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Update - Week 01, 2019
 
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

Statin and dementia – harms or benefits?
The reports on the potential effects of statins on cognitive function and dementia have been contradictory, ranging from causing pathological changes to protecting against cognitive decline. This meta-analysis queried the 4 major literature registries for publications on this topic between January 1, 1987 and January 1, 2018. After the initial identification of 122 studies, ultimately 23 were eligible for the meta-analysis. There were 13 articles that explored the effects dementia risk and 11 evaluated the effects on cognitive changes. When comparing 1 314 431 dementia patients with 1 836 539 The overall results showed a decreased dementia risk, OR: 0.64 (0.50-0.81) Using the mini-mental state examination (MMSE) score, dementia patients that used statins had better scores as compared to non-users, OR:0.46 (0.17-0.74). Alzheimer Disease Assessment Scale (ADAS-cog) scores showed no better outcomes in statin users. -0.26 (-1.13-0.62). Daily living performance was not significantly different when comparing both groups, R: -0.69 (-4.12-2.74). All Biomarkers studied in this meta-analysis significantly changed when statins were used. Amyloid β40, OR: 9.27 (0.71-17.84, plasma Aβ42 OR: 2.60 (1.07-4.13), LDL-c, OR: −16.95 ( −25.54 - −8.37), plasma Lathosterol, OR: −0.11 (−0.14 - −0.07), plasma 24s-hydroxycholesterol OR: −10.41 (−15.57 - −5.25), and cerebrospinal fluid (CSF) Lathosterol, OR: −0.07 (−0.12 - −0.01). This meta-analysis indicates the potential benefits of statins on dementia. More definite evidence is needed, larger RCT to properly evaluate statins effects as well as the clinical relevance of the observed positive outcomes in this meta-analysis.
Zhu XC, Dai WZ, Ma T. Overview the effect of statin therapy on dementia risk, cognitive changes and its pathologic change: a systematic review and meta-analysis. Annals of translational medicine 2018; 6:435. http://www.ncbi.nlm.nih.gov/pubmed/?term=30596065
 
The non-LDL-c lowering effects of statins; from fiction to facts?
The pleiotropic effects of statins were studied in a large Danish registry, focusing on anti-oxidant and anti-inflammatory properties in 19 795 participants of the Danish General Population Study. Urinary 8-oxodG and 8-oxoGuo as well as markers of oxidatively generated damage to DNA and RNA, were used to monitor oxidative stress. A composite score for chronic inflammation (INFLA score) of hsCRP, WBC, platelet count, and neutrophil granulocyte to lymphocyte ratio was used to evaluate anti-inflammatory properties of statins. The urine analysis was executed in 551 statin users and 2 869 non-users, the INFLA score was based on data of 2 922 statin users and 16 873 non-users. Overall a 4.3–6.0% lower 8-oxodG was noted in statin users (p < 0.05) but no differences in 8-oxoGuo were found. Elderly participants (>60 years) had 11.4% lower 8-oxodG (6.7–15.9%, Pi<0.001) and 3.9% lower 8-oxoGuo (0.1–7.5%, Pi=0.002), compared with non-users. Treated hypertension patients had an 11.1% (5.4–16.5%, Pi<0.001) lower 8-oxodG when using statins and on a similar note in CKD patients the 8-oxodG levels were 18.6% (6.8–28.9%, Pi<0.001) lower compared to non-statin use. INFLA scores were significantly reduced in statin users as well (P<0.001). Both 8-oxodG and 8-oxoGuo levels showed a positive correlation with chronic inflammation markers. The exploration of this large Danish registry provides new evidence that the CVD protective effects of statins are not only based on their LDL-c lowering properties, but that anti-oxidant as well as anti-inflammatory effects could potentially contribute to the observed (early?) benefits of statins as well.
Sorensen AL, Hasselbalch HC, Nielsen CH et al. Statin treatment, oxidative stress and inflammation in a Danish population. Redox biology 2018; 21:101088. http://www.ncbi.nlm.nih.gov/pubmed/?term=30594900
 
Lean and fit protects from statin induced NODM
The association between the statins and new onset type 2 diabetes (NODM) has been suggested as a reason not to use statins in a primary prevention setting. The role of physical fitness as well as body weight do play an important role in increasing this risk. The authors of this meta-analysis review explored the effects of both cardiorespiratory fitness (CRF) and adiposity on NODM in statin users and the general population. In 15 cohort studies data on NODM and the two related parameters was collected; 12 studies included general populations and 3 were statin user studies. A 1-metabolic equivalent CRF increase resulted in a NODM HR of 0.90 (0.86-0.94) for the general population, and 0.92 (0.87-0.97) for statin users. The latter showed an increased NODM risk in the low and moderate CRF risk categories, in high CRF statin users no increased risk was noted. The overweight/obesity-fit category versus the normal weight–fit category had a HR of 2.05 (1.55-2.70); larger than that for the normal weight–unfit category versus the normal weight–fit category, HR: 1.2 (1.06-1.52; Pinteraction = 0.004). The authors suggested that statin users, prone for NODM, could reduce their risk by simply improving their lifestyle. Both high CRF and decreased BMI can improve your chances not developing DM2, however reduced body weight was shown to be more powerful than CRF.
Qiu S, Cai X, Yang B et al. Association Between Cardiorespiratory Fitness and Risk of Type 2 Diabetes: A Meta-Analysis. Obesity (Silver Spring, Md.) 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30604925
 
