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Update - Week 29,  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

A simple and successful strategy to improve CV risk assessment and control
A simple strategy to improve CV risk detection and management was explored in the Valsartan Amlodipine and ROsuvastatin for global cardiovascular risk decrease in daily practice (VARO) study. Participating Czech physicians (N=263) agreed to screen for CV risk factors in patients that visited them for unrelated problems and to re-assess treatment goals in patients with manifest CV risk factors. Each physician recorded the clinical relevant information of 20 consecutive eligible patients compiling 3015 patients in this study, of which 2932 completed the 6 months follow-up. The SCORE system was advocated to evaluate CV risk and treatment was aimed to achieve national guideline goals. The preferential therapy was rosuvastatin, amlodipine and valsartan for hyperlipidemia and hypertension respectively, but additional medication could be prescribed according to the physicians preferences. Patients were examined at baseline, 3 months and 6 months. Overall the global CV risk decreased by 35%. Systolic, diastolic pressure and level of total cholesterol were reduced respectively by 12.5% (from 152 ±18 to 133 ±11, p < 0.001); 11.4% (from 88 ±11 to 78 ±7, p < 0.001) and 21% (from 6.3 ±1.2 to 5.0 ±0.9, p < 0.001). Lipoprotein fractions improved as well. LDL-C -28% (from 3.9 ±1.1 to 2.8 ±0.8, p < 0.001); HDL-C +7% (from 1.43 ±0.58 to 1.53 ±0.56, p < 0.001) and triglycerides -25% (from 2.4 ±1.3 to 1.8 ±0.9, p < 0.001). Targets for LDL-C and blood pressure were reached by 34% and 68%. The VARO study demonstrates that using a relatively simple approach may translate into an unexpectedly impressive cardiovascular risk reduction, when doctors were asked to do what they should have done anyway. The authors noted that participants will be re-evaluated a year after study completion to evaluate if the successful changes persist after less intensive monitoring and attention of participating physicians.
Stulc T, Lanska V, Snejdrlova M et al. A comprehensive guidelines-based approach reduces cardiovascular risk in everyday practice: the VARO study. Archives of medical science : AMS 2017; 13:705-710. http://www.ncbi.nlm.nih.gov/pubmed/?term=28721135
 
Exercise capacity best predictor for new onset DM in statin and non-statin users alike
In this retrospective cohort study of 43 337 US participants in the Henry Ford Exercise Testing (FIT) Project (January 1991 – May 31st 2009) were evaluated after a mean follow=up of 5.1 years (2.6-8.2). Patient were free of diabetes and CAD at baseline. There were 6 921 (14.6%) new cases of diabetes. Patients were stratified by baseline satin used and estimated peak MET’s. After adjusting for co-variates, higher exercises capacity (EC) was associated with a lower risk for developing DM irrespective of statin use (P-interaction =0.15).For each increase in 1-MET the risk of developing DM was reduced by 8% (total cohort) 8% (no statin) and 6% (statin) . The authors concluded that, with the limitations of an observational study and the lack of more precise data (statin dosage – intensity and more precise diagnosis of diabetes) EC dictates the development of new onset diabetes irrespective of statin use.
Shaya GE, Juraschek SP, Feldman DI et al. Relation of Exercise Capacity to Risk of Development of Diabetes in Patients on Statin Therapy (the Henry Ford Exercise Testing Project). Am J Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28716336
 
Can atorvastatin 20 mg improve endothelial function and reduce anginal complaints?
