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Update - Week 36, 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

Statins in the Elderly, only treating the diabetics?
Are statins indicated in elderly, diabetic or non- diabetic, patients without ASCVD complications? Will these patients benefits from reduced ASCVD complications or do the  pay the price of suffering from statin related side-effects? Using patient data collected in the Database of the Spanish Catalan primary care system (SIDIAP), 2006-15. Participants were elderly individuals (>75 years), without clinically diagnosed CVD. Patients were grouped by age: 77-84 years and > 85 years; by diabetes status and if they used a statin – started with a statin during the study or not. The total number of patients analyzed was 46 865; mean age 77 years and 63% were females. The median follow-up time was 5.6 years. In the non-diabetic 75-84-year-old the OR’s for CVD and all-cause mortality were 0.94 (0.86-1.04) and 0.98 (0.91-1.05). In the 85+ group 0.93 (0.82-1.06) and 0.97 (0.90-1.05), respectively. The diabetic, < 85 years, OR’s were   0.76 (0.65-0.89) and 0.84 (0.75-0.94) and in those 85 year or older 0.82 (0.53-1.26) and 1.05 (0.86-1.28) respectively. The authors concluded that in elderly non-diabetic patients, statin use was not associated with significant improved mortality or CVD complications. This was however observed in the diabetic elderly patients aged 75-84, but this trend weakened in the 85+ group and disappeared in the nonagenarians. Of note, that the incidence of ASCVD complications was significantly higher than the risk thresholds indicated for statin initiation.  
Ramos R, Comas-Cufi M, Marti-Lluch R et al. Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study. Bmj 2018; 362:k3359. http://www.ncbi.nlm.nih.gov/pubmed/?term=30185425
 
Meta-analysis on AF recurrence in statin users after catheter ablation
Meta-analysis based on PubMed, EMBAE and Cochrane libraries, covering the period when statins were introduced (1987) to April 2017. Nine studies and 1607 patients were included in the meta-analysis. Of these studies 5 were retrospective cohort studies and 4 RCT’s (encompassing 488/1607 patients). Of the nine studies, only one of the RCT’s was considered high quality. AF recurrence was the primary endpoint. Statin type and dosage were noted in the RCT’s but not in the cohort studies. Endpoint was the odds ratio and 95% confidence intervals for AF recurrence and pooled using a random-effects model. Statistical heterogeneity was evaluated using the I2 statistic. In the overall analysis statin use was not associated with less AF recurrences. The sub group analysis of the RCT’s showed that statins did improve the primary endpoint, AF recurrences; OR 0.47 (0.30–0.75, P=0.001) this was in contrast with the retrospective cohort studies; OR 1.03 (0.78–1.36, P=0.82). The authors concluded that large RCT’s are needed to confirm these initial observations and additional cohort studies are warranted to confirm these effects in a real-world setting
Peng H, Yang Y, Zhao Y, Xiao H. The effect of statins on the recurrence rate of atrial fibrillation after catheter ablation: A meta-analysis. Pacing and clinical electrophysiology : PACE 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30191566
 
Noninvasive imaging to improve IS/TIA risk prediction and prioritize statin use
Can non-invasive imaging help to improve reliable risk estimation for ischemic stroke (IS) and TIA’s. Participants in the MESA study (N=4720) were evaluated for IS and TIA. Coronary calcium calcification (CAC) and carotid intima media thickness (CIMT) in combination with traditional risk factors were used as IS and TIA predictors. The 10-year number needed to treat was calculated by applying the benefit observed in ASCOT-LLA and the events rates in MESA within CAC and CIMT strata. After a median follow-up time 13.1 years risk for IS/TIA progressively increased with each CAC category (0, 1–100, >100) among individuals with CIMT>75th percentile compared with individuals with no CAC and with CIMT<75th percentile. Patients eligible for statin treatment, based on the 2013 ASCVD guidelines and ASCVD risk >5%; 25% had a CAC=0 and a CIMT <75th percentile. Incidence of IS/TIA was calculated at 2.49 per 1000-person years and translated into a NNT of 292. In sharp contrast with an NNT of 57 for individuals with a CAC >200 and CIMT >75th percentile. The authors suggested that adding CIMT an CAC to traditional risk factor evaluation can improve statin eligibility by stratifying IS/TIA risk.
