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Update - Week 18, 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

Update from the SHARP study on non-vascular adverse events
The SHARP study evaluated the effects of reducing LDL-cholesterol, simvastatin 20 mg + ezetimibe 10 mg on CVD events in patients with chronic kidney disease. Although no evidence of excess deaths due to non-CVD causes was observed there are indications that harmful and/or beneficial effects. During the 4.9 years follow-up, there was a similar number of reported non-vascular serious adverse events. In the treatment group 3551 (76.4%) of the participants vs 3537 76.6% in the control group; RR 0.99 (95% CI 0.95-1.04). No effects on any of the 43 non-CVD outcomes, except for 3, showed a statistical significant difference with a P-value <0.05 (the smallest value p<0.02). For a more reliable assessment of nonvascular effects large-scale meta-analyses, such as those by the Cholesterol Treatment Trialists Collaboration are needed. The authors conclude that the use of simvastatin + ezetimibe in SHARP was not associated with any significant non-vascular hazard.
Reith C, Staplin N, Herrington WG et al. Effect on non-vascular outcomes of lowering LDL cholesterol in patients with chronic kidney disease: results from the Study of Heart and Renal Protection. BMC Nephrol 2017; 18:147. http://www.ncbi.nlm.nih.gov/pubmed/?term=28460629
 
What impact did the ACC/AHA guidelines have on initiating high intensity statins?
The ACC/AHA cholesterol management guidelines were released in November 2013. For a retrospective observational analysis an administrative medical and pharmacy claims data registry was used. The authors examined the prescription pattern for patients newly initiated on a high intensity statin (IHIS),  4 quarters prior, and 8 quarters after the release of the guidelines. The patients were divided in 4 statin benefits groups (SBG): SBG1 (with ASCVD; N=1046/quarter), SBG2 (without ASCVD, with LDLC-C ≥190 mg/dL; N=454/quarter), SBG3 (without ASCVD, aged 40–75 years, with diabetes mellitus, LDL-C 70–189 mg/dL; N=1391/quarter), SBG4 (no ASCVD or diabetes mellitus, age 40–75 years, LDL-C 70–189 mg/dL and an estimated 10-year ASCVD risk of ≥7.5%; N=705/quarter). For SBG1 participants the use of HIS increased from 19.4% per quarter prior to the guideline release, to 23.6% in the first year’s quarters and 31.1% in the second year. In SBG2 participants the use of HIS increased from 14.8% per quarter prior to the guideline release to 17.1% in the first year’s quarters and 19.0 % in the second year. The participants of SBG3 increased the use of HIS from 10.8% per quarter prior to the guideline release, to 14.8% in the first year’s quarters and 15.8% in the second year. For SBG4 participants the use of HIS + MIS combined increased from 80.3% per quarter prior to the guideline release, to 83.5% in the first year’s quarters and 85.0% in the second year. The authors concluded that initiation of high intensity statins gradually increased in SBG1, 2 and 3. In SBG 4 this was observed for moderate- and high intensity statin initiation. That patients in specialist care were more like to receive a high intensity statin. Women were least likely to start an appropriate statin before and after the release of the ACC/AHA guidelines.
Olufade T, Zhou S, Anzalone D et al. Initiation Patterns of Statins in the 2 Years After Release of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Cholesterol Management Guideline in a Large US Health Plan. J Am Heart Assoc 2017; 6. http://www.ncbi.nlm.nih.gov/pubmed/?term=28473405
 
