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Update - Week 09, 2019
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

Differences in non-culprit coronary lesions in men vs women
Differences in atherosclerotic progression and CVD between men in women is well recognized but poorly understood. In this retrospective observational analysis, a final number of 103 Chinese CAD patients [women (N=26) and men (N=77)] with 187 non-culprit lesions were analyzed using coronary angiography and optical coherence tomography (OCT). Lipid-rich plaque, maximum lipid arc, lipid-core length, lipid index, mean lipid arc multiplied by lipid-core length (LI), fibrous cap thickness, and the incidence of thin-cap fibroatheroma (TCFA) were measured. Women were less likely to smoke (P=0.007) but were older (mean age, 70.8 ± 7.3 vs 60.8 ± 9.8 years; P < 0.001) and had higher levels of LDL-c (92.2 ± 27.0 vs 79.4 ± 27.6 mg/dL; P = 0.043). Hypertension, diabetes mellitus, and drug use prior to admission were no difference between males and females. In men plaques exhibited greater lipid-core length (9.54 ± 4.5mm vs 7.3 ± 2.7 mm, P = 0.024) and an increased LI (1615.1 ± 893.8mm2 vs 1237.8 ± 859.8mm2, P = 0.035) compared with women. No differences were noted for all other measured variables. After multivariate linear regression analysis, sex and current smoking were associated with a larger lipid index. The only independent variable associated with a smaller lipid index was statin use. The authors concluded that non-culprit plaques contain reduced lipid cores in female patients with CAD compared to males and statin use was associated with a reduced LI.
Tian J, Wang X, Tian J, Yu B. Gender differences in plaque characteristics of nonculprit lesions in patients with coronary artery disease. BMC Cardiovasc Disord 2019; 19:45. http://www.ncbi.nlm.nih.gov/pubmed/?term=30808307
Statin use significantly lowers TAK relapse rates
Takayasu arteritis (TAK), a large vessel vasculitis is commonly treated with anti-inflammatory/immunosuppressant drugs. In this retrospective analysis of 74 TAK patients, diagnosed between 2012 – 2017, the effects of statins on relapse after remission was evaluated. Statins were used by 40 (54.1%) patients. Relapse was observed in 36 (48.6%) patients. Reduced relapse risk was observed in younger (44.5 ± 13.5 years vs 34.1 ± 12.6 years, p = 0.001), had lower prevalence of hypertension (63.2% vs 38.9%, p = 0.037), more commonly had carotidynia (7.9% vs 27.8%, p = 0.025), had higher LDL-cholesterol (84.8 ± 18.8 mg/dl vs 100.5 ± 26.1 mg/dl, p = 0.010), and were less commonly taking statins (71.1% vs 36.1%, p = 0.003). Statin use was significantly associated with lower relapse risk. Cox regression analysis HR 0.26 (0.120–0.563, p = 0.001); Inverse probability of treatment weighting adjusted analysis HR 0.15 (0.038–0.616, p = 0.008). Relapses are a common occurrence in TAK patients, adding statins to their anti-inflammatory/immunosuppressant regimen significantly reduces that risk. Due to the limitations of small sample size and the observational character of this study, confounding cannot be ruled out. A larger prospective controlled trial will be needed to confirm these promising findings.
Kwon OC, Oh JS, Park MC et al. Statins reduce relapse rate in Takayasu arteritis. Int J Cardiol 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30824260
Ischemic heart failure and statins; are all statin the same?
