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Update - Week 23, 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

Using IVUS and OCT to determine differences between atorvastatin and atorvastatin + ezetimibe
Using two complimentary intravascular imaging techniques, IVUS and OCT, the authors aimed to compare the efficacy of atorvastatin monotherapy 10-20 mg vs atorvastatin 10 -20 mg + ezetimibe 10 mg. Endpoints were changes in plaque color (lipid content) and plaque volume.
Patients included in this study were 131 stable Japanese CAD patients that had an elective PCI and yellow plaques. They were randomized to one of the two options and re-evaluated after 9 months. LDL-C levels were not significantly different at baseline: 103±28 mg/dl and 100±28 mg/dl. LDL-C levels reached were 63±18 mg/dL A+E group C and to 75±17 mg/dl in A Group M (in both P<0.001). Yellow color grade decreased significantly but with no difference between the two groups A (2.1±1.1 vs. 1.7±1.0, P=0.005) and A+E (2.2±1.2 vs. 1.8±1.2, P=0.002). plaque volume remained stable in the A group: 48.5±10.2% vs. 48.2±10.4% (P=0.4), but decreased significantly in A+E patients: 50.0±9.8% vs. 49.3±9.8% (P=0.03). This difference was related to the lower LDL-C levels achieved in the A+E patients.
Ueda Y, Hiro T, Hirayama A et al. Effect of Ezetimibe on Stabilization and Regression of Intracoronary Plaque- The ZIPANGU Study. Circulation journal: official journal of the Japanese Circulation Society 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28592751
 
Statins contribute to better diastolic blood pressure control
This was a post-hoc analysis of a large Italian blood pressure registry, were all patient had home, clinic and ambulatory blood pressure measurements. The data of 5634 adult individuals (women 48.9%, age 60.5±11.6 years) was analyzed. Statin use was observed in 956 patients (17.3%). Patient that received statins were older, had higher BMI and prevalence of risk factors and comorbidities (P<0.001for all). Diastolic BP was lower, in all measurements, for the patients using statins: 67.3±9.4 vs. 70.9±9.7 mmHg (P<0.001). Achieving BP control was improved in statin users. The 24 hr. and nighttime DBP control were more frequently observed in the statin users group OR: 1.513 (1.295–1.767) and 1.357 (1.161–1.587); P<0.001 for both outcomes. The authors concluded that Statins helped to control BP and that statin use was associated with significantly lower DBP levels.
Tocci G, Presta V, Citoni B et al. Favourable impact of statin use on diastolic blood pressure levels: analysis of a large database of 24-hour ambulatory blood pressure monitoring. J Hypertens 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28582284
 
Determining CVD risk in Danish diabetic’s vs non-diabetics and absence of obstructive CAD
In this 7-year prospective follow-up study patient that had a coronary angiogram (CAG) and diabetes were compared to non-diabetic patients. The risk of cardiac events was estimated based on the observed CAG findings. The Western Denmark Heart Registry was queried and between January 1st, 2003 and December 31st, 2012, 93 866 patients were included. Overall 12 544 (13.4%) were diabetic at the time of CAG. The median follow-up time was 4.3 years. Death, cardiac death and MI’s were similar in the patients with and without diabetes, and absent obstructive CAD; RR 1.03 (95% CI 0.92–1.15), RR 1.21 (95% CI 0.90–1.64) and RR 0.88 (95% CI 0.65–1.17) respectively. Statin and aspirin use was observed more frequently in patients with diabetes and CAD. For statins 75.3% vs. 46.0%; for aspirin 65.7% vs. 52.7%. This significant treatment difference could have contributed to the unexpected finding of similar CVD risk in patients with and without diabetes, and absent obstructive CAD.
Olesen KKW, Madsen M, Egholm G et al. Patients With and Without Diabetes Without Significant Angiographic Coronary Artery Disease Have the Same Risk of Myocardial Infarction in a Real-World Population Receiving Appropriate Prophylactic Treatment. Diabetes Care 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28596210
 
 
Meta-analysis and systematic review examining the impact of statins in chronic liver disease
The authors queried all relevant database from inception – October 17, 2016. Overall 10 studies (N= 259 453) were included in the analysis, 9 observational studies and 1 randomized controlled trial. There were 54 441 statin users vs 205 012 non-statin users. They examined the pooled effects of statins on hepatic fibrosis that resulted in a HR 0.49 (0.39–0.62). In the sub-group analysis using ICD-9 code, and an alternative method to detect cirrhosis, HR 0.58 (0.51-0.65). If only ICD-9 code was used, HR 0.36 (0.29-0.44). Hepatitis C patients with fibrosis progression, HR 0.52 (0.37–0.73). Cirrhotic patients with hepatic decompensation, HR 0.54 (0.46–0.65). Mortality in observational studies, HR 0.67 (0.46–0.98) and in the RCT’s, HR 0.39 (0.15–0.99). Although the presented data looks very promising the data quality of the included studies was very poor due to the retrospective design and potential confounding. The authors conclude that before statins can be recommended routinely, additional well designed and conducted studies are needed. This meta-analysis is in-line with the previous analysis published in May and the reference is noted below as well.
Kamal S, Khan MA, Seth A et al. Beneficial Effects of Statins on the Rates of Hepatic Fibrosis, Hepatic Decompensation, and Mortality in Chronic Liver Disease: A Systematic Review and Meta-Analysis. Am J Gastroenterol 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28585556
Kim RG, Loomba R, Prokop LJ, Singh S. Statin Use and Risk of Cirrhosis and Related Complications in Patients with Chronic Liver Diseases: a Systematic Review and Meta-analysis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28479502
 
