2013 Cholesterol Guidelines: Clarity and Controversy

Transcription

1 2013 Cholesterol Guidelines: Clarity and Controversy Sco9 J Deron DO, FACC Diplomate American Board Clinical Lipidology 2013 Cholesterol Guidelines: Background ATP III last updated NHLBI started data review CV Risk assessment Lifestyle modificaron to reduce CV risk Management of overweight/obesity Cholesterol management 1

2 InsRtute of Medicine: Only use high quality evidence Partner with organizarons 15 member commi9ee convened with no or minimal Res to industry Scope of 2013 Guideline The expert panel charged with updarng guidelines using only highest quality data RCTs SystemaRc Reviews Meta- analyses of RCTs Speaks to adults only CriRcal QuesRons: 1 What is the evidence for LDL- C and non- HDL- C goals for the secondary preven1on of ASCVD? 2 What is the evidence for LDL- C and non- HDL- C goals for the primary preven1on of ASCVD? 2

3 CriRcal QuesRons 3. For primary and secondary prevenron, what is the impact on lipid levels, effecrveness, and safety of specific cholesterol modifying drugs used for lipid management in general and in selected subgroups? It should be noted, 2 meta- analyses published a"er the compleron of the Expert Panel s systemarc review provide strong evidence that starns reduce total mortality in primary prevenron. The Expert Panel acknowledges that our process did not provide for a comprehensive approach to the detecron, evaluaron, and treatment of lipid disorders as was done in the prior ATP III Report. However, these guidelines were never intended to be a comprehensive approach to lipid management for purposes other than ASCVD risk reducron. 3

4 A limited number of expert opinion recommendarons were made only when RCT evidence was not present and aeer a thorough consideraron of what the Expert Panel had learned from the RCTs. For the many quesrons regarding complex lipid disorders that are beyond the scope of our systemarc evidence review, or for which li9le or no RCT data are available, it is anrcipated that clinicians with lipid experrse can contribute to their management. What s New? 4 starn benefit groups No more treat to goal No more rourne use of non- starn drugs Safety recommendarons Role of biomarkers and noninvasive tests A new tool for esrmarng 10 year risk* Wiggle room Lifestyle remains the foundaron of ASCVD risk reducron 4

5 The absolute reducron in ASCVD events is proporronal to baseline absolute risk Data overview: The panel found extensive and consistent data supporrng starn use for the prevenron of ASCVD in many higher risk groups and all secondary prevenron trials in those without NYHA class II- IV heart failure and who were not receiving dialysis Four StaRn Benefit Groups Those with clinical ASCVD LDL 190 mg/dl or above DiabeRcs 10 year ASCVD risk 7.5% or above 5

6 Clinical ASCVD ACS Hy MI Stable/unstable angina Coronary/peripheral revascularizaron Stroke/TIA PAD Clinical ASCVD Treatment Age 75 or less: High- intensity starn Age > 75: Moderate- intensity starn StaRn Intensity Moderate Typically lower LDL 30-50% Atorva 10, 20 Rosuva 5, 10 Simva 20,40 Prava 40, 80 Lova 40 Fluva XL 80 Pitava 2, 4 High Typically lower LDL > 50% Atorva 40, 80 Rosuva 20, 40 6

7 LDL 190+ High- intensity starn Moderate- intensity if not candidate for high- intensity DM: Type 1 or 2 Age Moderate intensity starn High intensity starn if 10 year risk 7.5% + 10 Year Risk Calculator 7

8 10- year ASCVD Risk 7.5% +: moderate- to- high intensity starn 5-7.5%: moderate intensity starn 8

9 Wiggle Room For those not in 1 of the 4 starn benefit groups, and for whom a decision to inirate starn therapy is otherwise unclear, addironal factors may be considered to inform treatment decision making LDL 160 mg/dl + GeneRc hyperlipidemias +FH premature disease: <55 male, <65 women hs- CRP > 2 mg/l CAC Agatston units or > 75 th percenrle age/sex/ethnicity Ankle- brachial index < 0.9 Elevated liferme ASCVD 9

10 Out with the old Treat to target: No clinical trial data indicate what the target should be Magnitude of benefit from one target vs another unknown Risk of mulr- drug therapy to get to goal not evaluated More trouble with targets Overtreat some Undertreat others Non- StaRn Drugs As of yet, there are no data to show that adding a nonstarn to high- intensity starn will provide incremental risk reducron with an acceptable margin of safety AIM- HIGH: adding niacin to those w high trigs and low HDL furle ACCORD: adding fenofibrate to diabercs furle 10

