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Update - Week 16, 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

The importance of statins in CKD patients with CAD
The impact of statin use in Chinese patients with stage 3-4 chronic kidney disease (CKD) + CAD (N=128) versus the ones with stage 3-4 CKD only (N=126), was evaluated using patient records from a single hospital. Patients were admitted to the hospital between December 2010 and 2012 and followed for a maximum of 4 years. The impact of CKD + CAD in patients without statins was impressive: MACE: 66.1%, death: 38.7%, cardiac death: 33.8%. Patient using statins had significant improved outcomes resulting in a 22% reduction in MACE (p=0.012) and 28% lower total mortality. Cardiovascular events 29/66 (43.9%) vs 41/62 (66.1%) P= 0.012; All-cause mortality 7/66 (10.6%) vs 24/62 (38.7%) P< 0.001 and Cardiac death 5/66(7.5%) 21/62 (33.8%) P< 0.001 for statin vs no statin users respectively. In CKD patients without CAD statins showed improved trends for mortality and CVD mortality but these were not statistical significant. The relatively small number of participants and limited follow up should be noted in this context. The authors highlight the surprising finding of extremely elevated risk in CKD patients with CAD as well as the striking protective effects of statins warrant larger and properly powered studies to confirm these preliminary findings.
Shen H, Chen X, Lu J et al. Effects of statin therapy on chronic kidney disease patients with coronary artery disease. Lipids Health Dis 2018; 17:84. http://www.ncbi.nlm.nih.gov/pubmed/?term=29665812
 
Effects of rosuvastatin + telmisartan in a single tablet
TELmisartan-rosuvaSTAtinfromYUhan (TELSTA-YU) study was set up to determine if a combination of rosuvastatin 20 mg and telmisartan 80 would be as efficacious and safe as mono-therapy rosuvastatin and telmisartan. The study conducted in 210 Korean patients with combined hypertension and dyslipidemia. Designed as an 8-week randomized double-blind phase III study, patients were allocated a fixed dose combination (FDC) - (N=84), telmisartan 80 mg (N=43), rosuvastatin 20 mg (N=42) or placebo (N=41). The FDC group showed bioequivalent results on BP and LDL-c when compared to co-administration of separate tablets. BP goal achievement (JNC VII guidelines) was achieved in 60.0% in FDC group, 65.1% in telmisartan group, 45% in rosuvastatin group and 30% in the placebo group. The LDL-c goal was reached in 88.8% of the FDC group, 16.3% in the telmisartan group, 92.3% in the rosuvastatin group and 5.1 % in the placebo group (the LDL-c goals were determined by the risk score and consisted of 3 separate targets: < 160 mg/dl; <130 mg/dl and <100 mg/dl). Treatment associated adverse effects were noted in 12 cases (9%) in the FDC group; 18 cases (31%) in the rosuvastatin group; 8 cases (14.0% in the telmisartan group and 10 cases (19.5%) in the placebo group. Intriguingly the FDC group experienced less AE’s compared with the rosuvastatin monotherapy group and the placebo group. Although no significant differences were noted in compliance between the groups, the proportion of patients with a ≥80% compliance was 98.8% in the FDC group, vs 95.0%, 93.0% and 95.1% in the rosuvastatin, telmisartan and placebo groups.  Although Larger-scale studies of a longer duration are needed, the TELSTA-YU study showed no significant differences in efficacy and safety of a one table FDC formulation compared to mono-therapy with rosuvastatin or telmisartan. The potential benefits of improved adherence and tolerability of FDC deserve further exploration.
Oh GC, Han JK, Han KH et al. Efficacy and Safety of Fixed-dose Combination Therapy With Telmisartan and Rosuvastatin in Korean Patients With Hypertension and Dyslipidemia: TELSTA-YU (TELmisartan-rosuvaSTAtin from YUhan), a Multicenter, Randomized, 4-Arm, Double-blind, Placebo-controlled, Phase III Study. Clinical therapeutics 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29673890
 
Statin use in pregancy?
