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Update - Week 48,  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

Visual field parameters showed les progression in statin users
The potential protective role of statins in age related eye disease has been studied but with equivocal results. In open angle glaucoma 5 out of 7 studies showed benefits.  One Chinese analysis showed that patients visual field loss was reduce in patients with normotensive glaucoma. The present study was conducted in 847 Caucasian and African American veterans with pre-existing glaucoma. Using a retrospective propensity score matched cohort design, statin users (N=196) and no-statin users (N=196) were followed for a mean treatment duration of 1 324 (±464) days.  Veteran glaucoma patients using statins had reduced glaucoma progression. Progression was noted in 56% of the no-statin users vs 35% in the statin users (P<0.001). Using statins was associated with reduced progression of open angle glaucoma in this cohort of US veterans. The authors suggested that this observed decreased progression of quantitative optic nerve parameters was purportedly related to the reduction of intra ocular pressure and/or intrinsic neuro-protective effects.
Whigham B, Oddone EZ, Woolson S et al. The influence of oral statin medications on progression of glaucomatous visual field loss: A propensity score analysis. Ophthalmic epidemiology 2017:1-8. http://www.ncbi.nlm.nih.gov/pubmed/?term=29172840
 
Is LDL-C <70 mg/dl with statins and ezetimibe realistic?
To evaluate the real-world use of ezetimibe to achieve guideline dictated LDL-C targets, the authors analyzed the Inovalon Medical Outcomes Research for Effectiveness and Economics Registry (MORE2 Registry). This nationwide registry contains data of 11.7 billion medical events of 137 million unique participants. A total of 125,330 patients met the patient selection criteria for clinical ASCVD and/or probable HeFH. Patients were >18 years and lipid measurement were collected between January 1, 2013, and June 30, 2014. Statins were used 1 year prior and post index period. Patients that started using ezetimibe within 90 days post index period were included in the final analysis.  Primary outcome was defined as patients that achieved LDL-C < 70 mg/dl. Patients were grouped by baseline LDL-C level:  < 70 mg/dL, 70-99 mg/dL, 100-129 mg/dL, or ≥ 130 mg/dL and 4 categories: all patients, ASCVD only, probable HeFH only, and ASCVD and probable HeFH. Mean baseline LDL-C was 90.7 (SD 34.0) mg/dl. Statin use was recorded in 70% of the patients and 1 309 patients (1.01%) added or switched to ezetimibe. LDL-C target of < 70 mg/dl was reached in 26% of this patient group. Goal was not achieved in 59.5% of the patients of which 14.4% did not have a follow-up lipid measurement. Targets were reached in 30%, 14% and 7% of patients with baseline LDL-C of <70-99 mg/dl, 100-129 mg/dl, and > 130 mg/dl respectively. The authors concluded that adding (or switching) to ezetimibe had a small impact on the number of patients achieving LDL-C <70mg/dl. Even with low the majority of patients with low baseline LDL-C were unable to reach guideline dictated targets. New treatments, such as PCSK9ab, are indispensable for the majority patients with CHD and/or probable HeFH in order to reach guideline dictated LDL-C targets.
Menzin J, Aggarwal J, Boatman B et al. Ezetimibe Use and LDL-C Goal Achievement: A Retrospective Database Analysis of Patients with Clinical Atherosclerotic Cardiovascular Disease or Probable Heterozygous Familial Hypercholesterolemia. Journal of managed care & specialty pharmacy 2017; 23:1270-1276. http://www.ncbi.nlm.nih.gov/pubmed/?term=29172973
 
Do German patients reach EAS/EAS guideline LDL-C targets?
