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Update - Week 32,  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

Should certain ethnic groups be screened before starting a statin?
Ethnic background is a relevant issue when determining safety and efficacy of drugs in general and statins in particular. One of the rare (1-2:1 million people) problematic statin side effects is statin-associated immune mediated necrotizing myopathy (IMNM) associated with anti-HMGCR antibodies. A serious muscle problem that progresses even when statins are stopped and require (life)long treatments with immunosuppressive drugs + corticosteroids. In this report, a single center in New Zealand center diagnosed 4 IMNM cases, two who were Pacific Islanders, over a two-year period (2014-2016). The HLA-DRB1*11:01 haplotype seem to be associated with anti-HMGCR antibodies. In the pacific island population, this is most frequent occurring allele. Observing 4 incident cases over 2 years in a relatively small population of 297 423 people, comprising of only 5 856 pacific islanders, is alarmingly excessive. The 6 HLA-DRB1 alleles, including DRB1*11:01) are present in in 2/3 of the pacific islanders. The odds ratio of developing statin-associated IMNM was 24.5 in whites and 56.5 in blacks. The authors noted that pacific islanders may have a notably increased risk of developing NINM when exposed to statins.
Woolley MC, Stebbings S, Highton J. Statin-associated immune mediated necrotising myopathy: a New Zealand case series showing possible over-representation in Pacific Islanders. Internal medicine journal 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28782163
 
High rates of reported SAMS! Are these facts or fake (news)?
Statin intolerance is emerging as almost unsurmountable hurdle when prescribing statin in (very) high CVD risk patients. The (fake) news covering this life-threatening compliance controversy, is dumbfounding but many patients see them as truths (https://www.youtube.com/watch?v=9trx6opxmBI ). In this meta-analysis, the authors are presenting us with facts collected in over 22 statin studies (comprising >1000 participants) with 66 024 patients using statins vs 63 656 on placebo. Over a mean follow-up period of 4.1 years the discontinuation rates were 13.2% vs 13.9% with no significant difference between the two treatment arms; OR 0.99 (0.93-1.06; p=0,39). No difference between primary prevention or secondary prevention. Reports of myopathy were again almost identical in statin and placebo users. OR: 1.2 (0.98-1.62; P=0.25). in this meta-analysis >125 000 patients were included. No increase in reported side-effects, including myopathy, were noted in the patient using statins versus the placebo groups. Limitations of the included studies were limited by duration of follow-up, lower dosages use compared to clinical practice today and the heterogeneity of the different populations that participated in the studies.
Riaz H, Khan AR, Khan MS et al. Meta-analysis of Placebo-Controlled Randomized Controlled Trials on the Prevalence of Statin Intolerance. Am J Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28779871
 
To bleed or not to bleed; that is the question!
Bleeding has been a sensitive topic amongst healthcare professionals caring for patients in setting where this complication could become life threatening. Statins are reported to have anti-coagulant properties, partly due to decreasing tissue factor concentrations. Sub analysis of several statin trials have shown reduced risk for VTE (JUPITER trial) and increased risk for hemorrhagic stroke (SPRACL study). In this Italian retrospective cohort analysis of patients that underwent an elective CABG; 441 atorvastatin users were compared to patients that never used a statin. The aim of the study was to evaluate risks for postoperative bleedings, blood products use and complications during or after the by-pass procedure. Patients did not differ in pre- or intraoperative variables. Statin users were less like to experience early and overall postoperative bleeding complications, if hsCRP levels were lower on the first post-operative day. Using propensity matching the odd ratio for bleeding complications in atorvastatin users was 0.28 (P<0.01). Similar benefits were observed for use of blood products, number of transfused patients and red-packed cells used per transfused patient. As the authors state: “The preoperative use of statins in cardiac surgery as ‘bleeding-preventers’ might have profound clinical implications.” However, to scientifically validate these observations, more robust, prospective follow-up trials are needed in order to implement this as an “evidence based” recommendation. Randomizing patients to a non-statin regimen prior to the procedure would be unethical due to the very high CVD risk of the type of patients studied.
Nenna A, Lusini M, Spadaccio C et al. Preoperative atorvastatin reduces bleeding and blood products use in patients undergoing on-pump coronary artery bypass grafting. Journal of cardiovascular medicine (Hagerstown, Md.) 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28787317
 