In the narrative review the authors address the potential role of statins in the prevention and treatment of pre-eclampsia, a serious and not seldom, life-threatening complication for mother as well as her unborn child. Based on animal and human studies, including a small group of randomized clinical trials, benefits could be expected and were observed. Partly based on the pleiotropic, anti-inflammatory effects of statins; in the context of the increased levels of inflammatory markers (hs CRP) observed in pre-eclamptic women. But gestational dyslipidemia could play an important role in accelerated atherosclerosis in the mother as well as her normo-cholesterolemic off-spring as well. Dyslipidemia, high total cholesterol and low HDL-cholesterol, is frequently observed in pre-eclampsia. Women at increased risk for CVD and a prolonged period of foregoing of statins due to longer time needed to get pregnant, as well as the pregnancy + lactation duration, run a risk of accelerated atherosclerosis and premature ASCVD after and perhaps even during pregnancy, if statins indicated for secondary prevention are interrupted. Also, children that are exposed to higher levels of LDL-c during gestation are more likely to develop advanced aortic atherosclerotic plaques, even when normal lipid levels are present in the newborn. The teratogenic effects of statin in the commonly used dosages seem virtually absent but cannot be fully excluded. Based on the current evidence, statins, and more specifically pravastatin, may be useful for women with- or at high-risk for pre-eclampsia. Several large RCT are in progress and will be able to provide more definite answers. The role of statins in women with (very) high LDL-cholesterol needs to be explored as well. Especially the therapeutic dilemma of managing young women with FH plus clinical manifestations of ASCVD and where interrupting statin treatment could be potentially life threatening, is in dire need of better delineated recommendations.
Maierean SM, Mikhailidis DP, Toth PP et al. The potential role of statins in preeclampsia and dyslipidemia during gestation: a narrative review. Expert opinion on investigational drugs 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29672173
 
Do children with NAFLD have actionable dyslipidemia?
lipid lowering drugs in children is becoming a more accepted treatment strategy. Familial hypercholesterolemia, diabetes and recently NALFD is not an uncommon pediatric diagnosis were statins are sometimes indicated. I this study The National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) was used to explore a multi-center longitudinal cohort of children between the ages of 9 and 18 years, with a biopsy confirmed NAFLD. At the start of the project, dietary recommendations were given, and the children were re-evaluated after 1 year. Lipid levels were measured and interpreted based on the NHLBI Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Participants (N=585) had a mean age of 12.8 years. LDL-c levels that matched actionable criteria, as observed at baseline, were present in 14% of the children. After 1 year 51% were able to reach LDL-c targets by changing their dietary habits. Enhanced dietary and lifestyle modifications were needed in 27% and 22% met criteria for pharmacologic intervention. Triglycerides were increased in 51% of the participating children. After 1 year 25% were able to reduce their TG’s by changing their diet. Enhanced dietary and lifestyle modifications were needed in 38%, and 37% met criteria for pharmacological intervention. The authors concluded that in children with NAFLD, actionable lipid levels are a very common finding and more than half qualified for lifestyle or pharmacological interventions.
Harlow KE, Africa JA, Wells A et al. Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease. J Pediatr 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29661561
 
Is hs-cTnI a new modifiable target for statin therapy?
Serum cardiac troponin (cTnI) is an established specific marker of cardiac myocyte damage and has become pivotal in the diagnosis of AMI. With improved measurement techniques this biomarker could be detected 100 times more sensitive and spot even very low levels of hs-cTnI. Measuring hs-cTnI in different populations exposed its potential role as an independent predictor of CV mortality, in secondary as well as primary prevention settings. A recent post hoc analysis of the WOSCOP study showed that pravastatin lowered hs-cTnI by 13% after one year. CVD risk was reduced 5-fold in the patients with the largest decline. To evaluate the effects of high intensity statins 80 stable CVD patients were randomized to increasing dosages of rosuvastatin (10, 20 and 40 mg) and atorvastatin (20, 40 and 80 mg) Patients were exposed to each dosage for 6 weeks consecutively, and 18 weeks in total. Statin treatment lowered hs-cTnI by -8.2% at 6 weeks (P=0.01) and -12.3% after 18 weeks (P=0.001). When comparing atorvastatin with rosuvastatin the changes at 18 weeks were -21.8% (P=0.001) and -4.1% (P=0.133) respectively. These changes were independent of LDL-cholesterol lowering effects and became apparent after only a few weeks suggesting effect beyond long term regression of atherosclerosis. The authors concluded that, within the limits of this explorative study, statins decreased hs-cTnI significantly in patients with stable CVD and atorvastatin showed more pronounced effects when compared to rosuvastatin. Further studies in diverse populations with increased CVD risk, are urgently needed to confirm these preliminary results and test if these changes are associated with improved CVD outcomes as well.
