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Update - Week 05, 2019
 
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

FOURIER in- and exclusion criteria tested in Real World patients
With the introduction of PCSK9ab therapy, choosing the right patients to ensure optimal use of this costly lipid-lowering drug is a charged debate. The FOURIER study included CHD patients and used quite strict in- and exclusion criteria. To evaluate these criteria in real-world patients, a large US administrative database was queried, The FOURIER inclusion criteria were compared for CVD risk, trial eligibility, and unrepresentativeness. Of the 233 977 CVD patients included in the registry between January 1 – December 2016, only 15.2% did fit the FOURIER inclusion criteria. Exclusion was quite common and 60% of the registered CHD patients had ≥2 of these exclusion conditions. Excluded patients had a lower risk compared to the patients eligible for inclusion, HR: 084 (0.81-0,88, P<0.001). Underrepresented patients were: minorities, women, and those without prior MI. The latter two had significantly calculated lower CVD risk as well, HR 0.77 (0.71-0.82, P<0.001 and HR 0.67 (0.63-0.72, P<.001) respectively. Moderate to high-intensity statin was prescribed in 47.25% of the CAD patients. The authors concluded that in real-world patients only one in seven would qualify if the FOURIER criteria were applied as a PCSK9ab prescription threshold. A significant number of patients were underrepresented if FOURIER inclusion criteria are used for eligibility, and although the majority were considered to have a lower CVD risk, a substantial number had a higher CVD risk as the compactor group who did match up to the inclusion criteria. A majority of CHD patients used an inappropriate lower intensity or lower dosage statin.  Health care professionals should ensure that standard cholesterol-lowering strategies with high intensity, high dose statins (and ezetimibe) have been fully deployed before initiating PCSK9ab treatments.
Yao X, Gersh BJ, Lopez-Jimenez F et al. Generalizability of the FOURIER trial to routine clinical care: Do trial participants represent patients in everyday practice? Am Heart J 2018; 209:54-62. http://www.ncbi.nlm.nih.gov/pubmed/?term=30685675
 
Significantly increased immune response to a  T-cell independent pneumococcal vaccine
The immune modulatory effects of statins, including T-cell dependent vaccine response, have been described in earlier publications. This study set out to study the immune response to a T-cell independent pneumococcus vaccine while using 40 mg of Atorvastatin over a 28-day period. Healthy volunteers (N=22) were randomized to active statin treatment (N=12) or placebo (N=10), Pneumovax was administered on day 7, after starting the first statin dose, and patients continued using statins for an additional 21 days. The primary endpoint was the increase in pneumococcal-specific antibody titer, described as a ratio of post-vaccination titer over baseline titer. Additional outcomes included serotype-specific pneumococcal antibody titer, seroconversion, complete blood counts (CBC), erythrocyte sedimentation rate (ESR), and serum cytokine analysis. The rise in antibody titer in the atorvastatin group increased from 32.58 (SD, 15.96) to 147.7 (SD, 71.52) lg/ml at 21 days post-vaccination. Participants that used a placebo showed a less robust increase from 30.81 (SD, 13.04) at baseline to 104.4 (SD, 45) lg/ml., after 21 days. The fold change of total anti-pneumococcal antibody titer in the atorvastatin users increased significantly compared to the placebo group (2-way ANOVA, p = .0177). The authors concluded that, based on these preliminary results, atorvastatin could become a novel adjuvant for poorly immunogenic polysaccharide-based vaccines. The small size of the studied cohort limits the external validity and confirmation in larger studies will be detrimental to elevate these preliminary findings to accepted clinical practice strategies.
Wildes TJ, Grippin A, Fasanya H et al. Effect of atorvastatin on humoral immune response to 23-valent pneumococcal polysaccharide vaccination in healthy volunteers: The StatVax randomized clinical trial. Vaccine 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30686636
 
