up-to-date with a click!
Update week 2  (January 8 -  January 15  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

New onset diabetes with statins, caused by the drug or cholesterol reduction?
In this meta-analysis of 8 large randomized controlled trials the percentage LDL-C reduction predicted the new onset of diabetes. Reductions of 30% - 40% and 40% - 50%   of respectively 13% (OR = 1.13; 95% CI 1.01-1.26) and 29% (OR = 1.29; 95% CI 1.13-1.47). Overall patient using a statin had an increased risk of 11% (OR = 1.11; 95% CI 1.03-1.20). The group that used intensive LDL-C lowering statins had an 18% increase in the likelihood of developing diabetes (OR = 1.18; 95% CI, 1.10-1.28). The authors concluded that LDL-c reduction is the most appropriate parameter related to new onset of diabetes and that all patients with LDL-C reductions > 30% should be monitored on a regular basis
Wang S, Cai R, Yuan Y et al. Association between reductions in low-density lipoprotein cholesterol with statin therapy and the risk of new-onset diabetes: a meta-analysis. Scientific reports 2017; 7:39982. http://www.ncbi.nlm.nih.gov/pubmed/?term=28071756
Reduced platelet reactivity and vitamin D increase after switch to a high intensity statins dosage
Exploring the pleiotropic effects of statins was the aim of this cross sectional observational study. In total 246 Italian CHD patients were analyzed 30 - 90 days after PCI and/or ACS event. There were 142 patients discharged on a new statin or switched to a high intensity statin dosage (Atorvastatin ≥ 20 mg; Rosuvastatin ≥10 mg or Simvastatin ≥40 mg) ; 104 patients remained on the high intensity statin they were using. Vitamin D plasma concentration increased and platelet agreeability decreased only in patients that were up titrated. Plasma calcium concentrations increased and LDL-cholesterol decreased. There was a linear relationship between the Vitamin D increase and LDL-C decrease. No difference in anti-platelet medication between the two groups and patients that increased the satins dosage were at higher risk (older, ↑diabetics, ↑hypertensives, ↑hypercholesterolemics, ↑ACS patients; less patients using anti-hypertensive medication and nitrates). Authors suggest that the pleiotropic benefits of statins could be (partely) related to the both increase of vitamin D lower platelet reactivity.
Verdoia M, Pergolini P, Rolla R et al. Impact of high-dose statins on vitamin D levels and platelet function in patients with coronary artery disease. Thrombosis research 2016; 150:90-95. http://www.ncbi.nlm.nih.gov/pubmed/?term=28068529
How your diabetic patients with CAD + leg amputation can get a 90% MACE reduction in 1 year!
Diabetic patients with CAD and PAD have a very high risk for recurrent events and death. In 2013, 179 diabetic patients with CAD and leg amputation were followed for 1 year. The intervention was a combination of Lifestyle advice (healthy diet, stop smoking and >30 min/day of physical activity) and the combination of statins, anti-hypertensives, anti-diabetic medication and dual anti platelets drugs. Of the 77 (44%) compliant patients (> 80% of prescribed pill count) 3 patients suffered an AMI vs 40 pts in the non-compliant group. Two patients died vs 26 deaths in the con-compliant group. The worse outcomes were observed in patients with extensive CAD, two- and three-vessel disease as compared to the ones with one-vessel disease or no obstructions. The one year MACE rate in these patients were: 95.24%, 70.5%, 17.2% and 8.6% respectively. Significant changes were already observed 10 days (!) post-surgery; deaths: 10(9.8%) vs 0 and AMI: 16 (15.6%) vs 3 (3.9%). Compliance to simple lifestyle and guideline dictated medication is pivotal when aiming to reduce events or death in very high risk patients.
Shalaeva EV, Saner H, Janabaev BB, Shalaeva AV. Tenfold risk increase of major cardiovascular events after high limb amputation with non-compliance for secondary prevention measures. Eur J Prev Cardiol 2017:2047487316687103. http://www.ncbi.nlm.nih.gov/pubmed/?term=28071959
Using internet postings as a pharmacovigilance tool for statins side effects
Using an internet site dedicated to share experiences with drugs, investigators examined the robustness of the published data for pharmacovigilance. This retrospective cross-sectional study collected public available date on a single day in 2012. They scored 96 narratives on adverse drug reactions (ADR’s) for statins on 16 key criteria. The 72 patients (40 women, 32 men mean age 59 years) reported 176 ADR’s. Most frequent reports reflected on musculoskeletal problems (42.6%) and nervous system disorders (15.3%). Only 2 patients (3%) reported ADR’s that could be considered serious: hospitalization and visit to emergency room. Changing or stopping their lipid lowering medication was reported by 24 patients (33%). On average 6/16, key elements were available per narrative, most frequently lacking were medical history (87%) and concomitant medication (86%). The authors conclude that Internet posts are an important and valuable source for surveying patient reported ADR’s, however the information should be interpreted cautiously and further assessed for relevance by using a post-marketing surveillance approach.
