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Update - Week 52,  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

Statin benefits beyond cholesterol for hemorrhagic stroke patients?
The potential protective role of statins in Patients with an intracerebral hemorrhage (ICH) were explored in this Chinese ICU setting. Patients (N=146) presenting with acute ICH were randomized to simvastatin or placebo. The dosages of simvastatin injections were 0.08, 0.16, 0.24, 0.30 or 0.36 mg/kg. The anti-inflammatory properties of simvastatin were evaluated by measuring the plasma concentrations of inflammatory markers: IL-4, IL-6, IL-8 and IL 10 as well as lymphocytes, granulocytes and mono-nuclear cells. Over a 72-hr. time period Inflammatory markers + cells were reduced in patients using simvastatin and this coincided with lessened vasospasms, cerebral edema and reduced bleeding volume. The simvastatin injections were also associated with adverse effects: hypertension, proteinuria, fatigue, diarrhea, vomiting, rash, constipation and peripheral edema. The investigators suggested simvastatin 0.20 mg/day as the preferred dosage, striking a balance between therapeutic efficacy and tolerability. Evaluation after 42 days showed significant functional improvements and after 5 years significant survival benefits in hemorrhagic stroke patients that received simvastatin compared to placebo. Although the number of patients included in this study is limited, the reported benefits of parenteral simvastatin in hemorrhagic stroke patients is provocative and deserves a larger follow up studies as to confirm this.
Zhou X, Chen J, Wang C, Wu L. Anti-inflammatory effects of Simvastatin in patients with acute intracerebral hemorrhage in an intensive care unit. Experimental and therapeutic medicine 2017; 14:6193-6200. http://www.ncbi.nlm.nih.gov/pubmed/?term=29285177
Preventing ischemia reperfusion injury, ticagrelor vs atorvastatin. And the winner is…
The problem of ischemia reperfusion injury (IR) is the paradoxical effect of tissue damage when re-establishing blood supply after a period of ischemia or anoxia. Cellular damage is caused by inflammation and oxidative stress. The increased production of reactive oxygen species (ROS) and impaired nitric oxide production play an important role in IR. Both atorvastatin and ticagrelor have been observed to prevent IR in animals. The investigators of this study aim to provide a proof of concept in humans.  They recruited32 healthy volunteers and randomized them to atorvastatin 80 mg or placebo for 14 days followed by a single dose of ticagrelor 180 mg. They were then subjected to a 20-minute period of fore-arm ischemia and with exposed to increasing dosages of acetylcholine (Ach) and glyceryl-trinitrate (GTN). The former is an endothelium dependent the latter and endothelium independent agonist. GTN induced vasodilation was unaffected by both drugs, but the ACH induced vasodilatory response was mitigated by ticagrelor but normalized with atorvastatin. Fore arm blood flow (FBF) - AChAUC ratio post vs. pre-ischemia 0.81 (ticagrelor) vs. 1.04 (atorvastatin + ticagrelor); P = 0.001). The authors concluded that ticagrelor exerted benefit on FBF response but (chronic) atorvastatin treatment normalized FBF. They emphasized the importance of initiating high dose high intensity statin in patients at risk for ASCVD complications not only to prevent progression and acute complications but also to reduce IR in patients were circulation is re-established.
Weisshaar S, Litschauer B, Kerbel T, Wolzt M. Atorvastatin combined with ticagrelor prevent ischemia-reperfusion induced vascular endothelial dysfunction in healthy young males - A randomized, placebo-controlled, double-blinded study. Int J Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29288055
Is fasting is no longer needed (in ACS patients) before a lipid measurement?
When to measure cholesterol? Is fasting necessary or can we refrain from advising all our patients to fast for at least 8 hours before checking their plasma-lipids? Recent studies in healthy participants and in patients with stable CVD indicated only very small, and clinically irrelevant, changes in measurements that were performed after fasting and those that were not. In this study, the investigators evaluated post ACS patients that participated in the PROVE IT-TIMI 22 study. Patients randomized to atorvastatin 80 mg or pravastatin 40mg, were evaluated after a median period of 7 days post the initiating ACS event and during follow-up. Observing a fasting period before the blood draw showed a higher LDL-C (+4.1 mg/dl) and Apo B (+2.6 mg/dl) concentrations as well as lower TG (-21.0 mg/dl) and hs CRP (-0.48mg/dl) levels. This resulted in a 3.8% LDL-C increase and a 11.3% TG decrease. Measurements of total cholesterol HDL-C, Apo A-I, Lp(a) and Apo C-III were unaffected by fasting. The authors re-affirmed that both in early ACS patients and during follow-up fasting did have a relative small effect on LDL-C, Apo B and TG’s but that their data support the general recommendations to refrain from fasting prior to a lipid measurement. However, recommendations to avoid consuming high fat meals or alcohol before the blood draw are still firm. Patients with TG >400 mg/dl could benefit from repeat measurements in the fasting state as well.