On a similar note as the previous analysis, this German study showed similar results, using data collected in Cegedim Longitudinal Practice Database in Germany. This registry contains aggregated patients date from of 600,813 patients from office-based practices of approximately 500 German general practitioners, from January 1, 2011 through December 31, 2013. Inclusion criteria: (a) presence of ≥1 lipid profile in 2013; (b) ≥20 years of age; (c) >1 high or very-high CV risk condition at baseline. Inclusion criteria were met by 42 767 patients, 35% using statins. ESC/EAS dictated LDL-C goal was achieved by 46.7% of patients with a recent ACS, 35.8% with recent stroke; 34.9% with other CHD; 26.9% with PAD and 23.6% of the diabetic patients. Only a small percentage of high risk patients used statins; the majority of statin treated patients were unable to achieve European Guideline dictated LDL-C targets. The use of additional lipid lowering treatment (e.g., ezetimibe) and statin adherence/tolerability was not assessed. The authors concluded that German primary care physicians are not utilizing lipid lowering therapies in the manner as advised by ESC and EAS guidelines. Re-affirmation of EAS/EAS lipid treatment guidelines as well as adding alternative lipid lowering options for high CVD risk patients that, despite maximally tolerated statins and/or ezetimibe, remained at risk because of persistent elevated LDL- C.
Marz W, Dippel FW, Theobald K et al. Utilization of lipid-modifying therapy and low-density lipoprotein cholesterol goal attainment in patients at high and very-high cardiovascular risk: Real-world evidence from Germany. Atherosclerosis 2017; 268:99-107. http://www.ncbi.nlm.nih.gov/pubmed/?term=29197254
 
Primary prevention patients most likely to benefit
Access to electronic patient data is instrumental for real world assessment of large patient numbers reflecting national quality of care parameters. In this Spanish evaluation, the Information System for the Development of Research in Primary Care (SIDIAP) was used. An impressive clinical database of anonymized longitudinal patient records of six million individuals (80% of the Catalan population and 10.2% of the total population of Spain). This registry covers 274 primary care practices, encompassing 3,414 general practitioners (GPs) and 14 million person years (2005-2014). New statin users (35 to 74 years) were divided in low adherence and high adherence reflected by < 70% or >70% of the days taking a statin (over a 6 month period), respectively. Main outcomes were ASCVD (myocardial infarction and ischemic stroke) events. All included patients were free of CVD and categorized according to their 10-year CHD risk (<5%, ≥5-7.4%, ≥7.5-9.9%, and ≥10-19.9%). High adherent patients reduced their coronary risk 16%-30%. The 5-year number needed to treat was 470 and 204 In the risk categories <5% and ≥5%-7.4%, respectively, and 75 and 62 in the ≥7.5%-9.9% and the ≥10%-19.9%. The authors concluded that statin therapy should remain a priority in high 10-year CVD risk patients (≥10%-19.9%). Patients with intermediate risk could benefit from statin treatment but the treatment decisions need to be individualized, emphasizing the net benefit, safety, and patient preference. In the lower risk category (10-year CVD risk < 7.5%) starting statins is questionable reflected by the high NNT of 470 and 202).
Garcia-Gil M, Comas-Cufi M, Blanch J et al. Effectiveness of statins as primary prevention in people with different cardiovascular risk: A population-based cohort study. Clinical pharmacology and therapeutics 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29194590
 
Statins for high TG + low SCORE risk patients?
The role of plasma triglycerides (TG) in CVD risk prediction are re-defined in this analysis of the Copenhagen Populations study (2003-2015). The selected individuals (N=58 547) were free of ASCVD or diabetes and did not uses statins at baseline. Using the European SCORE risk tables and ESC/EAS 2016 guidelines, approximately 14% of the subjects were eligible for starting statins. Not eligible, but with TG >3.0 mmol and TG<3.0 mmol, were 7% and 79% of the participants. A follow up of 456 057 patients years, resulted in 1 770 patients experiencing a MACE and 734 an AMI. The cumulative MACE incidence at age 70 was 8.1% (7.3-8.9) and 14.6% (12.6-16.8) in statin non-eligible subjects with TG <3.0 mmol/l and >3.0 mmol/l. MACE occurred in 16.5% (14.0-19.3) patients that would qualify for statins. For AMI, these cumulative incidences were 3.0% (2.7-3.3), 7.8% (6.4-9.5) and 7.1% (5.9-8.4). The 10-year MACE risk were 2.8% (2.6-3.0), 5.7% (4.9-6.6) and 7.6% (6.9-8.4) respectively. Median age in the three groups were 51, 51 and 60 years. Associated MI risk were 1.0% (0.9-1.1), 3.0% (2.4-3.7) and 3.3% (2.8-3.7). The authors point out that guidelines for primary prevention of ASCVD need to be updated to include individuals with elevated TG concentrations as eligible for statin treatment. They also called for placebo controlled trials in hypertriglyceridemic patients.
