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Update - Week 46, 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

The Earlier the Better
In a primary prevention setting, the decision to start with a statin is based on projecting risk for (preventable) CVD complications over a 10-year period. Although this is a generally accepted approach, the drawback is that young but high-risk individuals are not likely to experience serious CVD related complications <10 years. Early intervention could potentially stop the process of atherosclerosis before un-reparable damage has been done. A 28% lower LDL-c, as observed in patients with loss of function mutations in the PCSK9 gene, resulted in almost 90% reduced CVD risk. In this review the authors used data collected in the US NHANES registry (2009-2014) on individuals 40-60 years of age without ASCVD, diabetes, LDL-c >190 mg/dl or using statins. Representing 55 million Americans, a total of 1688 individuals in the NHANES registry were included in the analysis. Statin eligibility based on standard 10-year CVD risk >7.5% amounted to 9.5% of the NHANES participants (11 million Americans) that would need a statin. If a cut-off of 2.3% absolute risk reduction (ARR) over 10 years was used, 13% of the participants were deemed statin eligible (15 million Americans) and if a 30-year 15% ARR was used, 17.5% of NHANES participants (17.4 million Americans) would need to use a statin. With a 15% ARR over 30 years “benefit” approach the included individuals were younger; mean age, 50 (48-52] years, more likely to be Female, 43% (26%-59%) had lower 10-year risk mean risk, 4.7% ( 4.4%-5.1%) and higher LDL-c Levels 149mg/dL (142-155mg/dL) as compared to the ones with an ARR of 2.3% over 10 years. ASCVD events reduction over a period of 10 and 30 years were both highest when the 30-year benefit approach was used; 296 000 at 10 years and 2.03 million at 30 years. Based on 10-year risk prediction these numbers were 204 000 at 10 years and 1.18 million at 30 years. Using the long-term benefit approach would identify1:6 Americans in whom long-term benefits can be expected.  Individuals would be detected at a younger age and with higher LDL-c levels and not eligible for statins in the current guideline-based recommendations. With an estimated NNT of 7, this approach would be a superior strategy to initiate (earlier) primary prevention and prevent greater numbers of events and/or CVD related deaths.
Thanassoulis G, Sniderman AD, Pencina MJ. A Long-term Benefit Approach vs Standard Risk-Based Approaches for Statin Eligibility in Primary Prevention. JAMA cardiology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30422172
 
Review: Statins before CABG
In this updated review the authors discuss the benefits, and harms, of using statins pre-procedural in patients scheduled for a CABG. The observed improvements were most likely related to peri-procedural complications such as atrial fibrillation, reduced hospital/ICU stay. No clear benefits were observed on short-term mortality and CVD events. Post-op renal injury is a common complication observed after CABG. For studies using atorvastatin, no signals for an increased risk of renal function deterioration were found, in contrast with the STICS trial were rosuvastatin use was associated with a greater risk of renal damage. Overall several systematic reviews and meta-analyses were unable to show an increased risk for renal damage with pre-operative statin use.  Overall benefits can be expected from starting (ator)vastatin pre- peri procedural CABG interventions. No harms were observed and short-term benefits on AF and ICU/hospital stay duration make this an attractive approach.  
Siskos D, Tziomalos K. The Role of Statins in the Management of Patients Undergoing Coronary Artery Bypass Grafting. Diseases (Basel, Switzerland) 2018; 6. http://www.ncbi.nlm.nih.gov/pubmed/?term=30423861
 
The enigmatic aspects of CoQ10 supplementation.
Statin intolerance is a therapeutic challenge where effective solutions remain elusive. One much-debated approach is adding Co-enzyme Q10 (CoQ10) to statin regimens as to reduce the potential depletion of this important metabolite in the plasma and even more important in the mitochondrion. This updated meta-analysis evaluated the reported effects of statins on plasma CoQ10 levels. They were able to harvest 12 trials with 1776 participants from the standard publication data registries. Statin use did result in lower CoQ10 plasma levels, SMD: −2.12 (− 3.40 to − 0.84; p = 0.001) but these changes were not related to the duration of statin therapy. Exp, 1.00 (0.97 to 1.03; p = 0.994). Both lipophilic and hydrophilic statins had similar effects on lowering CoQ10 SMD, − 1.91 (− 3.62 to 0.2; p = 0.017) and SMD − 2.36 (− 4.30 to − 0.42; p = 0.028) respectively. No difference could be discerned between the two types of statins, SMD, − 0.20; (− 0.208 to 0.618; p = 0.320). On a similar note both low-medium intensity and high intensity statins both reduced plasma CoQ10 concentrations, SMD − 2.40 (− 3.992 to − 0.813; p < 0.001) and SMD − 1.727 (− 2.746 to − 0.709; p < 0.001) respectively, decreased circulating CoQ10. The data presented in this meta-analysis did show a reduction of Plasma CoQ10 but none of the expected modifying factors. Adding CoQ10 to address statin-associated myopathy remains enigmatic and better designed clinical studies, as well as advanced metabolic/lipidomic studies, are needed to properly evaluate the benefits of this approach.
