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Update - Week 24, 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

Asian ACS patients use statins, but are they getting the right one?
Optimal lipid management remains a challenge for even the very high-risk patients. In this sub analysis of the Dyslipidemia International Study II (DYSIS II) Taiwanese and Hong Kong patients admitted for ACS were evaluated. Prior to admission 125/246 (46.3%) patients were using statins. On target (< 70 mg/dl) were 28.2% of the patients that used statins at admission vs. 6.9% that did not. Simvastatin was the preferred statin in 46.8% of the patients, Atorvastatin 29.8% and rosuvastatin 11.3%, combination of statin with ezetimibe was used by only 4%. The average dosage used was the equivalent of atorvastatin 14 mg/day. After 4 months follow up target attainment was achieved in 45.1% and 43.3% of statin users and no statin use at admission, respectively. The average atorvastatin equivalent dosage increased to 18 mg/day. The preferred statin at 4 months remained simvastatin (42.3%), followed by atorvastatin (31.7%) and rosuvastatin (23.8%). Combination with ezetimibe was reduced to 1.3%. Of note is that only 43.7% of the patients had LDL-C measurements performed at in the 4 months follow-up period. Despite the fact that 88% of the patients were using statins after 4 months, the mean dosage did not increase as much as anticipated. The average LDL-C of Asian patients not using statins was 120.6 mg/dl, not that different of baseline levels in non-Asian patients! This analysis illustrates that more efforts need to be directed towards Hong Kong and Taiwanese physicians to improve management of patients at very high risk of CVD according to national and international guideline directives for lipid management. Addressing the treatment barriers in physicians (and patients) is of lifesaving importance.
Yan BP, Chiang FT, Ambegaonkar B et al. Low-density lipoprotein cholesterol target achievement in patients surviving an acute coronary syndrome in Hong Kong and Taiwan - findings from the Dyslipidemia International Study II. Int J Cardiol 2018; 265:1-5. http://www.ncbi.nlm.nih.gov/pubmed/?term=29885676
Simple genetic tool to predict (rosuva)statin response
Prediction of statin response by using a simple and inexpensive test are starting to surface. The authors of this article aimed to test if a simple and cheap restriction fragment length polymorphism (RFLP) analysis would be as reliable as the more expensive next generation sequencing approach. They targeted the SLCO1B1 c.1929A>C polymorphism. This polymorphism is associated with an increased activity of the organic anion transporter polypeptide 1B1 (OATP1B1) resulting in increased hepatic uptake of drugs. This polymorphism was shown to be associated with a decrease in plasma concentration of rosuvastatin and present in 6% of the Zimbabwean population studied. In comparison, Africans, Caucasians and South Asian have similar distributions of 7%, 5% and 5% respectively. The plasma concentration of Rosuvastatin was reduced by 75% in the carriers of the SLCO1B1 c.1929A>C polymorphism vs the non-carriers. The method described provided a quick, reliable and cost-effective approach to evaluate/predict rosuvastatin response in Zimbabwean patients. A similar approach would be warranted for other polymorphisms of the SLCO1B1 gene and that have been described with clinically relevant effects on increased and decreased plasma concentrations of statins. Examples are the SLCO1B1 521 T>C, SLCO1B1 388 A>G and ABCG2 421 C>A. Some of these polymorphisms have higher prevalence’s in populations of different ethnic background. 
Soko ND, Masimirembwa C, Dandara C. A cost effective RFLP method to genotype Solute carrier organic anion 1B1 (SLCO1B1) c.1929A>C (p.Leu643Phe, rs34671512); a variant with potential effect on rosuvastatin pharmacokinetics. BMC research notes 2018; 11:384. http://www.ncbi.nlm.nih.gov/pubmed/?term=29898760
Do we practice what we preach?