In this Slovenian study, the effects of statin on endothelial function in patients with anginal complaints but no angiographic abnormalities (Prinz-metal angina pectoris) were studied. In this double blinded study 58 patients with AP, noninvasively confirmed ischemia and normal angiogram were included. The studied groups were quite homogeneous, and potentially confounding factors affecting endothelial function were reduced due to a large number of exclusion criteria. Patients were randomized to atorvastatin 20 mg or placebo for 6 months after which they were re-evaluated by flow mediated dilatation (FMD) of the brachial artery, microcirculation by peripheral arterial tonometry (EndoPAT) measuring the reactive hyperemia index (RHI), reflecting microcirculatory endothelial function, and the augmentation index (AI), an indicator of arterial stiffness. The impact of AP on the quality of life was monitored using the Seattle Angina Questionnaire (SAQ). At baseline the majority of patients (91%) had an abnormal FMD and 41% a subnormal RH. Using atorvastatin for 6 months showed improved FMD compared to the placebo group at 3 months (+120.8% vs -21.2% and at 6 months (+70.8% vs -1.9%); P<0.001. For RH no difference was detected. The AI showed improvements (–114.49% vs. –30.77%, p = 0.077) as well but these differences were not significant. All the SAQ variables did improve in both groups, except for quality of life were both groups presented a lower score compared to baseline scores. The authors concluded that atorvastatin has a favorable effect on the endothelial function, measured by FMD in patients with AP and a normal CA. this could not be confirmed by endoPAT tests. Although the SAQ improved after 6 months there was no significant difference between the two treatment arms a both groups shared deterioration of perceived quality of life.   
Kabaklic A, Fras Z. Moderate-dose atorvastatin improves arterial endothelial function in patients with angina pectoris and normal coronary angiogram: a pilot study. Archives of medical science : AMS 2017; 13:827-836. http://www.ncbi.nlm.nih.gov/pubmed/?term=28721151
 
Are clinical stable DES patients better off with Atorvastatin 40 mg or is pravastatin 20 mg sufficient?
In this investigator initiated open label, randomized parallel, multi-center study, stable Korean CAD patients that received a drug-eluting stent + aspirin monotherapy 12 months prior were included. Out of a total of 12 287 patients, 2000 were enrolled between August 2010 and November 2014. The investigators compared a high intensity statin (atorvastatin 40 mg ) regimen with a less aggressive lipid lowering strategy (pravastatin 20 mg). Patients were  followed for 12 months. The primary endpoint was adverse clinical events at 12-month follow-up (a composite of all death, myocardial infarction, revascularization, stent thrombosis, stroke, renal deterioration, intervention for peripheral artery disease, and admission for cardiac events). This primary endpoints occurred in 25 (2.5%) patients treated with atorvastatin and 40 (4.1%) patients that received pravastatin. HR 0.58(0.36-0.92) P=0.018. Cardiac death (0 vs 0.4%; P=0.025) and non-target vessel myocardial infarction (0.1 vs 0.7%; P=0.033) were the main events responsible for the observed improved outcome. The authors concluded that, in Korean clinically stable DES-treated patients, high intensity atorvastatin 40 mg significantly reduced adverse events as compared to a low-intensity pravastatin 20 mg therapy.  
Im E, Cho YH, Suh Y et al. High-intensity Statin Treatments in Clinically Stable Patients on Aspirin Monotherapy 12 Months After Drug-eluting Stent Implantation: A Randomized Study. Rev Esp Cardiol (Engl Ed) 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28716428
 
Patients with PAD treated with guideline recommend statins lived longer and experienced less events
Evaluating the benefits of Low/moderate intensity (LMI) vs high intensity statins (HI) in patients with peripheral artery disease. This retrospective analysis used data collected in the PAD–University of California (UC) Davis Registry, included were patients with a clinical diagnosis of PAD who underwent lower extremity angiography or endovascular intervention between 2006 and 2013 and who were not using other lipid lowering medication. Overall 629 (69%) of the 909 patients were using statins. HI statins were used by 124 (13.6%) of the patients. LDL-C was not different between the two treatment groups HI 80±30 versus 87±44 mg/dL, P=0.14. There were no significant differences in age, smoking history, diabetes, and hypertension. However, a higher prevalence of CAD was noted in the HI patients (75% vs 56%; P=0.0001). Patients were propensity matched and after 3 years evaluated for the primary endpoint of total mortality and secondary endpoint of major cardiovascular events. Both endpoints were significantly reduced in the HI group compared to the LMI patients. The HR’s were respectively 0.52 (0.33-0.81; P=0.004) and 0.58 (0.37-0.92; P=0.02). No significant differences were observed for major adverse limb events (MALE), and amputation-free survival (AFS). The authors concluded that HI statin use was associated with improved survival and reduced cardiovascular events compared to LMI. Of note only a minority of these very high-risk patients (13.6%) were treated with a high dose high intensity statin.
