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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThis selected update in dyslipidemia discusses the ongoing controversy between fibrate and niacin treatments, as well as the best evidence for lipid-lowering therapy in regards to issues of cardiovascular risk with diabetes. Also discussed is the ongoing question of whether statins cause diabetes.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELipid Disorders\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EFibrate and Niacin \u2013 An Ongoing Controversy\u003C\/h2\u003E\n         \u003Cp id=\u0022p-2\u0022\u003EMarshall B. Elam, PhD, MD, University of Tennessee Health Sciences, Memphis, Tennessee, USA, used a case-based approach to discuss controversy surrounding the use of fibrates and niacin to reduce cardiovascular (CV) risk in the age of statins.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EPost hoc analyses of cardiovascular disease (CVD) events in dyslipidemic subgroups of major fibrate trials showed significant CVD risk reductions, ranging from 31% (p=0.03) in Action to Control Cardiovascular Risk in Diabetes [ACCORD; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00000620\u0026amp;atom=%2Fspmdc%2F12%2F10%2F16.atom\u0022\u003ENCT00000620\u003C\/a\u003E] study [Ginsberg HN et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010] to 78% (p=0.002) in the Helsinki Heart Study [Tenkanen L et al. \u003Cem\u003ECirculation\u003C\/em\u003E 1995] (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). The Fenofibrate Intervention and Event Lowering in Diabetes [FIELD; Keech A et al. \u003Cem\u003ELancet\u003C\/em\u003E 2005] and ACCORD-Lipid [Ginsberg HN et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010] substudies also showed renal microvascular benefits from fenofibrate, as well as significant relative percent risk reduction for retinopathy [Chew EY et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010].\u003C\/p\u003E\n         \u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/12738\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/12738\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12738\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-4\u0022 class=\u0022first-child\u0022\u003EPost Hoc Analyses of CVD Events in Dyslipidemic Subgroups of Major Fibrate Trials.\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EIn May 2011, the Endocrine and Metabolic Drug Advisory Panel of the US Food and Drug Administration (FDA) reviewed the indication for combined fenofibric acid plus statin therapy for dyslipidemia. It found insufficient evidence that adding a fibrate to statin therapy reduces the risk of CVD events in patients with type 2 diabetes and noted the need for a trial to test the hypothesis [Goldfine AB et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011].\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EA US Veterans Administration Cooperative study\u2014Fenofibric Acid Intervention to Reduce Residual Risk in Statin-Treated Patients [VA-FIRST] study\u2014has a proposed start date in the fall of 2013. A second new trial, The Fixed Dose Simvastatin + Niacin-ER trial [HPS-Thrive; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00461630\u0026amp;atom=%2Fspmdc%2F12%2F10%2F16.atom\u0022\u003ENCT00461630\u003C\/a\u003E], is exploring the role of niacin following the Atherothrombosis Intervention in Metabolic Syndrome With Low HDL\/High Triglycerides: Impact on Global Health Outcomes [AIM HIGH; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00880178\u0026amp;atom=%2Fspmdc%2F12%2F10%2F16.atom\u0022\u003ENCT00880178\u003C\/a\u003E] trial. Respective outcomes from these studies will help determine the safety and efficacy of fibrates for mixed high-risk primary and secondary prevention and of niacin for additional low-density lipoprotein (LDL)-lowering effect in statin-treated patients.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ECV Risk in Patients With Diabetes Mellitus\u2014What Is the Best Evidence for Lipid-Lowering Therapy?\u003C\/h2\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EAnne Carol Goldberg, MD, Washington University School of Medicine, St. Louis, Missouri, USA, discussed the status of the Adult Treatment Panel (ATP) IV guideline and major trials that show significant evidence favoring aggressive lipid-lowering treatment to reduce CV risk in people with diabetes.\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EATP IV recommendations will reflect evidence from randomized controlled trials of lipid-lowering therapy on CV outcomes as well as high-quality meta-analyses of randomized controlled CV outcomes trials.\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003ERobinson and Stone [Robinson JG, Stone NJ. \u003Cem\u003EAm J Cardiol\u003C\/em\u003E 2006] used published subgroup analyses from statin event trials to evaluate the relationship between LDL-cholesterol (LDL-C) level and absolute risk of a CV event. Their findings showed that patients with coronary heart disease (CHD) and diabetes had the highest risk (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E).\u003C\/p\u003E\n         \u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/10\/16\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Relationship Between LDL-C Level and Absolute Risk of a CV Event.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-923773521\u0022 data-figure-caption=\u0022Relationship Between LDL-C Level and Absolute Risk of a CV Event.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/10\/16\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/10\/16\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/10\/16\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12737\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-10\u0022 class=\u0022first-child\u0022\u003ERelationship Between LDL-C Level and Absolute Risk of a CV Event.