  11. Squizzato A, Suter MB, Nerone M et al. PCSK9 inhibitors for treating dyslipidemia in patients at different cardiovascular risk: a systematic review and a meta-analysis. Internal and emergency medicine 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28695455
  12. Ranjan R, Patil SR, H RV. Effect of in-situ application of simvastatin gel in surgical management of osseous defects in chronic periodontitis-A randomized clinical trial. Journal of oral biology and craniofacial research 2017; 7:113-118. http://www.ncbi.nlm.nih.gov/pubmed/?term=28706785
  13. Oommen AM, Nand K, Abraham VJ et al. Prevalence of statin use among high-risk patients in urban and rural Vellore, Tamil Nadu: A population-based cross-sectional study. Indian journal of pharmacology 2017; 49:201-204. http://www.ncbi.nlm.nih.gov/pubmed/?term=28706335
  14. Obonska K, Kasprzak M, Sikora J et al. The impact of the time of drug administration on the effectiveness of combined treatment of hypercholesterolemia with Rosuvastatin and Ezetimibe (RosEze): study protocol for a randomized controlled trial. Trials 2017; 18:316. http://www.ncbi.nlm.nih.gov/pubmed/?term=28697767
  15. Lin HF, Liao KF, Chang CM et al. Statin use correlates with reduced risk of chronic osteomyelitis: a nationwide case-control study in Taiwan. Current medical research and opinion 2017:1-13. http://www.ncbi.nlm.nih.gov/pubmed/?term=28699801
  16. Kim SW, Kang HJ, Bae KY et al. Interactions between pro-inflammatory cytokines and statins on depression in patients with acute coronary syndrome. Progress in neuro-psychopharmacology & biological psychiatry 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28689006
  17. Florentin M, Elisaf MS. Statin Therapy and Risk of Intracranial Hemorrhage in Patients with Ischemic Stroke. Drug Saf 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28695474
  18. El Mekki AB, Chaib A. [Drug induced angioedema: a rare side effect of simvastatin]. The Pan African medical journal 2017; 26:213. http://www.ncbi.nlm.nih.gov/pubmed/?term=28690728
  19. Cesena FHY, Laurinavicius AG, Valente VA et al. Cardiovascular Risk Stratification and Statin Eligibility Based on the Brazilian vs. North American Guidelines on Blood Cholesterol Management. Arquivos brasileiros de cardiologia 2017; 108:508-517. http://www.ncbi.nlm.nih.gov/pubmed/?term=28699974
  20. Buttar RS, Batra J, Kreimerman J et al. Rhabdomyolysis and AKI with Atorvastatin and Sitagliptin Use in the Setting of Low 25-Hydroxyvitamin D Levels. Journal of general internal medicine 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28707259
  21. Al-Kuraishy HM, Al-Gareeb AI. Acylation-stimulating protein is a surrogate biomarker for acute myocardial infarction: Role of statins. Journal of laboratory physicians 2017; 9:163-169. http://www.ncbi.nlm.nih.gov/pubmed/?term=28706385
Miscellaneous publications
  1. Xie Y, Tan X, Huang J et al. Atorvastatin-loaded micelles with bone-targeted ligand for the treatment of osteoporosis. Drug delivery 2017; 24:1067-1076. http://www.ncbi.nlm.nih.gov/pubmed/?term=28705021
  2. Saifi AM, Giraddi GB, Ahmed N. Healing of extraction socket following local application of simvastatin: A split mouth prospective study. Journal of oral biology and craniofacial research 2017; 7:106-112. http://www.ncbi.nlm.nih.gov/pubmed/?term=28706784
  3. Mathew LE, Rajagopal V, A H. Betulinic acid and fluvastatin exhibits synergistic effect on toll-like receptor-4 mediated anti-atherogenic mechanism in type II collagen induced arthritis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2017; 93:681-694. http://www.ncbi.nlm.nih.gov/pubmed/?term=28692940
  4. Mao Y, Koga JI, Tokutome M et al. Nanoparticle-Mediated Delivery of Pitavastatin to Monocytes/Macrophages Inhibits Left Ventricular Remodeling After Acute Myocardial Infarction by Inhibiting Monocyte-Mediated Inflammation. Int Heart J 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28701679
  5. Ghayour MB, Abdolmaleki A, Rassouli MB. Neuroprotective effect of Lovastatin on motor deficit induced by sciatic nerve crush in the rat. Eur J Pharmacol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28688913
  6. Knapik-Kowalczuk J, Wojnarowska Z, Rams-Baron M et al. Atorvastatin as a promising crystallization inhibitor of amorphous probucol. Dielectric studies at ambient and elevated pressure. Molecular pharmaceutics 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28692796
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