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Update - Week 20, 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

Lipid rich plaques (RLP) in “non-culprit” (NC) lesions associated with increased risk for MACE
In this prospective follow up study, 1 474 patients (six countries and 20 sites) had optical coherence tomography (OTC) of the target vessel. They were prospectively followed for up to 4 years (median of 2 years). Endpoints were major cardiovascular events (MACE) defined as composite of cardiac death, acute myocardial infarction, and ischemia-driven revascularization. In 1/3 of the patients a lipid rich plaque was present. The rate of non-culprit lesion related MACE (NC-MACE) was 7.2% vs 2.6% in patients with or without lipid rich NC lesions; RR: 2.538; (95% CI 1.246-5.173; P=0.003). ACS at presentation; RR: 2.538 (95% CI: 1.246 to 5.173; p = 0.010). Stopping statins for statin ≥1 year; RR: 4.517; 95% CI: 1.923 to 10.610; p=0.001), and LRP in non-culprit regions (risk ratio: 2.061; (95% CI: 1.050 to 4.044; p= 0.036) were independently associated with increased events as well. The authors concluded that the presence of RLP’s in NC lesions is associated with future NC-MACE, primarily driven by revascularization for recurrent ischemia.
Xing L, Higuma T, Wang Z et al. Clinical Significance of Lipid-Rich Plaque Detected by Optical Coherence Tomography: A 4-Year Follow-Up Study. J Am Coll Cardiol 2017; 69:2502-2513. http://www.ncbi.nlm.nih.gov/pubmed/?term=28521888
 
Diastolic dysfunction improved after 6 months of 40 mg Atorvastatin in peritoneal dialysis patients
Patients undergoing peritoneal dialysis (PD) are at hazard for left ventricular diastolic dysfunction (LVDD). Development and progression of LVDD are associated with inflammatory biomarkers e.g. hsCRP. In this randomized clinical trial 213 PD patients were screened and 32 selected, based on LDL-C < 130 mg/dl and hs-CRP > 1.5 mg/L plus the presence of LVDD. Participants were randomized to open label atorvastatin 40 mg vs. usual care. Patients were evaluated after six months. Patients assigned to Atorvastatin managed to reduce LDL-C (-43%) and hsCRP (-45%). The designated endpoints, tissue Doppler imaging (TDI) of mitral flow velocities divided by early diastolic peak velocities of the mitral annulus at the medial and lateral site improved in the participants on atorvastatin. The E/Emedial:-05.01 ± 6.36 vs 1.80 ± 6.59 (P=0.02) and E/SRIVR: 462.35  ±110.54 vs 634.09 ± 116.81 (P = 0.003) for atorvastatin and control respectively. The authors concluded that a 6 months regimen of Atorvastatin 40 mg significantly improved diastolic function.
Wu CK, Yeh CF, Chiang JY et al. Effects of atorvastatin treatment on left ventricular diastolic function in peritoneal dialysis patients-The ALEVENT clinical trial. J Clin Lipidol 2017; 11:657-666. http://www.ncbi.nlm.nih.gov/pubmed/?term=28506387
 
Meta-analysis of RCT’s evaluating lipid lowering intensity and CVD endpoints 
Because majority of intensive lipid lowering trials used a fixed statin dose, the benefits of statin dose titration or non-statin add on lipid lowering drugs have been hotly debated in lipid lowering guidelines. In this meta-analysis, only RCT of CVD end-points trials that compared two lipid reducing intensities were included. Overall 75 439 individuals participated in 10 RCT’s. The 10-year CVD risk in the control group was ± 50%. The mean additional LDL-C decrease was 0.95 mmol/l (36.7 mg/dl) . The 10-year NNT to prevent one CVD event was comparable in the single dose statin vs the add-on treatment studies of 17.1 vs 18.2; Pearson R=0.844 (P=0.001). A baseline LDL-C values of >4 mmol/(155 mg/dl) combined with reaching a target of <1.8 mmol/l (70 mg//dl) was the most effective strategy. Atorvastatin 80 mg, fixed dose was superior at lower starting levels of LDL-C.The least effective approach was aiming for a target of 40% non HDL-C reduction, regardless of pre-treatment LDL-C. The authors concluded that the addition of Ezetimibe or PCSK9 anti-bodies to standard statin treatment should be considered in patients were baseline LDL-C >4 mmol/l; that need to achieve a target LDL-C < 1.8 mmol/l, and were standard statin monotherapy is insufficient to reach this guideline dictated target.  
Soran H, Kwok S, Adam S et al. Evidence for more intensive cholesterol lowering. Curr Opin Lipidol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28509674
 
