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Update - Week 35,  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

Potential role for statins in AF prevention after CABG
The anti-arrhythmic effects of statins have been postulate before but the evidence supporting their use for this indication remains controversial. In this study, the authors performed a systematic review and meta-analysis to evaluate if statins would reduce postoperative atrial fibrillation (POAF) in patients that had cardiac surgery for the systematic review and.  They collected data from 22 RCT’s including 5243 patients. For the POAF outcomes 18 RCT’s with 3995 patients reported POAF outcomes. The risk of POAF was significantly reduced in the patients that had a CABG procedure, RR 0.69 (0.56-0.86; P=0.001), however in patients that underwent valve surgery no protective effects could be discerned. Surprisingly patients using rosuvastatin had an increased risk trend for POAF; RR 1.20 (0.94-1.51, P=0.120) When evaluating the risk for acute kidney injury (AKI) or myocardial infarction no protective effects were found. The observed RR’s: 0.98 (0.70-1.35; p=0.884) and 0.84 (0.58-1.23; P=0.380) respectively. The authors concluded that perioperative statin use seems to have a protective effect on POAF, most pronounced in post CABG patients. No benefits were observed for AKI and MI post (valve) cardiac surgery.
Zhen-Han L, Rui S, Dan C et al. Perioperative statin administration with decreased risk of postoperative atrial fibrillation, but not acute kidney injury or myocardial infarction: A meta-analysis. Scientific reports 2017; 7:10091. http://www.ncbi.nlm.nih.gov/pubmed/?term=28855628
 
Obesity paradox observed in Korean, obese, post-AMI patients using statins
The Korean Acute Myocardial Infarction Registry (KAMIR) was used to evaluate the benefits of statins in obese vs non-obese patients. The obesity paradox in post AMI patients has not been tested on mortality outcomes; by querying this large National registry and using a propensity score matched design the authors aimed to explore this question. Using a 4:1 cases & control matching for statin(N=2196) and no-statin (N=549) users, design. After one year follow-up, all-cause mortality and cardiovascular mortality were respectively 8.4% and 6.2% in the non-statin group vs 3.7% and 2.3% in the statin-users. (P<0.001). However, the statin using obese were better protected than the non-obese patients. Total mortality and cardiovascular mortality were significantly lower in the obese 1.7% vs 4.8% and 1.2% vs 2.9% (P<0.05) respectively, resulting in a corrected HR: 0.35 (p=0.001). In the overall group, no significant differences between obese and non-obese for total mortality 7.2% vs 9.0% and cardiovascular mortality 5.5% and 6.5% respectively, were observed. The authors concluded that the obesity paradox persist obese post AMI patients using statins.
Won KB, Hur SH, Nam CW et al. Evaluation of the impact of statin therapy on the obesity paradox in patients with acute myocardial infarction: A propensity score matching analysis from the Korea Acute Myocardial Infarction Registry. Medicine (Baltimore) 2017; 96:e7180. http://www.ncbi.nlm.nih.gov/pubmed/?term=28858077 
 
German review highlighting benefits of statin in chronic liver disease
The authors present a concise review on the published data of the role of statins in chronic liver disease. Despite initial concern of hepatotoxicity, statins are now increasingly used therapeutically in patients with a number of chronic liver conditions. The authors review the evidence of published studies on NASH/NAFLD, chronic viral infections, liver cirrhosis and hepatocellular carcinoma. The non-lipid lowering, pleiotropic effects of statin are seen as the most likely general explanation for the observed hepato-protective benefits of statins and the potential anti-inflammatory effects might play a pivotal role. The most convincing data was observed for atorvastatin and fluvastatin. One critical point highlighted by the authors is the observational nature of the available data and they point out the need for larger prospective randomized trials in patients with hepatic viral infections, NASH/NAFLD and as adjuvants treatment for hepatocellular carcinoma. No benefits of statins for alcohol related liver disease have been noted so far.
