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up-to-date with a click!
Update - Week 16, 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

How China managed the increase in ischemic heart disease over the last two 2 decades
CVD has now become the leading cause of non-communicable diseases in China. The number of ischemic heart disease events has doubled from 1990 (0.75 million) to 2013 (1.4 million in China significantly increased from 0.75 million in 1990 to 1.4 million in 2013; Today MI’s are s responsible for million deaths annually! This is changing disease pattern is reflected in the use of medications for secondary prevention as well. In this systematic review and meta-analysis, the authors studied changes in secondary prevention medication over a 20-year period (1995 -2015). From 13 940 publications initially, 35 studies, including 28 000 patients. were selected. In 1995 The estimated use of beta-blockers, statins, and nitrates in post AMI patients, was 32%, 17% and 96% respectively. Compared to 78%, 91.1%, and 59.3% in 2015. The pooled prevalence for aspirin, 92.5% (95%CI: 0.89-0.95), ACE-I, 63% (95%CI: 0.57-0.69) and ACE-I/ARB’s, 72% (95% CI: 0.60-0.82) use, did not change significantly over this period. No information was presented on how well risk factors were managed or if treatment targets were reached. The authors concluded that despite impressive improvement, a large number of Chinese patients are not treated appropriately and in order to address the increasing number of MI patients a comprehensive strategy on secondary prevention is warranted.
Zhao M, Klipstein-Grobusch K, Wang X et al. Prevalence of cardiovascular medication on secondary prevention after myocardial infarction in China between 1995-2015: A systematic review and meta-analysis. PLoS One 2017; 12:e0175947. http://www.ncbi.nlm.nih.gov/pubmed/?term=28426793
 
Less hospitalizations for bacterial infections in diabetics and not-diabetics using statins
Based on data collected in an administrative database from January 1st, 2011 – December 31st, 2015, the effects of statins on hospitalizations due to bacterial infections were evaluated. All Diabetic (N=128 207) and non-diabetics (N=3 304 906) patients, living in Tuscany-Italy were evaluated.  Over 5 years 31 543 hospitalizations for bacterial infections were observed in non-diabetic patients; 2.08(2.06–2.10)/1000 person-year and 5 679 hospitalizations in diabetics; 9.13(8.94–9.32)/1000 person-year. Having Diabetes resulted in a greater risk; HR: 2.04 (95% CI 1.97–2.10; P<0.0001). After adjusting for confounders, statin use reduced this risk significantly by 2.5% per month (approximate 30%/year), in diabetics and non-diabetics alike. The authors suggested that modulation of the innate and the adaptive immune system as well as a direct inhibitory effect on pathogenic microorganisms by statins, could explain the observed protective effects. Particular in diabetics these observations further reinforce the extended use of these drugs, in both primary and secondary prevention of cardiovascular events.
Policardo L, Seghieri G, Anichini R, Francesconi P. Effect of statins on hospitalization risk of bacterial infections in patients with or without diabetes. Acta diabetologica 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28421335
 
Are there patients that benefit more from adding Ezetimibe to as statin? HIJ-PROPER trial
Japanese patients that participated in the Heart Institute of Japan PRoper level of lipid lowering with Pitavastatin and Ezetimibe in acute coRonary syndrome (HIJ-PROPER) trial, were followed for ≥ 36 months (median 3.86 years). This study was a randomized, a multi-center, open-label, prospective, blinded end-point trial. Between January 2010 and April 2013, 1 734 Japanese ACS patient were randomized to a target of LDL-C ≤ 70 mg/dl (Pitavastatin + ezetimibe) or LDL-C ≤ 90 mg/dl (Pitavastatin mono-therapy). Primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina, and ischemia driven revascularization. In the overall cohort, no significant difference was observed when comparing both treatment arms. During the 3.86 yr. follow-up 2004 events were reported. In patients with an LDL-C ≤ 70 mg/dl, 32.8% (283/864 – 111.6/1000 patient-years experienced a second event compared to 36.9% (316/857 – 128.1/1000 patient-years) of the ones with an LDL-C ≤ 90 mg/dl; HR 0.89 (95% CI 0.76-1.04; P=0.152). Patients with a pre-treatment elevated sitosterol level, reflecting increased cholesterol absorption, did do better with the combination therapy of Pitavastatin and Ezetimibe, and or reaching a lower LDL-C target; HR 0.71 (95% CI 0.56-0.91). The Authors concluded that Ezetimibe may be more effective in ACS patients with increased cholesterol absorption as reflected by higher plasma sitosterol concentrations, but that further confirmation is needed.
Hagiwara N, Kawada-Watanabe E, Koyanagi R et al. Low-density lipoprotein cholesterol targeting with pitavastatin + ezetimibe for patients with acute coronary syndrome and dyslipidaemia: the HIJ-PROPER study, a prospective, open-label, randomized trial. Eur Heart J 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28430910
 
Primary PTCA patients with “statins on board” did better!