Adherence to statins reduces recurrent stroke risk in AFib and non AFib patients
Outpatients adherence to statins was studied in this 21-hospital integrated healthcare delivery system in the US. Overall 6 116 patients with ischemic stroke were discharged with a statin over a 5-year period, 1446 (23.6%) were diagnosed as AFib patients. The mean statin adherence rate (percentage of days covered) was 85%. The mean statin adherence rate (percentage of days covered) was 85. Better statin adherence over a 3-year period resulted in reduced risk for stroke recurrence, both in AFib patients HR 0.59 (0.43–0.81) and non-AFib patients HR 0.78 (0.63–0.97) A separate analysis for patients on warfarin showed comparable effects, HR 0.61 (0.41–0.89). The authors concluded that relation between adherence to statins and stroke recurrence is strong; no difference was observed for the patients with- or without AFib. AFib status is not a reason to exclude patients from secondary stroke prevention with statins.  
Flint AC, Conell C, Ren X et al. Statin Adherence Is Associated With Reduced Recurrent Stroke Risk in Patients With or Without Atrial Fibrillation. Stroke 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28596457

Relevant publications
  1. Vogel TJ, Goodman MT, Li AJ, Jeon CY. Statin treatment is associated with survival in a nationally representative population of elderly women with epithelial ovarian cancer. Gynecologic oncology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28596017
  2. Sherling DH, Perumareddi P, Hennekens CH. Metabolic Syndrome. Journal of cardiovascular pharmacology and therapeutics 2017; 22:365-367. http://www.ncbi.nlm.nih.gov/pubmed/?term=28587579
  3. Saeedi Saravi SS, Saeedi Saravi SS, Arefidoust A, Dehpour AR. The beneficial effects of HMG-CoA reductase inhibitors in the processes of neurodegeneration. Metabolic brain disease 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28578514
  4. Melendez QM, Krishnaji ST, Wooten CJ, Lopez D. Hypercholesterolemia: The role of PCSK9. Archives of biochemistry and biophysics 2017; 625-626:39-53. http://www.ncbi.nlm.nih.gov/pubmed/?term=28587771
  5. Kazi DS, Penko JM, Bibbins-Domingo K. Statins for Primary Prevention of Cardiovascular Disease: Review of Evidence and Recommendations for Clinical Practice. The Medical clinics of North America 2017; 101:689-699. http://www.ncbi.nlm.nih.gov/pubmed/?term=28577620
  6. Guglielmi V, Bellia A, Pecchioli S et al. Effectiveness of adherence to lipid lowering therapy on LDL-cholesterol in patients with very high cardiovascular risk: A real-world evidence study in primary care. Atherosclerosis 2017; 263:36-41. http://www.ncbi.nlm.nih.gov/pubmed/?term=28599257
  7. Braamskamp M, Langslet G, McCrindle BW et al. Effect of Rosuvastatin on Carotid Intima-Media Thickness in Children with Heterozygous Familial Hypercholesterolemia: The CHARON Study. Circulation 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28592434
  8. Allen SC, Mamotte CD. Pleiotropic and Adverse Effects of Statins- Do Epigenetics Play a Role? J Pharmacol Exp Ther 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28576976
  9. Sibbett RA, Russ TC, Deary IJ, Starr JM. Risk factors for dementia in the ninth decade of life and beyond: a study of the Lothian birth cohort 1921. BMC psychiatry 2017; 17:205. http://www.ncbi.nlm.nih.gov/pubmed/?term=28578665
  10. Kitrou P, Katsanos K, Karnabatidis D et al. Current Evidence and future perspectives on Anti-Platelet and Statin Pharmacotherapy for Patients with Symptomatic Peripheral Arterial Disease. Current vascular pharmacology 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28595535
  11. Christie R, Sketris I, Andreou P et al. Does the Number of Pharmacies a Patient Frequents Affect Adherence to Statins? Journal of population therapeutics and clinical pharmacology = Journal de la therapeutique des populations et de la pharamcologie clinique 2017; 24:e20-e50. http://www.ncbi.nlm.nih.gov/pubmed/?term=28594479
  12. Chang HY, Murimi I, Daubresse M et al. Effect of Direct-to-Consumer Advertising (DTCA) on Statin Use in the United States. Medical care 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28598891
  13. Ansheles AA, Rvacheva AV, Sergienko IV. Effect of Atorvastatin Therapy on the Level of CD34+CD133+CD309+ Endothelial Progenitor Cells in Patients with Coronary Heart Disease. Bulletin of experimental biology and medicine 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28577105

Miscellaneous publications
  1. Mitsuhashi T, Uemoto R, Ishikawa K et al. Endothelial Nitric Oxide Synthase-Independent Pleiotropic Effects of Pitavastatin Against Atherogenesis and Limb Ischemia in Mice. J Atheroscler Thromb 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28592707
  2. Lee YJ, Kim MJ, Yoon YS et al. Simvastatin treatment boosts benefits of apoptotic cell infusion in murine lung fibrosis. Cell death & disease 2017; 8:e2860. http://www.ncbi.nlm.nih.gov/pubmed/?term=28594406
  3. Fafilek B, Hampl M, Ricankova N et al. Statins do not inhibit the FGFR signaling in chondrocytes. Osteoarthritis and cartilage 2017. http://www.ncbi.nlm.nih.gov/pubmed/?term=28583899

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