Examining if practicing clinician not only are familiar with the 2013 ACC/AHA guidelines but do actually implement them, was the aim of this analysis of the PALM registry. Physicians (N=774) that participated in collecting data for this registry, were presented with three primary prevention and one mix primary/secondary prevention case. These were one diabetes case; one high 10-year ASCVD risk (≥7.5%) + high LDL-C (≥130 mg/dL); one low 10-year ASCVD risk (<7.5%) but with high LDL-C (130–189 mg/dL); and one primary/secondary prevention patient with persistently elevated LDL-C (≥130 mg/dL) despite the use of a high-intensity statin. The responses from the survey and observed practice were not in alignment. For diabetics the response was that statins would be prescribed by 85%, in the registry this was done in 68% of the diabetic patients. For high risk/high LDL-c patients and low risk but high LDL-c patients the survey showed willingness to prescribe statins by 93% and 40% respectively of the participating physicians. In the registry these numbers were 40% and 50%. Agreement between survey and registry was found in 64%, 39%, and 52% of the patients with diabetes, high-risk/high LDL-C, and low-risk/high LDL-C respectively. For patients that despite maximum statin treatment werer unable to reach guideline goals 55% of the physicians agreed that they would add a non-statin drug however only 22% of patients did get an extra lipid lowering medication added to their statin. The authors concluded that there is a discordant gap between the reported adoption of the 2013 ACC/AHA guidelines and implementing this in clinical practice. Not surprising but elegantly proven in this published study.
Lowenstern A, Li S, Navar AM et al. Does clinician-reported lipid guideline adoption translate to guideline-adherent care? An evaluation of the Patient and Provider Assessment of Lipid Management (PALM) registry. Am Heart J 2018; 200:118-124. http://www.ncbi.nlm.nih.gov/pubmed/?term=29898839
Can CVD risk estimation improve by using the Fatty Liver score?
Estimating CVD risk beyond the traditional risk factors is the topic of this secondary analysis of the IMPROVE-IT study. Introducing the nonalcoholic fatty liver fibrosis score (NFS) as a novel parameter to distinguish residual CVD risk and predict treatment response in post-ACS patients. The NFS score is a biomarker-based serum evaluation consisting of: age, BMI, Impaired fasting glucose or diabetes (yes/no), AST/ALT ratio, platelets numbers and albumin concentrations. A high NFS was defined as > 0.67 (N=2106); a low NFS < -1.45 (N=5440). Patients in the high NFS group had a significant higher CVD risk compared to the Low NFS group, HR 1.30 (1,19-1,43; P<0.001). The treatment with simvastatin + ezetimibe provided superior protection compared to placebo + simvastatin with an absolute risk reduction of 3.7% and a NNT of 27, after 7 years of treatment. This protective effect was absent in the low NFS group, HR 1.01 (0.91-1.12; P-interaction=0.053). The scores were validated in a second study, the SOLID-TIMI 52 trial. The observed HR for NFS >0.67 vs. NFS <−1.455=1.55 (1.32–1.81; p<0.001) confirmed the observations in the IMPROVE-IT study. The authors propose to use the NFS in post ACS patients to identify the very high-risk patients that would need add-on lipid lowering therapy to reduce their odds for recurrent CV events and eagerly await outcomes of other population studies that will set out to test their hypothesis and hopefully confirm the results and conclusion.
Simon TG, Corey KE, Cannon CP et al. The nonalcoholic fatty liver disease (NAFLD) fibrosis score, cardiovascular risk stratification and a strategy for secondary prevention with ezetimibe. Int J Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29903515
ACC/AHA 2013 or USPSTF 2016 which would you prefer?
The in 2016 released United States Preventive Services Task Force (USPSTF) guidelines on statins for primary prevention ASCVD were compared with the 2013 ACC/AHA guidelines, in participants of the Multi-Ethnic Study of Atherosclerosis (MESA) registry (2010-2012). The included individuals were aged 40 – 76 years and not using statins. A coronary calcium score (CAC) was measured at baseline and ASCVD events were corelated with the different criteria for statin eligibility in each guideline. At baseline Less persons were eligible for statins according to USPSTF guidelines, 34.4% vs 49.1%. the increase over time was less as well, 39.1% vs 59.1%. A calcium score of 0 at baseline was less frequently observed with the USPSTF score, 36.6% vs 41.2% and more cardiac events were observed in this group as well 11.6/1000 person-years (10.2-13.3) vs 10.0/1000-person years (8.9-11.3). The CAC score showed a strong correlation with observed events, 4.2 (2.7-6.7) events with a CAC score = 0 vs 12.8 (8.3-19.9) events in persons with a CAC score > 100. Overall statin eligibility according to USPSTF guidelines was observed in 15% less participants. However, the CAC scores were higher in this group as were the observed ASCVD events. Adding the CAC score for risk assessment could be an attractive alternative to optimize statin initiation by providing a more robust method of individualized risk assessment in a primary prevention setting.