Sauerbruch T, Schierwagen R, Trebicka J. [Statins as a Therapy of Chronic Liver Disease?]. Deutsche medizinische Wochenschrift (1946) 2017; 142:1313-1318. http://www.ncbi.nlm.nih.gov/pubmed/?term=28850969
 
Review on practical management of patients with statin associated muscle symptoms (SAMS)
In this combined European and US review, definitions and algorithms are provided for the proper classification as well as risk estimation of SAMS in patients using statins. Background information on the incidence of statin intolerance collected in large randomized controlled clinical trials is reviewed as well as the different consensus on the management of SAMS. A practical scoring system is presented to calculate if the muscle complaints are. An overview of non-invasive techniques to asses SAMS likelihood is provided. The review concludes with recommendations on managing strategies including the use of non-statins and nutraceuticals. Statin intolerance leads to higher ASCVD risk. Verification that a patient truly cannot tolerate statin therapy includes evaluation of symptoms after drug withdrawal and assessment of symptoms upon reinitiating with an alternative statin or lower doses of the same or a different statin.
Rosenson RS, Baker S, Banach M et al. Optimizing Cholesterol Treatment in Patients With Muscle Complaints. J Am Coll Cardiol 2017; 70:1290-1301. http://www.ncbi.nlm.nih.gov/pubmed/?term=28859793
 
EUROP-AF registry shows statin use reduces CV mortality in AF patients
The EURObservational Research Program Atrial Fibrillation (EUORP-AF) is a multicenter European wide registry of AF patients by managed by cardiologist in nine European countries. This registry was used to evaluate the 1-year outcomes in AF patients using statins at baseline. No data on statin type and dosage was available, and in 483 (48.8%) of the patients no information on statin use was available.  Of the 2636 patients included in the registry, 1286 (48.8%) were using statins. Those on statins had more co-morbidities. An adjusted regression analysis showed statin use to be associated with significant reduction in CV death OR: 0.50 (0.30-0.83)2; P<0.0001), all-cause mortality OR: 0.52 (0.37-0.73; p<0.0001) and the composite endpoint of CV death and any thromboembolic event or bleeding OR: 0.71 (0.52-0.98; P< 0.0001). Sub group analyses of certain “high risk” patients, such as elderly, post CABG, post AMI, PAD/TIA CVA and high CHA2DS2VASc score (≥2) patients, were not significantly different from the overall cohort. The authors suggest that AF persé can be considered as a CVD risk factor independent from their role in TIA/Stroke and cardiac arrhythmia’s. Despite the limitations of observational nature of this analysis the observed benefits fit with earlier studies.
Proietti M, Laroche C, Nyvad O et al. Use of statins and adverse outcomes in patients with atrial fibrillation: An analysis from the EURObservational Research Programme Atrial Fibrillation (EORP-AF) general registry pilot phase. Int J Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28859841
 
CETP inhibition on top of high intensity statins showed benefits and no harm in REVEAL
The REVEAL trial (n=30 449) presented at the ESC in Barcelona was the first study showing cardiovascular benefits of a CETP inhibitor. Anacetrapib 100 mg was evaluated for 4.1 years in 15 224 patient’s vs 15 525 patients using a placebo. All were ASCVD patients receiving high dose atorvastatin and a mean baseline LDL-c of 61 mg/dl. The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. HDL-c increased by 104 % and LDL-c was lowered by 41%. however the non-HDL-C only reached modest -18% reduction. In the anacetrapib cohort 1641 patients (10.8%) experienced the primary endpoint vs 1803 (11.8%) in the placebo group. A HR: 0.91 (0.85-0.97; p=0.004). The primary endpoint was largely driven by the MI’s; HR 0.87 (0.78-0.96; P=0.03). No CVD mortality difference was observed between the two treatment arms; HR 0.92 (0.80-1.06; P=0.25). No significant difference between prespecified subgroups were noted either. Anacetrapib was well tolerated and reported side effects were few. Noted were higher systolic (+0.7 mm Hg) and diastolic (+0.3 mmHg) blood pressures. Also e-GFR’s < 60 ml/min/1.73m2 were found more frequently in the anacetrapib group (11.5%) than in the patients using placebo (10.6%); P=0.00. The authors concluded that inhibition of CETP with anacetrapib in combination with intensive statin treatment in ASCVD patient significantly reduced event rates during 4 years of treatment.
Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease. N Engl J Med 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28847206
Relevant publications
  1. Zamani E, Mohammadbagheri M, Fallah M, Shaki F. Atorvastatin attenuates ethanol-induced hepatotoxicity via antioxidant and anti-inflammatory mechanisms. Research in pharmaceutical sciences 2017; 12:315-321. http://www.ncbi.nlm.nih.gov/pubmed/?term=28855943
  2. Meor Anuar Shuhaili MFR, Samsudin IN, Stanslas J et al. Effects of Different Types of Statins on Lipid Profile: A Perspective on Asians. International journal of endocrinology and metabolism 2017; 15:e43319. http://www.ncbi.nlm.nih.gov/pubmed/?term=28848611
  3. Karlson BW, Palmer MK, Nicholls SJ et al. Effects of age, gender and statin dose on lipid levels: Results from the VOYAGER meta-analysis database. Atherosclerosis 2017; 265:54-59. http://www.ncbi.nlm.nih.gov/pubmed/?term=28863328
  4. El-Tamalawy MM, Ibrahim OM, Hassan TM, El-Barbari AA. Effect of Combination Therapy of Ezetimibe and Atorvastatin on Remnant Lipoprotein Versus Double Atorvastatin Dose in Egyptian Diabetic Patients. Journal of clinical pharmacology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28858387
  5. Bellows BK, Sainski-Nguyen AM, Olsen CJ et al. Identification of Patients with Statin Intolerance in a Managed Care Plan: A Comparison of 2 Claims-Based Algorithms. Journal of managed care & specialty pharmacy 2017; 23:926-934. http://www.ncbi.nlm.nih.gov/pubmed/?term=28854079
  6. Bays HE, Leiter LA, Colhoun HM et al. Alirocumab Treatment and Achievement of Non-High-Density Lipoprotein Cholesterol and Apolipoprotein B Goals in Patients With Hypercholesterolemia: Pooled Results From 10 Phase 3 ODYSSEY Trials. J Am Heart Assoc 2017; 6. http://www.ncbi.nlm.nih.gov/pubmed/?term=28862926
  7. Abdelmaksoud AA, Girerd PH, Garcia EM et al. Association between statin use, the vaginal microbiome, and Gardnerella vaginalis vaginolysin-mediated cytotoxicity. PLoS One 2017; 12:e0183765. http://www.ncbi.nlm.nih.gov/pubmed/?term=28846702
  8. Wanmasae S, Sirintronsophon W, Porntadavity S, Jeenduang N. The effect of APOE, CETP, and PCSK9 polymorphisms on simvastatin response in Thai hypercholesterolemic patients. Cardiovasc Ther 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28851085
  9. Wade RL, Patel JG, Hill JW et al. Estimation of Missed Statin Prescription Use in an Administrative Claims Dataset. Journal of managed care & specialty pharmacy 2017; 23:936-942. http://www.ncbi.nlm.nih.gov/pubmed/?term=28854076
  10. Tsujita M, Goto N, Futamura K et al. Triglyceride metabolism in Japanese kidney transplant recipients. Clinical and experimental nephrology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28849320
  11. Thoma C. Prostate cancer: Postdiagnosis statin use reduces mortality. Nat Rev Urol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28858336
  12. Schroff P, Gamboa CM, Durant RW et al. Vulnerabilities to Health Disparities and Statin Use in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study. J Am Heart Assoc 2017; 6. http://www.ncbi.nlm.nih.gov/pubmed/?term=28847913
  13. Sattar N, Toth PP, Blom DJ et al. Effect of the Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Evolocumab on Glycemia, Body Weight, and New-Onset Diabetes Mellitus. Am J Cardiol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28844508
