Lipid Guidelines Who, What, and How Low. Anita Ralstin, MS, CNP Next Step Health Consultant, LLC New Mexico Heart Institute

Transcription

1 Lipid Guidelines Who, What, and How Low Anita Ralstin, MS, CNP Next Step Health Consultant, LLC New Mexico Heart Institute

2 Disclosures! None

3 Objectives! List factors used in screening for dyslipidemia in children, adolescents and adults! Discuss rational for pharmacological treatment as it relates to treatment goals.! Identify the role of statin and non-statin therapy in dyslipidemia management.! Name the significant differences between the ACA/ AHA and the AACE lipid guidelines.

4 Rationale of Guidelines! 2016 approximately 660,000 US residents had a new coronary event! 305,000 had recurrent events! Dyslipidemia is a primary, major risk factor! 30 year trends show improvement in LDL numbers but 69% have an LDL < 100! Doubling of obesity and elevated triglycerides levels

5 Whose Guidelines?! AHA/ACC 2013 guidelines with update 2017 for non-statin therapy.! 63/25_Part_B/2889.full.pdf! 70/14/1785.full.pdf! New guidelines expected this year.! American Association of Clinical Endocrinologists (AACE) 2017 guidelines!

6 Choices, choices

7 AHA/ACC 2013! Shared decision making! Lifestyle! Follow lab work to determine adherence! Approaches to statin intolerance! ACC Statin Intolerance app! Broad recommendations for non-statin therapy! Risk evaluation with

8 ACC ASCVD Risk App

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10 10 year CV Risk Score Example

11 AHA/ACC 2013 Four Statin Groups Benefit Groups Patient Group Adults > 21 years with clinical ASCVD Major Recommendations! < 75 years, high-intensity statin (or moderate with safety concerns)! > 75 moderate-intensity Adults > 21 years with LDL > 190! High-intensity to achieve > 50% LDL reduction! May consider combination therapy Adults without ASCVD with DM and LDL Adults without ASCVD, DM with LDL and 10 year risk >7.5! Moderate-intensity statin! 10 year risk > 7.5% consider high-intensity! High-intensity! 10 year risk 5-7.5% moderate intensity

12 Intensity of Statin Therapy ACC/AHA 2013 Guidelines High Moderate Low Lowers LDL > 50% Lowers LDL 30-50% Lowers LDL <30% Atorvastatin mg Rosuvastatin mg Atorvastatin mg Fluvastatin 40 mg BID Fluvastatin XL 80 mg Lovastatin 40 mg Pravastatin mg Rosuvastatin 5-10 mg Simvastatin mg Fluvastatin mg Lovastatin 20 mg Pitavastatin 1 mg Pravastatin mg Simvastatin 10 mg

13 ACC Statin Apps

14 AHA/ACC 2017 Update! IMPROVE-IT trial (2015): Patients with ACS statin + ezetimibe lowered LDL with clinically modest reduction in CV events over 7 years.! FDA approval: monoclonal antibodies to PCSK9 with favorable (18 month) outcome data, long term trials underway.

15 AHA/ACC 2013 Four Statin Benefit Groups 2017 Update Patient Group Major Recommendations Update Adults > 21 years with clinical ASCVD Adults > 21 years with LDL > 190 Adults without ASCVD with DM and LDL Adults40-75 without ASCVD, DM with LDL and 10 year risk >7.5! < 75 years, highintensity statin (or moderate with safety concerns)! > 75 moderate-intensity! High-intensity to achieve > 50% LDL reduction! May consider combination therapy! Moderate-intensity statin! 10 year risk > 7.5% consider high-intensity! High-intensity! 10 year risk 5-7.5% moderate intensity! LDL reduction of >50% and may consider LDL <70 or non HDL < 100! Add non-statin therapy

16 ACC/AHA 2013 Guideline 2017 Update High Moderate Low Lowers LDL > 50% Lowers LDL 30-50% Lowers LDL <30% Atorvastatin mg Rosuvastatin mg Atorvastatin mg Fluvastatin 40 mg BID Fluvastatin XL 80 mg Lovastatin 40 mg Pravastatin mg Rosuvastatin 5-10 mg Simvastatin mg Optional Interventions to Consider! Referral to lipid specialist and registered dietitian! Ezetimibe! Bile acid sequestrants! PCSK9 inhibitors! Mipomersen, loimtapide, LDL apheresis for familial hypercholesteremia Fluvastatin mg Lovastatin 20 mg Pitavastatin 1 mg Pravastatin mg Simvastatin 10 mg