Bodde MC, Welsh P, Bergheanu SC et al. A rapid (differential) effect of rosuvastatin and atorvastatin on high-sensitivity cardiac Troponin-I in subjects with stable cardiovascular disease. Clinical pharmacology and therapeutics 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29672821
Relevant publications
  1. Strandberg TE, Urtamo A, Kahara J et al. Statin Treatment Is Associated With a Neutral Effect on Health-Related Quality of Life Among Community-Dwelling Octogenarian Men. J Gerontol A Biol Sci Med Sci 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29659717
  2. Bekki M, Tahara N, Tahara A et al. Anti-inflammatory effect of statin in coronary aneurysms late after Kawasaki disease. Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29667011
  3. Patel RS, Scopelliti EM, Olugbile O. The Role of PCSK9 Inhibitors in the Treatment of Hypercholesterolemia. The Annals of pharmacotherapy 2018:1060028018771670. http://www.ncbi.nlm.nih.gov/pubmed/?term=29667842
  4. Lee J, Rhee SJ, Lee S, Yu KS. Evaluation of drug interactions between fimasartan and rosuvastatin after single and multiple doses in healthy Caucasians. Drug design, development and therapy 2018; 12:787-794. http://www.ncbi.nlm.nih.gov/pubmed/?term=29670335
  5. Fentanes E, Vande Hei AG, Holuby RS et al. Treatment in a Preventive Cardiology Clinic Utilizing Advanced Practice Providers (APPs) Effectively Closes Atherosclerotic Cardiovascular Disease (ASCVD) Risk Management Gaps Amongst a Primary Prevention Population Compared with a Propensity-Matched Primary Care Cohort: A Team Based Care Model and its Impact on Lipid and Blood Pressure Management. Clin Cardiol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29667200
  6. Braun MM, Stevens WA, Barstow CH. Stable Coronary Artery Disease: Treatment. American family physician 2018; 97:376-384. http://www.ncbi.nlm.nih.gov/pubmed/?term=29671538
  7. Yamac AH, Kilic U. Effect of statins on sirtuin 1 and endothelial nitric oxide synthase expression in young patients with a history of premature myocardial infarction. Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir 2018; 46:205-215. http://www.ncbi.nlm.nih.gov/pubmed/?term=29664427
  8. Welnicki M, Sliz D, Filipiak KJ et al. [Difference in efficacy of dyslipidaemia treatment in obese and not obese women. Analysis of date from 3ST-POL study]. Przeglad lekarski 2016; 73:353-358. http://www.ncbi.nlm.nih.gov/pubmed/?term=29668197
  9. Volgman AS, Dembowski E, Braun LT. Should Sex Matter When it Comes to High-Intensity Statins? J Am Coll Cardiol 2018; 71:1738-1740. http://www.ncbi.nlm.nih.gov/pubmed/?term=29673464
  10. Tvaryanas AP, Wagner JH, Maupin GM. Statins and Musculoskeletal Conditions in U.S. Air Force Active Duty Aviators. Aerosp Med Hum Perform 2018; 89:421-427. http://www.ncbi.nlm.nih.gov/pubmed/?term=29673426
  11. Peters SAE, Colantonio LD, Zhao H et al. Sex Differences in High-Intensity Statin Use Following Myocardial Infarction in the United States. J Am Coll Cardiol 2018; 71:1729-1737. http://www.ncbi.nlm.nih.gov/pubmed/?term=29673463
  12. Park HS, Gu JY, Yoo HJ et al. Thrombin Generation Assay Detects Moderate-Intensity Statin-Induced Reduction of Hypercoagulability in Diabetes. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 2018:1076029618766254. http://www.ncbi.nlm.nih.gov/pubmed/?term=29669440
  13. Ofori-Asenso R, Llomaki J, Tacey M et al. Patterns of Statin Use and Long-term Adherence and Persistence among Older Adults with Diabetes. Journal of diabetes 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29658177