Foley R, Singh GD, Kokkinidis DG et al. High-Intensity Statin Therapy Is Associated With Improved Survival in Patients With Peripheral Artery Disease. J Am Heart Assoc 2017; 6. http://www.ncbi.nlm.nih.gov/pubmed/?term=28711864
 
Are FH patients protected from diabetes?
The new onset of diabetes (NODM) in patients using statins has become a major focus of attention. Recently another intriguing relationship between the reduced risk of developing diabetes in patients diagnosed with familial hypercholesterolemia (FH), surfaced as well. In this article, the effects of statins in combinations with a mutation in the LDL-receptor gene and plasma LDL-concentrations are assessed. Using data from the Spanish Arteriosclerosis Society dyslipidemia register, Adult patients with a “probable” or “definite” FH diagnoses were compared with the general population. There were 1737 patient included that had a Dutch Lipid Clinic Network Score ≥6 (354 probable and 1378 definite). The incidence of diabetes was almost 40% lower. In the FH patients 5.94% vs 9.44% in the general population; OR 0.606 (0.486-0.755, P<0.001). Risk factors for developing diabetes were the same for FH patients as in the general population: male gender, age, BMI, hypertension, baseline triglycerides and years of statin treatment. Plasma LDL-C or gene mutations were not associated with NODM in FG patients. Statin use preceded the diagnosis of diabetes in most FH patients and the risk for NODM was similar to what was shown in statin trials. The authors noted that potential confounders such as a healthier lifestyle and shorter life expectancy could play an important role. In the Spanish FH patient’s hypertension, overweight, obesity and tobacco use was much lower than that observed in the Spanish general population. The lower BMI scores could already explain 1/3 of the lower DM risk observed in this cohort.
Climent E, Perez-Calahorra S, Marco-Benedi V et al. Effect of LDL cholesterol, statins and presence of mutations on the prevalence of type 2 diabetes in heterozygous familial hypercholesterolemia. Scientific reports 2017; 7:5596. http://www.ncbi.nlm.nih.gov/pubmed/?term=28717233
Relevant Publications
  1. Tanner RM, Safford MM, Monda KL et al. Primary Care Physician Perspectives on Barriers to Statin Treatment. Cardiovasc Drugs Ther 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28710589
  2. Murin J. [What has the GLAGOV clinical study shown?]. Vnitr Lek 2017; 63:329-332. http://www.ncbi.nlm.nih.gov/pubmed/?term=28726431
  3. Kunutsor SK, Whitehouse MR, Blom AW, Laukkanen JA. Statins and venous thromboembolism: do they represent a viable therapeutic agent? Expert Rev Cardiovasc Ther 2017:1-9. http://www.ncbi.nlm.nih.gov/pubmed/?term=28724320
  4. Elnaem MH, Mohamed MHN, Huri HZ et al. Statin Therapy Prescribing for Patients with Type 2 Diabetes Mellitus: A Review of Current Evidence and Challenges. J Pharm Bioallied Sci 2017; 9:80-87. http://www.ncbi.nlm.nih.gov/pubmed/?term=28717329
  5. Bertoluci MC, Moreira RO, Faludi A et al. Brazilian guidelines on prevention of cardiovascular disease in patients with diabetes: a position statement from the Brazilian Diabetes Society (SBD), the Brazilian Cardiology Society (SBC) and the Brazilian Endocrinology and Metabolism Society (SBEM). Diabetology & metabolic syndrome 2017; 9:53. http://www.ncbi.nlm.nih.gov/pubmed/?term=28725272
  6. Xie W, Zhu Q, Liu Q et al. Statin use and endometrial cancer risk: a meta-analysis. Oncotarget 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28711915
  7. Venegas Sanabria LC, Barbosa Balaquera S, Suarez Acosta AM et al. [Statin and risk of falls in the elderly: A sytematic review of the literature]. Revista espanola de geriatria y gerontologia 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28728682
