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Update - Week 06, 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

Can ezetimibe neutralize the glycemic dysregulation of high dose statins?
One of the well-recognized statin side effects is disruption of the glucose homeostasis. Although more pronounced in diabetics as well as patients with metabolic syndrome (MS) characteristics and despite the reduction of CVD events in these type of patients, it remains an unwanted metabolic effect of these lifesaving drugs. Studies with ezetimibe have shown some contradictory results, increasing insulin resistance as well as reducing insulin resistance and improving glucose metabolism. Remarkable effects of reducing hepatic lipid accumulation and other NAFLD markers have been observed as well. suggested mechanisms implicated in glycemic improvements were a diminished release of free fatty acid in the plasma, a reduction of chylomicron synthesis in the small intestine and even Bèta-cell protective effects in the pancreas. In this meta-analysis statins, high and low dose were compared to statin + ezetimibe combination therapy. Of the 2 440 screened articles, 16 RCT’s were included. Parameters used to study the effects were fasting blood glucose (FBG) and HbA1c. Ezetimibe use did not result in unfavorable changes of these parameters. This was similar in the combination of ezetimibe with low dose statin, compared to high dose statin. In the latter comparison combination therapy showed improved FBG: weighted mean difference (WMD) -1,78% (-3,13 - +1,90%); HbA1c WMD: -0.05% (-0.14 - +0.05%). Longer treatment (> 3months) seemed improve glycemic parameters even more, but because of the limited number of studies the data was inconclusive. Based on this limited meta-analysis the author postulated that combining ezetimibe with low dose statins is an alternative to high dose statins in patients were glycemic control is diminished or were patient run a high risk of developing diabetes. The effects of ezetimibe on glucose metabolism are still poorly understood and further studies are needed to confirm the protective effects of this cholesterol absorption inhibitor.
Wu H, Shang H, Wu J. Effect of ezetimibe on glycemic control: a systematic review and meta-analysis of randomized controlled trials. Endocrine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29397561
 
Statins to prevent VTE what is the evidence?
The authors reviewing the published trials that evaluated the protective effects of statins on VTE and PE come to the sobering conclusion that more questions than answers emerged from the collected data. Although earlier studies, starting with the 2009 Jupiter trial, seemed promising, recent data from RCT’s failed to confirm these findings. There seems to be a potential for statins in targeted therapy of patients with recurrent VTE and post thrombotic complication, especially as an add on treatment to standard anticoagulants. The safety of statins as well the lack of interaction with commonly used anti-coagulant therapies, are attractive properties, particularly in patients with high bleeding risk. Differences between statins as well as targeting specific statin types in specific patients, surfaced in the studies and presented in this review. What remains to be properly elucidated are the mechanisms of action by which statins influence and possibly improve VTE risk. The reduction of vascular inflammation might be one of the most prominent factors that statins can improve and explained the observed benefits in a number of studies. But the ultimate proof can only be provided if well designed additional prospective randomized trials are conducted. Differences and shared effects of the currently available types of statins as well as dosing, treatment duration and even specific clinical indications have to be determined before the we can confidently prescribe this class of drugs for VTE prevention.
Wallace A, Albadawi H, Hoang P et al. Statins as a preventative therapy for venous thromboembolism. Cardiovascular diagnosis and therapy 2017; 7:S207-s218. http://www.ncbi.nlm.nih.gov/pubmed/?term=29399524
 
Young DM patients headed for premature macro- and micro-vascular complications!
