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Update - Week 20, 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

Are post-op PAD patients benefiting from optimal medical management?
Peripheral vascular disease (PAD) is characterized by not only ischemia of the distal arterial circulation but associated with an extremely elevated risk for coronary and cerebral atherothrombotic complications. To reduce that risk optimizing CV risk factors and using appropriate medication is of great importance. In this study the CV risk of these patient was determined as well as the protective effects of pharmacological interventions. Patients (N=140) from a single University hospital in Lyon, France were followed for 41 (1-48) months after hospitalization for a lower extremity re-vascularization (January 1 – June 30, 2013). The protocol was set up as a prospective observational study. Information on guideline recommend medications (ACE, ARB, Satins and anti-platelets or anti-coagulants) were recorded at discharge and after study completion. Data on mortality, CV events and renewed vascular surgical interventions were collected after completion of the follow-up period. Optimal medical treatments were prescribed to 54% of the discharged patients, and this remained unchanged at the end of the follow-up period. No significant difference was observed in cardiovascular complications. Mortality after a mean follow up of 41 (1-48) months was observed in 24%, CV events in 12%. Renewed vascular interventions showed a non-significant trend toward les intervention in optimally treated patients RR 0.5777 (0.3001-1.06; P=0.08) The study limitations of small sample size and limited follow up time were suggested a possible reason this study did not show the expected improvements. No information was provided on dosages, achieved targets and medication compliance during the study, making interpretations on successful effects of treatment even harder. However, despite the guideline recommendations and the setting of an academic medical center only half of PAD postop patients received the appropriate medications. The observed trend in lessened re-vascularization’s, despite the trial limitation, are pointing in the right direction. The results of this study warrant a more proper prospective analysis of PAD patients as well as improving postop prescriptions as well as achieving guideline targets.  
Thiney M, Della Schiava N, Ecochard R et al. Effects on mortality and cardiovascular events of adherence to guideline-recommended therapy 4 years after lower extremity arterial revascularization. Annals of vascular surgery 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29777848
50-Years of coronary arteries, reflected in 15 questions and answers  
In this 23-page editorial William C Roberts, one of the great American trialists, explores 15 clinical relevant question for health care professionals involved in prevention and management of coronary atherosclerosis. Providing salient answers to questions that are not that easy to answer when querying PubMed or Google Scholar.  The addition of numerous graphs tables and illustrations not only facilitates a more comprehensive understanding but allows for use in presentations as well. Covering a broad range of topics from the nature of atherosclerosis, to the different manifestations, locations and impact on vessel lumen as well as the causes and the appropriate management of ASCVD risk by using statins and lifestyle. A must read for specifically cardiologists that just started their career as well as seasoned senior staff members needing to update their knowledge with pearls of wisdom from the past as well as the present.
Roberts WC. Quantitative Extent of Atherosclerotic Plaque in the Major Epicardial Coronary Arteries in Patients with Fatal Coronary Heart Disease, in Coronary Endarterectomy Specimens, in Aorta-Coronary Saphenous Venous Conduits, and Means to Prevent the Plaques: A Review after Studying the Coronary Arteries for 50 Years. Am J Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29753395
Can prior statin use prevent fatal arrhythmias in ACS-PCI patients?

The aim of the authors, was to evaluate if statins “on board” could reduce the incidence of tachycardia/ventricular fibrillation (TC/VT) in hospital admitted Korean post ACS – primary PCI patients. Using data collected in the Korean Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH). In this retrospective observational study 1117 patients were included, of which 823 (70%) were using statins on admission. A reduced incidence of TC/VT was noted in patients with statin prior to the ACS event. Using an adjusted propensity score analysis OR 0.414, (0.198-0.865, P = .019) and adjusted inverse probability of treatment weight analysis OR 0.463, (0.216-0.994, P = .048). However, in hospital death or Major CV event were not significantly different. HR 0.416 (0.112-1.548, P =.191) and HR 0.486, (0.243-0.974, P =.042). Based on these results the authors concluded that the use of station before an ACS event reduces the risk of developing TC/VT arrhythmia’s, but were unable to improve short and long term clinical outcomes. Prior statin use, low left ventricular ejection fraction, and non-STEMI were independent predictors of in-hospital VT/VF event.