The benefits of statins prior to PTCA have been established in a number of studies. The authors of this article aimed to evaluate the protective benefits of long term statin use in patients admitted for Primary PTCA (P-PTCA). Patients admitted for primary P-PTCA in the Kunming General Hospital in China. In this retrospective analysis, the records of 213 patients that underwent a P-PTCA between January 2014 – March 2015, were evaluated. Rosuvastatin 10 mg or Atorvastatin 20 mg was used in 35/213 patients ≥1 month before AMI; 170/213 patients did not use any statin. Note that patients in the statin group were older (67.3±4.9 vs. 61.8±10.4 years, respectively; P=0.003); more likely to have hyperlipidemia and anginal complaints, 97.1 vs. 29.2%; P<0.001 and 25.7 vs. 10.1%; P=0.011, respectively. For the other baseline variables or post P-PTCA treatments, no between group differences could be distinguished. After 3 months patients were evaluated for corrected TIMI frame count (cTFC) and major adverse cardiac events. The corrected cTFC was significantly lower in the statin group than in the control group (24.1±12.8 vs. 29.4±14.3; P=0.043). Major adverse cardiac events in the non-statin group were noted in 16.8% of the patients vs. 2.9% in the patients that used statins prior to P-PTCA (P=0.032). The authors concluded that improved outcomes were observed in patients on long-term statins prior to P-PTCA. Despite the obvious limitations: small sample size, single institution, baseline differences and retrospective design of this study, the results do prompt for better designed and larger studies to re assess the potential benefits of statins “on board” prior to ACS and/or P-PTCA
Guo R, Yang L, Mu L et al. Long-term statin use before primary percutaneous coronary intervention improves treatment outcomes of acute myocardial infarction. Experimental and therapeutic medicine 2017; 13:1578-1583. http://www.ncbi.nlm.nih.gov/pubmed/?term=28413512
 
High intensity statin adherence is insufficient in US Medicare patients
Despite the universal guidelines recommendations to use high intensity statins following a myocardial infarction, in real life following these recommendations as well long-term adherence remains a challenge. The authors aimed to evaluate US Medicare beneficiaries that initiated the appropriate statin within 30 days after discharge, and what factors determined adherence after 6 months and 2 years. Participants were hospitalized for an AMI between 2007 and 2012, between 66 and 77 years, half were women and 80% were Caucasians. High adherence was defined by a proportion of days covered of at least 80%. At 6 months and 2 years after discharge among beneficiaries 66 to 75 years of age, 17 633 (58.9%) and 10 308 (41.6%) were taking high-intensity statins with high adherence, 2605 (8.7%) and 3315 (13.4%) down-titrated, 5182 (17.3%) and 4727 (19.1%) had low adherence, and 3705 (12.4%) and 4648 (18.8%) discontinued their statin, respectively. Adherence increased during the period studied. Reduced adherence was observed in African American patients and Hispanic patients. New high-intensity statin users were less likely to adhere to their regimen as well. Those with dual Medicare/Medicaid coverage, more cardiologist visits and who participated in cardiac rehabilitation were more likely to take high-intensity statins with high adherence. There was no difference between patients aged 66-75 years and older patients. The authors concluded that a substantial number of patients discontinue high intensity statins and that special interventions, such as additional post-discharge cardiologist visits and cardiac rehabilitation contribute to improving these numbers.
Colantonio LD, Huang L, Monda KL et al. Adherence to High-Intensity Statins Following a Myocardial Infarction Hospitalization Among Medicare Beneficiaries. JAMA cardiology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28423147 
 