Deshpande S, Quek RG, Forbes CA et al. A systematic review to assess the adherence and persistence with statins. Current medical research and opinion 2017:1-23. http://www.ncbi.nlm.nih.gov/pubmed/?term=28076703
Should you prescribe statins to patients with renal disease?
Patients with early stages of chronic kidney disease (CKD) showed better outcomes when using statins but in advanced disease (eGFR <30ml/min/1.73 m2) this was not the case. This Korean retrospective analysis (2003 – 2013) using data from a single hospital, analyzed 14 497 CKD patients; 1 955 patients (13.5%) used statins; 858 statin users, were paired with non-users after which a propensity score matching was implemented. Overall only the patients with eGFR>30/min/1.73 m2 showed superior outcomes.  A delay of serum Creatinine doubling (HR, 0.824; 95% CI, 0.722±0.939; P = 0.004) was observed in the unmatched cohort (independent of eGFR!) but not in the matched cohort. The Incidence of creatinine doubling was less both the unmatched (HR,0.744; 95% CI, 0.635±0.873; P < 0.001) and matched (HR, 0.767; 95% CI, 0.596±0.986; P = 0.039) cohorts. Risk of dying was reduced in both the unmatched (HR, 0.518; 95% CI, 0.365±0.734; P < 0.001 and matched (HR, 0.457; 95% CI, 0.214±0.979; P = 0.044) cohorts as well. In the patients with an eGFR <30 mL/min/1.73 m2. No mortality benefits due to statins could be determined. The authors concluded that initiation of statins in patients with early CKD may provide protection, however randomized controlled clinical trials are needed to furnish the final proof.
Cho EY, Myoung C, Park HS et al. Efficacy of Statin Treatment in Early-Stage Chronic Kidney Disease. PLoS One 2017; 12:e0170017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28081262
Predicting recurrent events in SPARCLE study using Oxidized-Phospholipids on apo-B
Improving CVD risk prediction by measuring OxPL –apoB showed promise. Patients in the randomized controlled clinical outcome trial SPARCLE, suffered from prior cerebrovascular events. The study showed that Atorvastatin 80 mg protects against stroke recurrence and coronary events. In this retrospective subgroup analysis, patients with elevated plasma levels of Ox-PL-apoB (highest quartile), were at much higher risk for recurrent stroke (HR: 4.3; p < 0.0001), first major coronary events (HR: 4.0; p < 0.0001), and any cardiovascular event (HR: 4.4; p < 0.0001). At baseline, there was no difference in OxPL concentrations between patients randomized to Atorvastatin or placebo. However, Patients experiencing a stroke recurrence had higher baseline levels. Median: 15.5 nmol/l (interquartile range [IQR]: 11.0 to 21.3 nmol/l) versus 11.6 nmol/l (IQR: 6.3 to 18.2 nmol/l), p < 0.0001. Baseline levels in patients with diabetes were elevated as well compared to those without DM (mean 13.1 nmol/l [IQR: 7.3 to 19.0 nmol/l] vs. 12.0 nmol/l [IQR: 6.6 to 18.6 nmol/l]; p = 0.0389). Taking Atorvastatin did not influence the outcomes. Lp(a) is the particle associated with OxPL, they carry >85% of all lipoprotein associated OxPL. Statins are known to not only increase Lp(a) (±10%) but OxPL-apoB (±24%) as well. Although in SPARCL OxPL-Apob declined in both treatment arms, this could reflect the acute phase response after the stroke that tapered off after 6-8 months. Unfortunately, Lp(a) was not measured in SPARCL and OxPL-apoB was only measured at baseline and at study completion. The Authors concluded that OxPL-apoB levels are an independent and clinically informative biomarker in predicting cerebrovascular events in post stroke patients and further research could reveal potentially novel biological pathways and disover new modalities to target OxPL directly to reduce risk.
