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The State of Dyslipidemia Treatment USA-145-101385 © 2014 Amgen Inc. All rights reserved. Not for Reproduction.

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Presentation on theme: "The State of Dyslipidemia Treatment USA-145-101385 © 2014 Amgen Inc. All rights reserved. Not for Reproduction."— Presentation transcript:

1 The State of Dyslipidemia Treatment USA-145-101385 © 2014 Amgen Inc. All rights reserved. Not for Reproduction.

2 Table of Contents

3 Dyslipidemia

4 Mean Blood Cholesterol in the United States Is Among Highest in the World  193 mg/dL 180–193 mg/dL  166 mg/dL No data 167–179 mg/dL WHO = World Health Organization. 1 mg/dL=0.0259 mmol/L Adapted from WHO, Mean Blood Cholesterol in Males over 25 Years of Age, 1980–2008. 1. World Health Organization. Global Health Observatory (GHO). World Health Organization website. www.who.int/gho/ncd/risk_factors/cholesterol_prevalence/en/. Accessed October 23, 2014.

5 Total Cholesterol Levels Increase During Development and Remain Higher Than Those in Hunter-Gatherer Populations 50 40 30 20 10 0 US Population (%) TC Level (mg/dL) 2 80120160200240280320360400 Cholesterol levels for modern hunter- gatherer populations range from: 3 101 mg/dL–146 mg/dL Distribution of Total Serum Cholesterol Levels in ~34,000 US Adults From NHANES III (1988–1994) Developmental Period 1 Birth Weaned High fat Low fat Breast fed 250 200 150 50 0 100 Plasma TC (mg/dL) FetalNursing InfantAdult Formula diet TC Changes During Fetal Development Through Adulthood Exact N is not available for Hunter-gatherer data, but is likely in the hundreds. 1. Adapted from Dietschy JM, et al. J Lipid Res. 2004;45:1375-1397. 2. Schwartz LM, Woloshin S. Eff Clin Pract. 1999;2:76-85. 3. Eaton SB, et al. Am J Med. 1988;84:739-749. This information is meant to inform on levels at different stages of human development This information is meant to inform on levels at different stages of human development

6 In utero (wk) 1,c n = 79 Infants (mo) 2 n = 18 Adults (y) 3,* n = 8,174 a Formula fed. b Breast fed. c Umbilical cord plasma concentrations *NHANES trends in mean LDL-C serum levels of US adult respondents from 1999-2006, estimates are age adjusted to the 2000 standard US population using the direct method. †Mean Age-adjusted LDL-C levels- approx. 15,000 US adults from NHANES (1988-2010) 1. Parker CR Jr, et al. Metabolism. 1983;32:919-923. 2. Wong WW, et al. J Lipid Res. 1993;34:1403-1411. 3. Cohen JD, et al. Am J Cardiol. 2010;106:969-975. 4. Carroll MD, et al. JAMA. 2012;308:1545-1554 Mean LDL-C (mg/dL) Mean LDL-C by Age LDL-C Levels Rise After Adulthood and Remain Higher Than Those in Early Development b Age: Average LDL-C Levels in the US Years 4,† a LDL-C (mg/dL)

7 Clinical Guidelines Recommend LDL-C Lowering 1. American Diabetes Association. Diabetes Care. 2014;37(suppl 1):S14-S80. 2. Jellinger PS, et al. Endocr Pract. 2012;18(suppl 1):1-78. 3. Grundy SM, et al. J. Clin Lipidol. 2013;8:29-60. 4. Reiner Z, et al. Eur Heart J. 2011;32:1769-1818. 5. Stone NJ, et al. J Am Coll Cardiol. 2014;63:2889-2934. 6. Keaney JF, et al. N Engl J Med. 2014;370:275-278. ADA = American Diabetes Association; AACE = American Association of Clinical Endocrinologists; IAS = International Atherosclerosis Society; ESC = European Society of Cardiology; EAS = European Atherosclerosis Society; AHA = American Heart Association; ACC = American College of Cardiology AACE Guidelines 2 Targets LDL-C level Targets statin therapy intensity ADA Recommendations 1 ADA Recommendations 1 AACE Guidelines 2 AACE Guidelines 2 IAS Recommendations 3 IAS Recommendations 3 ESC/EAS Guidelines 4 ESC/EAS Guidelines 4 ACC/AHA Guidelines 5,6 ACC/AHA Guidelines 5,6