  8. Vaclavik J. [News in the treatment of hypertension and dyslipidemia]. Vnitr Lek 2017; 63:333-337. http://www.ncbi.nlm.nih.gov/pubmed/?term=28726432
  9. Tvaryanas AP, Mahaney HJ, Schroeder VM, Maupin GM. Statin Therapy in Low-Risk Air Force Aviators with Isolated Hypercholesterolemia. Aerosp Med Hum Perform 2017; 88:752-759. http://www.ncbi.nlm.nih.gov/pubmed/?term=28720185
  10. Thomas T, Zhou H, Karmally W et al. CETP (Cholesteryl Ester Transfer Protein) Inhibition With Anacetrapib Decreases Production of Lipoprotein(a) in Mildly Hypercholesterolemic Subjects. Arterioscler Thromb Vasc Biol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28729361
  11. Sung PH, Chiang HJ, Lee MS et al. Combined renin-angiotensin-aldosterone system blockade and statin therapy effectively reduces the risk of cerebrovascular accident in autosomal dominant polycystic kidney disease: a nationwide population-based cohort study. Oncotarget 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28711910
  12. Suda G, Ito J, Nagasaka A et al. Add-on effects of fluvastatin in simeprevir/pegylated-interferon/ribavirin combination therapy for patients with genotype 1 hepatitis C virus infection: a randomized controlled study. Hepatology research : the official journal of the Japan Society of Hepatology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28722780
  13. Smith A, Murphy L, Zgaga L et al. Pre-diagnostic statin use, lymph node status and mortality in women with stages I-III breast cancer. Br J Cancer 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28720842
  14. Pirillo A, Catapano AL. Pitavastatin and HDL: Effects on plasma levels and function(s). Atherosclerosis. Supplements 2017; 27:e1-e9. http://www.ncbi.nlm.nih.gov/pubmed/?term=28716185
  15. Moazen-Zadeh E, Shirzad F, Karkhaneh-Yousefi MA et al. Simvastatin as an Adjunctive Therapy to Risperidone in Treatment of Autism: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Journal of child and adolescent psychopharmacology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28719227
  16. Loch A, Bewersdorf JP, Kofink D et al. Generic atorvastatin is as effective as the brand-name drug (LIPITOR(R)) in lowering cholesterol levels: a cross-sectional retrospective cohort study. BMC research notes 2017; 10:291. http://www.ncbi.nlm.nih.gov/pubmed/?term=28716156
  17. Lasam G, Shambhu S, Fishberg R. Heterozygous Familial Hypercholesterolemia With APOE Haplotype: A Prospective Harbinger of a Catastrophic Cardiovascular Event. Cardiology research 2017; 8:117-122. http://www.ncbi.nlm.nih.gov/pubmed/?term=28725328
  18. Khan TM, Iqbal S, Rashid MA. Comparison Of Lipid Lowering Effect Of Extra Virgin Olive Oil And Atorvastatin In Dyslipidaemia In Type 2 Diabetes Mellitus. Journal of Ayub Medical College, Abbottabad : JAMC 2017; 29:83-86. http://www.ncbi.nlm.nih.gov/pubmed/?term=28712181
  19. Jaworski K, Jankowski P, Kosior DA. PCSK9 inhibitors - from discovery of a single mutation to a groundbreaking therapy of lipid disorders in one decade. Archives of medical science : AMS 2017; 13:914-929. http://www.ncbi.nlm.nih.gov/pubmed/?term=28721159
  20. Groeneveld ME, van der Reijden JJ, Tangelder GJ et al. Peroxynitrite Footprint in Circulating Neutrophils of Abdominal Aortic Aneurysm Patients Is Lower in Statin than in Non-statin Users. European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28712812
  21. Ghanim H, Green K, Abuaysheh S et al. Ezetimibe and simvastatin combination inhibits and reverses the pro-inflammatory and pro-atherogenic effects of cream in obese patients. Atherosclerosis 2017; 263:278-286. http://www.ncbi.nlm.nih.gov/pubmed/?term=28711708