Steen DL, Umez-Eronini AA, Guo J et al. The effect of fasting status on lipids, lipoproteins, and inflammatory biomarkers assessed after hospitalization for an acute coronary syndrome: Insights from PROVE IT-TIMI 22. Clin Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29283450
Japanese patients with a low admission LDL-c are less likely receive a statin at discharge and end up with a higher mortality risk
Starting the appropriate statin therapy in ACS patients with LDL-c <100 mg/dl at admission, proved to be a hurdle in this Japanese registry of 2 Kanazawa hospitals. The 942 consecutive ACS patients were grouped by baseline LDL-C < 100 mg/dl (N=267), group A and group B, ≥ 100 mg/dl (N=675). Statin or no-statin at discharge was noted as well. In a retrospective analysis, all-cause mortality was the designated primary endpoint. Patients with a baseline LDL-C <100 mg/dl were older and more likely to suffer from multiple co-morbidities. Statin prescription was higher in group B compared to A (77.3% vs 57.7%, P<0.001). Patients were followed for a mean period of 4 years during which 122 patients died. A multi variate Cox proportional hazard analysis showed a HR of 1.61 (1.09-2.39, p<0.05) for patients with an LDL-c <100 mg. having been prescribed a statin at discharge resulted in an overall 48% relative risk reduction; HR 0.52 (0.36-0,76; p<0.001). Patients in group A, and no statin at discharge, showed increasing LDL-c plasma concentrations during follow-up (79 ± 15–96 ± 29 mg/dL, p < 0.001), while those that were discharged with a statin did not show LDL-c increases (79 ± 15–77 ± 22 mg/dL, p = 0.30). Based on these observed results the authors concluded that in Japan a low admission LDL-c was likely to result in a higher likelihood to leave the hospital without a statin and consequently an increased risk of dying.
Nagar SP, Rane PP, Fox KM et al. Treatment Patterns, Statin Intolerance, and Subsequent Cardiovascular Events Among Japanese Patients With High Cardiovascular Risk Initiating Statin Therapy. Circulation journal : official journal of the Japanese Circulation Society 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29276211
Integrated backscatter (IB)-IVUS to discern differences between lipo- and hydrophilic statins
Although statins are seen as a uniform class of drugs that lower LDL-c, there are distinct difference between the individual statins that can impact safety and efficacy beyond their cholesterol lowering capacity. One clear distinction is their chemical structures that determines lipo- or hydrophilicity. In this randomized open label, parallel-group, single center study, the investigators determined the impact of lipophilic atorvastatin vs hydrophilic rosuvastatin in Japanese ACS patients that received a PCI as well as IB-IVUS between December 2008 and August 2011. Patients were allocated to atorvastatin 10 mg or rosuvastatin 2.5 mg. The observed decreases of LDL-c in both groups was similar -41,2% vs 38.3% (P=0.87) respectively. Follow-up IVUS were scheduled 6-12 months after the primary PCI. Of the 67 included patients only 35 were evaluable and received a serial IB IVUS. Plaque volumes decreased 82.0 ± 46.2 to 74.9 ± 41.3 mm3 (P = 0.01) and from 74.7 ± 35.3 to 67.7 ± 27.0 mm3 (P = 0.02), in the patients allocated to atorvastatin and rosuvastatin. There were no significant differences in percentage changes of plaque volumes between both groups. IB-IVUS revealed a significant reduction in fibrous volume from 33.8 ± 20.0 to 27.5 ± 14.9 mm3 (P < 0.01) and from 29.6 ± 13.6 to 24.8 ± 7.6 mm3 (P < 0.05) respectively. Lipid pool changes remained the same in both groups. The authors concluded that lipophilic and hydrophilic statins showed very similar quantitative and qualitative plaque changes in Japanese ACS patients. The limitations of their study design would warrant for additional investigations to determine if there are clinically relevant differences between water- and fat-soluble statins.
