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Update - Week 39, 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

High dose Atorvastatin or Rosuvastatin prevents CI-AKI in CKD patients
A recurrent theme in statin research aims at alleviating the confusion on the potential benefits and/or harms of statins in CKD patients. The focus of this recent meta-analysis is the effects of statins on contrast induced acute kidney injury (CI-AKI) in CKD patients, a not uncommon finding with an incidence of 2% -7%. The authors systematically searched major literature depositories such as Embase, PubMed, the
Cochrane Library, and ClinicalTrials.gov, from inception to January 31, 2018. This resulted in evaluating 377 potential studies (!) and a final selection of 23 RCT’s, where CKD patients underwent a coronary cath. and where renal outcomes e.g. CI-AKI were noted. Data of 6385 patients was analyzed using both pairwise and network meta-analysis. Pre-procedural statin loading proved to be protective and significantly reduced the incidence of CI-AKI; OR 0.46 (p<0.05). Both Atorvastatin and Rosuvastatin proved to be the most effective statins and showed similar reduced incidence rates. Compared to placebo this resulted in an OR: 0.41 (0.27-0.62, P < 0.05) and an OR: 0.49 (0.27-0.88, P = 0.018) for high dose atorvastatin and rosuvastatin respectively. When compared to regular statins the OR’s for atorvastatin and rosuvastatin were OR: 0.42 (0.28-0.63, P < 0.05) and OR: 0.43, (0.23-0.80, P=.007) respectively. The authors concluded that short term treatment with rosuvastatin and atorvastatin high dose proved to be a very effective and safe prophylactic strategy to prevent CI-AKI in patients with CKD.
Zhou X, Dai J, Xu X et al. Comparative Efficacy of Statins for Prevention of Contrast-Induced Acute Kidney Injury in Patients With Chronic Kidney Disease: A Network Meta-Analysis. Angiology 2018:3319718801246. http://www.ncbi.nlm.nih.gov/pubmed/?term=30261736
 
Can pharmaco-genetic testing reliably predict statin related myopathy?
To predict statin related (muscle) side effects by a simple genetic test would be very helpful in selecting the right statin for the right patient. In this updated meta-analysis, the authors evaluated publications where patients were tested for a polymorphism in the SLCO1B1 gene. This gene provides the information for the organic anion transporter protein (OATP1B1) of liver cells, controlling the hepatic influx of statins and through this process determining statin plasma concentrations. The three polymorphisms studied were: 521TC; 521CC and the 521CC + TC. Overall 14 studies (3265 myopathy patients and 7734 controls), published since inception and October 2017, were included in the analysis. Statin related myopathy was observed more frequently as compared to the 521 TT genotype. The observed OR’s for 521TC: 2.31 (1.15-4.63; P=0019); for 521CC: 1.34 (1.02-1.76; p=0.034) and for 521TC+ 521CC: 1.82 (1.32-2.51; P<0.001). The presence of the C allele, compared to the T allele was significantly correlated with a higher risk of statin induced myopathy, OR: 1.89; (1.36–2.62; P < 0.001). The 521CC + TC genotype showed an increased myopathy risk for simvastatin and rosuvastatin, when compared to the 521TT; OR: 2.35 (1.08–5.12; P = 0.032) and OR: 1.69 (1.07–2.67; P = 0.024) respectively. For cerivastatine the observed OR was 1.95 (1.47–2.57; P < 0.001). The authors conclude that simvastatin, rosuvastatin and cerivastatin users carrying the T521C genotype were more likely to develop statin induced myopathy. However, the limited number of studies as well as differences in the type of patients studied as well as variance in myopathy severity warrants larger and better designed studies before definite recommendations can be made.