Statin in pre-dialysis patients do benefits outweigh harms?
The benefits of statins in patients with advanced renal disease have been evaluated in the 4D and AURORA trials where rosuvastatin did not provide the expected CVD risk reduction. In patients with less advanced renal disease statins do seem to reduce CVD risk. In this retrospective analysis of the Taiwanese National Health Insurance Research Database, pre-dialysis, advanced CKD patients were selected. Patients with dyslipidemia as well were divided in 2 groups. In the statin group 14 412 patients were matched with the same number of patients not prescribed statins. The average follow-up periods were 3.7 and 3.0 years respectively. The final analysis was based on 2:1 propensity score matching. Endpoints evaluated were: all-cause mortality, ischemic stroke and intracranial hemorrhage. The HR for all-cause mortality, when comparing statin vs. no statin use was 0.73; (95% CI: 0.68–080 P<0.001):  143.99 vs 109.50 per 1000 person-years; No significant differences for ischemic and hemorrhagic stroke were noted. Risk for progression to dialysis was greater in the no statin group, 1269.45 vs 1095.00 per 1000 person-years respectively (P =0.002). The authors concluded that prescribing statins in pre-dialysis patients seemed to reduce mortality and decreased the risk of dialysis however no benefits could be discerned for ischemic or hemorrhagic stroke.
Chung CM, Lin MS, Hsu JT et al. Effects of statin therapy on cerebrovascular and renal outcomes in patients with predialysis advanced chronic kidney disease and dyslipidemia. J Clin Lipidol 2017; 11:422-431.e422. http://www.ncbi.nlm.nih.gov/pubmed/?term=28502499
 
No difference between Hydrophilic and lipophilic statins in CV risk reduction and tolerability
One of the remaining unanswered questions regarding statins is: are there differences between lipophilic and hydrophilic statins in CVD risk reduction and in reported side-effects and tolerability. In this meta-analysis data from 11 RCT’s in which 11 967 patients were randomly allocated hydrophilic (N=5961) or lipophilic (N=5726) statins. Mean follow-up time was 14 months. No differences were noted for CV endpoints as well as drug discontinuations and statin associated muscle symptoms. Only the rate of CV hospitalizations was lower (0.789, 95% CI: 0.643–0.969, P=0.024) and the rise in plasma transaminases was higher (2.689, 95% CI: 1.841–3.954, P≤0.001) in the group allocated lipophilic statins.
Bytyci I, Bajraktari G, Bhatt DL et al. Hydrophilic vs lipophilic statins in coronary artery disease: A meta-analysis of randomized controlled trials. J Clin Lipidol 2017; 11:624-637. http://www.ncbi.nlm.nih.gov/pubmed/?term=28506385
 
One month high dose rosuvastatin improved left ventricular function post AMI patients
The combination of AMI + disturbances in glucose metabolism are associated with increased mortality and subsequent CV events. In this randomized controlled study 140 consecutive STEMI/NSTEMI patients were randomized <48 hrs. after admission at a single Danish coronary care unit. Patients randomized to the intensive care group (ICG) received a loading dose of 80 mg rosuvastatin followed by 40 mg daily. Patients in the usual care group (UCG) were given 40 mg of simvastatin. Change in culprit strain, by speckle-tracking echocardiography was used to measure regional longitudinal systolic strain (RLSS) in the infarct area. After one month 59 patients in the ICG and 56 patients in the UCG could be evaluated. Overall RLSS in the infarct area improved by a mean (±SD) of –4.22% (±5.19) in the intensive-care group and –2.48% (±4.01) in the usual-care group (p = 0.047). In patients with abnormal glucose tolerance, RLSS improved by –5.01% (±5.28) in the intensive-care group and –2.15% (±4.22) in the usual-care group (p = 0.01). The authors concluded that starting high dose – high intensity statins immediately after an AMI showed significant benefits in RLSS of the infarct area. This was even more pronounced in patients with abnormal glucose tolerance.
Auscher S, Logstrup BB, Moller JE et al. Effects of Intensive Statin Therapy on Left Ventricular Function in Patients with Myocardial Infarction and Abnormal Glucose Tolerance. Cardiology 2017; 138:16-25. http://www.ncbi.nlm.nih.gov/pubmed/?term=28514784