11 Caveats 190 mg/dl + or Trigs > 500 Evaluate for secondary causes: 4 Ds Diet Drugs Diseases Disorders of metabolism Diet LDL Saturated or trans fats Weight gain Anorexia nervosa Triglycerides Weight gain Very low fat diets Highly processed carbs Etoh Drugs LDL DiureRcs Cyclosporine Steroids amiodarone Triglycerides Oral estrogens Steroids BAS Protease inhibitors ReRnoic acid 11

12 Diseases LDL Biliary obstrucron NephroRc syndrome Triglycerides NephroRc syndrome Chronic renal failure lipodystrophies Disorders of metabolism LDL Hypothyroidism Obesity Pregnancy Triglycerides Poorly controlled DM Hypothyroidism Obesity Pregnancy LDL 190 mg/dl + IniRate cascade screening 12

13 LDL 190 mg/dl + Check for secondary cause High- intensity of maximally tolerated Aim for 50 % + reducron Consider adding nonstarn agents if inadequate response Primary PrevenRon < 190 Use 10 year risk esrmator (pooled cohort equaron If 7.5 % +, moderate of high intensity starn If %, moderate intensity (weak strength of evidence) Secondary PrevenRon High- intensity or maximal tolerated dose 13

14 Safety Issues Before treatment Check ALT If normal, does not need followed unless signs/symptoms of heparc compromise On Treatment Check Lipid panel 8-12 weeks Verifies compliance Screens for up regularon of PCSK9 In group if < 50% reducron opens doors to other treatment oprons 14

15 Adverse Events Significant myopathy: 1:10,000 Hemorrhagic stroke: 1:10,000 Asian ancestry Adverse Events StaRn Rx New onset DM Varies by starn intensity Moderate 1:1000 High 3:1000 The long- term adverse effects of starn associated cased of diabetes over a 10 year period are unclear and are unlikely to be equivalent to an MI, stroke or ASCVD death. Muscle Symptom Algorithim Helpful to document pre rx degree of muscle symptoms including severity metric RouRne CK not needed pre rx Unexplained severe muscle symptoms or fargue: Stop starn CK CreaRnine UA for myoglobinuria 15

16 Muscle Symptom Algorithm Mild to moderate symptoms: Stop starn Screen for other causes: Etoh Hypothyroidism Reduced renal/heparc fx Rheumatologic diseases; PMR Steroid myopathy Vitamin D deficiency Muscle Symptom Algorithm If symptoms resolve while holding starn resume at original or lower dose of same starn to establish cause/effect If symptoms recur try low dose alternarve starn If symptoms persist x 2 months aeer stopping, assess for other causes Confusion/Memory Issues Eval for non starn causes Sepsis Neuropsych issues Consider starn erology 16

17 StaRns in Women of childbearing age Contraindicated But 2 forms of birth control if not surgically sterilized ideally NYHA FC II- IV HF Chronic Hemodialysis StaRns no be9er then placebo, even when HF is ischemic Controversy 17

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22 It should be noted, 2 meta- analyses published aeer the compleron of the Expert Panel s systemarc review provide strong evidence that starns reduce total mortality in primary prevenron. 22

23 Clinical Conundrum: How many rounds are you willing to go toe- to- toe with the pharmacophobe? Key element from morvaronal interviewing: RULE Use the benefits of Epic, keep the door open These guidelines are not a replacement for clinical judgement; they are meant to guide and inform decision- making. 23

24 Areas of Uncertainty Hypertriglyceridemia Role of non- HDL cholesterol measurements Role of Advanced Lipid TesRng Understanding LifeRme ASCVD risk Whether subgroups of HF/HD parents benefit from lipid intervenron Areas of Uncertainty Long- term effects of starn- associated new onset DM Safety and efficacy of starns in groups excluded from RCTs: HIV pts and organ transplant pts, those w rheumatologic/ inflammatory disease state Role of pharmacogenerc tesrng One Lipidologist s Thoughts Relying on RCTs only is problemarc The 6 most dangerous words in EBM: there is no data to suggest Largely ignored: Family history Pathophysiology Residual risk Metabolic syndrome parents 24