MD Conference Express ADA 2012 - (Page 17)
ATP 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. Robinson and Stone [Robinson JG, Stone NJ. Am J Cardiol 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 (Figure 1). Figure 1. Relationship Between LDL-C Level and Absolute Risk of a CV Event.
80 Cardiovascular Event Rate (%) 70 60 50 40 30 20 10 0 CHD + MS or IFG CHD+diabetes
According 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. Lancet 2010]. However, the body of evidence of an association between statins and incident diabetes mellitus is growing. In the Stroke Prevention by Aggressive Reduction of Cholesterol [SPARCL; NCT00147602] trial [Waters DD et al. J Am Coll Cardiol 2011; Amarenco P et al. N Engl J Med 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—ie, a 44% (95% CI, 14% to 83%) increase in new-onset diabetes mellitus. In the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin [JUPITER; NCT00239681] trial [Ridker PM et al. N Engl J Med 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. JAMA 2011] found that intensivedose statin therapy was associated with an increased risk of new-onset diabetes compared with moderatedose statin therapy. As compared with moderate-dose 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. Given this evidence, the US FDA recently added information to statin labels regarding an effect of these agents on diabetes, noting that “increases in glycosylated hemoglobin (HbA1C) and fasting serum glucose levels have been reported with statin use,” but adding that the “FDA continues to believe that the CV benefits of statins outweigh these small increased risks” [Goldfine AB. N Engl J Med 2012]. Ultimately, statin recommendations will not change, but new data might prompt physicians to measure glucose/HbA1C when considering statins [Sattar N, Preiss D. Diabetologia 2012], warn patients about a slight risk of diabetes mellitus, and use that information as an additional incentive to promote lifestyle changes [Goldfine AB. N Engl J Med 2012].
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CHD - No MS or IFG Diabetes - No CVD No CVD - No Diabetes 0 20 40 60 80 100 120 LDL (mg/dL) 140 160 180 200
Reproduced with permission from Elsevier. Robinson JG, Stone NJ. Identifying Patients for Aggressive Cholesterol Lowering: The Risk Curve Concept. Am J Cardiol 2006;98(10):1405-1408.
A 2008 meta-analysis by the Cholesterol Treatment Trialists’ 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’ (CTT) Collaborators. Lancet 2008]. Statins are the evidence-based drugs of choice for primary and secondary CV risk reduction. The CTT Collaboration [Baigent C et al. Lancet 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%. Do Statins Cause Diabetes? Trials of statin therapy have had conflicting findings on the risk of developing diabetes mellitus in patients who are given statins [Sattar N et al. Lancet 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.
Peer-Reviewed Highlights from the American Diabetes Association 72nd Annual Scientific Sessions
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Table of Contents for the Digital Edition of MD Conference Express ADA 2012
MD Conference Express ADA 2012
Contents
ORIGIN Trial Results
New Lessons in Hypertension and Diabetes
Closed-Loop Insulin Therapy in Young Children
The Precocious “AGE’ing” Effect of Type 1 Diabetes in Children
Abatacept in Patients with New-Onset Type 1 Diabetes: One-Year Follow-Up
Explaining the UKPDS Legacy Effect
Insulin and Cancer
Insulin Analogs
Dyslipidemia
Insulin Therapy
Incretin Therapies
Diabetes and Chronic Kidney Disease Guidelines Update
Managing Hyperglycemia in Hospitalized Patients
CVD Prevention and Treatment in Women With Diabetes
China Da Qing Study: Lifestyle Change in Women With IGT Extends Life
Markers of Macrovascular Complications in Pediatric Diabetes
Nonoperative Management of the Infected Diabetic Foot
Diabetic Retinopathy: Changing Prevalence and Severity Require Flexible Interventions
New ADA/EASD Position Statement Endorses a Patient-Centered Approach
MD Conference Express ADA 2012
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