Ishikawa Y, Itoh T, Satoh M et al. Impact of Water- and Lipid-Soluble Statins on Nonculprit Lesions in Patients with Acute Coronary Syndrome. Int Heart J 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29279527
Relevant publications
  1. Zuo HJ, Wang WH, Deng LQ, Su JL. Control of cardiovascular disease risk factors among patients with type II diabetes in a primary-care setting in Beijing. Journal of the American Society of Hypertension : JASH 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29289467
  2. Zhang N, Zhang M, Liu RT et al. Statins reduce the expressions of Tim-3 on NK cells and NKT cells in atherosclerosis. Eur J Pharmacol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29288118
  3. Vavlukis M, Kedev S. Effects of High Intensity Statin Therapy in the Treatment of Diabetic Dyslipidemia in Patients with Coronary Artery Disease. Current pharmaceutical design 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29283060
  4. Rocha VZ, Santos RD. Safety of statin treatment in children with familial hypercholesterolemia: Filling the gaps. J Clin Lipidol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29287917
  5. Nissen SE, Nicholls SJ. Results of the GLAGOV trial. Cleveland Clinic journal of medicine 2017; 84:e1-e5. http://www.ncbi.nlm.nih.gov/pubmed/?term=29281604
  6. Joseph P, Lonn E, Bosch J et al. Long-term Effects of Statins, Blood Pressure-Lowering, and Both on Erectile Function in Persons at Intermediate Risk for Cardiovascular Disease: A Substudy of the Heart Outcomes Prevention Evaluation-3 (HOPE-3) Randomized Controlled Trial. Can J Cardiol 2018; 34:38-44. http://www.ncbi.nlm.nih.gov/pubmed/?term=29275880
  7. Sturlaugsdottir R, Aspelund T, Bjornsdottir G et al. Predictors of carotid plaque progression over a 4-year follow-up in the Reykjavik REFINE-study. Atherosclerosis 2017; 269:57-62. http://www.ncbi.nlm.nih.gov/pubmed/?term=29274849
  8. Semenova AE, Sergienko IV. [Lisinopril, Amlodipine, Rosuvastatin as a Novel Fixed Combination in the Fight Against Cardiovascular Disease]. Kardiologiia 2017; 57:73-79. http://www.ncbi.nlm.nih.gov/pubmed/?term=29276932
  9. Logue JM, Kiani B, Bitting RL. Pazopanib and Statin-Induced Rhabdomyolysis. Case reports in oncology 2017; 10:954-957. http://www.ncbi.nlm.nih.gov/pubmed/?term=29279698
  10. Kong Y, Cao XN, Zhang XH et al. Atorvastatin enhances bone marrow endothelial cell function in corticosteroid-resistant immune thrombocytopenia patients. Blood 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29288170
  11. Kawai H, Ihara K, Kera T et al. Association between statin use and physical function among community-dwelling older Japanese adults. Geriatrics & gerontology international 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29278297
  12. Jamnagerwalla J, Howard LE, Allott EH et al. Serum cholesterol and risk of high-grade prostate cancer: results from the REDUCE study. Prostate Cancer Prostatic Dis 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29282360
  13. Nakahashi T, Tada H, Sakata K et al. Paradoxical impact of decreased low-density lipoprotein cholesterol level at baseline on the long-term prognosis in patients with acute coronary syndrome. Heart Vessels 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29288404
  14. Guercio V, Turati F, Bosetti C et al. Bladder cancer risk in users of selected drugs for cardiovascular disease prevention. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29280915
  15. Bucheit JD, Helsing H, Nadpara P et al. Clinical pharmacist understanding of the 2013 American College of Cardiology/American Heart Association cholesterol guideline. J Clin Lipidol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29277495
  16. Aghazadeh J, Samadi Motlagh P, Salehpour F et al. Effects of Atorvastatin in Patients with Acute Spinal Cord Injury. Asian spine journal 2017; 11:903-907. http://www.ncbi.nlm.nih.gov/pubmed/?term=29279745
Miscellaneous publications
  1. Zhu S, Wang J, Wang X, Zhao J. Protection against monocrotaline-induced pulmonary arterial hypertension and caveolin-1 downregulation by fluvastatin in rats. Mol Med Rep 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=29286128
  2. Andalib S, Molhemazar P, Danafar H. In vitro and in vivo delivery of atorvastatin: A comparative study of anti-inflammatory activity of atorvastatin loaded copolymeric micelles. Journal of biomaterials applications 2017:885328217750821. http://www.ncbi.nlm.nih.gov/pubmed/?term=29283039
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