With an increasing number of individuals being overweight or obese in our global adult population, it was to be expected that young adults and even adolescents would follow suit. The rapid rise in the incidence of DM2 in this younger generations is of serious concern. The associated development of atherothrombotic macro-vascular complications as well as the debilitating micro vascular complications needs to be addressed by a targeted interventions. In this analysis the authors aimed to analyze changes in lipids and inflammatory markers in young type 2 diabetics that started with insulin, compared to those that continued with oral medication only. The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study was designed to compare the effect of 3 treatment regimens to maintain glycemic control in youth with recent-onset type 2 diabetes. Between July 2004 and February 2009; 699 young adolescents (10-17 years) with DM2, diagnosed <2years, were included. In this sub-analysis the impact of insulin on lipids and inflammatory markers in participants with poorly controlled DM2 was evaluated. An HbA1c cut-off level of 8.0% at 6 months was used for initiating insulin therapy. HbA1c levels improved marginally. Dyslipidemia improved in parallel with glycemic control and adding insulin had a modest effect on total cholesterol, LDL-cholesterol and total Apo B plasma concentrations. Statin use increased from 8.6% to 22% (per protocol statins were started if LDL-C reached ≥130 mg/dl). Triglycerides and non-esterified fatty acids stabilized after insulin therapy, this was not influenced by HbA1. Hs CRP continued to increase after insulin, and this was in parallel with HbA1c and percent overweight. The authors concluded that young   adolescents with type 2 diabetics show a rapid progression of biomarkers related to inflammation as well as a deteriorating lipid profile. If insulin fails to improve hyperglycemia none or only a modest effect on these important CVD risk factors can be expected. Based on these observations, adolescents are prone to experience accelerated atherosclerosis and subsequent macro and micro vascular complications much earlier in life. Based on these findings the urgency to come up with better management strategies, including lifestyle improvements are urgently needed.
Levitt Katz LE, Bacha F, Gidding SS et al. Lipid Profiles, Inflammatory Markers, and Insulin Therapy in Youth with Type 2 Diabetes. J Pediatr 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29398050
 
 
Are CAD intervention trials adhering to guideline dictated medical management?
Comparing trials that evaluated outcomes after PCI or CABG were the focus of this analysis. The authors aimed to evaluate how well patients were managed medically in these intervention trials and formulated two guideline-directed medical therapy (GDMT) benchmarks; GDMT1: any antiplatelet agent plus beta-blocker plus statin and GMDT2: any antiplatelet agent plus beta-blocker plus statin plus angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. They examined publications and reports in MEDLINE plus The Cochrane Central Register of Controlled Trials. Out of a total of 439 references, 5 trials were selected for evaluation using the methodological recommendations of The Cochrane Collaboration. The overall compliance to GDMT1 was surprisingly low, from 67% at the first year to 53% at year 5. The results for GDMT2 were even worse with a first-year percentage of 40% and a 5-year result of 38%. Intriguingly patients in the PCI studies had higher GDMT1 and GDMT2 scores at all time points, compared to post CABG patients. A meta regression analysis supported that adverse clinical outcomes were more frequently observed in patients with lower GDMT scores. The authors concluded that proper guideline dictated medical management in post procedural CAD patients was poor and that comparing outcomes in trials where patients were not treated in a similar fashion would make comparisons of clinical outcomes at 5 years quite challenging.
Pinho-Gomes AC, Azevedo L, Ahn JM et al. Compliance With Guideline-Directed Medical Therapy in Contemporary Coronary Revascularization Trials. J Am Coll Cardiol 2018; 71:591-602. http://www.ncbi.nlm.nih.gov/pubmed/?term=29420954
 
 
Modifiable risk factors in FH patients and CVD events
In the Netherlands the successful national Familial Hypercholesterolemia (FH) screening program has increased awareness of this disease among health care professionals significantly of the increased LDL-c levels improved as well. Diagnosed patients are now treated with high intensity- high dose statins not seldom combined with ezetimibe and if needed with PCSK9ab. One important question, addressed in this analysis is how to recognize good responder’s vs patients that continue to develop CV complications despite adequate management. In total 821 FH patients (53% women, median age 47.4 years), managed at a single specialized outpatient clinic at the Erasmus medical center in Rotterdam, were selected for this time -dependent analysis. Median duration of statin use was 9.5 (5.1-14.2) years and 64% used maximum lipid lowering treatment. Over the course of treatment 102/821 patients (12%) developed ASCVD complications (8 538-person years statin exposure time). Patients with ASCVD events had a median age of 53 year; more often experienced CVD events in the past  (32% vs 9%; p<0.001); had a positive family history of premature atherosclerosis 58% vs 40%; P<0.001), were hypertensive (70% vs 22%; P<0.001), had a higher on treatment LDL-c (162 ± 54 vs 135 ± 58 mg/dl; P<0.001); had a lower on treatment HDL-c (50 ± 15 vs 54 ± 15 mg/dl P<0.001) and were smokers (32% vs 14%; P<0.001). Additional CVD recurrences were observed in 31 patients (30%). The median time interval between the first and subsequent event was 5.7 years. Smoking was the factor that distinguished these patients form the patients that did not develop additional CVD complications (32% vs 10%; P< 0.01). The authors concluded that FH patients despite being treated with LDL-c lowering drugs are at risk for developing ASCVD complications. In this registry the driving force of developing CVD events were avoidable or treatable classic cardiovascular risk factors such as smoking and hypertension. These findings underline the importance of addressing all risk factors, including behavioral in addition to maximum lipid lowering therapy.