Osawa K, Trejo MEP, Nakanishi R et al. Coronary artery calcium and carotid artery intima-media thickness for the prediction of stroke and benefit from statins. Eur J Prev Cardiol 2018:2047487318798058. http://www.ncbi.nlm.nih.gov/pubmed/?term=30183342
 
Improved BP control related to LDL-c and statin use
The interaction between statin use and blood pressure control was observed in this German Blood pressure control study the Berlin Aging Study II. A cohort of 1654 elderly patients (60-85 years) were evaluated for hypertension and blood pressure control. The majority of the participants (75,9%) were hypertensive and 40.6% were not using BP lowering medications. Of the ones using antihypertensives 42% were prescribed mono therapy, majority used RAAS inhibitors and β-blockers. A BP of < 140/90 mmHg was reached in 38.5% of hypertensive individuals. BP control was not associated with the number or type of BP medications as were age, glycated hemoglobin (HbA1c), kidney function, or number of healthcare visits. BP control was associated with sex, lower LDL-c and current smoking. Statin use was significantly higher in in individuals with controlled hypertension; 31.4% vs 23.8% (p=0.023). The observed positive association between BP and LDL-c was stronger and statistically significant in statin users. The association between lipid levels and BP has been observed in earlier studies and dyslipidemia is seen as a risk factor for hypertension. Reducing LDL-c with statins could have a small but clinically relevant anti-hypertensive effect. The authors emphasized the importance of improving BP management in elderly patients as well as promoting more research to study the  link between LDL-c, statins and BP.
Konig M, Gollasch M, Rosada A et al. Antihypertensive Treatment Patterns and Blood Pressure Control in Older Adults: Results from the Berlin Aging Study II. Drugs Aging 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30187292
 
Do atorvastatin/rosuvastatin differ in protecting eGFR decline
The PLANET I and PLANET II trials compared the effects of atorvastatin and rosuvastatin on renal function in patients with progressive renal disease. In this post hoc analysis of 471 proteniuric patients the authors assessed the individual lowering of urine protein:creatinine ratio variability of (Upcr)and total cholesterol (TC) and of these factors predict eGFR decline over a 9-month period. In the earlier presented and published results the response to rosuvastatin and atorvastatin differed despite comparable cholesterol lowering effects in the participants. In this post-hoc evaluation showed not only a variable effect on Upcr and TC based on the type of statin but also a highly variable individual response for both statins. A lower Upcr was not associated with a lower TC in a large number of patients. Surprisingly the individual Upcr and TC response correlated with individual changes in renal function; Patients that were non-responders of these biomarkers, were characterized by the fastest rate of eGFR decline, independent of type of statin or diabetic status. The proteinuria lowering effect were independent of the cholesterol lowering efficacy. The variability of albuminuria response was reproducible with re-exposure and suggest that this a pharmacological and not a random effect. The authors emphasize the importance of monitoring cholesterol lowering effects as well changes in proteinuria in proteniuric patients after initiating statins.