Statin pre-loaders do better during and after elective or primary PCI
Statin pre-loading prior to PTCA has become, in most interventional centers, an integrated approach when prepping patients for their procedure. In this overview, the authors aimed to provide the readers an overview of all published trial data to date.  Overall 18 studies recruiting 7 102 patients were included in their review. For patients that were selected for an elective procedure, the ARMYDA recapture, NAPLES II, ARMYDA-RECAPTURE, ROMA and ROMA II study uniformly showed significant benefit in patients using statins. Comparing rosuvastatin with atorvastatin in the ROMA II study did no demonstrated any differences in outcomes between the two statins. For patients that underwent a primary PTCA, the Study by Chyrchel, ARMYDA-ACS, PCI-PROVE-IT, STATIN-STEMI and the studies conducted in a Korean setting by Yong and Kim, again proved that high dose atorvastatin as well as rosuvastatin were safe and protective.  High dose – high intensity statins should be used in all patients undergoing elective PCI because of stable angina as well as in NSTEMI-ACS patients. A limitation of the present evidence, as noted by the authors, is the absence of long term follow-up data. To fill in this gap in our understanding, additional RCT in the setting of PTCA should be initiated.
Lampropoulos K, Megalou A, Bazoukis G et al. Pre-loading therapy with statins in patients with angina and acute coronary syndromes undergoing PCI. J Interv Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28786142
 
Calcium scoring or simply treat everybody at intermediate or higher CVD risk
To select the patient at risk for CVD and reduce that risk to prevent him to suffer the consequences of ASCVD complications is a no brainer. But in a primary prevention setting this is slightly more challenging. Calculating risk and estimating costs benefits are discussed in this article. The authors calculated costs effectiveness of coronary artery calcium scoring (CA) with the treatment recommendations based on the 2013 ACC/AHA guidelines for long-term statin therapy. A strategy that included all patients with a 10-year CVD risk > 5% (Intermediate + high-  risk patients) and receiving a moderate intensity statin vs a strategy whereby a calcium score >100 dictated high intensity statin; 1-100 intermediate dose statin and <1 no statin. On the premise of willingness to- pay threshold of $50,000, both strategies showed comparable clinical outcomes and had similar economic consequences. The authors suggested that based on the observed results clinicians should account for individual preferences in the context of shared decision making when choosing the most appropriate strategy to guide statin initiation.
Hong JC, Blankstein R, Shaw LJ et al. Implications of Coronary Artery Calcium Testing for Treatment Decisions Among Statin Candidates According to the ACC/AHA Cholesterol Management Guidelines: A Cost-Effectiveness Analysis. JACC. Cardiovascular imaging 2017; 10:938-952. http://www.ncbi.nlm.nih.gov/pubmed/?term=28797417
 
What impact has statin use on grip strength in frail elderly patients?
Statins have gained a negative reputation with respect to muscle related problems. In this study grip strength, in frail elderly statin users, was evaluated. The authors were interested to examine what factors influence grip strength, a simple method used to objectively measure frailty.  In the study 80 patients, aged 78.6±7.0 years (68.8% women) were evaluated if cognitive function, somatic comorbidity and medical treatment affect grip strength. A multivariate linear regression analysis was applied and revealed that grip strength was positively associated with two independent measures, the Mini-Mental State Examination score (β=0.239; P=0.001) and statin use (β=0.213; P=0.002). Grip strength was not predictive of 2-year mortality in this group. Surprisingly statin use was associated with improved grip strength, this is not only related to muscle function, but also associated with better cognitive function in elderly patients. Due to the observational nature of this study the detected relationship between statin use and grip strength can only be considered as hypothesis generation and will need to be confirmed by properly designed prospective randomized clinical trial.
Dudzinska-Griszek J, Szuster K, Szewieczek J. Grip strength as a frailty diagnostic component in geriatric inpatients. Clin Interv Aging 2017; 12:1151-1157. http://www.ncbi.nlm.nih.gov/pubmed/?term=28794619
 