Do statins increase risk for cataracts?
The risk of cataract development was a concern when statins were introduced, however in in RCT’s this never emerged as a relevant side effect. Two earlier published meta-analyses, using RCT’s + observational data, were unable to demonstrate cataract related harms of statins  This meta-analysis is based on observational comparative studies only. Overall 20 publications were used for the final analysis. They included 21 observational studies: 11 cohorts, 8 case-controls and 2 cross-sectionals. Treatment with statins was associated with an increased risk of cataracts OR 1.11 (1.02–1.21; p=0.017; I2=97.5%). When different study designs were compared only in case control studies the risk of cataracts only remained statistically significant. In the cohort studies contradictory results were observed, six estimated statistically significant increased risks, but the remaining five presented opposite results. Noted were significant between-studies heterogeneity. Elderly patients and studies that lasted at least 5 years showed increased cataract risk however in two cohort studies with an average follow-up ≥5 years reported a decreased risk, while an increased risk was found in several studies with a <5 years follow-up. A surprising finding was that diabetes mellitus, had an inverse relationship with cataract risk. The authors concluded that, although statistically significant risks have been estimated, the low OR, heterogeneity of the populations and methodological variability among studies, do not support a cataractogenic effect of statins.  They therefore see no concerns when prescribing statins.
Alves C, Mendes D, Batel Marques F. Statins and risk of cataracts: a systematic review and meta-analysis of observational studies. Cardiovasc Ther 2018:e12480. http://www.ncbi.nlm.nih.gov/pubmed/?term=30597753
 