 Xiang Q, Chen SQ, Ma LY et al. Association between SLCO1B1 T521C polymorphism and risk of statin-induced myopathy: a meta-analysis. Pharmacogenomics J 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30250148
 
The SAMS toolkit
The critical issue with statin prescription is not initiating statins but choosing the appropriate high dose – high intensity statin as well as long term/life time adherence remain major barriers between what should be done and what is observed in observational registries. To assist physicians in conquering these hurdles, the authors present an updated appraisal on how to deal with statin associated myopathy symptoms or SAMS. In this review they address 4 important aspects: 1. The range and variability of reported muscle side effects, 2. Estimates on incidence and prevalence of SAMS, 3. How to confirm a SAMS diagnosis and 4. Advice on how to manage patients that experience SAMS. The authors point out that there are still multiple confusing aspects in the understanding of SAMS, partly because a lack of well-designed trials and the challenge of including the right “true” SAMS patients in trials. Subjective symptoms and lack of objective biomarkers are mostly to blame for this. With the tricks, tips and traps they provide in this review physicians will undoubtedly improve their knowledge and skills to address the enigmatic aspects of managing SAMS patients.
Taylor BA, Thompson PD. Statin-Associated Muscle Disease: Advances in Diagnosis and Management. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30251222
 
Mendelian randomization shows unexpected effects of lipids on breast cancer
The non-lipid lowering, or pleiotropic effects of statins are undoubtedly a topic were there are basically two distinct opinions, the believers and the non-believers. In 2018 there were no less than 100 publications dedicated to this specific topic, illustrating the heightened interest in topic. In this article the authors took a different approach and performed a mendelian randomizations study to explore the effects of life long plasma cholesterol levels and the risk of breast cancer. Based on registry data collected in the Global Lipids Genetics Consortium (N>180 000) and Breast Cancer Association Consortium (N>180 000) They found a positive association between plasma LDL-c and breast cancer risk; per standard deviation an increase OR: 1.09 (1.02-1.18; P=0.02). For estrogen positive breast-cancer the OR was 1.14 (1.05-1.24; P=0.004). Genetically raised HDL- c showed a positive association as well, OR: 1.13 (1.06-1.26; 0.037). A separate analysis of CETP polymorphism associated with increased HDL-c, was associated with an amplified incidence of breast cancer as well, OR: 1.07 (1.03-1.11; p<0.001). Patients with estrogen-positive breast cancer showed an OR :1.08 (1.03-1.13; 0.001). LDL-c lowering variants of the PCSK9 gene were associated with a decreased breast- cancer incidence (P< 0.014). Intriguingly no effects were observed for HMG-CoA (mimicking statins) and NPC1L1 (mimicking ezetimibe) LDL-c lowering polymorphisms. The surprising findings in this meta-analysis are thought provoking and need to be repeated in additional large cohorts were phenotype data pertaining to breast cancer and genotype data is available. If confirmed these finding could have important implications for breast cancer prevention and clinical trials.
Nowak C, Arnlov J. A Mendelian randomization study of the effects of blood lipids on breast cancer risk. Nature communications 2018; 9:3957. http://www.ncbi.nlm.nih.gov/pubmed/?term=30262900
 
Atorvastatin 80 mg pre-PCI loading dose reduces 30-day MACE’s primarily in STEMI patients
In this secondary analysis of the SECURE-PCI study, the timing of an atorvastatin loading dose was evaluated. This large double-blind placebo controlled clinical end point trial included 4191 patients in 53 sites. These ACS patients were recruited between April 2012 and October 2016. They were subsequently randomized to two doses of atorvastatin 80, or placebo, before and 24 hrs. after a planned PCI. After the second loading dose all patients continued with atorvastatin 40 mg for the remaining follow-up period. The primary outcome, MACE during a 30 days follow-up period, included all-cause mortality, MI, stroke, and unplanned coronary revascularization. Loading dose of Atorvastatin 80 mg was associated with a reduce MACE risk at 30 days OR: 0.72 (0.54-0,97; P=0.03). Approximately half of the patients (45.1%) received the first loading dose <2 hrs. prior the procedure and 54.3% with a 2-12-hour window pre-PCI. No differences were observed between the two time strategies, but increased benefits were observed in STEMI patients as compared to NON-STEMI patients; HR: 0.59 (0.38-0.92; P=0.02) vs HR 0.85 (0.58-1.27; P=0.43). The authors concluded that a loading dose of 80 mg Atorvastatin <12 hrs. before a planned PCI showed a reduce MACE incidence, primarily in STEMI patients and the beneftis were not influenced by administering the medication < 2 hours or between 2-12 hours before the planned PCI.