The use of statin in heart failure patients has been associated with conflicting study results. In this single-center, retrospective observational study, the effects of statins in hospitalized ischemic heart failure patients were studied. Between January 2014 and December 2017, 155 HF patients were included and followed for a period of 2 years. Primary endpoints were: rehospitalization, in-hospital death, mortality after 6 months, 1 year and 2 years. All-cause mortality included cardiovascular events or worsening heart failure. Statins were used by 58.9% of the HF patients; atorvastatin in 33.9% and rosuvastatin in 25%. Re-hospitalizations were observed in 66.7% of the patients without statins; 64.1% in patients using rosuvastatin and 31.2% atorvastatin users, between-group differences were all significant (P< 0.001). Mortality benefit at 6, 12 months and 2 years were noted in patients using statins (P=0.001). Heart failure progression was the most frequently observed cause of death, in 31.7% of patients without a statin, 12.8% in rosuvastatin users and 3.8% in atorvastatin users (P=0.004). The results of this observational study suggest a survival benefit in patients using atorvastatin as compared to no statins or rosuvastatin. The only large RCT clinical endpoint study in patients with heart failure (> 60% = NYHA III) compared rosuvastatin with placebo and did not show any significant clinical benefit. The evidence of this recent analysis can only be considered hypothesis generating but is in line with the posthoc observations in the TNT study. If confirmed in a larger prospective follow-up study could have important clinical implications for statin use and choice in patients with HF.
Zvizdic F, Godinjak A, Durak-Nalbantic A et al. Impact of Different Types of Statins on Clinical Outcomes in Patients Hospitalized for Ischemic Heart Failure. Medical archives (Sarajevo, Bosnia and Herzegovina) 2018; 72:401-405. http://www.ncbi.nlm.nih.gov/pubmed/?term=30814769
How soon should I start statins after ACS?

The timing of statins after ACS seems a simple question, but despite the plethora of statin studies in ACS patients, the impact of early <24 hr. vs Late(r) >48hr. initiation remains elusive. The Convergent Registry of Catholic and Chonnam University for AMI (COREA-AMI) is a nine-center, web-based observational cohort registry (N=4 748). This registry was used to query eligible patients, and 3 921 consecutive ACS patients that underwent a primary PCI and were statin naïve at admission, were included.  Patients were divided into 3 groups, based on the timing of statin initiation. Group I started statins <24hrs (N=2 665); group II started statins 24-48hrs (N=480) and group III started statins >48rhs (N=776). Comparisons were based on 3 models. Model 1 compared < 24 hrs. vs >24hrs; model 2 compared < 48 hrs. vs > 48 hrs. and model 3 compared < 24 hrs. vs 24-48 hrs. The primary endpoint was major coronary events (MACE) defined as a composite of cardiac death, myocardial infarction, and target-vessel revascularization. Patients outcomes were recorded at 1,6, 12 months and annually over a median follow up time of 3.8 years. Statin prescription >48 hrs. was observed in 19.8% of the patients; females and elderly patients were overrepresented in this group. Early statin initiation resulted in more favorable outcomes in model 1; 14.3% vs. 18.4%, HR 0.77; (0.66–0.91; p=0.002) and model 2; 14.6% vs. 19.7%, HR, 0.81 (0.67–0.97; p=0.022). Propensity score matching did no alter the observed outcomes. When analyzing model 3 no differences were noted in patients that initiated statin < 24 hrs. vs 24-48 hrs. Based on this observational data early initiation of statins (<48 hrs.) in Korean patients that were statin naïve was associated with reduced long-term MACE outcomes. The timing of statin initiation seems to be critical when aiming to maximize benefits. Admission for ACS provides an optimal window to initiate proper prevention strategies that include guideline endorsed medication and lifestyle improvement.
Kim MC, Ahn Y, Cho JY et al. Benefit of Early Statin Initiation within 48 Hours after Admission in Statin-Naive Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention. Korean Circ J 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30808084
NDPR and lipid lowering drugs – Real world data on Japanese type 2 diabetics
The Japan Diabetes Complication and its Prevention prospective (JDCP) study is a nationwide registry. This registry provides real-world practice data on Japanese type 1 and type 2 diabetic patients. Data was collected of 7 700 patients in 464 hospitals and clinics. A total of 5 852 patients were included for the analysis of risk factors associated with non-proliferative diabetic retinopathy (NDPR). In diabetes type 1 patients (N=363), 83 (22.8%) were diagnosed with NDPR. Factors associated with an increased risk for developing NDPR in DM type 1 patients were the duration of diabetes and reduced HDL-c. The number of patients using statins or fibrates was 84 and 3 respectively, insufficient for an evaluation on outcomes.  In DM type 2 patients (N=5 489), NDPR was observed in 1 515 (27.6%) participants. Factors associated with increased NDPR risk were Female gender, duration of diabetes, lifetime maximum body weight, treatment types, systolic blood pressure, and the number of oral hypoglycemic agents (OHA) and antihypertensive drugs. Protective factors included diastolic BP, body mass index, alcohol intake, and the number of lipid-lowering drugs. After propensity score adjustment the uses of statins or fibrates resulted in an NDPR odds ratio of 0.80 (0.70-0.92; p=0.002. The authors concluded that statins and fibrates reduced the risk of developing NPDR in the observational registry of Japanese DM type 2 patients.