First meta-analysis of observational trials confirms pro diabetogenic effects of statins
Meta-analysis of randomized controlled trials showed statin use was associated with an increased risk (9-13%) of new onset diabetes (NOD). In this first meta-analysis of observational studies this relationship was confirmed. Based on the final selection of 20 studies (18-cohort studies and 2 case-control studies). Studies included ≥1000 subjects that were followed for ≥1year. Careful statistical analysis showed an overall NOD risk in statin users vs non-statin users; RR 1.44 (95%CI 1.31-1.58). Estimates for separate statins showed a class effect; Rosuvastatin RR 1.61 (95% CI 1.30-1.98) – simvastatin RR 1.38 (95% CI 1.19-1.61). This increased risk in observational studies is higher than in the RCT meta-analysis, and most likely due to longer exposure time, exclusion of individuals at higher risk of adverse events in RCT’s. indication and detection bias are well recognized limitations of observational studies. Potential mechanisms of statin induced NOD are discussed, as well as the contradictory results of Pitavastatin trials and meta-analyses. The authors concluded that this meta-analysis confirmed, and even re-enforced, the pro-diabetogenic of statins, underscoring rigorous monitoring of patients taking statins at risk for developing diabetes.
Casula M, Mozzanica F, Scotti L et al. Statin use and risk of new-onset diabetes: A meta-analysis of observational studies. Nutrition, metabolism, and cardiovascular diseases : NMCD 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28416099

Relevant publications
  1. Verdoodt F, Kjaer Hansen M, Kjaer SK et al. Statin use and mortality among ovarian cancer patients: A population-based cohort study. International journal of cancer. Journal international du cancer 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28411390
  2. Sniderman AD, Kiss RS, Reid T et al. Statins, PCSK9 inhibitors and cholesterol homeostasis: a view from within the hepatocyte. Clinical science (London, England : 1979) 2017; 131:791-797. http://www.ncbi.nlm.nih.gov/pubmed/?term=28424373
  3. Pagidipati NJ, Navar AM, Mulder H et al. Comparison of Recommended Eligibility for Primary Prevention Statin Therapy Based on the US Preventive Services Task Force Recommendations vs the ACC/AHA Guidelines. Jama 2017; 317:1563-1567. http://www.ncbi.nlm.nih.gov/pubmed/?term=28418481
  4. Nicholls SJ, Ray KK, Ballantyne CM et al. Comparative effects of cholesteryl ester transfer protein inhibition, statin or ezetimibe on lipid factors: The ACCENTUATE trial. Atherosclerosis 2017; 261:12-18. http://www.ncbi.nlm.nih.gov/pubmed/?term=28412650
  5. Lum CJ, Nakagawa K, Shohet RV et al. The Cost-Benefit Balance of Statins in Hawai'i: A Moving Target. Hawai'i journal of medicine & public health : a journal of Asia Pacific Medicine & Public Health 2017; 76:99-102. http://www.ncbi.nlm.nih.gov/pubmed/?term=28428922
  6. Davies GM, Vyas A, Baxter CA. Economic evaluation of ezetimibe treatment in combination with statin therapy in the United States. Journal of medical economics 2017:1-20. http://www.ncbi.nlm.nih.gov/pubmed/?term=28426345
  7. Zhu B, Gong Y, Yan G et al. Atorvastatin treatment modulates p16 promoter methylation to regulate p16 expression. The FEBS journal 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28425161
  8. Tarr PE, Kovari H. Another statin option in HIV. The lancet. HIV 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28416196
  9. Tan Q, Zhang S, Zou X et al. Fluvastatin therapy could not decrease progression of paroxysmal atrial fibrillation in non-valvular disease patients. Anatol J Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28430117
  10. Sultan Alvi S, Ansari IA, Khan I et al. Potential role of lycopene in targeting proprotein convertase subtilisin/kexin type-9 to combat hypercholesterolemia. Free radical biology & medicine 2017; 108:394-403. http://www.ncbi.nlm.nih.gov/pubmed/?term=28412198
  11. Martande SS, Kumari M, Pradeep AR et al. Comparative evaluation of efficacy of subgingivally delivered 1.2% Atorvastatin and 1.2% Simvastatin in the treatment of intrabony defects in chronic periodontitis: a randomized controlled trial. Journal of dental research, dental clinics, dental prospects 2017; 11:18-25. http://www.ncbi.nlm.nih.gov/pubmed/?term=28413591
  12. Malo S, Aguilar-Palacio I, Feja C et al. Different approaches to the assessment of adherence and persistence with cardiovascular-disease preventive medications. Current medical research and opinion 2017:1-18. http://www.ncbi.nlm.nih.gov/pubmed/?term=28422521