Statin persistence after 1 year extremely poor in male Spanish workers
Using data collected in the prospective longitudinal Aragon Workers’ Health Study (N = 5400), statin persistence for primary cardiovascular disease prevention was assessed after 1 year. The prevalence of CVD risk factors was high but there was a low prevalence of CVD in these male Spanish workers. Statins were started in 725 patients, but after 1 year <1/3 were still using a statin. Of the patients that stopped statins, 15% did so after the 1st prescription. Of these almost half (42.1%) did not re-initiate statins in the next 12 months. Older patients and patients that were using anti-hypertensive medication were less likely to stop statins; HR 0.55 (95%CI:  0.39-0.77) and HR: 0.68 (95%CI, 0.56-0.82) respectively. No such effects were observed in patients using antidiabetic or antithrombotic drugs or baseline LDL-C levels/total cholesterol levels. The statins most prescribed were simvastatin 40.4%, atorvastatin 24.7% and rosuvastatin 24.4%; Simvastatin users were least likely to top statins. The authors concluded that based on this, and similar observational studies that showed comparable results, statin adherence remains an important challenge  and more research efforts are needed in how to address this treatment gap.
Malo S, Aguilar-Palacio I, Feja C et al. Persistence With Statins in Primary Prevention of Cardiovascular Disease: Findings From a Cohort of Spanish Workers. Rev Esp Cardiol (Engl Ed) 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28473266
 
US Guideline recommendations for statins and clinical practice show a substantial gap
Did the 2013 ACC/AHA guidelines have an impact on high intensity statin prescriptions in secondary prevention patients. Patients with CVD were selected from a US commercial health plans claims data registry (January 2006 to June 2014). In this retrospective observational study 273,308 patients with ASCVD were included.  Only 38% of the 273,308 patients with ASCVD initiated statin therapy in this study, and high-intensity statins were started in 8.8% (N = 24,106) of the total population. Patient adherence (defined as proportion of days covered ≥80%) to statin therapy was 27.0% and 26.4% in the high-intensity statin and low-/moderate-intensity statin cohorts respectively. Ischemic strokes occurred in 25.3% of patients who did not use statins versus 16.9% in low-/moderate-intensity statin users, and 8.8% in high intensity. Baseline LDL-C levels  were comparable across the cohorts. Males and recent ACS patients were more likely and post ischemic stroke patients were less likely to receive high-intensity statins. Approximately 16% of the patients in either of the matched cohorts had at least 1 CV event during the available follow-up period. These lack of improved outcomes could be a reflection of the overall poor adherence to treatment and the likelihood that patients who were prescribed high-intensity statins by their cardiologist had greater overall disease risks. There remains an impressive gap between guideline recommendations and the use of the appropriate statins in clinical practice practical and closing this gap could result in significant MACE reductions.
Huang Q, Grabner M, Sanchez RJ et al. Clinical Characteristics and Unmet Need Among Patients with Atherosclerotic Cardiovascular Disease Stratified by Statin Use. American health & drug benefits 2016; 9:434-444. http://www.ncbi.nlm.nih.gov/pubmed/?term=28465771
 
Cardiologist convinced high-intensity dose statins are better but fail to implement
Enforcing guidelines requires knowledge of and actively implementing the recommendations in daily clinical practice. In this study both issues were evaluated by a questionnaire and retrospective chart reviews in a large mid-western University health care system. Patients that had a consultation with a cardiologist or CV nurse in 2015 were selected for this evaluation. Subjects were randomly selected and queried. Overall healthcare providers strongly believed that high-intensity statins will reduce secondary cardiovascular events and showed a strong self-reported intention to prescribe high intensity statins. However high intensity dose statins were prescribed in 2/3 of the eligible patients; 24% used a moderate intensity dose statin; 4% a low-intensity dose statin and 5% did not use any statin. In 4.7% a non-statin lipid lowering treatment was prescribed as well. Patients with non-STEMI (79.4%) were more likely to receive high-intensity dose statin vs STEMI (60.5%). Conversely no statin was observed in 3.8% of the non-STEMI vs 7.4% in the STEMI patients. In unstable angina patients, high-intensity dose statin were used by 69.4%; no statin in 3.1%. The authors concluded that more studies are needed to identify healthcare provider barriers that may contribute to the disparity between intention to prescribe and actual prescribing behaviors of high-intensity dose statins for patients with CAD.
Housholder-Hughes SD, Martin MM, McFarland MR et al. Healthcare provider compliance with the 2013 ACC/AHA Adult Cholesterol Guideline recommendation for high-intensity dose statins for patients with coronary artery disease. Heart & lung : the journal of critical care 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28460888