Relevant publications
  1. Voorneveld PW, Reimers MS, Bastiaannet E et al. Statin Use After Diagnosis of Colon Cancer and Patient Survival. Gastroenterology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28512021
  2. Takata K, Psaltis PJ, Nicholls SJ. Investigating the long-term legacy of statin therapy. J Thorac Dis 2017; 9:936-939. http://www.ncbi.nlm.nih.gov/pubmed/?term=28523141
  3. Stanifer JW, Charytan DM, White J et al. Benefit of Ezetimibe Added to Simvastatin in Reduced Kidney Function. Journal of the American Society of Nephrology : JASN 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28507057
  4. Silvennoinen R, Turunen JH, Kovanen PT et al. Attitudes and actions: A survey to assess statin use among Finnish patients with increased risk for cardiovascular events. J Clin Lipidol 2017; 11:485-494. http://www.ncbi.nlm.nih.gov/pubmed/?term=28502506
  5. Ling Y, Jiang J, Wu B, Gao X. Serum triglyceride, high-density lipoprotein cholesterol, apolipoprotein B, and coronary heart disease in a Chinese population undergoing coronary angiography. J Clin Lipidol 2017; 11:646-656. http://www.ncbi.nlm.nih.gov/pubmed/?term=28506386
  6. Lin CJ, Liao WC, Chen YA et al. Statin Therapy Is Associated with Reduced Risk of Peptic Ulcer Disease in the Taiwanese Population. Frontiers in pharmacology 2017; 8:210. http://www.ncbi.nlm.nih.gov/pubmed/?term=28503146
  7. Li R, White CM, Mehmeti J et al. Impact of a Perioperative Prophylaxis Guideline on Post-Cardiothoracic Surgery Atrial Fibrillation. The Annals of pharmacotherapy 2017:1060028017709290. http://www.ncbi.nlm.nih.gov/pubmed/?term=28511557
  8. Knopf HC, Busch MA, Du Y et al. [Changes in the prevalence of statin use in Germany - findings from national health interview and examination surveys 1997-1999 and 2008-2011]. Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28511896
  9. Kampangkaew J, Pickett S, Nambi V. Advances in the management of dyslipidemia. Current opinion in cardiology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28505047
  10. Hsieh HC, Hsu JC, Lu CY. 10-year trends in statin utilization in Taiwan: a retrospective study using Taiwan's National Health Insurance Research Database. BMJ Open 2017; 7:e014150. http://www.ncbi.nlm.nih.gov/pubmed/?term=28515189
  11. Gamou T, Sakata K, Tada H et al. Effect of Reverse Vessel Remodeling on Regression of Coronary Atherosclerosis in Patients Treated With Aggressive Lipid- and Blood Pressure-Lowering Therapy- Insight From MILLION Study. Circulation journal : official journal of the Japanese Circulation Society 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28515369
  12. Athyros VG, Alexandrides TK, Bilianou H et al. The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An Expert Panel Statement. Metabolism 2017; 71:17-32. http://www.ncbi.nlm.nih.gov/pubmed/?term=28521870
  13. Agus A, Hulme C, Verghis RM et al. Simvastatin for patients with acute respiratory distress syndrome: long-term outcomes and cost-effectiveness from a randomised controlled trial. Crit Care 2017; 21:108. http://www.ncbi.nlm.nih.gov/pubmed/?term=28511660
  14. Adhyaru BB, Jacobson TA. Role of Non-Statins, LDL-C Thresholds, and Special Population Considerations: A Look at the Updated 2016 ACC Consensus Committee Recommendations. Curr Atheroscler Rep 2017; 19:29. http://www.ncbi.nlm.nih.gov/pubmed/?term=28500517
  15. Xue Y, Tao L, Wu S et al. Red yeast rice induces less muscle fatigue symptom than simvastatin in dyslipidemic patients: a single center randomized pilot trial. BMC Cardiovasc Disord 2017; 17:127. http://www.ncbi.nlm.nih.gov/pubmed/?term=28521773
  16. Wang P, Yang J, Yang Y, Ding Z. Effect of azithromycin in combination with simvastatin in the treatment of chronic obstructive pulmonary disease complicated by pulmonary arterial hypertension. Pak J Med Sci 2017; 33:260-264. http://www.ncbi.nlm.nih.gov/pubmed/?term=28523018
  17. Tjia J, Kutner JS, Ritchie CS et al. Perceptions of Statin Discontinuation among Patients with Life-Limiting Illness. Journal of palliative medicine 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28520522
  18. Son WD, Teng CL. Do statins adversely affect the HbA1c of diabetic patients? Malaysian family physician : the official journal of the Academy of Family Physicians of Malaysia 2017; 12:39-40. http://www.ncbi.nlm.nih.gov/pubmed/?term=28503276