Qu H, Meng YY, Chai H et al. The effect of statin treatment on circulating coenzyme Q10 concentrations: an updated meta-analysis of randomized controlled trials. European journal of medical research 2018; 23:57. http://www.ncbi.nlm.nih.gov/pubmed/?term=30414615
 
For HFpREF patients statins shows promise
The Japanese heart failure Syndrome with Preserved Ejection fRaction (JASPER) trial is a Japanese multicenter observational cohort study in patients admitted for acute heart failure and an LVEF of > 50%. In this trial patients without CAD (N=414) were analyzed for CV-related outcomes and grouped by statin use (N=81) or no statin use (N=333). Mean follow up time was 25 months. Statin users (N=56) were matched using a propensity score model (PSM) with no-statin users (N=56) as well. Both the complete and the PSM cohorts were assessed for the primary endpoint, all-cause mortality and secondary endpoints, non-cardiac death, cardiac death, or rehospitalization for HF. The PSM cohort statin users showed better survival, HR: 0.21; (0.06–0.72; P=0.014), improved non-cardiac death (P=0.028) and rehospitalization for HF (P<0.001). Cardiac deaths were equally distributed in both cohorts. No outcome changes related to modifying factors such as LDL-c levels or HF severity could be discerned. The number of patients that were evaluated was small, but the clear benefits observed in this non-randomized study does warrant an adequately powered RCT in HF patients with preserved ejection fraction and abscessed of ASCVD.
Marume K, Takashio S, Nagai T et al. Effect of Statins on Mortality in Heart Failure With Preserved Ejection Fraction Without Coronary Artery Disease- Report From the JASPER Study. Circulation journal : official journal of the Japanese Circulation Society 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30416189
 
Loading dose of atorvastatin 80 in primary PTCA?
The “No Reflow” (NR) phenomena (a hampered myocardial perfusion and microvascular failure) is a frequently occurring complication in post-AMI patients. This complication impairs revascularization efforts and results in poor outcomes. Earlier reports suggested that a high dose – high-intensity statin e.g. atorvastatin 80 mg, could prevent NR. The authors aimed to determine if 80 mg atorvastatin, given 12 hr. prior to a primary PTCA would reduce the risk of NR. Patients (N=103) were randomly assigned to atorvastatin 80 mg vs standard care (SC). Primary outcomes were the occurrence of NR, changes in hsCRP and IL6. Secondary outcomes: 30-day MACE. Patients assigned to atorvastatin 80 mg (N= 54) were better protected for NR, this was observed in 27% of statin users vs 63% in SC patients (P< 0.0001). Plasma levels of hsCRP reached 2.2 mg/dl in the atorvastatin cohort vs 2.7 mg in the SC group. IL6 levels were very similar as well, 5.2 pg/ml vs 6.35 pg/ml.  For both biomarkers, no significant difference was noted when comparing the two treatment modalities. Based on a Cox regression analysis of the observed NR, the hazard ratio (HR) was significantly lower in the statin allocated patients, HR: 0.34 (0.18-0.61, P< 0.001), and an NNT of 2.7. For MACE an 18% relative risk reduction was observed at 30 days. An event free 30 days follow up was observed in 73.5% of the atorvastatin-treated patient’s vs 37% of the SC group. The observed improved NR as well as the reduction in 30-day MACE and absence of adverse effects warrants using atorvastatin 80 mg as a loading dose before primary PCI in AMI patients. Although this was not a placebo-controlled trial the data is confirmed with what was observed in earlier publications.