Park JS, Kim BW, Hong TJ et al. Lower In-Hospital Ventricular Tachyarrhythmia in Patients With Acute Myocardial Infarction Receiving Prior Statin Therapy. Angiology 2018:3319718775902. http://www.ncbi.nlm.nih.gov/pubmed/?term=29758993
Dyslipidemia and risk for SAH
The authors investigated the relationship of dyslipidemia and subarachnoid hemorrhage (SAH) risk in a large prospective Finnish cohort, The National FINRISK study. In this study baseline risk factor data was collected between 1972 and 2007. Hospitalizations for SAH were observed in 543 individuals, from the 1.52 million years follow-up data that was collected until 2014. SAH risk increased with dyslipidemic characteristics of elevated T-c, LDL-c, Apo B as well as lower HDL-c and Apo A1. For each SD increase of: TC (1.28 mmol/l), HR 1.15  (1.00-1.32); LDL-C (SD 1.07 mmol/l) and ApoB (SD 0.28 g/l), HR 1.15 (1.01-1.31) in men and HR 1.26 (1.10-1.44)in women. HDL-c declines boosted SAH risk as well, for each SD decrease (0.37 mmol/l), HR 1.20 (1.141.27) in men and HR 1.29 (1.07-1.55) in women. Similar impacts were observed for Apo A1, each SD increment (0.29 g/l) of ApoA1 decreased SAH risk in men, HR 0.88 (0.76-1.02) and women, HR 0.85 (0.74-0.97). the authors concluded that dyslipidemia seems to increase SAH risk, comparable to what is observed in other cardiovascular diseases. If this risk will be positively affected when statins are used needs to be determined.
Lindbohm J, Korja M, Jousilahti P et al. Adverse lipid profile elevates risk for subarachnoid hemorrhage: A prospective population-based cohort study. Atherosclerosis 2018; 274:112-119. http://www.ncbi.nlm.nih.gov/pubmed/?term=29772479
What is the optimal LDL-c target post ACS elderly patients
To answer the question if aggressive LDL-c lowering would benefit elderly post ACS patients in a real-world setting, the authors analyzed the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) cohort. A linked set of multiple individual-level databases using encoded personal identifiers. Data collected between 2014 and 2017 generated 19 544 post ACS, statin using elderly (≥65 years) individuals. Two LDL-c targets, ≤70 mg/dl and ≤50 mg/dl were compared to current recommendations, for AMI and death endpoints. The afore mentioned targets were observed in 61.6% and 25.5% of the participants. Based on a Cox Proportional hazards model statistical analysis, it was estimated that 2.3 (-0.7 to 5.4, P=0.62) adverse events per 1000 patients treated for a period of 8.1 years could be prevented, if patients were reaching the lower LDL-c targets of ≤70 mg/dl or ≤50 mg/dl, instead of current goals. Based on these assumptions the authors question the use of new agents such as PCSK9ab in elderly post ACS patients. Limitations of this analysis should be noted and are addressed extensively in the accompanied editorial. The observational nature and relatively short median follow-up time of 2.1 years as well as lack of information on baseline levels of LDL-c, type + dosage of statins used, and statin adherence are a few relevant issues that could play havoc on the observed results, if properly addressed. Individualized approaches for elderly, as well as younger patients, based on additional information such as biological age, fragility and AS burden based on (non-invasive) imaging need to be included in the decision process. As pointed out by the editorialist, instead of debating the benefits of reaching LDL-c targets of ≤50 or ≤70 mg/dl, more efforts need to be invested in ensuring long term medication adherence to reduce CVD complications.   