  22. Ershova AI, Meshkov AN, Bazhan SS et al. The prevalence of familial hypercholesterolemia in the West Siberian region of the Russian Federation: A substudy of the ESSE-RF. PLoS One 2017; 12:e0181148. http://www.ncbi.nlm.nih.gov/pubmed/?term=28719663
  23. Casula M, Pirillo A, Norata GD, Catapano AL. PCSK9 inhibition in statin-intolerant HeFH patients: What's new? Eur J Prev Cardiol 2017:2047487317721980. http://www.ncbi.nlm.nih.gov/pubmed/?term=28728483
  24. Almalki ZS, Guo JJ, Alahmari A et al. Cost-effectiveness of Simvastatin Plus Ezetimibe for Cardiovascular Prevention in Patients with a History of Acute Coronary Syndrome: Analysis of Results of the IMPROVE-IT Trial. Heart, lung & circulation 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28716519
Basic Science Publications
  1. Wu S, Yang R, Wang G. Anti-asthmatic effect of pitavastatin through aerosol inhalation is associated with CD4+ CD25+ Foxp3+ T cells in an asthma mouse model. Scientific reports 2017; 7:6084. http://www.ncbi.nlm.nih.gov/pubmed/?term=28729731
  2. Tan LC, Zhao L, Liu XH et al. [Antagonism of lovastatin on oxidative stress and apoptosis in primary rat hippocampal neurons induced by beta-amyloid peptide]. Zhonghua bing li xue za zhi = Chinese journal of pathology 2017; 46:491-496. http://www.ncbi.nlm.nih.gov/pubmed/?term=28728224
  3. Sun T, Zhang HJ, Krittanawong C et al. Acute atorvastatin treatment restores the cardioprotective effects of ischemic postconditioning in hyperlipidemic rats. Oncotarget 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28732362
  4. Sonvico F, Zimetti F, Pohlmann AR, Guterres SS. Drug delivery to the brain: how can nanoencapsulated statins be used in the clinic? Therapeutic delivery 2017; 8:625-631. http://www.ncbi.nlm.nih.gov/pubmed/?term=28730939
  5. Obayashi H, Kobayashi N, Nezu Y et al. Plasma 2-hydroxyglutarate and hexanoylcarnitine levels are potential biomarkers for skeletal muscle toxicity in male Fischer 344 rats. The Journal of toxicological sciences 2017; 42:385-396. http://www.ncbi.nlm.nih.gov/pubmed/?term=28717097
  6. Leite GAA, Figueiredo TM, Sanabria M et al. Ascorbic acid supplementation partially prevents the delayed reproductive development in juvenile male rats exposed to rosuvastatin since prepuberty. Reproductive toxicology (Elmsford, N.Y.) 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28729172
  7. Ke X, Ke B, Wang X et al. Additive effects of atorvastatin combined with sitagliptin on rats with myocardial infarction: a pilot study. Archives of medical science : AMS 2017; 13:956-961. http://www.ncbi.nlm.nih.gov/pubmed/?term=28721163
  8. Gehrke T, Scherzad A, Hackenberg S et al. Additive antitumor effects of celecoxib and simvastatin on head and neck squamous cell carcinoma in vitro. International journal of oncology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28713941
  9. de Wolf E, Abdullah MI, Jones SM et al. Dietary geranylgeraniol can limit the activity of pitavastatin as a potential treatment for drug-resistant ovarian cancer. Scientific reports 2017; 7:5410. http://www.ncbi.nlm.nih.gov/pubmed/?term=28710496
  10. Carillion A, Feldman S, Na N et al. Atorvastatin reduces beta-Adrenergic dysfunction in rats with diabetic cardiomyopathy. PLoS One 2017; 12:e0180103. http://www.ncbi.nlm.nih.gov/pubmed/?term=28727746
  11. Devalapalli MMR, Cheruvu HS, Yertha T et al. Hansen solubility parameters for assay method optimization of simvastatin, ramipril, atenolol, hydrochlorothiazide and aspirin in human plasma using liquid chromatography with tandem mass spectrometry. Journal of separation science 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28722356
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