Miedema MD, Dardari ZA, Kianoush S et al. Statin Eligibility, Coronary Artery Calcium, and Subsequent Cardiovascular Events According to the 2016 United States Preventive Services Task Force (USPSTF) Statin Guidelines: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Heart Assoc 2018; 7. http://www.ncbi.nlm.nih.gov/pubmed/?term=29899017
Relevant publications
  1. Packard CJ. Determinants of Achieved LDL Cholesterol and "Non-HDL" Cholesterol in the Management of Dyslipidemias. Current cardiology reports 2018; 20:60. http://www.ncbi.nlm.nih.gov/pubmed/?term=29904807
  2. Musich S, Wang SS, Schwebke K et al. Underutilization of Statin Therapy for Secondary Prevention of Cardiovascular Disease Among Older Adults. Population health management 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29893617
  3. Tsivgoulis G, Safouris A, Kim DE, Alexandrov AV. Recent Advances in Primary and Secondary Prevention of Atherosclerotic Stroke. J Stroke 2018; 20:145-166. http://www.ncbi.nlm.nih.gov/pubmed/?term=29886715
  4. Reiss AB, Shah N, Muhieddine D et al. PCSK9 in cholesterol metabolism: from bench to bedside. Clinical science (London, England : 1979) 2018; 132:1135-1153. http://www.ncbi.nlm.nih.gov/pubmed/?term=29895529
  5. Nanna MG, Navar AM, Zakroysky P et al. Association of Patient Perceptions of Cardiovascular Risk and Beliefs on Statin Drugs With Racial Differences in Statin Use: Insights From the Patient and Provider Assessment of Lipid Management Registry. JAMA cardiology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29898219
  6. Martin SS, Giugliano RP, Murphy SA et al. Comparison of Low-density Lipoprotein Cholesterol Assessment by Martin/Hopkins Estimation, Friedewald Estimation, and Preparative Ultracentrifugation: Insights From the FOURIER Trial. JAMA cardiology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29898218
  7. Kim MC, Yun SC, Lee SO et al. Statins increase the risk of herpes zoster: A propensity score-matched analysis. PLoS One 2018; 13:e0198263. http://www.ncbi.nlm.nih.gov/pubmed/?term=29902266
  8. Kamari VE, Hileman CO, Gholam PM et al. Statin Therapy Does Not Reduce Liver Fat Scores in Patients Receiving Antiretroviral Therapy for HIV Infection. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29908359
  9. Gitt AK, Lautsch D, Ferrieres J et al. Contemporary data on treatment practices for low-density lipoprotein cholesterol in 6794 patients with stable coronary heart disease across the world. Data in brief 2018; 18:1937-1940. http://www.ncbi.nlm.nih.gov/pubmed/?term=29904698
  10. Ferrieres J, Lautsch D, Gitt AK et al. Body Mass Index impacts the choice of lipid lowering treatment with no correlation to blood cholesterol - findings from 52,916 patients in the Dyslipidemia International Study (DYSIS). Diabetes Obes Metab 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29888459
  11. Choi J, Kim Y, Kim HS et al. Phenotyping of Korean patients with better-than-expected efficacy of moderate-intensity statins using tensor factorization. PLoS One 2018; 13:e0197518. http://www.ncbi.nlm.nih.gov/pubmed/?term=29897980
  12. Yamanaka JS, Ribeiro KEC, Yanagihara GR et al. Effects of simvastatin associated with exercise on the mechanical resistance of muscle and bone in rats. Revista brasileira de ortopedia 2018; 53:287-292. http://www.ncbi.nlm.nih.gov/pubmed/?term=29892578
  13. Vershinina EO, Repin AN, Timofeev MS, Udut VV. [Prevention of periprocedural kidney ingury by loading doses of statins in elective percutaneous small es, Cyrillicoronary interventions]. Kardiologiia 2018:20-29. http://www.ncbi.nlm.nih.gov/pubmed/?term=29894673
  14. Verbree-Willemsen L, Zhang YN, Gijsberts CM et al. LDL extracellular vesicle coagulation protein levels change after initiation of statin therapy. Findings from the METEOR trial. Int J Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29898827