Garcia-Mendez RC, Almeida-Gutierrez E, Serrano-Cuevas L et al. Reduction of No Reflow with a Loading Dose of Atorvastatin before Primary Angioplasty in Patients with Acute ST Myocardial Infarction. Arch Med Res 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30446246
Relevant publications
  1. Yuan HW, Ji RJ, Lin YJ et al. Intensive Versus Moderate Statin Therapy Discontinuation in Patients With Acute Ischemic Stroke or Transient Ischemic Attack. Clinical therapeutics 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30420288
  2. Szarek M, White HD, Schwartz GG et al. Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events in the ODYSSEY OUTCOMES Trial. J Am Coll Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30428396
  3. Sabatine MS. PCSK9 inhibitors: clinical evidence and implementation. Nat Rev Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30420622
  4. Oshakbayev K, Bimbetov B, Manekenova K et al. Severe nonalcoholic steatohepatitis and type 2 diabetes: liver histology after weight loss therapy in a randomized clinical trial. Current medical research and opinion 2018:1-24. http://www.ncbi.nlm.nih.gov/pubmed/?term=30431378
  5. Wilson PWF, Polonsky TS, Miedema MD et al. Systematic Review for the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30423394
  6. Moczygemba LR, Bhathena S, DiPiro CV, Snead R. Pharmacist documentation of gaps in care identified during diabetes coaching. Journal of the American Pharmacists Association : JAPhA 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30446422
  7. Marazzi G, Campolongo G, Pelliccia F et al. Usefulness of Low-Dose Statin Plus Ezetimibe and/or Nutraceuticals in Patients With Coronary Artery Disease Intolerant to High-Dose Statin Treatment. Am J Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30420184
  8. Co MLF, Agdamag AC, Co MZ et al. Intensity-Dependent Benefit of Statins in Survival Among Prospective Kidney Transplant Patients. Am J Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30442361
  9. Lloyd-Jones DM, Braun LT, Ndumele CE et al. Use of Risk Assessment Tools to Guide Decision-Making in the Primary Prevention of Atherosclerotic Cardiovascular Disease: A Special Report From the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30423392
  10. Kobayashi Y, Banno K, Kunitomi H et al. Is antidyslipidemic statin use for cancer prevention a promising drug repositioning approach? European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30418231
  11. Klug E, Raal FJ, Marais AD et al. South African dyslipidaemia guideline consensus statement: 2018 update A joint statement from the South African Heart Association (SA Heart) and the Lipid and Atherosclerosis Society of Southern Africa (LASSA). South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 2018; 108:973-1000. http://www.ncbi.nlm.nih.gov/pubmed/?term=30421699
  12. Essers D, Schaublin M, Kullak-Ublick GA, Weiler S. Statin-associated immune-mediated necrotizing myopathy: a retrospective analysis of individual case safety reports from VigiBase. Eur J Clin Pharmacol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30430215
  13. Colantonio LD, Deng L, Chen L et al. Medical Expenditures Among Medicare Beneficiaries with Statin-Associated Adverse Effects Following Myocardial Infarction. Cardiovasc Drugs Ther 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30446883
  14. Bhatt DL, Steg PG, Miller M et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30415628
  15. Angelidi AM, Stambolliu E, Adamopoulou KI, Kousoulis AA. Is Atorvastatin Associated with New Onset Diabetes or Deterioration of Glycemic Control? Systematic Review Using Data from 1.9 Million Patients. Int J Endocrinol 2018; 2018:8380192. http://www.ncbi.nlm.nih.gov/pubmed/?term=30425742
  16. Amariei DE, Reed RM. The role of statins in chronic obstructive pulmonary disease: is cardiovascular disease the common denominator? Statins, chronic obstructive pulmonary disease, and inflammation: is cardiovascular disease closing the loop? Current opinion in pulmonary medicine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30418244
  17. Akimoto H, Negishi A, Oshima S et al. Onset timing of statin-induced musculoskeletal adverse events and concomitant drug-associated shift in onset timing of MAEs. Pharmacol Res Perspect 2018; 6:e00439. http://www.ncbi.nlm.nih.gov/pubmed/?term=30443347
  18. Abdilla Y, Chircop C, Vella N. Anti-HMGCR antibody-associated necrotising myopathy and its association with statin use. BMJ case reports 2018; 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30420560
  19. Yucel H, Yucel A, Arbag H et al. Effect of Statins on Hearing Function and Subjective Tinnitus in Hyperlipidemic Patients. Romanian journal of internal medicine = Revue roumaine de medecine interne 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30447148
  20. Tiwari V, Nagar M, Behera P, Santoshi JA. Letter to the Editor on "The Role of Perioperative Statin Use in the Prevention of Delirium After Total Knee Replacement Under Spinal Anesthesia". The Journal of arthroplasty 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30442466
  21. Talreja O, Cassagnol M. Simvastatin. In: StatPearls. Treasure Island (FL): StatPearls Publishing StatPearls Publishing LLC.; 2018.
  22. Superko HR, Williams PT, Dansinger M, Schaefer E. Trends in LDL-cholesterol Blood Values between 2012 and 2017 suggest Sluggish Adoption of the recent 2013 Treatment Guidelines. Clin Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30444024
  23. Sizar O, Talati R. Ezetimibe. In: StatPearls. Treasure Island (FL): StatPearls Publishing StatPearls Publishing LLC.; 2018.