A pharmacist centered approach to increase statin prescription in diabetics
Statins remain sub-optimally used in patients with increased CVD risk. In this study, pharmacists were used to optimizing statin treatment in 40-75-year-old diabetic patients from an internal medicine residency clinic. The US Preventive Services Task Force (USPSTF), and ADA recommendations with this age group were used as a guideline. The primary outcome was defined as the change in the prevalence of patients on statins. Additional outcomes included recommendation acceptance rates and reported adverse effects. Patients that had a scheduled visit with their primary care physician within the next 3 months, were included. The intervention was executed by a clinical pharmacist and pharmacy resident. They evaluated the electronic patient files, costs of statin therapy, shared their recommendations with the patient's primary care physicians, facilitated prescription and organized educational sessions for patients. Of the evaluated patients (N=454), 343 (75.6%) used a statin prior to the study. After the 3-month intervention, this percentage increased to 82.6% (P<0.0001). The mean age was 58 years, 59.7% were female, 76.4% were black, and 90% had hypertension. The majority of the patients (90.2%) accepted the recommendations and were content with the proposed change of their medication regimens. No significant adverse events were reported. The authors concluded that a collaborative effort to improve statin use in eligible diabetic patients, that included a pharmacist centered approach, was successful and well accepted by the patients. Statin prescription increased significantly in diabetic patients, most of which were black and had hypertension.
Vincent R, Kim J, Ahmed T, Patel V. Pharmacist Statin Prescribing Initiative in Diabetic Patients at an Internal Medicine Resident Clinic. Journal of pharmacy practice 2019:897190018824820. http://www.ncbi.nlm.nih.gov/pubmed/?term=30696337
 
“ Statins on board” can reduce infarct size in ischemic stroke patients
Ischemic stroke (IS) patients should be prescribed high dose – high-intensity statins, based on the evidence generated in placebo-controlled randomized trials as well as observational cohort generated confirmations. The benefits on final infarct volume (FIV) and collateral circulation status prior to an ischemic stroke was evaluated in this meta-analysis. Using a primary search strategy to query Embase/MEDLINE and Scopus databases 730 published studies were screened and from the 16 potentially eligible studies, nine, that included 1186 patients, were selected. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews and meta-analyses were adopted. Prior statin use in patients the experienced a IS was associated with a reduce FIV, Standard mean difference (SMD) = 0.25 (0.07–0.42, p=0.005). In patients with atherosclerotic IS, SMD=0.49 (0.19–0.80, p=0.001). For collateral scores, a trend towards improvement was observed as well, OR: 1.45; (0.92–2.29, p=0.11). The authors concluded that the results of this meta-analysis add to the increasing evidence that statins “on-board” in IS patients has beneficial effects on final infarct size. Confirmation of these preliminary observations is warranted in larger prospective observational studies.
Malhotra K, Safouris A, Goyal N et al. Association of statin pretreatment with collateral circulation and final infarct volume in acute ischemic stroke patients: A meta-analysis. Atherosclerosis 2019; 282:75-79. http://www.ncbi.nlm.nih.gov/pubmed/?term=30708178
 