  15. Thomopoulos C, Michalopoulou H. Letter by Thomopoulos and Michalopoulou Regarding Article, "Prevention of Stroke With the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial)". Circulation 2018; 137:2656-2657. http://www.ncbi.nlm.nih.gov/pubmed/?term=29891622
  16. May AN, Lin LIP, Feneley M. Coronary Plaque Regression After Statin Therapy. Heart, lung & circulation 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29895485
  17. Koh KK. Letter by Koh Regarding Article, "Prevention of Stroke With the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial)". Circulation 2018; 137:2660-2661. http://www.ncbi.nlm.nih.gov/pubmed/?term=29891624
  18. Hadzi-Petrushev N, Dimovska K, Jankulovski N et al. Supplementation with Alpha-Tocopherol and Ascorbic Acid to Nonalcoholic Fatty Liver Disease's Statin Therapy in Men. Advances in pharmacological sciences 2018; 2018:4673061. http://www.ncbi.nlm.nih.gov/pubmed/?term=29887885
  19. Del Pinto R, Ferri C, Borghi C. Letter by Del Pinto et al Regarding Article, "Prevention of Stroke With the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial)". Circulation 2018; 137:2654-2655. http://www.ncbi.nlm.nih.gov/pubmed/?term=29891621
  20. Day J, Limaye V. Over-representation of statin-associated necrotising myopathy in patients of Aboriginal and Torres Strait Islander heritage. Internal medicine journal 2018; 48:749-751. http://www.ncbi.nlm.nih.gov/pubmed/?term=29898279
  21. Cordero A, Bertomeu-Gonzalez V, Rodriguez-Manero M. Letter by Cordero et al Regarding Article, "Prevention of Stroke With the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial)". Circulation 2018; 137:2658-2659. http://www.ncbi.nlm.nih.gov/pubmed/?term=29891623
  22. Chen X, Barywani SB, Sigurjonsdottir R, Fu M. Improved short and long term survival associated with percutaneous coronary intervention in the elderly patients with acute coronary syndrome. BMC geriatrics 2018; 18:137. http://www.ncbi.nlm.nih.gov/pubmed/?term=29898676
  23. Bohula EA, Wiviott SD, Giugliano RP et al. Response by Bohula et al to Letters Regarding Article, "Prevention of Stroke With the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial)". Circulation 2018; 137:2662-2663. http://www.ncbi.nlm.nih.gov/pubmed/?term=29891625
  24. Ananwattanasuk T, Chiewchalermsri C, Tongdee P, Nimkuntod P. Venipuncture Rate of Liver Function Tests for Patients being Treatment with Statin in Clinical Practice: A Therapeutic Dilemma. Journal of the Medical Association of Thailand = Chotmaihet thangphaet 2016; 99 Suppl 7:S69-75. http://www.ncbi.nlm.nih.gov/pubmed/?term=29901925
  25. High-Dose Atorvastatin after Stroke or Transient Ischemic Attack. N Engl J Med 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29898369
Miscellaneous publications
  1. Santos C, Dourado DM, Silva B et al. Effect of Ischemic Postconditioning and Atorvastatin in the Prevention of Remote Lung Reperfusion Injury. Brazilian journal of cardiovascular surgery 2018; 33:115-121. http://www.ncbi.nlm.nih.gov/pubmed/?term=29898139
  2. Jones HM, Fang Z, Sun W et al. Erratum: Atorvastatin exhibits anti-tumorigenic and anti-metastatic effects in ovarian cancer in vitro. American journal of cancer research 2018; 8:915. http://www.ncbi.nlm.nih.gov/pubmed/?term=29888764
  3. Golab-Janowska M, Paczkowska E, Machalinski B et al. Statins therapy is associated with increased populations of early endothelial progenitor (CD133+/VEGFR2+) and endothelial (CD34-/CD133-/VEGFR2+) cells in patients with acute ischemic stroke. Current neurovascular research 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29886830
  4. Lee JS, Roberts A, Juarez D et al. Statins enhance efficacy of venetoclax in blood cancers. Science translational medicine 2018; 10. http://www.ncbi.nlm.nih.gov/pubmed/?term=29899021
  5. Huo Z, Kong Y, Meng M et al. Atorvastatin enhances endothelial adherens junctions through promoting VE-PTP gene transcription and reducing VE-cadherin-Y731 phosphorylation. Vascul Pharmacol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29894844
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