  14. Rane PB, Patel J, Harrison DJ et al. Patient Characteristics and Real-World Treatment Patterns Among Early Users of PCSK9 Inhibitors. Am J Cardiovasc Drugs 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28849360
  15. Mayor S. Index indicates cholesterol management strategy for statin related muscle pain. Bmj 2017; 358:j4041. http://www.ncbi.nlm.nih.gov/pubmed/?term=28851746
  16. Marlatt KL, Steinberger J, Rudser KD et al. The Effect of Atorvastatin on Vascular Function and Structure in Young Adult Survivors of Childhood Cancer: A Randomized, Placebo-Controlled Pilot Clinical Trial. Journal of adolescent and young adult oncology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28853979
  17. Hyun KK, Brieger D, Woodward M et al. The effect of socioeconomic disadvantage on prescription of guideline-recommended medications for patients with acute coronary syndrome: systematic review and meta-analysis. International journal for equity in health 2017; 16:162. http://www.ncbi.nlm.nih.gov/pubmed/?term=28859658
  18. Furuyama F, Koba S, Yokota Y et al. Effects of Cardiac Rehabilitation on High-Density Lipoprotein-mediated Cholesterol Efflux Capacity and Paraoxonase-1 Activity in Patients with Acute Coronary Syndrome. J Atheroscler Thromb 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28855433
  19. Bertl K, Parllaku A, Pandis N et al. The effect of local and systemic statin use as an adjunct to non-surgical and surgical periodontal therapy-A systematic review and meta-analysis. Journal of dentistry 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28855141
  20. Bensimon L, Hale G. Acclimating to the Increase in Statin Use in Accountable Care Organizations Based on Changes in Quality Measures: A Report from the Accountable Care Organization Research Network, Services, and Education. Journal of managed care & specialty pharmacy 2017; 23:943-944. http://www.ncbi.nlm.nih.gov/pubmed/?term=28854072
Miscellaneous publications
  1. Wu M, Zhang WG, Liu LT. Red yeast rice prevents atherosclerosis through regulating inflammatory signaling pathways. Chin J Integr Med 2017; 23:689-695. http://www.ncbi.nlm.nih.gov/pubmed/?term=28861889
  2. Shen MH, Samsel P, Shen LL et al. Assessment of Response of Kidney Tumors to Rapamycin and Atorvastatin in Tsc1+/- Mice. Translational oncology 2017; 10:793-799. http://www.ncbi.nlm.nih.gov/pubmed/?term=28844017
  3. Lin PY, Chen CH, Wallace CG et al. Therapeutic effect of rosuvastatin and propylthiouracil on ameliorating high-cholesterol diet-induced fatty liver disease, fibrosis and inflammation in rabbit. American journal of translational research 2017; 9:3827-3841. http://www.ncbi.nlm.nih.gov/pubmed/?term=28861173
  4. Lai HY, Hsu LW, Tsai HH et al. CCAAT/enhancer-binding protein delta promotes intracellular lipid accumulation in M1 macrophages of vascular lesions. Cardiovascular research 2017; 113:1376-1388. http://www.ncbi.nlm.nih.gov/pubmed/?term=28859294
  5. Chen L, Li R, Huang X. [Role of atorvastatin in improving the inflammation-induced adipokine imbalance in mice with acute myocardial infarction]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 2017; 42:790-795. http://www.ncbi.nlm.nih.gov/pubmed/?term=28845002
  6. Li N, Li M, Yu Z et al. [One-step fermentation for producing simvastatin via RNAi silencing of lovF gene in Aspergillus terreus]. Sheng wu gong cheng xue bao = Chinese journal of biotechnology 2016; 32:478-486. http://www.ncbi.nlm.nih.gov/pubmed/?term=28853269
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