Galema-Boers AM, Lenzen MJ, Engelkes SR et al. Cardiovascular risk in patients with familial hypercholesterolemia using optimal lipid-lowering therapy. J Clin Lipidol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29398430
Relevant publications
  1. Filippatos TD, Panagiotopoulou T, Tzavella E, Elisaf MS. Hypolipidemic Drugs and Diabetes Mellitus-Mechanisms and Data From Genetic Trials. Journal of cardiovascular pharmacology and therapeutics 2018:1074248418757011. http://www.ncbi.nlm.nih.gov/pubmed/?term=29409336
  2. Etxeberria A, Alcorta I, Perez I et al. Results from the CLUES study: a cluster randomized trial for the evaluation of cardiovascular guideline implementation in primary care in Spain. BMC Health Serv Res 2018; 18:93. http://www.ncbi.nlm.nih.gov/pubmed/?term=29422049
  3. D'Elia L, La Fata E, Iannuzzi A, Rubba PO. Effect of statin therapy on pulse wave velocity: A meta-analysis of randomized controlled trials. Clinical and experimental hypertension (New York, N.Y. : 1993) 2018:1-8. http://www.ncbi.nlm.nih.gov/pubmed/?term=29420075
  4. Alghalyini B, El Shamieh S, Salami A et al. Effect of SLCO1B1 gene polymorphisms and vitamin D on statin-induced myopathy. Drug Metab Pers Ther 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29420305
  5. Al-Zakwani I, Al-Mahruqi F, Al-Rasadi K et al. Sex disparity in the management and outcomes of dyslipidemia of diabetic patients in the Arabian Gulf: findings from the CEPHEUS study. Lipids Health Dis 2018; 17:25. http://www.ncbi.nlm.nih.gov/pubmed/?term=29402296
  6. Zambrano T, Hirata RDC, Hirata MH et al. Statins differentially modulate microRNAs expression in peripheral cells of hyperlipidemic subjects: A pilot study. Eur J Pharm Sci 2018; 117:55-61. http://www.ncbi.nlm.nih.gov/pubmed/?term=29427701
  7. Yildizeli SO, Balcan B, Eryuksel E et al. Influence of Statin Therapy on Exacerbation Frequency in Patients with Chronic Obstructive Pulmonary Disease. Turkish thoracic journal 2017; 18:29-32. http://www.ncbi.nlm.nih.gov/pubmed/?term=29404156
  8. Wong ITY, Huang Y, Zhou Y. Drug Eruption to Rosuvastatin With Recurrence on Simvastatin: A Case Report. Journal of cutaneous medicine and surgery 2018:1203475418756376. http://www.ncbi.nlm.nih.gov/pubmed/?term=29400079
  9. Trivedi LU, Alvarez CA, Mansi IA. Association of Statin Therapy With Risk of Epilepsy in 2 Propensity Score-Matched Cohorts. The Annals of pharmacotherapy 2018:1060028018756650. http://www.ncbi.nlm.nih.gov/pubmed/?term=29400081
  10. To MS, Prakash S, Poonnoose SI, Bihari S. Dose-dependent effects of statins for patients with aneurysmal subarachnoid hemorrhage: meta-regression analysis. World neurosurgery 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29425980
  11. Talbot D, Delaney JAC, Sandfort V et al. Importance of the lipid-related pathways in the association between statins, mortality, and cardiovascular disease risk: The Multi-Ethnic Study of Atherosclerosis. Pharmacoepidemiol Drug Saf 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29405501
  12. Spiro J, Butts M. Atorvastatin-Induced Dermatomyositis: Resolution With Change in Statin? Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29424763
  13. Smit RAJ, Jukema JW, Postmus I et al. Visit-to-visit lipid variability: Clinical significance, effects of lipid-lowering treatment, and (pharmaco)genetics. J Clin Lipidol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29422286
  14. Shen H, Li R, Yan R et al. Adjunctive therapy with statins in schizophrenia patients: A meta-analysis and implications. Psychiatry research 2018; 262:84-93. http://www.ncbi.nlm.nih.gov/pubmed/?term=29427912