Alter DA, Tu JV, Koh M et al. Projected Real-World Effectiveness of Using Aggressive Low-Density Lipoprotein Cholesterol Targets Among Elderly Statin Users Following Acute Coronary Syndromes in Canada. J Am Heart Assoc 2018; 7. http://www.ncbi.nlm.nih.gov/pubmed/?term=29754125
Kuller LH. Reducing Low-Density Lipoprotein Cholesterol After Myocardial Infarction in Older Individuals, Levels Versus Change: Can Observational Studies Answer the Questions? J Am Heart Assoc 2018; 7. http://www.ncbi.nlm.nih.gov/pubmed/?term=29754126
Relevant publications
  1. Yebyo HG, Aschmann HE, Yu T, Puhan MA. Should statin guidelines consider patient preferences? Eliciting preferences of benefit and harm outcomes of statins for primary prevention of cardiovascular disease in the sub-Saharan African and European contexts. BMC Cardiovasc Disord 2018; 18:97. http://www.ncbi.nlm.nih.gov/pubmed/?term=29776337
  2. Vos E, Biron P. Strokes, cholesterol and statins: When mortality is an endpoint. Atherosclerosis 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29764697
  3. Mechtouff L, Haesebaert J, Viprey M et al. Secondary Prevention Three and Six Years after Stroke Using the French National Insurance Healthcare System Database. European neurology 2018; 79:272-280. http://www.ncbi.nlm.nih.gov/pubmed/?term=29758555
  4. Lin J, Banathy A, Winters C et al. Achieving Guideline-Driven High-Intensity Statin Dose in Cardiac Rehabilitation Patients With Coronary Artery Disease. Journal of cardiopulmonary rehabilitation and prevention 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29762264
  5. Liberale L, Carbone F, Bertolotto M et al. Serum PCSK9 levels predict the occurrence of acute coronary syndromes in patients with severe carotid artery stenosis. Int J Cardiol 2018; 263:138-141. http://www.ncbi.nlm.nih.gov/pubmed/?term=29754909
  6. Hong N, Lee YH, Tsujita K et al. Comparison of the Effects of Ezetimibe-Statin Combination Therapy on Major Adverse Cardiovascular Events in Patients with and without Diabetes: A Meta-Analysis. Endocrinol Metab (Seoul) 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29766679
  7. Cai L, Bai X, Lei H et al. High Plasma Exposure of Statins Associated With Increased Risk of Contrast-Induced Acute Kidney Injury in Chinese Patients With Coronary Artery Disease. Frontiers in pharmacology 2018; 9:427. http://www.ncbi.nlm.nih.gov/pubmed/?term=29760658
  8. Ayers J, Cook J, Koenig RA et al. Recent Developments in the Role of Coenzyme Q10 for Coronary Heart Disease: a Systematic Review. Curr Atheroscler Rep 2018; 20:29. http://www.ncbi.nlm.nih.gov/pubmed/?term=29766349
  9. Simonson W. Update on statin drugs for lipid disorders. Geriatric nursing (New York, N.Y.) 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29776686
  10. Moreno-Arellano S, Delgado-de-Mendoza J, Santi-Cano MJ. Sex disparity persists in the prevention of cardiovascular disease in women on statin therapy compared to that in men. Nutrition, metabolism, and cardiovascular diseases : NMCD 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29754716
  11. Magan-Fernandez A, Rizzo M, Montalto G, Marchesini G. Statins in liver disease: not only prevention of cardiovascular events. Expert Rev Gastroenterol Hepatol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29768950
  12. Lin XL, Xiao LL, Tang ZH et al. Role of PCSK9 in lipid metabolism and atherosclerosis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2018; 104:36-44. http://www.ncbi.nlm.nih.gov/pubmed/?term=29758414
  13. Le Bras A. Genetic variation explains residual CHD risk with statin therapy. Nat Rev Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29777181
  14. Li H, Lin H, Zhao H et al. Statins use and risk of new-onset diabetes in hypertensive patients: a population-based retrospective cohort study in Yinzhou district, Ningbo city, People's Republic of China. Therapeutics and clinical risk management 2018; 14:823-832. http://www.ncbi.nlm.nih.gov/pubmed/?term=29765224
  15. Korman MJ, Retterstol K, Kristiansen IS, Wisloff T. Are PCSK9 Inhibitors Cost Effective? PharmacoEconomics 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29777433
  16. Ihle P, Dippel FW, Schubert I. Statin-associated myopathy. Assessment of frequency based on data of all statutory health insurance funds in Germany. Pharmacol Res Perspect 2018; 6:e00404. http://www.ncbi.nlm.nih.gov/pubmed/?term=29760929
  17. Holl DC, Volovici V, Dirven CMF et al. Pathophysiology and non-surgical treatment of chronic subdural hematoma: from past to present to future. World neurosurgery 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29772364
  18. Emad M, Arjmand H, Farpour HR, Kardeh B. Lipid-lowering drugs (statins) and peripheral neuropathy. Electronic physician 2018; 10:6527-6533. http://www.ncbi.nlm.nih.gov/pubmed/?term=29765578