Byun YS, Yang X, Bao W et al. Oxidized Phospholipids on Apolipoprotein B-100 and Recurrent Ischemic Events Following Stroke or Transient Ischemic Attack. J Am Coll Cardiol 2017; 69:147-158. http://www.ncbi.nlm.nih.gov/pubmed/?term=28081824 Feske SK. A New Treatable Risk Factor for Stroke and Atherosclerotic Cardiovascular Disease? J Am Coll Cardiol 2017; 69:159-161. http://www.ncbi.nlm.nih.gov/pubmed/?term=28081825

Relevant publications
  1. Zhang W, Ji F, Yu X, Wang X. Factors associated with unattained LDL-cholesterol goals in Chinese patients with acute coronary syndrome one year after percutaneous coronary intervention. Medicine (Baltimore) 2017; 96:e5469. http://www.ncbi.nlm.nih.gov/pubmed/?term=28072688
  2. Calcagno S, Stio RE, Mancone M et al. The statin therapy to prevent atrial fibrillation after cardiac surgery: Shakespearean dilemma. J Thorac Dis 2016; 8:2986-2990. http://www.ncbi.nlm.nih.gov/pubmed/?term=28066564
  3. Vogt A. [PCSK9 inhibitors : Current clinical relevance]. Internist (Berl) 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28083599
  4. Sridharan K, Sivaramakrishnan G. Periodic dosing regimens of atorvastatin and rosuvastatin for dyslipidemia: A systematic review and meta-analysis of randomized controlled trials. Eur J Intern Med 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28063659
  5. Qiu Y, Wu Y, Meng M et al. Rosuvastatin improves myocardial and neurological outcomes after asphyxial cardiac arrest and cardiopulmonary resuscitation in rats. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2017; 87:503-508. http://www.ncbi.nlm.nih.gov/pubmed/?term=28076830
  6. O'Keefe JH, DiNicolantonio JJ, Lavie CJ. Statins, Ezetimibe, and Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors to Reduce Low-Density Lipoprotein Cholesterol and Cardiovascular Events. Am J Cardiol 2016. http://www.ncbi.nlm.nih.gov/pubmed/?term=28081940
  7. Kwon OC, Hong S, Ghang B et al. Risk of Colchicine-Associated Myopathy in Gout: Influence of Concomitant Use of Statin. Am J Med 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28065770
  8. Galyfos G, Sianou A, Filis K. Pleiotropic effects of statins in the perioperative setting. Annals of cardiac anaesthesia 2017; 20:S43-s48. http://www.ncbi.nlm.nih.gov/pubmed/?term=28074822
  9. Eisen A, Cannon CP, Braunwald E et al. Predictors of Nonuse of a High-Potency Statin After an Acute Coronary Syndrome: Insights From the Stabilization of Plaques Using Darapladib-Thrombolysis in Myocardial Infarction 52 (SOLID-TIMI 52) Trial. J Am Heart Assoc 2017; 6. http://www.ncbi.nlm.nih.gov/pubmed/?term=28077384
  10. Chung YR, Park SW, Choi SY et al. Association of statin use and hypertriglyceridemia with diabetic macular edema in patients with type 2 diabetes and diabetic retinopathy. Cardiovascular diabetology 2017; 16:4. http://www.ncbi.nlm.nih.gov/pubmed/?term=28061854
  11. Caffrey AR, Timbrook TT, Noh E et al. Evidence to support continuation of statin therapy in patients with Staphylococcus aureus bacteremia. Antimicrobial agents and chemotherapy 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28069650
  12. Bosomworth NJ. Statin Therapy as Primary Prevention in Exercising Adults: Best Evidence for Avoiding Myalgia. Journal of the American Board of Family Medicine : JABFM 2016; 29:727-740. http://www.ncbi.nlm.nih.gov/pubmed/?term=28076256
  13. Arrieta A, Page TF, Veledar E, Nasir K. Economic Evaluation of PCSK9 Inhibitors in Reducing Cardiovascular Risk from Health System and Private Payer Perspectives. PLoS One 2017; 12:e0169761. http://www.ncbi.nlm.nih.gov/pubmed/?term=28081164
  14. Vonbank A, Agewall S, Kjeldsen KP et al. Comprehensive efforts to increase adherence to statin therapy. Eur Heart J 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28077470
  15. Tournadre A, Pereira B, Dubost JJ et al. Management of dyslipidemia in high-risk patients with recent-onset rheumatoid arthritis: targets still not met despite specific recommendations. Results from the ESPOIR cohort during the first five years of follow-up. Clinical and experimental rheumatology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28079508
  16. Tonstad S. [Statin intolerance]. Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke 2017; 137:36-38. http://www.ncbi.nlm.nih.gov/pubmed/?term=28073228
  17. Spagnuolo V, Galli L, Poli A et al. Associations of statins and antiretroviral drugs with the onset of type 2 diabetes among HIV-1-infected patients. BMC infectious diseases 2017; 17:43. http://www.ncbi.nlm.nih.gov/pubmed/?term=28061820