  24. Roy S, Vallepu S, Barrios C, Hunter K. Comparison of Comorbid Conditions Between Cancer Survivors and Age-Matched Patients Without Cancer. Journal of clinical medicine research 2018; 10:911-919. http://www.ncbi.nlm.nih.gov/pubmed/?term=30425764
  25. Panich J, Gooden A, Shirazi FM, Malone DC. Warnings for drug-drug interactions in consumer medication information provided by community pharmacies. Journal of the American Pharmacists Association : JAPhA 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30416068
  26. Ofori-Asenso R, Ilomaki J, Tacey M et al. Predictors of statin use among older adults: A nationwide cross-sectional study. J Clin Lipidol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30446321
  27. Matz O, Arndt A, Litmathe J et al. [Risk factors for hypertensive and cerebral amyloid angiopathy associated intracerebral hemorrhage: a retrospective comparison]. Fortschritte der Neurologie-Psychiatrie 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30419583
  28. Larsson BAM, Sundh D, Mellstrom D et al. Association between cortical bone microstructure and statin use in older women. J Clin Endocrinol Metab 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30423123
  29. Koskinas KC, Windecker S, Buhayer A et al. Design of the Randomized, Placebo-Controlled Evolocumab for Early Reduction of LDL-Cholesterol Levels in Patients with Acute Coronary Syndromes (EVOPACS) Trial. Clin Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30421481
  30. Guo WC, Cui M, Wang X et al. [Correlation between serum CD147 and carotid intraplaque hemorrhage]. Zhonghua yi xue za zhi 2018; 98:3437-3441. http://www.ncbi.nlm.nih.gov/pubmed/?term=30440140
  31. Bykov K, Mittleman MA, Glynn RJ et al. The case-crossover design for drug-drug interactions: considerations for implementation. Epidemiology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30433922
Miscellaneous publications
 
 
  1. Wang L, Zhou B, Zhou X et al. Combined lowering effects of rosuvastatin and L. acidophilus on cholesterol levels in rat. Journal of microbiology and biotechnology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30415528
  2. Su F, Shi M, Zhang J et al. Simvastatin Protects Heart from Pressure Overload Injury by Inhibiting Excessive Autophagy. International journal of medical sciences 2018; 15:1508-1516. http://www.ncbi.nlm.nih.gov/pubmed/?term=30443172
  3. Qu L, Li D, Gao X et al. Di'ao Xinxuekang Capsule, a Chinese Medicinal Product, Decreases Serum Lipids Levels in High-Fat Diet-Fed ApoE(-/-) Mice by Downregulating PCSK9. Frontiers in pharmacology 2018; 9:1170. http://www.ncbi.nlm.nih.gov/pubmed/?term=30443213
  4. Pontremoli M, Brioschi M, Baetta R et al. Identification of DKK-1 as a novel mediator of statin effects in human endothelial cells. Scientific reports 2018; 8:16671. http://www.ncbi.nlm.nih.gov/pubmed/?term=30420710
  5. Mehibel M, Ortiz-Martinez F, Voelxen N et al. Statin-induced metabolic reprogramming in head and neck cancer: a biomarker for targeting monocarboxylate transporters. Scientific reports 2018; 8:16804. http://www.ncbi.nlm.nih.gov/pubmed/?term=30429503
  6. Bukiya AN, Blank PS, Rosenhouse-Dantsker A. Cholesterol intake and statin use regulate neuronal G protein-gated inwardly rectifying potassium channels. Journal of lipid research 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30420402
  7. Atef MM, Hafez YM, Alshenawy HA, Emam MN. Ameliorative effects of autophagy inducer, simvastatin on alcohol-induced liver disease in a rat model. Journal of cellular biochemistry 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30417426
  8. Li J, Yang M, Xu WR. Enhanced oral bioavailability of fluvastatin by using nanosuspensions containing cyclodextrin. Drug design, development and therapy 2018; 12:3491-3499. http://www.ncbi.nlm.nih.gov/pubmed/?term=30425452
  9. Domokos D, Ducza E, Gaspar R. RhoA and Rho-kinase inhibitors modulate cervical resistance: the possible role of RhoA/Rho-kinase signalling pathway in cervical ripening and contractility. Eur J Pharmacol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30445018
  10. Acimovic MG, Milic NB. Perspectives of the Apiaceae Hepatoprotective Effects - A Review. Natural product communications 2017; 12:309-317. http://www.ncbi.nlm.nih.gov/pubmed/?term=30428236
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