Lopes RD, de Barros ESPGM, de Andrade Jesuino I et al. Timing of Loading Dose of Atorvastatin in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes: Insights From the SECURE-PCI Randomized Clinical Trial. JAMA cardiology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30264159
Relevant publications
  1. Zhao FL, Mi DH, Zhang CQ et al. A cohort study of isolated brainstem infarction based on head MR imaging and clinical findings. J Int Med Res 2018:300060518788253. http://www.ncbi.nlm.nih.gov/pubmed/?term=30246581
  2. Turk Veselic M, Erzen B, Hanzel J et al. Improving Arterial Wall Characteristics in Patients After Myocardial Infarction with a Very Low Dose of Fluvastatin and Valsartan: A Proof-of-Concept Study. Medical science monitor : international medical journal of experimental and clinical research 2018; 24:6892-6899. http://www.ncbi.nlm.nih.gov/pubmed/?term=30266894
  3. Shameer K, Perez-Rodriguez MM, Bachar R et al. Pharmacological risk factors associated with hospital readmission rates in a psychiatric cohort identified using prescriptome data mining. BMC medical informatics and decision making 2018; 18:79. http://www.ncbi.nlm.nih.gov/pubmed/?term=30255805
  4. Sakata K, Gamou T, Tada H et al. Low Baseline High-Sensitive C-Reactive Protein is Associated with Coronary Atherosclerosis Regression: Insights from the MILLION Study. J Atheroscler Thromb 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30249940
  5. Putzu A, de Carvalho ESC, de Almeida JP et al. Perioperative statin therapy in cardiac and non-cardiac surgery: a systematic review and meta-analysis of randomized controlled trials. Ann Intensive Care 2018; 8:95. http://www.ncbi.nlm.nih.gov/pubmed/?term=30264290
  6. Patyk I, Rybacki C, Kalicka A et al. Simvastatin Therapy and Bronchoalveolar Lavage Fluid Biomarkers in Chronic Obstructive Pulmonary Disease. Advances in experimental medicine and biology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30255302
  7. Nam CW, Kim DS, Li J et al. Efficacy and safety of alirocumab in Korean patients with hypercholesterolemia and high cardiovascular risk: subanalysis of the ODYSSEY-KT study. The Korean journal of internal medicine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30257549
  8. McGurnaghan S, Blackbourn LAK, Mocevic E et al. Cardiovascular disease prevalence and risk factor prevalence in Type 2 diabetes: a contemporary analysis. Diabetic medicine : a journal of the British Diabetic Association 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30246473
  9. Martinez AI, Freeman PR, Moga DC. Statin Use and Gastrointestinal Hemorrhage: A Large Retrospective Cohort Study. Am J Cardiovasc Drugs 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30255477
  10. Hu YB, Hu ED, Fu RQ. Statin Use and Cancer Incidence in Patients with Type 2 Diabetes Mellitus: A Network Meta-Analysis. Gastroenterology research and practice 2018; 2018:8620682. http://www.ncbi.nlm.nih.gov/pubmed/?term=30254671
  11. Hernandez-Mijares A, Ascaso JF, Blasco M et al. Residual cardiovascular risk of lipid origin. Components and pathophysiological aspects. Clin Investig Arterioscler 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30262442
  12. Zheng F, Qiu C, Yang S, Krischek B. Statin Use in Patients Undergoing Carotid Artery Endarterectomy May Significantly Reduce the Occurrence of 30-Day Stroke and Myocardial Infarction. World neurosurgery 2018; 118:395. http://www.ncbi.nlm.nih.gov/pubmed/?term=30248819
  13. Orkaby AR, Rich MW, Sun R et al. Pravastatin for Primary Prevention in Older Adults: Restricted Mean Survival Time Analysis. J Am Geriatr Soc 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30251369