Idzerda NMA, Pena MJ, Parving HH et al. Proteinuria and cholesterol reduction are independently associated with less renal function decline in statin-treated patients; apost hoc analysis of the PLANET trials. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30184238
Relevant publications
  1. Ziff OJ, Werring DJ. Statins after intracranial haemorrhage: seizing a new opportunity? Br J Clin Pharmacol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30192019
  2. Wall HK, Ritchey MD, Gillespie C et al. Vital Signs: Prevalence of Key Cardiovascular Disease Risk Factors for Million Hearts 2022 - United States, 2011-2016. MMWR. Morbidity and mortality weekly report 2018; 67:983-991. http://www.ncbi.nlm.nih.gov/pubmed/?term=30188885
  3. Sobhy M, El Etriby A, El Nashar A et al. Prevalence of lipid abnormalities and cholesterol target value attainment in Egyptian patients presenting with an acute coronary syndrome. The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology 2018; 70:129-134. http://www.ncbi.nlm.nih.gov/pubmed/?term=30190636
  4. Roopmani P, Krishnan UM. Harnessing the pleiotropic effects of atorvastatin-fenofibrate combination for cardiovascular stents. Materials science & engineering. C, Materials for biological applications 2018; 92:875-891. http://www.ncbi.nlm.nih.gov/pubmed/?term=30184817
  5. Munoz-Hernandez L, Ortiz-Bautista RJ, Brito-Cordova G et al. Cholesterol efflux capacity of large, small and total HDL particles is unaltered by atorvastatin in patients with type 2 diabetes. Atherosclerosis 2018; 277:72-79. http://www.ncbi.nlm.nih.gov/pubmed/?term=30176567
  6. Li X, Sun S, Xu X et al. The Association between Genetic Polymorphisms and Simvastatin-Induced Myopathy: A Narrative Synthesis of Evidence. Drug research 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30193394
  7. Jorge AM, Lu N, Keller SF et al. The Effect of Statin Use on Mortality in Systemic Autoimmune Rheumatic Diseases. The Journal of rheumatology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30173155
  8. Gitt AK, Rieber J, Hambrecht R et al. Do acute coronary events affect lipid management and cholesterol goal attainment in Germany? : Results from the Dyslipidemia International study II. Wien Klin Wochenschr 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30178071
  9. Chiu HT, Shen LJ, Chen YC et al. Effect of statin use on the risk of medically attended acute respiratory illness among influenza vaccinated elderly. Vaccine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30174239
  10. Ambrosy AP, Cerbin LP, Fudim M et al. Natural History of Patients Postacute Coronary Syndrome Based on Heart Failure Status. Am J Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30180960
  11. Toribio M, Fitch KV, Stone L et al. Assessing statin effects on cardiovascular pathways in HIV using a novel proteomics approach: Analysis of data from INTREPID, a randomized controlled trial. EBioMedicine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30174281
  12. Olmastroni E, Shlyakhto EV, Konradi AO et al. Epidemiology of cardiovascular risk factors in two population-based studies. Atherosclerosis. Supplements 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30177370
  13. Mintzer S, Trinka E, Kraemer G et al. Impact of carbamazepine, lamotrigine, and levetiracetam on vascular risk markers and lipid-lowering agents in the elderly. Epilepsia 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30178473
  14. Hui SK, Lindale E, Sun L, Ruel M. Genetics of coronary artery disease: should they impact the choice of revascularization? Current opinion in cardiology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30188420
  15. He W, Huang Y, Zhang Y et al. Cardiac rehabilitation therapy for coronary slow flow phenomenon. Herz 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30191265
  16. Fathy S, Shahin MH, Langaee T et al. Pharmacogenetic and clinical predictors of response to clopidogrel plus aspirin after acute coronary syndrome in Egyptians. Pharmacogenetics and genomics 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30188374
  17. Banerjee S, Wells C, Grobelna A. CADTH Rapid Response Reports. In: PCSK-9 Inhibitors for Hyperlipidemia: A Review of the Comparative Clinical Effectiveness. Ottawa (ON): Canadian Agency for Drugs and Technologies in HealthCopyright (c) 2017 Canadian Agency for Drugs and Technologies in Health.; 2017.