\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from Elsevier. Robinson JG, Stone NJ. Identifying Patients for Aggressive Cholesterol Lowering: The Risk Curve Concept. \u003Cem\u003EAm J Cardiol\u003C\/em\u003E 2006;98(10):1405\u20131408.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EA 2008 meta-analysis by the Cholesterol Treatment Trialists\u0027 Collaborators included 14 randomized statin outcomes trials and used individual patient-level analyses in patients with diabetes. Similar effects on CV event reduction were seen in patients with diabetes with and without vascular disease. There was a 21% reduction in major vascular events per 39-mg\/dL LDL-C reduction [Cholesterol Treatment Trialists\u0027 (CTT) Collaborators. \u003Cem\u003ELancet\u003C\/em\u003E 2008].\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EStatins are the evidence-based drugs of choice for primary and secondary CV risk reduction. The CTT Collaboration [Baigent C et al. \u003Cem\u003ELancet\u003C\/em\u003E 2010] found that further reductions in LDL-C safely produce greater declines in the incidence of heart attack, revascularization, and ischemic stroke. Each 1.0-mmol\/L (18-mg\/dL) reduction in LDL-C lowers the annual rate of these major vascular events by just over one-fifth. Evidence suggests a 2-mmol\/L to 3-mmol\/L (36-mg\/dL to 54-mg\/dL) decrease in LDL-C would reduce risk by 40% to 50%.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EDo Statins Cause Diabetes?\u003C\/h2\u003E\n         \u003Cp id=\u0022p-13\u0022\u003ETrials of statin therapy have had conflicting findings on the risk of developing diabetes mellitus in patients who are given statins [Sattar N et al. \u003Cem\u003ELancet\u003C\/em\u003E 2010]. Naveed Sattar, MBChB, MRCP, British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom, discussed the relationship between statins and diabetes.\u003C\/p\u003E\n         \u003Cp id=\u0022p-14\u0022\u003EAccording to Prof. Sattar, skeptics of a relationship between statins and incident type 2 diabetes point to nonsignificant associations in trials with glucose data (OR 1.078; 95% CI, 0.97 to 1.17; p=32%); an analysis of 11 trials with biochemical analyses led to null results (p=0.10) and no link to baseline factors [Sattar N et al. \u003Cem\u003ELancet\u003C\/em\u003E 2010]. However, the body of evidence of an association between statins and incident diabetes mellitus is growing.\u003C\/p\u003E\n         \u003Cp id=\u0022p-15\u0022\u003EIn the Stroke Prevention by Aggressive Reduction of Cholesterol [SPARCL; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00147602\u0026amp;atom=%2Fspmdc%2F12%2F10%2F16.atom\u0022\u003ENCT00147602\u003C\/a\u003E] trial [Waters DD et al. J \u003Cem\u003EAm Coll Cardiol\u003C\/em\u003E 2011; Amarenco P et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2006], Waters et al. found that treatment with 80 mg of atorvastatin led to new-onset diabetes in 166 of 1905 patients versus 115 of 1898 who took placebo (HR, 1.44; 95% CI, 1.14 to 1.83). Researchers also found that the strongest predictors of new-onset type 2 diabetes were baseline fasting glucose and other features of the metabolic syndrome and that the greater the number of risk factors, the higher the risk of developing new-onset type 2 diabetes. There were 9 new cases of diabetes mellitus per 10 patients who were protected from major CVD events\u2014ie, a 44% (95% CI, 14% to 83%) increase in new-onset diabetes mellitus.\u003C\/p\u003E\n         \u003Cp id=\u0022p-16\u0022\u003EIn the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin [JUPITER; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00239681\u0026amp;atom=%2Fspmdc%2F12%2F10%2F16.atom\u0022\u003ENCT00239681\u003C\/a\u003E] trial [Ridker PM et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2008], investigators reported 7 new cases of diabetes mellitus per 10 patients who were protected from major CVD events (myocardial infarction, stroke, CVD death), or a 26% (95% CI, 4% to 51%) increase in new-onset diabetes mellitus. Similarly, in a pooled analysis of data from 5 statin trials, Preiss et al. [Preiss D et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2011] found that intensive-dose statin therapy was associated with an increased risk of new-onset diabetes compared with moderatedose statin therapy. As compared with moderatedose statin therapy, the number needed to harm per year for intensive-dose statin therapy was 498 for new-onset diabetes, while the number needed to treat per year for intensive-dose statin therapy was 155 for CV events.\u003C\/p\u003E\n         \u003Cp id=\u0022p-17\u0022\u003EGiven this evidence, the US FDA recently added information to statin labels regarding an effect of these agents on diabetes, noting that \u201cincreases in glycosylated hemoglobin (HbA1C) and fasting serum glucose levels have been reported with statin use,\u201d but adding that the \u201cFDA continues to believe that the CV benefits of statins outweigh these small increased risks\u201d [Goldfine AB. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2012].\u003C\/p\u003E\n         \u003Cp id=\u0022p-18\u0022\u003EUltimately, statin recommendations will not change, but new data might prompt physicians to measure glucose\/HbA1C when considering statins [Sattar N, Preiss D. \u003Cem\u003EDiabetologia\u003C\/em\u003E 2012], warn patients about a slight risk of diabetes mellitus, and use that information as an additional incentive to promote lifestyle changes [Goldfine AB. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2012].\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2012 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/12\/10\/16.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nznez2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nznez2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nznez2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}