  14. Texakalidis P, Giannopoulos S, Kokkinidis DG et al. In Reply to "Statin Use in Patients Undergoing Carotid Artery Endarterectomy May Significantly Reduce the Occurrence of 30-day Stroke and Myocardial Infarction". World neurosurgery 2018; 118:396. http://www.ncbi.nlm.nih.gov/pubmed/?term=30248820
  15. Shakour N, Bianconi V, Pirro M et al. In silico evidence of direct interaction between statins and beta-amyloid. Journal of cellular biochemistry 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30260016
  16. Lee MS, Tadwalkar RV, Fearon WF et al. Cardiac allograft vasculopathy: A review. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30265435
  17. Krysiak R, Drosdzol-Cop AB, Skrzypulec-Plinta V, Okopien B. The effect of atorvastatin on sexual function and depressive symptoms in young women with elevated cholesterol levels: a pilot study. Endokrynol Pol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30259501
  18. Gaba K, Ringleb PA, Halliday A. Asymptomatic Carotid Stenosis: Intervention or Best Medical Therapy? Current neurology and neuroscience reports 2018; 18:80. http://www.ncbi.nlm.nih.gov/pubmed/?term=30251204
  19. Baldassari LE, Fox RJ. Therapeutic Advances and Challenges in the Treatment of Progressive Multiple Sclerosis. Drugs 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30255442
  20. Andrade C. The Use of Statins for Antipsychotic Augmentation in Schizophrenia: Examination of Meta-Analyses With Flawed Methods and Conclusions. The Journal of clinical psychiatry 2018; 79. http://www.ncbi.nlm.nih.gov/pubmed/?term=30256553
Miscellaneous publications
 
 
  1. Zhang QS, Deater M, Phan N et al. Combination therapy with atorvastatin and celecoxib delays tumor formation in a Fanconi anemia mouse model. Pediatric blood & cancer 2018:e27460. http://www.ncbi.nlm.nih.gov/pubmed/?term=30255556
  2. Zhang L, Kang W, Lu X et al. Weighted gene co-expression network analysis and connectivity map identifies lovastatin as a treatment option of gastric cancer by inhibiting HDAC2. Gene 2018; 681:15-25. http://www.ncbi.nlm.nih.gov/pubmed/?term=30266498
  3. Tirawanchai N, Supapornhemin S, Somkasetrin A et al. Regulatory effect of Phikud Navakot extract on HMG-CoA reductase and LDL-R: potential and alternate agents for lowering blood cholesterol. BMC complementary and alternative medicine 2018; 18:258. http://www.ncbi.nlm.nih.gov/pubmed/?term=30249222
  4. Mohajeri M, Banach M, Atkin SL et al. MicroRNAs: Novel Molecular Targets and Response Modulators of Statin Therapy. Trends in pharmacological sciences 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30249403
  5. Ji RC, Eshita Y, Kobayashi T et al. Role of simvastatin in tumor lymphangiogenesis and lymph node metastasis. Clin Exp Metastasis 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30255290
  6. Ferreira Junior DB, Pizziolo VR, Oliveira TT et al. Biometric, histomorphometric, and biochemical profile in atorvastatin calcium treatment of female rats with dexamethasone-induced osteoporosis. Revista brasileira de ortopedia 2018; 53:607-613. http://www.ncbi.nlm.nih.gov/pubmed/?term=30245999
  7. Cheng L, Wang X, Liu T et al. Modulation of Ion Channels in the Superior Cervical Ganglion Neurons by Myocardial Ischemia and Fluvastatin Treatment. Front Physiol 2018; 9:1157. http://www.ncbi.nlm.nih.gov/pubmed/?term=30246810
  8. Bayat N, Izadpanah R, Ebrahimi-Barough S et al. The Anti-Angiogenic Effect of Atorvastatin in Glioblastoma Spheroids Tumor Cultured in Fibrin Gel: in 3D in Vitro Model. Asian Pacific journal of cancer prevention : APJCP 2018; 19:2553-2560. http://www.ncbi.nlm.nih.gov/pubmed/?term=30256055
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