Kawasaki R, Kitano S, Sato Y et al. Factors associated with non-proliferative diabetic retinopathy in patients with type 1 and type 2 diabetes: the Japan Diabetes Complication and its Prevention prospective study (JDCP study 4). Diabetology international 2019; 10:3-11. http://www.ncbi.nlm.nih.gov/pubmed/?term=30800559
Relevant publications
  1. Ruscica M, Banach M, Sahebkar A et al. ETC-1002 (Bempedoic acid) for the management of hyperlipidemia: from preclinical studies to phase 3 trials. Expert Opin Pharmacother 2019:1-13. http://www.ncbi.nlm.nih.gov/pubmed/?term=30810432
  2. Offer A, Arnold M, Clarke R et al. Assessement of Vascular Event Prevention and Cognitive Function Among Older Adults With Preexisting Vascular Disease or Diabetes: A Secondary Analysis of 3 Randomized Clinical Trials. JAMA network open 2019; 2:e190223. http://www.ncbi.nlm.nih.gov/pubmed/?term=30821829
  3. Martin Navarro JA, Gutierrez Sanchez MJ, Petkov Stoyanov V, Jimenez Herrero MC. Acute renal failure secondary to rhabdomyolysis in a patient receiving treatment with ticagrelor and atorvastatin. Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30798999
  4. Kim J, You NY, Lee JW et al. Inverse Association Between Statin Use and Overall Cancer Incidence in Individuals With Hypercholesterolemia, Based on the Korean Health Insurance Service Between 2002 and 2015. Asia-Pacific journal of public health 2019:1010539519830235. http://www.ncbi.nlm.nih.gov/pubmed/?term=30808200
  5. Durand M, Machuron C, Guillet L et al. Preoperative Statin Treatment Is Not Associated with Reduced Postoperative Mortality or Morbidity in Patients Undergoing Isolated Valve Surgery. The heart surgery forum 2019; 22:E057-e062. http://www.ncbi.nlm.nih.gov/pubmed/?term=30802199
  6. Dudum R, Whelton SP. Non-statin lipid lowering and coronary plaque composition. Journal of cardiovascular computed tomography 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30803836
  7. Cheung KS, Chen L, Chan EW et al. Statins reduce the progression of non-advanced adenomas to colorectal cancer: a postcolonoscopy study in 187 897 patients. Gut 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30808646
  8. Bosch J, O'Donnell M, Swaminathan B et al. Effects of blood pressure and lipid lowering on cognition: Results from the HOPE-3 study. Neurology 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30814321
  9. Alexopoulos AS, Qamar A, Hutchins K et al. Triglycerides: Emerging Targets in Diabetes Care? Review of Moderate Hypertriglyceridemia in Diabetes. Current diabetes reports 2019; 19:13. http://www.ncbi.nlm.nih.gov/pubmed/?term=30806837
  10. Lacroix O, Couttenier A, Vaes E et al. Statin use after diagnosis is associated with an increased survival in esophageal cancer patients: a Belgian population-based study. Cancer Causes Control 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30820714
  11. Kao LT, Hung SH, Kao PF et al. Inverse association between statin use and head and neck cancer: A population-based case-control study in Han population. Head & neck 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30809863
  12. Jang HS, Choi J, Shin J et al. The Long-Term Effect of Cancer on Incident Stroke: A Nationwide Population-Based Cohort Study in Korea. Frontiers in neurology 2019; 10:52. http://www.ncbi.nlm.nih.gov/pubmed/?term=30804874