Madsen CM, Varbo A, Nordestgaard BG. Unmet need for primary prevention in individuals with hypertriglyceridaemia not eligible for statin therapy according to European Society of Cardiology/European Atherosclerosis Society guidelines: a contemporary population-based study. Eur Heart J 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29182745
 
Start a statin in patients at risk of intra cerebral hemorrhage Yes/No/Maybe?
The protective effects of statin in patient at risk for ischemic stroke are well established. The benefits or harms of these agents in patients at risk for intracerebral hemorrhagic (ICH) are still debated. In this review, the authors presented the published, and sometimes conflicting, data from a number of observational studies as well as intervention trials and the SPARCL study (the only randomized placebo controlled study that was designed to study the effects of rosuvastatin, or placebo, in post-stroke patients). Based on their elaborate and up-to date analysis, the authors gave the following recommendations: 1. not to stop statins in the acute phase of ICH. 2. After the acute phase decisions to continue or stop statins should be based on the long-term prognosis of the patient. Benefits of continuing statins are clear in patient with an elevated global ASCVD risk. Bleeding risk might outweigh the benefits if the ICH is a lobar bleed. Also, patients presenting with multiple bleeds or small vessel disease, reflected by (multiple) micro bleeds seem to be prone to worse outcomes when statins are used. They would not recommend starting statins in ICH patients, in the acute or in the chronic phase. However, patients with an elevated ASCVD risk would, despite these aforementioned reservations, most likely derive benefits from initiating statins. The recently introduced PCSK9ab could become an attractive alternative to lower LDL-C in ICH patients, but only if bleeding risk is not increased by this class of drugs. Properly designed RCT with PCSK9ab in ICH patients are needed to confirm this.
Endres M, Nolte CH, Scheitz JF. Statin Treatment in Patients With Intracerebral Hemorrhage. Stroke 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29191849
Relevant publications
  1. Ye Y, Nylander S, Birnbaum Y. Unraveling the Interaction of Aspirin, Ticagrelor, and Rosuvastatin on the Progression of Atherosclerosis and Inflammation in Diabetic Mice. Cardiovasc Drugs Ther 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29185103
  2. Prado Y, Arancibia A, Zambrano T, Salazar LA. Gender-specific Association between ABCC2 -24C>T SNP and Reduction in Triglycerides in Chilean Patients treated with Atorvastatin. Basic & clinical pharmacology & toxicology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29178257
  3. Lau SR, Kriegbaum M. Medication non-adherence in the context of situated uncertainty: Moving beyond simple, dichotomous approaches. Research in social & administrative pharmacy : RSAP 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29174075
  4. Kimando MW, Otieno FCF, Ogola EN, Mutai K. Adequacy of control of cardiovascular risk factors in ambulatory patients with type 2 diabetes attending diabetes out-patients clinic at a county hospital, Kenya. BMC endocrine disorders 2017; 17:73. http://www.ncbi.nlm.nih.gov/pubmed/?term=29191193
  5. Bataillard M, Beyens MN, Mounier G et al. Muscle Damage Due to Fusidic Acid-Statin Interaction: Review of 75 Cases From the French Pharmacovigilance Database and Literature Reports. American journal of therapeutics 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29189310
  6. Huang CY, Lin TT, Yang YH et al. Effect of statin therapy on the prevention of new-onset acute coronary syndrome in patients with rheumatoid arthritis. Int J Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29174015
  7. Harvey PD, Sabbagh MN, Harrison JE et al. No evidence of neurocognitive adverse events associated with alirocumab treatment in 3340 patients from 14 randomized Phase 2 and 3 controlled trials: a meta-analysis of individual patient data. Eur Heart J 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29186504