  14. Lin SH, Cheng PC, Tu ST et al. Effect of metformin monotherapy on serum lipid profile in statin-naive individuals with newly diagnosed type 2 diabetes mellitus: a cohort study. PeerJ 2018; 6:e4578. http://www.ncbi.nlm.nih.gov/pubmed/?term=29666753
  15. Dare RK, Tewell C, Harris B et al. Statin Coadministration Increases the Risk of Daptomycin-Associated Myopathy. Clin Infect Dis 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29668884
Miscellaneous publications
 
 
  1. Zhang GQ, Tao YK, Bai YP et al. Inhibitory Effects of Simvastatin on Oxidized Low-Density Lipoprotein-Induced Endoplasmic Reticulum Stress and Apoptosis in Vascular Endothelial Cells. Chinese medical journal 2018; 131:950-955. http://www.ncbi.nlm.nih.gov/pubmed/?term=29664056
  2. Wang JJ, Tian Y, Xu KL et al. [Statins Regulate the Proliferation and Apoptosis of T-ALL Cells through the Inhibition of Akt Pathway]. Zhongguo shi yan xue ye xue za zhi 2018; 26:359-367. http://www.ncbi.nlm.nih.gov/pubmed/?term=29665899
  3. Thabit S, El Sayed NSE. Effect of pioglitazone and simvastatin in lipopolysaccharide-induced amyloidogenesis and cognitive impairment in mice: possible role of glutamatergic pathway and oxidative stress. Behavioural pharmacology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29659380
  4. Miranda HF, Sierralta F, Aranda N et al. Antinociception induced by rosuvastatin in murine neuropathic pain. Pharmacological reports : PR 2017; 70:503-508. http://www.ncbi.nlm.nih.gov/pubmed/?term=29660653
  5. McMahon RA, Fletcher JL, Aden JK et al. Preinjury statin use and thromboembolic events in trauma: a 10-year retrospective evaluation. J Surg Res 2018; 226:100-111. http://www.ncbi.nlm.nih.gov/pubmed/?term=29661275
  6. Garrett N, Pombo J, Umpierrez M et al. Pravastatin therapy during preeclampsia prevents long-term adverse health effects in mice. JCI insight 2018; 3. http://www.ncbi.nlm.nih.gov/pubmed/?term=29669946
  7. Ekerbicer N, Gurpinar T, Sisman AR et al. Statins reduce testicular and ocular VEGF: A potential compromise to microcirculation. Microvascular research 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29678729
  8. Chen Y, Chang Y, Zhang N et al. Atorvastatin Attenuates Myocardial Hypertrophy in Spontaneously Hypertensive Rats via the C/EBPbeta/PGC-1alpha/UCP3 Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2018; 46:1009-1018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29669326
  9. Ames PRJ, Di Girolamo G, D'Andrea G et al. Predictive Value of Oxidized Low-Density Lipoprotein/beta2-Glycoprotein-I Complexes (oxLDL/beta2GPI) in Nonautoimmune Atherothrombosis. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 2018:1076029618767752. http://www.ncbi.nlm.nih.gov/pubmed/?term=29669439
  10. Matsubara A, Oda S, Akai S et al. Establishment of a drug-induced rhabdomyolysis mouse model by co-administration of ciprofloxacin and atorvastatin. Toxicology letters 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29679711
  11. Liu Y, Feng Y, Cheng D et al. Dynamics of bacterial composition and the fate of antibiotic resistance genes and mobile genetic elements during the co-composting with gentamicin fermentation residue and lovastatin fermentation residue. Bioresource technology 2018; 261:249-256. http://www.ncbi.nlm.nih.gov/pubmed/?term=29673993
  12. Lim YI, Han J, Woo YA et al. Rapid quantitation of atorvastatin in process pharmaceutical powder sample using Raman spectroscopy and evaluation of parameters related to accuracy of analysis. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy 2018; 200:26-32. http://www.ncbi.nlm.nih.gov/pubmed/?term=29660679
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