Do dialysis treated with a statin live longer?
The benefits of statins in end-stage renal disease patients have been refuted in two large clinical endpoint trials, the 4D study using atorvastatin and the Aurora study where the drug of choice was rosuvastatin. The SHARP study showed a trend an insignificant trend towards reducing cardiovascular events. This retrospective analysis was conducted in a single vascular center for chronic dialysis in patients where vascular access surgery was performed. Consecutive end stage renal disease patients that were admitted between 2006 and 2013 were reviewed. Primary endpoint of this study was 5-year survival. The number of patients evaluated was 359 (230 males; mean age 68,9 years (±13.7), a mean follow-up time of 35 months and 35.4% where using statins. Survival at 3 and 5 years for patients using statins was 84.4% and 75.9%; for the group not using statins: 77.0% and 65.1%; P=0.18. Using a Cox regression model the two independent predictors of death were age; OR:1.05 (1.03–1.08; P<0.0001) and statin use; OR:0.55 (0.32–0.950; P=0.032). Despite the limitations of the observational design of this study the authors pointed out there are still unanswered questions regarding the benefits of statins in end stage renal disease patients and more robust data is needed for a better understanding of the potential benefits of statins when applied to a large ESRD population in real world practice.
De Rango P, Parente B, Farchioni L et al. Effect of statins on survival in patients undergoing dialysis access for end-stage renal disease. Seminars in vascular surgery 2016; 29:198-205. http://www.ncbi.nlm.nih.gov/pubmed/?term=28779787
Relevant publications
  1. Weiss MC, Berger JS, Gianos E et al. Lipoprotein(a) screening in patients with controlled traditional risk factors undergoing percutaneous coronary intervention. J Clin Lipidol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28801030
  2. Wawruch M, Zatko D, Wimmer G, Jr. et al. Age-Related Differences in Non-Persistence with Statin Treatment in Patients after a Transient Ischaemic Attack. Clinical drug investigation 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28791591
  3. Rochlani Y, Kattoor AJ, Pothineni NV et al. Balancing Primary Prevention and Statin-Induced Diabetes Mellitus Prevention. Am J Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28797470
  4. Marazzi G, Campolongo G, Pelliccia F et al. Comparison of Low-Dose Statin Versus Low-Dose Statin + Armolipid Plus in High-Intensity Statin-Intolerant Patients With a Previous Coronary Event and Percutaneous Coronary Intervention (ADHERENCE Trial). Am J Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28781026
  5. Levy A, Berinstein E. Recent developments and future directions for the use of pharmacogenomics in cardiovascular disease treatments. Expert Opin Drug Metab Toxicol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28792790
  6. Leiter LA, Muller-Wieland D, Baccara-Dinet MT et al. Efficacy and safety of alirocumab in people with prediabetes vs those with normoglycaemia at baseline: a pooled analysis of 10 phase III ODYSSEY clinical trials. Diabetic medicine : a journal of the British Diabetic Association 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28799203
  7. Dunbar RL, Movva R, Bloedon LT et al. Oral Apolipoprotein A-I Mimetic D-4F Lowers HDL-Inflammatory Index in High-Risk Patients: A First-in-Human Multiple-Dose, Randomized Controlled Trial. Clinical and translational science 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28795506
  8. Camerino GM, Musumeci O, Conte E et al. Risk of Myopathy in Patients in Therapy with Statins: Identification of Biological Markers in a Pilot Study. Frontiers in pharmacology 2017; 8:500. http://www.ncbi.nlm.nih.gov/pubmed/?term=28798690