  8. Gurgel MHC, Montenegro Junior RM, Melo Ponte CM et al. Metabolic syndrome, diabetes and inadequate lifestyle in first-degree relatives of acute myocardial infarction survivors younger than 45 years old. Lipids Health Dis 2017; 16:224. http://www.ncbi.nlm.nih.gov/pubmed/?term=29179759
  9. Graham I, Shear C, De Graeff P et al. New Strategies for the Development of Lipid Lowering Therapies to Reduce Cardiovascular Risk. European heart journal. Cardiovascular pharmacotherapy 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29194462
  10. Worthington HC, Cheng L, Majumdar SR et al. The impact of a physician detailing and sampling program for generic atorvastatin: an interrupted time series analysis. Implement Sci 2017; 12:141. http://www.ncbi.nlm.nih.gov/pubmed/?term=29178960
  11. Toutouzas K, Skoumas J, Koutagiar I et al. Vascular inflammation and metabolic activity in hematopoietic organs and liver in familial combined hyperlipidemia and heterozygous familial hypercholesterolemia. J Clin Lipidol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29174439
  12. Schwartz RG. What is this image? 2017: Image 4 result : Improvement of ischemia with statin therapy. Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29196912
  13. Koga M, Toyoda K, Minematsu K et al. Long-Term Effect of Pravastatin on Carotid Intima-Media Complex Thickness: The J-STARS Echo Study (Japan Statin Treatment Against Recurrent Stroke). Stroke 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29191850
  14. Kapoor S. Neoplastic growth-restricting effects of fluvastatin in systemic malignancies. J Surg Res 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29183627
  15. Iannelli F, Lombardi R, Milone MR et al. Targeting Mevalonate Pathway in Cancer Treatment: Repurposing of Statins. Recent patents on anti-cancer drug discovery 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29189178
  16. Braillon A. Letter by Braillon Regarding Article, "Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting". Circulation 2017; 136:2204-2205. http://www.ncbi.nlm.nih.gov/pubmed/?term=29180501
  17. Bakke A, Cooper JG, Thue G et al. Type 2 diabetes in general practice in Norway 2005-2014: moderate improvements in risk factor control but still major gaps in complication screening. BMJ open diabetes research & care 2017; 5:e000459. http://www.ncbi.nlm.nih.gov/pubmed/?term=29177051
Miscellaneous publications
  1. Sun P, Hernandez-Guillamon M, Campos-Martorell M et al. Simvastatin blocks soluble SSAO/VAP-1 release in experimental models of cerebral ischemia: Possible benefits for stroke-induced inflammation control. Biochim Biophys Acta 2017; 1864:542-553. http://www.ncbi.nlm.nih.gov/pubmed/?term=29175057
  2. Paskeviciute M, Petrikaite V. Differences of statin activity in 2D and 3D pancreatic cancer cell cultures. Drug design, development and therapy 2017; 11:3273-3280. http://www.ncbi.nlm.nih.gov/pubmed/?term=29180851
  3. Oliveira CV, Grigoletto J, Canzian JM et al. Effect of atorvastatin on behavioral alterations and neuroinflammation during epileptogenesis. Epilepsy & behavior : E&B 2017; 78:109-117. http://www.ncbi.nlm.nih.gov/pubmed/?term=29186698
  4. Hu SG, Li H, Kang PF et al. [Effects of simvastatin on aortic vascular endothelial cell apoptosis and Bcl-2 protein expression in a rat model of atherosclerosis]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 2017; 37:1456-1460. http://www.ncbi.nlm.nih.gov/pubmed/?term=29180324
  5. Corso CR, Martins DF, Borges SC et al. Effect of simvastatin on sensorial, motor, and morphological parameters in sciatic nerve crush induced-neuropathic pain in rats. Inflammopharmacology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29188473
  6. Christen T, Trompet S, Noordam R et al. Mendelian randomization analysis of cholesteryl ester transfer protein and subclinical atherosclerosis: A population-based study. J Clin Lipidol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29174438
  7. Zhang X, Jiang W, Liu Y et al. Human adipose-derived stem cells and simvastatin-functionalized biomimetic calcium phosphate to construct a novel tissue-engineered bone. Biochem Biophys Res Commun 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29175390
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