Relevant publications
  1. Berger JS, Ladapo JA. Underuse of Prevention and Lifestyle Counseling in Patients With Peripheral Artery Disease. J Am Coll Cardiol 2017; 69:2293-2300. http://www.ncbi.nlm.nih.gov/pubmed/?term=28473134
  2. Hiatt WR, Rogers RK. The Treatment Gap in Peripheral Artery Disease. J Am Coll Cardiol 2017; 69:2301-2303. http://www.ncbi.nlm.nih.gov/pubmed/?term=28473135
  3. Yousef Yengej FA, Limper M, Leavis HL. Statins for prevention of cardiovascular disease in systemic lupus erythematosus. The Netherlands journal of medicine 2017; 75:99-105. http://www.ncbi.nlm.nih.gov/pubmed/?term=28469051
  4. Umeh G, Huffman MD. Challenges and opportunities in accessing trial data: an example from statin primary prevention trials. Heart Asia 2017; 9:99-101. http://www.ncbi.nlm.nih.gov/pubmed/?term=28469714
  5. Rosenson RS, Gandra SR, McKendrick J et al. Identification and Management of Statin-Associated Symptoms in Clinical Practice: Extension of a Clinician Survey to 12 Further Countries. Cardiovasc Drugs Ther 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28466399
  6. Heydari B, Khalili H, Beigmohammadi MT et al. Effects of atorvastatin on biomarkers of acute kidney injury in amikacin recipients: A pilot, randomized, placebo-controlled, clinical trial. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences 2017; 22:39. http://www.ncbi.nlm.nih.gov/pubmed/?term=28465698
  7. Vangala C, Lenihan CR, Montez-Rath ME et al. Statin use and hip fractures in U.S. kidney transplant recipients. BMC Nephrol 2017; 18:145. http://www.ncbi.nlm.nih.gov/pubmed/?term=28460645
  8. Thakkar D, Dash RP. Pharmacokinetic interactions between glimepiride and rosuvastatin in healthy Korean subjects: does the SLCO1B1 or CYP2C9 genetic polymorphism affect these drug interactions? Observations and introspection of the bioanalysis. Drug design, development and therapy 2017; 11:1263-1265. http://www.ncbi.nlm.nih.gov/pubmed/?term=28461740
  9. Sweidan AJ, Leung A, Kaiser CJ et al. A Case of Statin-Associated Autoimmune Myopathy. Clinical medicine insights. Case reports 2017; 10:1179547616688231. http://www.ncbi.nlm.nih.gov/pubmed/?term=28469499
  10. Landray MJ, Reveal Collaborative G. Randomized Evaluation of the Effects of Anacetrapib through Lipid-modification (REVEAL)-A large-scale, randomized, placebo-controlled trial of the clinical effects of anacetrapib among people with established vascular disease: Trial design, recruitment, and baseline characteristics. Am Heart J 2017; 187:182-190. http://www.ncbi.nlm.nih.gov/pubmed/?term=28454801
  11. Hellberg S, Sippola S, Liljenback H et al. Effects of atorvastatin and diet interventions on atherosclerotic plaque inflammation and [18F]FDG uptake in Ldlr-/-Apob100/100 mice. Atherosclerosis 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28457625
  12. Hawkes N. Patients told about muscle pain are more likely to report it, statin study finds. Bmj 2017; 357:j2144. http://www.ncbi.nlm.nih.gov/pubmed/?term=28468751
  13. Freedman DM, Pfeiffer RM. Ascertainment Bias in Statin Use and Alzheimer Disease Incidence. JAMA neurology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28459949
  14. Finsterer J, Frank M. Management of statin myopathy. Journal of cachexia, sarcopenia and muscle 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28466578
  15. Eslami SM, Nikfar S, Ghasemi M, Abdollahi M. Does Evolocumab, as a PCSK9 Inhibitor, Ameliorate the Lipid Profile in Familial Hypercholesterolemia Patients? A Meta-Analysis of Randomized Controlled Trials. Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques 2017; 20:81-96. http://www.ncbi.nlm.nih.gov/pubmed/?term=28459663
  16. Deska P, Nowicki M. Short-term changes of serum potassium concentration induced by physical exercise in patient with arterial hypertension treated with angiotensin-converting enzyme inhibitor alone or in combination with statin. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 2017; 68:133-138. http://www.ncbi.nlm.nih.gov/pubmed/?term=28456777
  17. Chen M, Lu J, Chen Q et al. [Statin in the treatment of ALI/ARDS: a systematic review and Meta-analysis based on international databases]. Zhonghua wei zhong bing ji jiu yi xue 2017; 29:51-56. http://www.ncbi.nlm.nih.gov/pubmed/?term=28459404
  18. Brosnahan G, Abebe KZ, Rahbari-Oskoui FF et al. Effect of statin therapy on the progression of autosomal dominant polycystic kidney disease. A secondary analysis of the HALT PKD trials. Current hypertension reviews 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28460625