  15. Pokrywka GS. PCSK9 inhibitors: a non-statin cholesterol-lowering treatment option. Postgraduate medicine 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29411675
  16. Podzolkov VI, Bragina AE, Osadchiy KK. [A fixed-dose lisinopril+amlodipine+rosuvastatin combination: prospects for its use in patients with hypertension and concomitant dyslipidemia]. Ter Arkh 2017; 89:133-140. http://www.ncbi.nlm.nih.gov/pubmed/?term=29411773
  17. Otvos JD, Guyton JR, Connelly MA et al. Relations of GlycA and lipoprotein particle subspecies with cardiovascular events and mortality: A post hoc analysis of the AIM-HIGH trial. J Clin Lipidol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29409728
  18. Niu H, Wei Z, Zhang Y et al. Atorvastatin improves coronary flow and endothelial function in patients with coronary slow flow. Experimental and therapeutic medicine 2018; 15:904-908. http://www.ncbi.nlm.nih.gov/pubmed/?term=29399097
  19. Mittal S, Mohan A, Hadda V et al. Atorvastatin in Bronchiectasis With Chronic Pseudomonas Infection. Chest 2018; 153:579-580. http://www.ncbi.nlm.nih.gov/pubmed/?term=29406230
  20. Matsubara S, Bokuda K, Asano Y et al. Mitophagy in three cases of immune-mediated necrotizing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies: ultrastructural and immunohistochemical studies. Neuromuscular disorders : NMD 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29402601
  21. Lin TK, Liou YS, Lin CH et al. High-potency statins but not all statins decrease the risk of new-onset osteoporotic fractures: a nationwide population-based longitudinal cohort study. Clinical epidemiology 2018; 10:159-165. http://www.ncbi.nlm.nih.gov/pubmed/?term=29403315
  22. Kreuter M, Costabel U, Richeldi L et al. Statin Therapy and Outcomes in Trials of Nintedanib in Idiopathic Pulmonary Fibrosis. Respiration; international review of thoracic diseases 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29414827
  23. Kobalava ZD, Villevalde SV, Vorobyeva MA. [Alirocoumab: new perspectives of lipid-lowering therapy]. Ter Arkh 2017; 89:114-121. http://www.ncbi.nlm.nih.gov/pubmed/?term=29411770
  24. Einbond LS, Manservisi F, Wu HA et al. A transcriptomic analysis of turmeric: curcumin represses the expression of cholesterol biosynthetic genes and synergizes with simvastatin. Pharmacol Res 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29408497
  25. Desai P, Wallace R, Anderson ML et al. An analysis of the association between statin use and risk of endometrial and ovarian cancers in the Women's Health Initiative. Gynecologic oncology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29422345
  26. deFilippi C, Christenson R, Joyce J et al. Statin Effects on Myocardial Fibrosis Markers in People Living with HIV. J Acquir Immune Defic Syndr 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29419569
  27. Dawe DE, Ye X, Czaykowski P et al. The effect of statin use on the incidence of prostate cancer: A population-based nested case-control study. International journal of cancer. Journal international du cancer 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29405283
  28. Cohen AJ, Adamsky MA, Nottingham CU et al. Impact of Statin Intake on Kidney Stone Formation. Urology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29421299
  29. Chlebus K, Cybulska B, Gruchala M et al. Prevalence, diagnosis, and treatment of familial hypercholesterolaemia in outpatient practice in Poland. Kardiol Pol 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29399758