  19. Schwartz GG, Fayyad R, Szarek M et al. Early, intensive statin treatment reduces 'hard' cardiovascular outcomes after acute coronary syndrome. Eur J Prev Cardiol 2017:2047487317708677. http://www.ncbi.nlm.nih.gov/pubmed/?term=28504565
  20. Pokharel Y, Chinnakondepalli K, Vilain K et al. Impact of Ezetimibe on the Rate of Cardiovascular-Related Hospitalizations and Associated Costs Among Patients With a Recent Acute Coronary Syndrome: Results From the IMPROVE-IT Trial (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circ Cardiovasc Qual Outcomes 2017; 10. http://www.ncbi.nlm.nih.gov/pubmed/?term=28506979
  21. O'Donnell TFX, Deery SE, Darling JD et al. Adherence to lipid management guidelines is associated with lower mortality and major adverse limb events in patients undergoing revascularization for chronic limb-threatening ischemia. Journal of vascular surgery 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28506476
  22. Michiels S, Dierickx D, Taelman V et al. One biopsy, two diagnoses: statin-induced autoimmune myopathy in combination with extranodal marginal zone lymphoma. Clinical and experimental rheumatology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28516888
  23. Lama S, Souraya D, Youssef F. Statin prescription strategies and atherogenic cholesterol goals attainment in Lebanese coronary artery disease patients. Int J Clin Pharm 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28523462
  24. Kim H, Kim N, Lee DH, Kim HS. Analysis of National Pharmacovigilance Data Associated with Statin Use in Korea. Adverse Drug Reactions with Statins. Basic & clinical pharmacology & toxicology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28500776
  25. Kelly SG, Krueger KM, Grant JL et al. Statin prescribing practices in the comprehensive care for HIV-infected patients. J Acquir Immune Defic Syndr 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28520617
  26. Kareem H, Sahu D, Rao MS, Devasia T. Statin Induced Rhabdomyolysis with Non Oliguric Renal Failure: A Rare Presentation. J Clin Diagn Res 2017; 11:Fd01-fd02. http://www.ncbi.nlm.nih.gov/pubmed/?term=28511404
  27. Iraji F, Banihashemi SH, Faghihi G et al. A Comparison of Betamethasone Valerate 0.1% Cream Twice Daily Plus Oral Simvastatin Versus Betamethasone Valerate 0.1% Cream Alone in the Treatment of Vitiligo Patients. Advanced biomedical research 2017; 6:34. http://www.ncbi.nlm.nih.gov/pubmed/?term=28516068
  28. Huang F, Marzin K, Koenen R et al. Effect of Steady-State Faldaprevir on Pharmacokinetics of Atorvastatin or Rosuvastatin in Healthy Volunteers: A Prospective Open-Label, Fixed-Sequence Crossover Study. Journal of clinical pharmacology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28513969
  29. Hallengren E, Almgren P, Rosvall M et al. Fasting levels of growth hormone are associated with carotid intima media thickness but are not affected by fluvastatin treatment. BMC Cardiovasc Disord 2017; 17:125. http://www.ncbi.nlm.nih.gov/pubmed/?term=28511669
  30. Gray RT, Loughrey MB, Bankhead P et al. Statin use, candidate mevalonate pathway biomarkers, and colon cancer survival in a population-based cohort study. Br J Cancer 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28524155
  31. Galema-Boers AMH, Lenzen MJ, Sijbrands EJ, Roeters van Lennep JE. Proprotein convertase subtilisin/kexin 9 inhibition in patients with familial hypercholesterolemia: Initial clinical experience. J Clin Lipidol 2017; 11:674-681. http://www.ncbi.nlm.nih.gov/pubmed/?term=28506389
  32. Caliceti C, Rizzo P, Ferrari R et al. Novel role of the nutraceutical bioactive compound berberine in lectin-like OxLDL receptor 1-mediated endothelial dysfunction in comparison to lovastatin. Nutrition, metabolism, and cardiovascular diseases : NMCD 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28511903
  33. Benet LZ, Wu HF. Understanding the Potential Interethnic Difference in Rosuvastatin Pharmacokinetics. Journal of pharmaceutical sciences 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28502797
  34. Beale DJ. Mislabeling of Study Design and Overstatement of Findings in "Rechallenging Statin Therapy in Veterans With Statin-Induced Myopathy Post Vitamin D Replenishment". Journal of pharmacy practice 2017; 30:385. http://www.ncbi.nlm.nih.gov/pubmed/?term=28511632
  35. Abtan J, Bhatt DL, Elbez Y et al. Geographic variation and risk factors for systemic and limb ischemic events in patients with symptomatic peripheral artery disease: Insights from the REACH Registry. Clin Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28520087