Statins for everyone? – a practical update on lipid management
For those that manage patients at risk for CVD, choosing the right lipid-lowering strategy for the right patients might at times be confusing. New guidelines with moving LDL-c targets as well as changing views on risk estimation and preferred (novel) therapeutic strategies for improving a broad range of lipid fractions can be challenging. Keeping abreast of science and scientific literature is time-consuming and that has become a precious commodity for busy clinicians. This review provides a concise overview with simplified lipid management approaches based on latest published research as well as updated guidelines. The authors highlight the specific patients were statins are mandatory; those considered secondary prevention and FH. And refresh understanding on groups of patients where debate regarding statin use still prevails. These are primary prevention patients that have elevated plasma LDL-c levels (but not FH patients), those considered at low 10-year risk for CVD, patients that are affected by chronic kidney diseases (CKD), diabetes mellitus type 2 (DM2), heart failure and elderly patients. Data from clinical trials, that included these patients as well recently published Mendelian randomization studies are shared to illustrate the views an recommendations of the authors. They close their suggestions with a provocative statement supported, by a number of arguments, to treat all. Reflecting on the statement put forward by sir Geoffrey Rose in the Prevention Paradox. A prevention measure which brings benefit to the population but offers less to the participating individual. A thought-provoking argument that deserves to be contemplated. If this controversial strategy is ready for implementation in the Real World remains for the readers to decide.
Hadjiphilippou S, Ray KK. Cholesterol-Lowering Agents. Circulation research 2019; 124:354-363. http://www.ncbi.nlm.nih.gov/pubmed/?term=30702991
Relevant publications
  1. Yang S, Gu YY, Jing F et al. The Effect of Statins on Levels of Dehydroepiandrosterone (DHEA) in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. Medical science monitor : international medical journal of experimental and clinical research 2019; 25:590-597. http://www.ncbi.nlm.nih.gov/pubmed/?term=30698163
  2. Hwang YC, Jun JE, Jeong IK et al. Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus. Diabetes Metab J 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30688048
  3. Waters DD, Hsue PY. Lipid Abnormalities in Persons Living With HIV Infection. Can J Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30704819
  4. Strandberg TE. Challenges of a Statin Trial in Older People. J Am Geriatr Soc 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30688358
  5. Scognamiglio M, Costa D, Sorriento A, Napoli C. Current therapy and nutraceuticals for the treatment of patients with dyslipidemias. Current pharmaceutical design 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30706799
  6. Phillips WJ, Johnson C, Law A et al. Comparison of Framingham risk score and chest-CT identified coronary artery calcification in breast cancer patients to predict cardiovascular events. Int J Cardiol 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30696608
  7. Perucha E, Melchiotti R, Bibby JA et al. The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells. Nature communications 2019; 10:498. http://www.ncbi.nlm.nih.gov/pubmed/?term=30700717
  8. Park SJ, Park H, Kang D et al. Association of statin therapy with clinical outcomes in patients with vasospastic angina: Data from Korean health insurance review and assessment service. PLoS One 2019; 14:e0210498. http://www.ncbi.nlm.nih.gov/pubmed/?term=30699150
  9. Ogura M. [Familial Hypercholesterolemia and Its Related Molecules]. Rinsho Byori 2016; 64:657-666. http://www.ncbi.nlm.nih.gov/pubmed/?term=30695320
  10. Nguyen LS, Procopi N, Salem JE et al. Relation between baseline LDL-cholesterol and cardiovascular outcomes in high cardiovascular risk hypertensive patients: A post-hoc SPRINT data analysis. Int J Cardiol 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30685099
  11. Mulchandani R, Lyngdoh T, Chakraborty P, Kakkar AK. Satisfaction With Statin Treatment Among Adult Coronary Artery Disease Patients: An Experience From a Resource-Constrained Setting. Heart, lung & circulation 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30704841
  12. Kotti A, Holmqvist A, Albertsson M, Sun XF. Survival benefit of statins in older patients with rectal cancer: A Swedish population-based cohort study. Journal of geriatric oncology 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30692020
  13. Kido K, Oyen AA, Beckmann MA, Brouse SD. Musculoskeletal toxicities in patients receiving concomitant statin and daptomycin therapy. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists 2019; 76:206-210. http://www.ncbi.nlm.nih.gov/pubmed/?term=30689699
  14. Karasek D. Combined lipid-lowering therapy. Vnitr Lek 2019; 64:1177-1184. http://www.ncbi.nlm.nih.gov/pubmed/?term=30704254
  15. Gaisenok OV, Kurnosov PA, Leonov AS, Zateeyshikov DA. Screening of familial hypercholesterolemia among patients in age under 40 years old exposed by duplex scanning of carotid arteries, by the local registry data. Ter Arkh 2018; 90:37-41. http://www.ncbi.nlm.nih.gov/pubmed/?term=30701733
  16. Elnaem MH, Mohamed MHN, Huri HZ, Shah ASM. Effectiveness and prescription pattern of lipid-lowering therapy and its associated factors among patients with type 2 diabetes mellitus in Malaysian primary care settings. Therapeutics and clinical risk management 2019; 15:137-145. http://www.ncbi.nlm.nih.gov/pubmed/?term=30705590
  17. Elamin AFM, Grafton-Clarke C, Wen Chen K et al. Potential use of PCSK9 inhibitors as a secondary preventative measure for cardiovascular disease following acute coronary syndrome: a UK real-world study. Postgraduate medical journal 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30709868
  18. Di Taranto MD, de Falco R, Guardamagna O et al. Lipid profile and genetic status in a familial hypercholesterolemia pediatric population: exploring the LDL/HDL ratio. Clin Chem Lab Med 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30710474
  19. Ceska R, Taborsky M, Vrablik M. Consensus statement of professional associations on prescribing of PCSK9-inhibitors. Vnitr Lek 2019; 64:1131-1136. http://www.ncbi.nlm.nih.gov/pubmed/?term=30704246
  20. Blaha V. Lipoprotein(a) - the cardiovascular risk factor: significance and therapeutic possibilities. Vnitr Lek 2019; 64:1160-1168. http://www.ncbi.nlm.nih.gov/pubmed/?term=30704252
  21. Bezin J, Moore N. Pharmacoepidemiology of statins. Therapie 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30704765
  22. Yun UJ, Lee JH, Shim J et al. Anti-cancer effect of doxorubicin is mediated by downregulation of HMG-Co A reductase via inhibition of EGFR/Src pathway. Lab Invest 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30700846
  23. Riestenberg RA, Furman A, Cowen A et al. Differences in statin utilization and lipid lowering by race, ethnicity, and HIV status in a real-world cohort of persons with human immunodeficiency virus and uninfected persons. Am Heart J 2018; 209:79-87. http://www.ncbi.nlm.nih.gov/pubmed/?term=30685678
  24. Oh TK, Chang CB, Shin HJ et al. Association between perioperative statin use and postoperative pain after total knee arthroplasty. Regional anesthesia and pain medicine 2019; 44:221-226. http://www.ncbi.nlm.nih.gov/pubmed/?term=30700616
  25. Lui DTW, Lee ACH, Yap DYH et al. A young Chinese man with nephrotic syndrome due to lipoprotein glomerulopathy. J Clin Lipidol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=30685233
  26. Lankin VZ, Tikhaze AK, Viigimaa M, Chazova Icapital Ie C. PCSK9 Inhibitor causes a decrease in the level of oxidatively modified low-density lipoproteins in patients with coronary artery diseases. Ter Arkh 2018; 90:27-30. http://www.ncbi.nlm.nih.gov/pubmed/?term=30701731
  27. Kelly KE, Jiroutek MR, Lewis K, Zagar B. Assessing Changes in Statin Prescribing Patterns Surrounding the 2013 American College of Cardiology/American Heart Association Lipid Guidelines. Clinical therapeutics 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30686571
Miscellaneous publications
 