8 When Compared to Adult Treatment Panel III LDL-C Goals, ~ 48 Million American Adults With High LDL-C Were Not Treated or Not Adequately Treated 37 million are untreated 23 million were treated and at goal ‡ 11 million were treated, but not at goal ‡ Prevalence, Treatment, and Control of LDL-C Based on NHANES 2005-2008* *Extrapolated from data from 3,996 adults with high LDL-C aged ≥ 20 years in the National Health and Nutrition Examination Survey (NHANES) 2005- 2008. † High LDL-C defined as > 160 mg/dL for low-risk adults; > 130 mg/dL for moderate-risk adults; and > 100 mg/dL for high-risk adults or the use of cholesterol-lowering medication. ‡ Adult Treatment Panel (ATP) III LDL-C goals: < 160 mg/dL for low-risk adults; < 130 mg/dL for moderate-risk adults; and < 100 mg/dL for high-risk adults. Kuklina EV, et al. Morbidity and Mortality Weekly Report. 2011;60:109-114. US Adult Population US Adults With High LDL-C

9 A Substantial Percentage Do Not Achieve LDL-C < 70 mg/dL Despite Maximal Statin Therapy Individual patient data pooled meta-analysis, N=32,258 of 37 studies, comparing efficacy of various statins in At Risk Groups (VOYAGER). On multivariate analysis, baseline lipid level (p < 0.0001) and increasing statin dose (p < 0.0001) were strong predictors of achieving treatment goals in high risk patients. Studies were identified by a comprehensive search of the Cochrane Controlled Trials Registry, Medline (1999-2007), EMBASE (1999-2007) Citeline Trialtrove, and collection of all published research. Maximal intensity included average between two high dose groups of † 20 and 40 mg of statin 1 and ‡ 40 and 80 mg of statin 2. High dose statin per ACC/AHA guidelines = statin 2, 40-80 mg; statin 1, 20-40 mg. 1. Nicholls SJ, et. al. Am J Cardiol. 2010; 105:69-76. 2. Stone NJ, et al. J Am Coll Cardiol. 2014;63:2889-2934. LDL-C > 70 mg/dL < 130 mg/dL130-160 mg/dL> 160 mg/dL While on Maximal Statin Therapy The Percent of Patients Not Achieving LDL-C < 70 mg/dL By Baseline LDL-C Maximal Intensity † (20 and 40 mg) of Statin 1 Maximal Intensity ‡ (40 and 80 mg) of Statin 2 Baseline LDL-C

10 Number of High Risk US Adults Achieving LDL-C Levels of < 100 mg/dL or LDL-C Levels of < 70 mg/dL, Respectively LDL-C < 100 mg/dLLDL-C < 70 mg/dL Percent of Total Jones, PH, et al. J Am Heart Assoc. 2012;1:e001800. High-risk patients were defined as patients older than 18 years with a history of CHD or CHD risk equivalent who had the latest complete lipid panel measurement and were treated with statin monotherapy for > 90 days. EMR = electronic medical record database collected from 40,000 clinicians and 20,000 NP and PA (GE Centricity); Administrative Claims Database of the medical and pharmacy claims for 42MM patients enrolled in a large US managed care plan (Clinformatics DataMart, a product of Optuminsight Life Sciences); NHANES=National Health and Nutrition Examination Survey, a national public health survey conducted by the CDC of a nationally representative sample of 5000 individuals each year across a country. As per NCEP ATP III, the LDL-C goal patients was <100 mg/dL. High-risk patients were also evaluated for the optional goal of LDL-C <70 mg/dL, as per the 2004 update to the NCEP ATP III Guidelines.

11 Multiple Causes Exist For Failure To Achieve Desired LDL-C Patients with very high baseline 1 Adherence difficulties 2 Inability to tolerate optimal therapy 3 Limited access to optimal therapy 1,4 Insufficient/limited access to screening 5 Other causes 1. Pijlman AH, et al. Atherosclerosis. 2010;209:189-194. 2. National Cholesterol Education Program (NCEP). Circulation. 2002;106:3143-3421. 3. Cohen JD et al. J Clin Lipidol. 2012;6:208-215. 4. Elis A, et al. Am J Cardiol. 2011;108:223-226. 5. Kuklina EV, et al. CDC Morbidity and Mortality Weekly Report. 2011;60:109-114.

12 Dyslipidemia in Diabetes

13 2009-2010 NHANES Data Show Those With Diabetes Are NOT Achieving Desired Lipid Levels Wong ND, et al. Am J Cardiol. 2013;112:373-379. Diabetes Population NOT Achieving Desired Levels (%) LDL cholesterol goal: 2 risk factors and Framingham risk score >20% or other previous CVD, diabetes, or chronic kidney disease; 40 mg/dL in men and >50 mg/dL in women. Triglyceride normal level: <150 mg/dL.