  18. Sodi R, Eastwood J, Caslake M et al. Relationship between circulating microRNA-30c with total- and LDL-cholesterol, their circulatory transportation and effect of statins. Clinica chimica acta; international journal of clinical chemistry 2017; 466:13-19. http://www.ncbi.nlm.nih.gov/pubmed/?term=28062296
  19. Park JH, Choi BH, Ku SK et al. Amelioration of high fat diet-induced nephropathy by cilostazol and rosuvastatin. Archives of pharmacal research 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28084586
  20. Park DB, Jang K, Lee JW et al. Pharmacokinetic and bioequivalence study comparing a candesartan cilexetil/rosuvastatin calcium fixed-dose combination with the concomitant administration of candesartan cilexetil and rosuvastatin calcium in healthy Korean subjects. International journal of clinical pharmacology and therapeutics 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28079517
  21. Ou HT, Chang KC, Li CY et al. Intensive statin regimens for reducing risk of cardiovascular diseases among human immunodeficiency virus-infected population: A nation-wide longitudinal cohort study 2000-2011. Int J Cardiol 2016. http://www.ncbi.nlm.nih.gov/pubmed/?term=28062146
  22. Last AR, Ference JD, Menzel ER. Hyperlipidemia: Drugs for Cardiovascular Risk Reduction in Adults. American family physician 2017; 95:78-87. http://www.ncbi.nlm.nih.gov/pubmed/?term=28084704
  23. Kheloufi F, Default A, Blin O, Micallef J. Investigating patient narratives posted on Internet and their informativeness level for pharmacovigilance purpose: The example of comments about statins. Therapie 2016. http://www.ncbi.nlm.nih.gov/pubmed/?term=28065444
  24. He Y, Huang H, Farischon C et al. Combined effects of atorvastatin and aspirin on growth and apoptosis in human prostate cancer cells. Oncology reports 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28075470
  25. Garattini L, Padula A. Cholesterol-lowering drugs: Science and marketing. Journal of the Royal Society of Medicine 2016:141076816681951. http://www.ncbi.nlm.nih.gov/pubmed/?term=28084157
  26. Ferket BS, Hunink MG, Khanji M et al. Cost-effectiveness of the polypill versus risk assessment for prevention of cardiovascular disease. Heart 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28077465
  27. Djebli N, Martinez JM, Lohan L et al. Target-Mediated Drug Disposition Population Pharmacokinetics Model of Alirocumab in Healthy Volunteers and Patients: Pooled Analysis of Randomized Phase I/II/III Studies. Clinical pharmacokinetics 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28063030
  28. Alkhail BA, Iftikhar R, Shaikh AA. Use of Aspirin and Statin as primary prevention for cardiovascular diseases. Pak J Med Sci 2016; 32:1336-1339. http://www.ncbi.nlm.nih.gov/pubmed/?term=28083021

Miscellaneous publications
  1. Sadat Pajohanfar N, Mohebbi E, Rad A et al. Protective effects of atorvastatin against morphine-induced tolerance and dependence in mice. Brain Res 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28062186
  2. Rodriguez S, Raurell I, Torres-Arauz M et al. A Nitric Oxide-Donating Statin Decreases Portal Pressure with a Better Toxicity Profile than Conventional Statins in Cirrhotic Rats. Scientific reports 2017; 7:40461. http://www.ncbi.nlm.nih.gov/pubmed/?term=28084470
  3. Medeiros VF, Azevedo IM, Carvalho MD et al. Effects of cococonut water and simvastatin in the treatment of sepsis and hemorrhagic shock in rats. Acta Cir Bras 2016; 31:826-833. http://www.ncbi.nlm.nih.gov/pubmed/?term=28076507
  4. Ferretti G, Bacchetti T, Banach M et al. Impact of Statin Therapy on Plasma MMP-3, MMP-9, and TIMP-1 Concentrations. Angiology 2016:3319716688301. http://www.ncbi.nlm.nih.gov/pubmed/?term=28068800
  5. Blanquiceth Y, Rodriguez-Perea AL, Tabares Guevara JH et al. Increase of Frequency and Modulation of Phenotype of Regulatory T Cells by Atorvastatin Is Associated with Decreased Lung Inflammatory Cell Infiltration in a Murine Model of Acute Allergic Asthma. Frontiers in immunology 2016; 7:620. http://www.ncbi.nlm.nih.gov/pubmed/?term=28066430
  6. Beg MS, Gupta A, Sher D et al. Impact of Concurrent Medication Use on Pancreatic Cancer Survival-SEER-Medicare Analysis. American journal of clinical oncology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28079594
  7. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Recommendation Statement. American family physician 2017; 95:Online. http://www.ncbi.nlm.nih.gov/pubmed/?term=28084711
  8. Yim CS, Jeong YS, Lee SY et al. Specific Inhibition of the Distribution of Lobeglitazone to the Liver by Atorvastatin in Rats: Evidence for an rOATP1B2-Mediated Interaction in Hepatic Transport. Drug metabolism and disposition: the biological fate of chemicals 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28069721

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