  18. Allott EH, Freeman MR, Freedland SJ. Statin Therapy to Improve Prostate Cancer Outcomes: Who, When, and for How Long? European urology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30177293
Miscellaneous publications
 
 
  1. Yoshikado T, Toshimoto K, Maeda K et al. PBPK modeling of coproporphyrin I as an endogenous biomarker for drug interactions involving inhibition of hepatic OATP1B1 and OATP1B3. CPT Pharmacometrics Syst Pharmacol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30175555
  2. Tahta A, Izgi N, Bagci-Onder T et al. Assessment of the MRI and Behavioral Test Results in a Focal Cerebral Ischemia-Reperfusion Model in the Rat after Separate and Combined Use of Mouse-Derived Neural Progenitor Cells, Human-Derived Neural Progenitor Cells and Atorvastatin. Turkish neurosurgery 2018; 28:571-581. http://www.ncbi.nlm.nih.gov/pubmed/?term=30192361
  3. Sun B, Rui R, Pan H et al. Effect of Combined Use of Astragaloside IV (AsIV) and Atorvastatin (AV) on Expression of PPAR-gamma and Inflammation-Associated Cytokines in Atherosclerosis Rats. Medical science monitor : international medical journal of experimental and clinical research 2018; 24:6229-6236. http://www.ncbi.nlm.nih.gov/pubmed/?term=30190450
  4. Lu D, Mai HC, Liang YB et al. Beneficial Role of Rosuvastatin in Blood-Brain Barrier Damage Following Experimental Ischemic Stroke. Frontiers in pharmacology 2018; 9:926. http://www.ncbi.nlm.nih.gov/pubmed/?term=30186167
  5. Koohestanimobarhan S, Salami S, Imeni V et al. Lipophilic statins antagonistically alter the major epithelial-to-mesenchymal transition signaling pathways in breast cancer stem-like cells via inhibition of the mevalonate pathway. Journal of cellular biochemistry 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30191610
  6. Knezl V, Sotnikova R, Brnoliakova Z et al. Monotherapy of experimental metabolic syndrome: II. Study of cardiovascular effects. Interdisciplinary toxicology 2017; 10:86-92. http://www.ncbi.nlm.nih.gov/pubmed/?term=30174531
  7. Bolat MS, Bakirtas M, Firat F et al. The effect of atorvastatin on penile intracavernosal pressure and cavernosal morphology in normocholesterolemic rats. Turkish journal of urology 2018:1-6. http://www.ncbi.nlm.nih.gov/pubmed/?term=30183612
  8. Bezek S, Brnoliakova Z, Sotnikova R et al. Monotherapy of experimental metabolic syndrome: I. Efficacy and safety. Interdisciplinary toxicology 2017; 10:81-85. http://www.ncbi.nlm.nih.gov/pubmed/?term=30174530
  9. Bahammam MA, Attia MS. Effects of Systemic Simvastatin on the Concentrations of Visfatin, Tumor Necrosis Factor-alpha, and Interleukin-6 in Gingival Crevicular Fluid in Patients with Type 2 Diabetes and Chronic Periodontitis. Journal of immunology research 2018; 2018:8481735. http://www.ncbi.nlm.nih.gov/pubmed/?term=30186882
  10. Agarwal D, Schmader KE, Kossenkov AV et al. Immune response to influenza vaccination in the elderly is altered by chronic medication use. Immunity & ageing : I & A 2018; 15:19. http://www.ncbi.nlm.nih.gov/pubmed/?term=30186359
  11. Zhou F, Rao F, Deng YQ et al. Atorvastatin ameliorates the contractile dysfunction of the aorta induced by organ culture. Naunyn-Schmiedeberg's archives of pharmacology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30182188
  12. Yao GT, Song LP, Xue WH et al. Nano-particle engineered atorvastatin delivery to support mesenchymal stem cell survival in infarcted myocardium. Saudi journal of biological sciences 2018; 25:1016-1021. http://www.ncbi.nlm.nih.gov/pubmed/?term=30174496
  13. Ozdogan AI, Ilarslan YD, Kosemehmetoglu K et al. In Vivo Evaluation of Chitosan Based Local Delivery Systems for Atorvastatin in Treatment of Periodontitis. Int J Pharm 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30194012
  14. Mirzapour H, Panahi HA, Moniri E, Feizbakhsh A. Magnetic nanoparticles modified with organic dendrimers containing methyl methacrylate and ethylene diamine for the microextraction of rosuvastatin. Mikrochimica acta 2018; 185:440. http://www.ncbi.nlm.nih.gov/pubmed/?term=30173349
  15. Jiang S, Li S, Hu J et al. Combined delivery of angiopoietin-1 gene and simvastatin mediated by anti-intercellular adhesion molecule-1 antibody-conjugated ternary nanoparticles for acute lung injury therapy. Nanomedicine : nanotechnology, biology, and medicine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30193816
  16. Hadzieva Gigovska M, Petkovska A, Acevska J et al. Comprehensive Assessment of Degradation Behavior of Simvastatin by UHPLC/MS Method, Employing Experimental Design Methodology. International journal of analytical chemistry 2018; 2018:7170539. http://www.ncbi.nlm.nih.gov/pubmed/?term=30174695
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