Miscellaneous publications
  1. Yamada Y, Takeuchi S, Yoneda M et al. Atorvastatin reduces cardiac and adipose tissue inflammation in rats with metabolic syndrome. Int J Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28499669
  2. Offman E, Davidson M, Nilsson C. Assessment of pharmacokinetic interaction between omega-3 carboxylic acids and the statins rosuvastatin and simvastatin: Results of 2 phase I studies in healthy volunteers. J Clin Lipidol 2017; 11:739-748. http://www.ncbi.nlm.nih.gov/pubmed/?term=28506390
  3. Nishimura S, Mishra-Gorur K, Park J et al. Combined HMG-COA reductase and prenylation inhibition in treatment of CCM. Proceedings of the National Academy of Sciences of the United States of America 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28500274
  4. Mansouri E, Jangaran A, Ashtari A. Protective effect of pravastatin on doxorubicin-induced hepatotoxicity. Bratislavske lekarske listy 2017; 118:273-277. http://www.ncbi.nlm.nih.gov/pubmed/?term=28516789
  5. Licarete E, Sesarman A, Rauca VF et al. HIF-1alpha acts as a molecular target for simvastatin cytotoxicity in B16.F10 melanoma cells cultured under chemically induced hypoxia. Oncology letters 2017; 13:3942-3950. http://www.ncbi.nlm.nih.gov/pubmed/?term=28521491
  6. Jin H, Welzig CM, Aronovitz M et al. QRS/T-Wave and Calcium Alternans in a Type I Diabetic Mouse Model for Spontaneous Post Myocardial Infarction Ventricular Tachycardia: A Mechanism for the Antiarrhythmic Effect of Statins. Heart rhythm 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28522367
  7. Fang SC, Xie H, Chen F et al. Simvastatin ameliorates memory impairment and neurotoxicity in streptozotocin-induced diabetic mice. Neuroscience 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28499972
  8. An W, Han B, Li K et al. The protective study about alleviation of simvastatin on the damages of PEG-BNs in mice. Environmental toxicology and pharmacology 2017; 53:64-73. http://www.ncbi.nlm.nih.gov/pubmed/?term=28505473

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