Miscellaneous publications
  1. Yang Z, Su Z, DeWitt JP et al. Fluvastatin Prevents Lung Adenocarcinoma Bone Metastasis by Triggering Autophagy. EBioMedicine 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28454732
  2. Yamashita S, Hasegawa T, Tachihara M et al. Quantitative Analysis of the Transporter Mediated drug-drug Interaction Between Atorvastatin and Rifampicin using a Stable Isotope-IV Method. Journal of pharmaceutical sciences 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28457720
  3. Walker ME, Souza PR, Colas RA, Dalli J. 13-series resolvins mediate the leukocyte-platelet actions of atorvastatin and pravastatin in inflammatory arthritis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28465323
  4. MacDougall DA, Pugh SD, Bassi HS et al. Simvastatin Promotes Cardiac Myocyte Relaxation in Association with Phosphorylation of Troponin I. Frontiers in pharmacology 2017; 8:203. http://www.ncbi.nlm.nih.gov/pubmed/?term=28469574
  5. Kim EK, Cho JH, Jeong AR et al. Anti-inflammatory effects of simvastatin in nonsteroidal anti-inflammatory drugs-induced small bowel injury. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 2017; 68:69-77. http://www.ncbi.nlm.nih.gov/pubmed/?term=28456771
  6. Desai P, Helkin A, Odugbesi A et al. Fluvastatin inhibits intimal hyperplasia in wild-type but not Thbs1-null mice. J Surg Res 2017; 210:1-7. http://www.ncbi.nlm.nih.gov/pubmed/?term=28457315
  7. Chowdhury K, Sharma A, Sharma T et al. Simvastatin and MBCD Inhibit Breast Cancer-Induced Osteoclast Activity by Targeting Osteoclastogenic Factors. Cancer investigation 2017:1-11. http://www.ncbi.nlm.nih.gov/pubmed/?term=28463564
  8. Choi SY, Park JS, Roh MS et al. Inhibition of Angiotensin II-Induced Cardiac Fibrosis by Atorvastatin in Adiponectin Knockout Mice. Lipids 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28474247
  9. Yoshikado T, Toshimoto K, Nakada T et al. Comparison of methods for estimating unbound intracellular-to-medium concentration ratios in rat and human hepatocytes using statins. Drug metabolism and disposition: the biological fate of chemicals 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28468836
  10. Shilpi D, Kushwah V, Agrawal AK, Jain S. Improved Stability and Enhanced Oral Bioavailability of Atorvastatin Loaded Stearic Acid Modified Gelatin Nanoparticles. Pharm Res 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28466393

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