  19. Egan BM, Li J, Davis RA et al. Differences in primary cardiovascular disease prevention between the 2013 and 2016 cholesterol guidelines and impact of the 2017 hypertension guideline in the United States. Journal of clinical hypertension (Greenwich, Conn.) 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29774988
  20. Ebell MH, Grad R. Top 20 Research Studies of 2017 for Primary Care Physicians. American family physician 2018; 97:581-588. http://www.ncbi.nlm.nih.gov/pubmed/?term=29763267
  21. Danchin N, Almahmeed W, Al-Rasadi K et al. Achievement of low-density lipoprotein cholesterol goals in 18 countries outside Western Europe: The International ChoLesterol management Practice Study (ICLPS). Eur J Prev Cardiol 2018:2047487318777079. http://www.ncbi.nlm.nih.gov/pubmed/?term=29771156
  22. Calza L, Colangeli V, Borderi M et al. Rosuvastatin and atorvastatin preserve renal function in HIV-1-infected patients with chronic kidney disease and hyperlipidaemia. HIV clinical trials 2018; 19:120-128. http://www.ncbi.nlm.nih.gov/pubmed/?term=29770749
  23. Cainzos-Achirica M, Miedema MD, McEvoy JW et al. The prognostic value of high sensitivity C-reactive protein in a multi-ethnic population after >10years of follow-up: The Multi-Ethnic Study of Atherosclerosis (MESA). Int J Cardiol 2018; 264:158-164. http://www.ncbi.nlm.nih.gov/pubmed/?term=29776564
  24. Boland AJ, Gangadharan N, Kavanagh P et al. Simvastatin Suppresses Interleukin Ibeta Release in Human Peripheral Blood Mononuclear Cells Stimulated With Cholesterol Crystals. Journal of cardiovascular pharmacology and therapeutics 2018:1074248418776261. http://www.ncbi.nlm.nih.gov/pubmed/?term=29764192
  25. Bandyopadhyay D, Ashish K, Hajra A et al. Cardiovascular Outcomes of PCSK9 Inhibitors: With Special Emphasis on Its Effect beyond LDL-Cholesterol Lowering. Journal of lipids 2018; 2018:3179201. http://www.ncbi.nlm.nih.gov/pubmed/?term=29770231
  26. Awad K, Banach M. The optimal time of day for statin administration: a review of current evidence. Curr Opin Lipidol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29771699
  27. Andrews J, Psaltis PJ, Bartolo BAD et al. Coronary arterial calcification: A review of mechanisms, promoters and imaging. Trends Cardiovasc Med 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29753636
Miscellaneous publications
  1. Zheng D, Cai A, Xu R et al. Effects and potential mechanism of atorvastatin treatment on Lp-PLA2 in rats with dyslipidemia. Archives of medical science : AMS 2018; 14:629-634. http://www.ncbi.nlm.nih.gov/pubmed/?term=29765452
  2. Zhang M, Bian YQ, Tao HM et al. Simvastatin induces osteogenic differentiation of MSCs via Wnt/beta-catenin pathway to promote fracture healing. Eur Rev Med Pharmacol Sci 2018; 22:2896-2905. http://www.ncbi.nlm.nih.gov/pubmed/?term=29771446
  3. Wang YZ, Yang L, Li CF. Protective effect of atorvastatin meditated by HMGCR gene on diabetic rats with atherosclerosis: An in vivo and in vitro study. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2018; 104:240-251. http://www.ncbi.nlm.nih.gov/pubmed/?term=29775891
  4. Ogura S, Yoshida Y, Kurahashi T et al. Targeting the mevalonate pathway is a novel therapeutic approach to inhibit oncogenic FoxM1 transcription factor in human hepatocellular carcinoma. Oncotarget 2018; 9:21022-21035. http://www.ncbi.nlm.nih.gov/pubmed/?term=29765517
  5. Di Donna L, Bartella L, Napoli A et al. Assay of lovastatin containing dietary supplement by LC-MS/MS under MRM condition. Journal of mass spectrometry : JMS 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29770527
  6. da Silva KLC, Camacho AP, Mittestainer FC et al. Atorvastatin and diacerein reduce insulin resistance and increase disease tolerance in rats with sepsis. Journal of inflammation (London, England) 2018; 15:8. http://www.ncbi.nlm.nih.gov/pubmed/?term=29760586
  7. Beckwitt CH, Shiraha K, Wells A. Lipophilic statins limit cancer cell growth and survival, via involvement of Akt signaling. PLoS One 2018; 13:e0197422. http://www.ncbi.nlm.nih.gov/pubmed/?term=29763460
  8. Yu SM, Kim SJ. Kruppel-like factor 4 (KLF-4) plays a crucial role in simvastatin (SVT)-induced differentiation of rabbit articular chondrocytes. Biochem Biophys Res Commun 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29775609
  9. Spreider PA, Breit B. Palladium-Catalyzed Stereoselective Cyclization of in Situ Formed Allenyl Hemiacetals: Synthesis of Rosuvastatin and Pitavastatin. Organic letters 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29771125
  10. Chang JH, Zhang X, Messick K et al. Unremarkable Impact of Oatp Inhibition on the Liver Concentration of Fluvastatin, Lovastatin and Pitavastatin in Wild-Type and Oatp1a/1b Knockout Mouse. Xenobiotica 2018:1-28. http://www.ncbi.nlm.nih.gov/pubmed/?term=29768081
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