  9. Ye S, Kronish IM. To Persist or Not to Persist: Learning From Precision Medicine to Optimize Statin Adherence. Rev Esp Cardiol (Engl Ed) 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28779966
  10. Turrell FK, Kerr EM, Gao M et al. Lung tumors with distinct p53 mutations respond similarly to p53 targeted therapy but exhibit genotype-specific statin sensitivity. Genes & development 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28790158
  11. Siddiqui MK, Veluchamy A, Maroteau C et al. CKM Glu83Gly Is Associated With Blunted Creatine Kinase Variation, but Not With Myalgia. Circ Cardiovasc Genet 2017; 10. http://www.ncbi.nlm.nih.gov/pubmed/?term=28790154
  12. Ogura M. PCSK9 inhibition in the management of familial hypercholesterolemia. J Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28784313
  13. Maggi P, Di Biagio A, Rusconi S et al. Cardiovascular risk and dyslipidemia among persons living with HIV: a review. BMC infectious diseases 2017; 17:551. http://www.ncbi.nlm.nih.gov/pubmed/?term=28793863
  14. Ma H, Liu Y, Xie H et al. The renoprotective effects of simvastatin and atorvastatin in patients with acute coronary syndrome undergoing percutaneous coronary intervention: An observational study. Medicine (Baltimore) 2017; 96:e7351. http://www.ncbi.nlm.nih.gov/pubmed/?term=28796030
  15. Cheng J, Ukwatta E, Shavakh S et al. Sensitive three-dimensional ultrasound assessment of carotid atherosclerosis by weighted average of local vessel wall and plaque thickness change. Medical physics 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28782187
  16. Cancienne JM, Brockmeier SF, Rodeo SA, Werner BC. Perioperative Serum Lipid Status and Statin Use Affect the Revision Surgery Rate After Arthroscopic Rotator Cuff Repair. Am J Sports Med 2017:363546517717686. http://www.ncbi.nlm.nih.gov/pubmed/?term=28787187
  17. Campitelli MA, Maxwell CJ, Giannakeas V et al. The Variation of Statin Use Among Nursing Home Residents and Physicians: A Cross-Sectional Analysis. J Am Geriatr Soc 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28791683
  18. Ballard AY, Kessler M, Scheitel M et al. Exploring differences in the use of the statin choice decision aid and diabetes medication choice decision aid in primary care. BMC medical informatics and decision making 2017; 17:118. http://www.ncbi.nlm.nih.gov/pubmed/?term=28797295
Miscellaneous publications
  1. axKim ML, Sung KR, Shin JA et al. Statins reduce TGF-beta2-modulation of the extracellular matrix in cultured astrocytes of the human optic nerve head. Experimental eye research 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28789942
  2. Caparros-Martin JA, Lareu RR, Ramsay JP et al. Statin therapy causes gut dysbiosis in mice through a PXR-dependent mechanism. Microbiome 2017; 5:95. http://www.ncbi.nlm.nih.gov/pubmed/?term=28793934
  3. Ziegler V, Henninger C, Simiantonakis I et al. Rho inhibition by lovastatin affects apoptosis and DSB repair of primary human lung cells in vitro and lung tissue in vivo following fractionated irradiation. Cell death & disease 2017; 8:e2978. http://www.ncbi.nlm.nih.gov/pubmed/?term=28796249
  4. Wang Y, Zhang L, Zhao X et al. An experimental study of the protective effect of simvastatin on sepsis-induced myocardial depression in rats. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2017; 94:705-711. http://www.ncbi.nlm.nih.gov/pubmed/?term=28800541
  5. Perez-Sanchez A, Uribe-Carvajal S, Cabrera-Orefice A, Barrios-Gonzalez J. Key role of alternative oxidase in lovastatin solid-state fermentation. Applied microbiology and biotechnology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28791446
  6. Alahmad S, Elfatatry HM, Mabrouk MM et al. Development and Validation of Chemometric Spectrophotometric Methods for Simultaneous Determination of Simvastatin and Nicotinic Acid in Binary Combinations. Curr Drug Discov Technol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28799486
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