14 A Substantial Number of People With Diabetes Have High LDL-C < 100 mg/dL LDL-C > 100 mg/dL LDL-C < 70 mg/dL LDL-C > 70 mg/dL LDL-C Individuals With Diabetes and Cardiovascular Disease Ali MK, et al. N Engl J Med. 2013; 368:1613-1624. Data shown are from 3,355 adults in the National Health and Nutrition Examination Survey (NHANES) with a diagnosis of diabetes from a health care professional, and 97,310 adults who reported having diabetes from the Behavioral Risk Factor Surveillance System (BRFSS) survey. Data is from 2007-2010. (P<0.001)

15 Dyslipidemia in Familial Hypercholesterolemia

16 Familial Hypercholesterolemia Phenotypes FH HeterozygotesFH Homozygotes ~ 1 in 200 to 1:500 persons worldwide 1,4 ~ 1 in 1,000,000 persons worldwide 1 1 mutated allele 1 2 mutated alleles 1 TC: 350 to 500 mg/dL 3 TC: > 500 to > 1,000 mg/dL 1 LDL-C: 200–400 mg/dL 1,2 LDL-C: > 600 mg/dL 2 Half the number of LDLR expressed 3 LDLR activity absent or dysfunctional 3 TC = total cholesterol 1. Rader DJ, et al. In: Longo DL, et al, eds. Harrison’s Principles of Internal Medicine. Vol II.18th ed. New York, NY: McGraw Hill Medical. 2012:3145-3161. 2. Robinson JG. J Manag Care Pharm. 2013;19:139-149. 3. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Circulation. 2002;106:3143-3421. 4. Nordestgaard BG, et al. European Heart Journal. 2013;34:3478–3490.

17 Familial Hypercholesterolemia MotherFather X Offspring FH Heterozygotes FH Homozygote Goldstein JL, et al. Arterioscler Thromb Vasc Biol. 2009;29:431-438. Nordestgaard BG, et al. European Heart Journal. 2013;34:3478–3490. 1 in 200 to 1:500 in most populations Half-normal number of LDL receptors 2-fold increase in plasma LDL 1 in 1 million population Absent or dysfunctional LDL receptors 6- to 10-fold increase in plasma LDL

18 67% LDLR 16.7% Others 2.3% PCSK9 14% ApoB *Autosomal Dominant Hypercholesterolemia. LDLR = LDL receptor; PCSK9 = Proprotein Convertase Subtilisin Kexin Type 9; ApoB = apolipoprotein B Seidah NG, et al. J Mol Med. 2007;85:685-696. Multiple Genetic Defects Causing Changes in Lipoprotein Metabolism Can Be Associated With Familial Hypercholesterolemia (FH)*

19 Nordestgaard BG, et al. European Heart Journal. 2013; 34: 3478-3490 Diagnosis of FH in the US is Approximately <1% of Estimated Prevalence Estimated percent of individuals diagnosed with FH in different countries/territories* *As a fraction of those theoretically predicted based on a frequency of 1/500 in the general population. As most countries do not have valid nationwide registries for FH, several values represent informed estimates from clinicians/experts in their respective countries.

20 Despite Maximal Treatment, A Low Percentage of Patients with HeFH Achieve LDL-C < 100 mg/dL *NCEP Adult Treatment Panel III Risk Category: Medium Risk: 20%).18 week RCT, double-blind parallel group where heterozygous (He) FH patients initiated statin treatment at 20 mg with forced titration to 40 and 80 mg in 1999-2000. N = 623 randomized; p Values were obtained from a logistic regression model. Global population consisted of 31% US patients. **Adults with HeFH were part of a cross-sectional study. 96% were on statin treatment where 34% were on maximum dose. N = 1249 met inclusion criteria. n = 304 patients on maximal therapy; Maximum lipid-lowering therapy was defined as maximum statin doses in combination with ezetimibe. Using outpatient visits to Lipid Clinics after February 2006. 1. Stein EA, et al. Am J Cardiol. 2003; 92:1287-1293. 2. Pijlman AH, et al. Atherosclerosis. 2010; 209:189-194. In Netherlands Estimates of HeFH Patients On Maximal Lipid Lowering Therapy Achieving LDL-C < 100 mg/dL** In a Randomized Global Clinical Trial of HeFH Patients, A Low Percentage Achieved LDL-C Levels of < 100 mg/dL on Maximal Treatment* < 100 mg/dL > 100 mg/dL % of Patients Achieving LDL-C Goal Per Risk Category Statin 1 Statin 2 † p < 0.05, n = 103 n = 37 n = 67 ‡ p < 0.001, n = 155


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