 
  1. Yu XB, Zhang HN, Dai Y et al. Simvastatin prevents and ameliorates depressive behaviors via neuroinflammatory regulation in mice. Journal of affective disorders 2019; 245:939-949. http://www.ncbi.nlm.nih.gov/pubmed/?term=30699879
  2. Wei H, Yang M, Yu K et al. Atorvastatin Protects Against Cerebral Aneurysmal Degenerative Pathology by Promoting Endothelial Progenitor Cells (EPC) Mobilization and Attenuating Vascular Deterioration in a Rat Model. Medical science monitor : international medical journal of experimental and clinical research 2019; 25:928-936. http://www.ncbi.nlm.nih.gov/pubmed/?term=30710072
  3. Tong XK, Trigiani LJ, Hamel E. High cholesterol triggers white matter alterations and cognitive deficits in a mouse model of cerebrovascular disease: benefits of simvastatin. Cell death & disease 2019; 10:89. http://www.ncbi.nlm.nih.gov/pubmed/?term=30692517
  4. Taniguti EH, Ferreira YS, Stupp IJV et al. Atorvastatin prevents lipopolysaccharide-induced depressive-like behaviour in mice. Brain research bulletin 2019; 146:279-286. http://www.ncbi.nlm.nih.gov/pubmed/?term=30690060
  5. Sariisik E, Kocak M, Baloglu FK, Severcan F. Interaction of the cholesterol reducing agent simvastatin with zwitterionic DPPC and charged DPPG phospholipid membranes. Biochimica et biophysica acta. Biomembranes 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30707888
  6. Leggiero E, Labruna G, Iaffaldano L et al. Helper-dependent adenovirus-mediated gene transfer of a secreted LDL receptor/transferrin chimeric protein reduces aortic atherosclerosis in LDL receptor-deficient mice. Gene therapy 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30700805
  7. Huai J, Yang Z, Yi YH, Wang GJ. [Changes of Rheb gene and protein expression in preeclampsia-like mouse model treated with pravastatin]. Zhonghua fu chan ke za zhi 2019; 54:38-43. http://www.ncbi.nlm.nih.gov/pubmed/?term=30695905
  8. Gobel A, Breining D, Rauner M et al. Induction of 3-hydroxy-3-methylglutaryl-CoA reductase mediates statin resistance in breast cancer cells. Cell death & disease 2019; 10:91. http://www.ncbi.nlm.nih.gov/pubmed/?term=30692522
  9. Andrews GP, Li S, Almajaan A et al. Fixed Dose Combination Formulations: Multi-Layered Platforms Designed for the Management of Cardiovascular Disease. Molecular pharmaceutics 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30702301
  10. Vogeli B, Shima S, Erb T, Wagner T. Crystal structure of archaeal HMG-CoA reductase: insights into structural changes of the C-terminal helix of the class-I enzyme. FEBS letters 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30702149
  11. Umeda R, Takanari H, Ogata K et al. Direct free radical scavenging effects of water-soluble HMG-CoA reductase inhibitors. Journal of clinical biochemistry and nutrition 2019; 64:20-26. http://www.ncbi.nlm.nih.gov/pubmed/?term=30705508
  12. Li X, Xiao H, Lin C et al. Synergistic effects of liposomes encapsulating atorvastatin calcium and curcumin and targeting dysfunctional endothelial cells in reducing atherosclerosis. International journal of nanomedicine 2019; 14:649-665. http://www.ncbi.nlm.nih.gov/pubmed/?term=30697048
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This activity is supported by an educational grant from Pfizer.