  13. Ho W, Choo DW, Wu YJ et al. Statins Use and the Risk of Prostate Cancer in Ischemic Heart Disease Patients in Taiwan. Clinical pharmacology and therapeutics 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30801679
  14. Godinho R, Bugnon S, Gracin T, Tataw J. Severe rhabdomyolysis-induced acute kidney injury following concomitant use of Genvoya(R) (EVG/COBI/FTC/TAF) and simvastatin; a case report. BMC Nephrol 2019; 20:69. http://www.ncbi.nlm.nih.gov/pubmed/?term=30808332
  15. Lorenzatti AJ, Eliaschewitz FG, Chen Y et al. Randomised Study of Evolocumab in Patients With Type 2 Diabetes and Dyslipidaemia on Background Statin: Primary Results of the BERSON Clinical Trial. Diabetes Obes Metab 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30821053
Basic Science publications
  1. Zhang T, Gillies M, Wang Y et al. Simvastatin Protects Photoreceptors from all-trans-retinal Induced Oxidative Stress with Up-regulation of Interphotoreceptor Retinoid Binding Protein. Br J Pharmacol 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30825184
  2. Sroda-Pomianek K, Michalak K, Palko-Labuz A et al. The Combined Use of Phenothiazines and Statins Strongly Affects Doxorubicin-Resistance, Apoptosis, and Cox-2 Activity in Colon Cancer Cells. Int J Mol Sci 2019; 20. http://www.ncbi.nlm.nih.gov/pubmed/?term=30813251
  3. Real J, Miranda C, Olofsson CS, Smith PA. Lipophilicity predicts the ability of nonsulphonylurea drugs to block pancreatic beta-cell KATP channels and stimulate insulin secretion; statins as a test case. Endocrinology, diabetes & metabolism 2018; 1:e00017. http://www.ncbi.nlm.nih.gov/pubmed/?term=30815553
  4. Liu H, Yang J, Wang K et al. Moderate- and Low-Dose of Atorvastatin Alleviate Cognition Impairment Induced by High-Fat Diet via Sirt1 Activation. Neurochemical research 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30820818
  5. Liang CL, Chen HJ, Liliang PC et al. Simvastatin and Simvastatin-Ezetimibe Improve the Neurological Function and Attenuate the Endothelial Inflammatory Response after Spinal Cord Injury in Rat. Annals of clinical and laboratory science 2019; 49:105-111. http://www.ncbi.nlm.nih.gov/pubmed/?term=30814085
  6. Hu K, Wan Q. Biphasic influence of pravastatin on human cardiac microvascular endothelial cell functions under pathological and physiological conditions. Biochem Biophys Res Commun 2019; 511:476-481. http://www.ncbi.nlm.nih.gov/pubmed/?term=30803760
  7. Feng PF, Zhang B, Zhao L et al. Intracellular mechanism of rosuvastatin-induced decrease in mature hERG protein expression on membrane. Molecular pharmaceutics 2019. http://www.ncbi.nlm.nih.gov/pubmed/?term=30807184
  8. Cho O, Jang YJ, Park KY, Heo TH. Beneficial anti-inflammatory effects of combined rosuvastatin and cilostazol in a TNF-driven inflammatory model. Pharmacological reports : PR 2018; 71:266-271. http://www.ncbi.nlm.nih.gov/pubmed/?term=30822620
  9. Beg S, Alam MN, Ahmad FJ, Singh B. Chylomicron mimicking nanocolloidal carriers of rosuvastatin calcium for lymphatic drug targeting and management of hyperlipidemia. Colloids and surfaces. B, Biointerfaces 2019; 177:541-549. http://www.ncbi.nlm.nih.gov/pubmed/?term=30825846
  10. Al-Kuraishy HM, Al-Gareeb AI. Effects of rosuvastatin on metabolic profile: Versatility of dose-dependent effect. Journal of advanced pharmaceutical technology & research 2019; 10:33-38. http://www.ncbi.nlm.nih.gov/pubmed/?term=30815386
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