  30. Caro-Maldonado A, Camacho L, Zabala-Letona A et al. Low-dose statin treatment increases prostate cancer aggressiveness. Oncotarget 2018; 9:1494-1504. http://www.ncbi.nlm.nih.gov/pubmed/?term=29416709
  31. Cahill MS, Seifried RM, Cheringal JH et al. Implications of New Cholesterol Treatment Guidelines on Statin Utilization, Intensity, and Costs in Active Duty Service Members. Military medicine 2018; 183:e66-e70. http://www.ncbi.nlm.nih.gov/pubmed/?term=29401328
  32. Bravata DM, Myers LJ, Arling G et al. Quality of Care for Veterans With Transient Ischemic Attack and Minor Stroke. JAMA neurology 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29404578
  33. Addison D, Lawler PR, Emami H et al. Incidental Statin Use and the Risk of Stroke or Transient Ischemic Attack after Radiotherapy for Head and Neck Cancer. J Stroke 2018; 20:71-79. http://www.ncbi.nlm.nih.gov/pubmed/?term=29402065
Miscellaneous publications
  1. Zhou M, Zheng J, Bi J et al. Synergistic inhibition of colon cancer cell growth by a combination of atorvastatin and phloretin. Oncology letters 2018; 15:1985-1992. http://www.ncbi.nlm.nih.gov/pubmed/?term=29399200
  2. Yang F, Feng X, Rolfs A, Luo J. Lovastatin promotes myelin formation in NPC1 mutant oligodendrocytes. J Neurol Sci 2018; 386:56-63. http://www.ncbi.nlm.nih.gov/pubmed/?term=29406968
  3. Wang S, Zhang X, Zhai L et al. Atorvastatin Attenuates Cognitive Deficits and Neuroinflammation Induced by Abeta1-42 Involving Modulation of TLR4/TRAF6/NF-kappaB Pathway. Journal of molecular neuroscience : MN 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29417448
  4. Trogden KP, Battaglia RA, Kabiraj P et al. An image-based small-molecule screen identifies vimentin as a pharmacologically relevant target of simvastatin in cancer cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2018:fj201700663R. http://www.ncbi.nlm.nih.gov/pubmed/?term=29401610
  5. Song L, Tao X, Lin L et al. Cerasomal Lovastatin Nanohybrids for Efficient Inhibition of Triple-Negative Breast Cancer Stem Cells To Improve Therapeutic Efficacy. ACS applied materials & interfaces 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29405062
  6. Liang H, Feng Y, Cui R et al. Simvastatin protects against acetaminophen-induced liver injury in mice. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2018; 98:916-924. http://www.ncbi.nlm.nih.gov/pubmed/?term=29421861
  7. Demir C, Anil C, Bozkus Y et al. Do Statins Affect Thyroid Volume and Nodule Size in Patients with Hyperlipidemia in a Mildly to Moderately Iodine-Deficient Region? A Prospective Study. Medical principles and practice : international journal of the Kuwait University, Health Science Centre 2018. http://www.ncbi.nlm.nih.gov/pubmed/?term=29402848
  8. Delgado-Leon TG, Salas-Pacheco JM, Vazquez-Alaniz F et al. Apoptosis in pancreatic beta-cells is induced by arsenic and atorvastatin in Wistar rats with diabetes mellitus type 2. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) 2018; 46:144-149. http://www.ncbi.nlm.nih.gov/pubmed/?term=29413104
  9. Advani AS, Li H, Michaelis LC et al. Report of the relapsed/refractory cohort of SWOG S0919: A phase 2 study of idarubicin and cytarabine in combination with pravastatin for acute myelogenous leukemia (AML). Leukemia research 2018; 67:17-20. http://www.ncbi.nlm.nih.gov/pubmed/?term=29407182
  10. Wang J, Sun JY, Sha CJ et al. Optimization, validation and application of an assay for the activity of HMG-CoA reductase in vitro by LC-MS/MS. Journal of pharmaceutical analysis 2015; 5:383-388. http://www.ncbi.nlm.nih.gov/pubmed/?term=29403953