  13. Liakopoulos OJ, Kuhn EW, Slottosch I et al. Statin Therapy in Patients Undergoing Coronary Artery Bypass Grafting for Acute Coronary Syndrome. The Thoracic and cardiovascular surgeon 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28427094
  14. Kilit C, Kocak FE, Pasali Kilit T. Comparison of the effects of high-dose atorvastatin and high-dose rosuvastatin on oxidative stress in patients with acute myocardial infarction: A pilot study. Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir 2017; 45:235-243. http://www.ncbi.nlm.nih.gov/pubmed/?term=28429691
  15. Kanate AS, Hari PN, Pasquini MC et al. Recipient Immune-Modulation with Atorvastatin for Acute Graft-Versus-Host Disease Prophylaxis Following Allogeneic Transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28412518
  16. Godino C, Pavon AG, Mangieri A et al. Platelet reactivity in response to loading dose of atorvastatin or rosuvastatin in patients with stable coronary disease before percutaneous coronary intervention: The STATIPLAT randomized study. Clin Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28422300
  17. Epstein MM, Divine G, Chao CR et al. Statin use and risk of multiple myeloma: An analysis from the Cancer Research Network. International journal of cancer. Journal international du cancer 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28425616
  18. Di Bartolo B, Scherer DJ, Brown A et al. PCSK9 Inhibitors in Hyperlipidemia: Current Status and Clinical Outlook. BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28424973
  19. Cheng Y, Luo R, Zheng H et al. Synergistic anti-tumor efficacy of sorafenib and fluvastatin in hepatocellular carcinoma. Oncotarget 2017; 8:23265-23276. http://www.ncbi.nlm.nih.gov/pubmed/?term=28423574
  20. Busanello ENB, Marques AC, Lander N et al. Pravastatin Chronic Treatment Sensitizes Hypercholesterolemic Mice Muscle to Mitochondrial Permeability Transition: Protection by Creatine or Coenzyme Q10. Frontiers in pharmacology 2017; 8:185. http://www.ncbi.nlm.nih.gov/pubmed/?term=28424622
  21. Balder JW, de Vries JK, Mulder DJ, Kamphuisen PW. Time to improve statin prescription guidelines in low-risk patients? Eur J Prev Cardiol 2017:2047487317698585. http://www.ncbi.nlm.nih.gov/pubmed/?term=28429651
  22. Arai H, Yamashita S, Yokote K et al. Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor alpha modulator (SPPARMalpha), in combination with statin treatment: Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia. Atherosclerosis 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28410749
  23. Alsabbagh MW, Eurich D, Lix LM et al. Does the association between adherence to statin medications and mortality depend on measurement approach? A retrospective cohort study. BMC medical research methodology 2017; 17:66. http://www.ncbi.nlm.nih.gov/pubmed/?term=28427340
  24. Aberg JA, Sponseller CA, Ward DJ et al. Pitavastatin versus pravastatin in adults with HIV-1 infection and dyslipidaemia (INTREPID): 12 week and 52 week results of a phase 4, multicentre, randomised, double-blind, superiority trial. The lancet. HIV 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28416195
  25. Elevated Baseline C-Reactive Protein as a Predictor of Outcome After Aneurysmal Subarachnoid Hemorrhage: Data From the Simvastatin in Aneurysmal Subarachnoid Hemorrhage (STASH) Trial: Erratum. Neurosurgery 2016; 79:945. http://www.ncbi.nlm.nih.gov/pubmed/?term=28426854

Miscellaneous publications
  1. Pasha R, Moon TW. Coenzyme Q10 protects against statin-induced myotoxicity in zebrafish larvae (Danio rerio). Environmental toxicology and pharmacology 2017; 52:150-160. http://www.ncbi.nlm.nih.gov/pubmed/?term=28414942
  2. Mansouri MT, Naghizadeh B, Ghorbanzadeh B, Alboghobeish S. Systemic and local anti-nociceptive effects of simvastatin in the rat formalin assay: Role of peroxisome proliferator-activated receptor gamma and nitric oxide. Journal of neuroscience research 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28419516
  3. Husain I, Akhtar M, Vohora D et al. Rosuvastatin Attenuates High-Salt and Cholesterol Diet Induced Neuroinflammation and Cognitive Impairment via Preventing Nuclear Factor KappaB Pathway. Neurochemical research 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28417263
  4. Wang K, Wang Y, Zhao X et al. Sustained release of simvastatin from hollow carbonated hydroxyapatite microspheres prepared by aspartic acid and sodium dodecyl sulfate. Materials science & engineering. C, Materials for biological applications 2017; 75:565-571. http://www.ncbi.nlm.nih.gov/pubmed/?term=28415500

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