Meta-analysis of 80 mg atorvastatin loading in pre-primary-PCI
The effects of a loading dose of 80 mg atorvastatin pre-PCI in ACS patient was explored in this meta-analysis. The compiled data of 13 trials enrolling 22 095 patients; 11 214 (50,7%) allocated to 80 mg atorvastatin was analyzed. Overall CV endpoints improved in the ACS patients that used the pre-PCI loading dose. The RR for MACE: 0.66 (0.58-0.80), MI: 0.61 (0.46-0.80), revasc.: 0.76 (69-0.83) and stroke: 0.69 (0.49-0.96). Death and rehospitalizations were not different between the two treatment arms. When comparing CV outcomes <30 days post event with complications that were observed >30 days, MACE and MI were reduced RR: 0.57 (0.39–0.85) and RR: 0.61 (CI 0.42–0.89) respectively, <30 days. After 30 days MACE RR: 0.70 (0.55–0.89), MI RR: 0.58, (0.36–0.95), and revascularization RR: 0.76 (0.69–0.84) improved with atorvastatin. no differences were noted for stroke and death either <30- and >30 days post procedure. This meta-analysis confirms the benefits of a loading dose of atorvastatin 80 in primary PCI.
Ye Z, Lu H, Su Q et al. Short-term and long-term effects of a loading dose of atorvastatin before percutaneous coronary intervention on major adverse cardiovascular events in patients with acute coronary syndrome: a meta-analysis of 13 randomized controlled trials. Eur Heart J 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30608526
Relevant publications
  1. Seo JH, Chun KJ, Lee BK et al. Statins Have No Role in Preventing the Progression of Aortic Valve Sclerosis. Journal of cardiovascular imaging 2018; 26:229-237. http://www.ncbi.nlm.nih.gov/pubmed/?term=30607391
  2. Ramakumari N, Indumathi B, Katkam SK, Kutala VK. Impact of pharmacogenetics on statin-induced myopathy in South-Indian subjects. Indian Heart J 2018; 70 Suppl 3:S120-s125. http://www.ncbi.nlm.nih.gov/pubmed/?term=30595243
  3. Kumar M, Rehan HS, Puri R et al. Randomized controlled trial comparing the efficacy of daily and every other day atorvastatin therapy and its correlation with serum hydroxymethylglutaryl-CoA reductase enzyme levels in naive dyslipidemic patients. Indian Heart J 2018; 70 Suppl 3:S64-s67. http://www.ncbi.nlm.nih.gov/pubmed/?term=30595323
  4. Pitha J, Topinkova E, Blaha V et al. Statin therapy in elderly patients. Vnitr Lek 2018; 64:1021-1027. http://www.ncbi.nlm.nih.gov/pubmed/?term=30606018
  5. Peverelle MR, Baradi A, Paleri S et al. Higher long-term adherence to statins in rural patients at high atherosclerotic risk. J Clin Lipidol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30594444
  6. Nannoni S, Sirimarco G, Cereda CW et al. Determining factors of better leptomeningeal collaterals: a study of 857 consecutive acute ischemic stroke patients. Journal of neurology 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30610425
  7. Nabati M, Janbabai G, Esmailian J, Yazdani J. Effect of Rosuvastatin in Preventing Chemotherapy-Induced Cardiotoxicity in Women With Breast Cancer: A Randomized, Single-Blind, Placebo-Controlled Trial. Journal of cardiovascular pharmacology and therapeutics 2019:1074248418821721. http://www.ncbi.nlm.nih.gov/pubmed/?term=30599756
  8. Moayedi Y, Kozuszko S, Knowles JW et al. Safety and Efficacy of PCSK9 Inhibitors After Heart Transplantation. Can J Cardiol 2019; 35:104.e101-104.e103. http://www.ncbi.nlm.nih.gov/pubmed/?term=30595172
  9. Kazi DS, Penko J, Coxson PG et al. Cost-Effectiveness of Alirocumab: A Just-in-Time Analysis Based on the ODYSSEY Outcomes Trial. Annals of internal medicine 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30597485
  10. Kaufman TM, Warden BA, Minnier J et al. Application of PCSK9 Inhibitors in Practice. Circulation research 2019; 124:32-37. http://www.ncbi.nlm.nih.gov/pubmed/?term=30605414
  11. Kameda A, Nakamura A, Kondo Y et al. Effects of switching to low-dose rosuvastatin (5 mg/day) on glucose metabolism and lipid profiles in Japanese patients with type 2 diabetes and dyslipidemia: a single-arm, prospective, interventional trial. Diabetology international 2017; 8:383-391. http://www.ncbi.nlm.nih.gov/pubmed/?term=30603344
  12. Fan W, Song Y, Inzucchi SE et al. Composite Cardiovascular Risk Factor Target Achievement and its Predictors in US Adults with Diabetes: The Diabetes Collaborative Registry. Diabetes Obes Metab 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30609214
  13. Fan W, Philip S, Granowitz C et al. Hypertriglyceridemia in statin-treated US adults: the National Health and Nutrition Examination Survey. J Clin Lipidol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30594443
  14. El-Korashi LA, Soliman MH, Attwa EM, Mohamed NA. Role of Atorvastatin in Treatment of Chronic Spontaneous Urticaria Patients: A Controlled Clinical Trial. The Egyptian journal of immunology 2018; 25:133-139. http://www.ncbi.nlm.nih.gov/pubmed/?term=30600956
  15. Dykun I, Wiefhoff D, Totzeck M et al. Disconcordance between ESC prevention guidelines and observed lipid profiles in patients with known coronary artery disease. International journal of cardiology. Heart & vasculature 2019; 22:73-77. http://www.ncbi.nlm.nih.gov/pubmed/?term=30603665
  16. Bogari NM, Aljohani A, Amin AA et al. A genetic variant c.553G > T (rs2075291) in the apolipoprotein A5 gene is associated with altered triglycerides levels in coronary artery disease (CAD) patients with lipid lowering drug. BMC Cardiovasc Disord 2019; 19:2. http://www.ncbi.nlm.nih.gov/pubmed/?term=30606120
  17. Agrawal D, Manchanda SC, Sawhney JPS et al. To study the effect of high dose Atorvastatin 40mg versus 80mg in patients with dyslipidemia. Indian Heart J 2018; 70 Suppl 3:S8-s12. http://www.ncbi.nlm.nih.gov/pubmed/?term=30595326
  18. Wasko JA, Dietrich E, Davis K. Risk of Daptomycin Associated Myopathy with Concomitant Statin Use. Clin Infect Dis 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30596967
  19. Rasmussen DB, Bodtger U, Lamberts M et al. Beta-blocker, aspirin and statin usage after first-time myocardial infarction in patients with chronicAuthor information obstructive pulmonary disease: a nationwide analysis from 1995 to 2015 in Denmark. European heart journal. Quality of care & clinical outcomes 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30608575
  20. Grabie M, Tai CH, Frishman WH. Is Anacetrapib Better Than Its CETP Inhibitor Counterparts? Cardiology in review 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30601160
  21. Eliasson L, Esguerra JLS, Wendt A. Lessons from basic pancreatic beta cell research in type-2 diabetes and vascular complications. Diabetology international 2017; 8:139-152. http://www.ncbi.nlm.nih.gov/pubmed/?term=30603317
  22. Chen JF, Smilowitz NR, Kim JT et al. Medical therapy for atherosclerotic cardiovascular disease in patients with myocardial injury after non-cardiac surgery. Int J Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30598249
Miscellaneous publications
 
 
  1. Kim TH, Yun YP, Shim KS et al. In Vitro Anti-Inflammation and Chondrogenic Differentiation Effects of Inclusion Nanocomplexes of Hyaluronic Acid-Beta Cyclodextrin and Simvastatin. Tissue engineering and regenerative medicine 2018; 15:263-274. http://www.ncbi.nlm.nih.gov/pubmed/?term=30603552
  2. Falfushynska H, Sokolov EP, Haider F et al. Effects of a common pharmaceutical, atorvastatin, on energy metabolism and detoxification mechanisms of a marine bivalve Mytilus edulis. Aquatic toxicology (Amsterdam, Netherlands) 2018; 208:47-61. http://www.ncbi.nlm.nih.gov/pubmed/?term=30610964
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This activity is supported by an educational grant from Pfizer.