  11. Talluri M, Kalyankar A, Ragampeta S. Synchronized separation of atorvastatin-an antihyperlipidemic drug with antihypertensive, antidiabetic, antithrombotic drugs by RP-LC for determination in combined formulations. Journal of pharmaceutical analysis 2012; 2:285-292. http://www.ncbi.nlm.nih.gov/pubmed/?term=29403755
  12. Sharaf El-Din MMK, Salama FMM, Nassar MWI et al. Validated spectrofluorimetric method for the determination of atorvastatin in pharmaceutical preparations. Journal of pharmaceutical analysis 2012; 2:200-205. http://www.ncbi.nlm.nih.gov/pubmed/?term=29403743
  13. Ramesh B, Manjula N, Bijargi SR et al. Comparison of conventional and supported liquid extraction methods for the determination of sitagliptin and simvastatin in rat plasma by LC-ESI-MS/MS. Journal of pharmaceutical analysis 2015; 5:161-168. http://www.ncbi.nlm.nih.gov/pubmed/?term=29403928
  14. Polagani SR, Pilli NR, Gandu V. High performance liquid chromatography mass spectrometric method for the simultaneous quantification of pravastatin and aspirin in human plasma: Pharmacokinetic application. Journal of pharmaceutical analysis 2012; 2:206-213. http://www.ncbi.nlm.nih.gov/pubmed/?term=29403744
  15. Polagani SR, Pilli NR, Gajula R, Gandu V. Simultaneous determination of atorvastatin, metformin and glimepiride in human plasma by LC-MS/MS and its application to a human pharmacokinetic study. Journal of pharmaceutical analysis 2013; 3:9-19. http://www.ncbi.nlm.nih.gov/pubmed/?term=29403791
  16. Partani P, Verma SM, Gurule S et al. Simultaneous quantitation of atorvastatin and its two active metabolites in human plasma by liquid chromatography/(-) electrospray tandem mass spectrometry. Journal of pharmaceutical analysis 2014; 4:26-36. http://www.ncbi.nlm.nih.gov/pubmed/?term=29403866
  17. Mei ZB, Xiao Y. ACE Inhibitors and Statins in Adolescents with Type 1 Diabetes. N Engl J Med 2018; 378:579. http://www.ncbi.nlm.nih.gov/pubmed/?term=29419270
  18. Lu Y, Hu Q, Chen L et al. Interaction of deoxyschizandrin and schizandrin B with liver uptake transporters OATP1B1 and OATP1B3. Xenobiotica 2018:1-8. http://www.ncbi.nlm.nih.gov/pubmed/?term=29405807
  19. Karanam SR, Katakam P, Chandu BR et al. Simultaneous determination of ezetimibe and simvastatin in rat plasma by stable-isotope dilution LC-ESI-MS/MS and its application to a pharmacokinetic study. Journal of pharmaceutical analysis 2014; 4:286-294. http://www.ncbi.nlm.nih.gov/pubmed/?term=29403892
  20. Jonnalagadda VG, Metety VK, Choudhary K. ACE Inhibitors and Statins in Adolescents with Type 1 Diabetes. N Engl J Med 2018; 378:579. http://www.ncbi.nlm.nih.gov/pubmed/?term=29419269
  21. Flynn JT. ACE Inhibitors and Statins in Adolescents with Type 1 Diabetes. N Engl J Med 2018; 378:580. http://www.ncbi.nlm.nih.gov/pubmed/?term=29419271
  22. Dunger DB, Marcovecchio ML, Deanfield J. ACE Inhibitors and Statins in Adolescents with Type 1 Diabetes. N Engl J Med 2018; 378:580-581. http://www.ncbi.nlm.nih.gov/pubmed/?term=29414269
  23. Belal TS, Daabees HG, Abdel-Khalek MM et al. New simple spectrophotometric method for determination of the binary mixtures (atorvastatin calcium and ezetimibe; candesartan cilexetil and hydrochlorothiazide) in tablets. Journal of pharmaceutical analysis 2013; 3:118-126. http://www.ncbi.nlm.nih.gov/pubmed/?term=29403805
  24. Abdelwahab NS, El-Zeiny BA, Tohamy SI. Two spectrophotometric methods for simultaneous determination of some antihyperlipidemic drugs. Journal of pharmaceutical analysis 2012; 2:279-284. http://www.ncbi.nlm.nih.gov/pubmed/?term=29403754
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