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18 AACE Atherosclerotic CV Risk Factors Major Risk Factors Additional Risk Factors Nontraditional RF! Advancing age! High total cholesterol level! High Non HDL! High LDL! DM! HTN! CKD 3,4! Cigarette smoking! Family Hx! Obesity, abdominal obesity! Family Hx, hyperlipidemia! High small dense LDL! High Apo B! High LDL concentration! PCOS! Dyslipidemia triad! High lipoprotein (a)! High Clotting factors! High inflammatory markers (hscrp, Lp- PLA2)! High Homocysteine! Apo E4 isoform! High uric acid! High TG-rich remnants

19 AACE Screening Tools! Framingham Risk Assessment ( coronary-heart-disease/hard-10-year-risk.php)! Multi-Ethnic Study of Atherosclerosis ( org/mesachdrisk/mesariskscore/ RiskScore. aspx)! Reynolds Risk Score ( United Kingdom Prospective Diabetes Study (UKPDS) ( uk/riskengine)

20 AACE Screening Considerations! Women s ASCVD risk is frequently under assessed.! Use Reynolds or Framingham! Childhood and adolescence should be diagnosed early to reduce CV events in adulthood.! HDL > 60, subtract 1 risk factor! Elevated TG should be incorporated in risk assessment

21 Screening: Who and When! Familial hypercholesterolemia with family history of! Premature ASCVD (MI, SCD <55 yo father; < 65 yo mother (or first degree relative)! Adults with DM! Annual! Young adults! Every 5 years, age 20 or higher! Middle age adults (men 45-65; women 55-65)! 1-2 years! Older Adults (over 65)! Screen annually; both men and women! Children at risk (family Hx of premature ASCVD or high cholesterol! Initial screening at age 3, repeat 9-11 and age 18

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23 Lab Tests! Lipid profile! Can be done non-fasting if fasting is impractical! Apolipoproteins! ApoB reflects the particle concentration of LDL and all other atherogenic lipoproteins.! hscrp! Indicated inflammation in the body! Used to further assess risk when labs borderline.! Lipoprotein-associated phospholipase A2 (Lp-PLA2)! Further assess risk when hscrp elevated.

24 AACE Risk Categories Risk Category Extreme Very High Risk factors/10 year risk! Progressive ASCVD including unstable angina with LDL < 70! Established CV disease with DM, CKD 3-4 or HeFH! History of premature ASCVD! Established re recent hospitalization for ACS, 10 year risk > 20%! DM or CKD 3-4! HeFH High! > 2 risk factors and 10 yr risk 10-20%! DM or CKD 3-4 with no other risk Moderate! < 2 risk factors and 10 year risk < 10% Low! No risk factors

25 Treatment Goals Adults Risk LDL Non-HDL ApoB Extreme <55 <80 <70 Very High <70 <100 <80 High <100 < 130 < 90 Moderate < 100 < 130 < 90 Low < 130 < 160 NR

26 Triglyceride Level Classification TG Category TG Concentration mg/dl Normal < 150 Goal Borderline < 150 High < 150 Very High >500 < 150

27 Children and Adolescent LDL Levels Category LDL, mg/dl Acceptable < 100 Borderline High > 130

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29 Screening in Children and Adolescents! USPSTF December 2016 recommendations! Asymptomatic children and adolescents 20 years or younger there is insufficient evidence of benefit! Risk assessment to include obesity, familial hypercholesterolemia! When needed screen with lipid panel! Intervention: lifestyle

30 Screening in Children and Adolescents Cont d! National Heart Lung and Blood Institute endorsed by the American Academy of Pediatrics 2017! Universal screening 9-11 year olds with non-fasting lipid panel! Children with DM, HTN, over 95 th BMI or smoke! Screen between 2-8 and with fasting lipid.! AACE! Children at risk (family Hx of premature ASCVD or high cholesterol)! Initial screening at age 3, repeat 9-11 and age 18! Ongoing debate

31 The Over 75 Patient! Fewer older patients involved in trials.! Consider the 10 year ASCVD risk! Consider moderate vs high intensity statin therapy! Drug-drug interactions! Patient preference

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33 Treatment! Lifestyle! Physical activity! 4-6 times weekly 30 minutes! Nutrition! Reduced calorie, reduce saturated, trans fats, increase fiber and plant stanols/sterols! Nutrition counseling! Smoking cessation! Co-decision with patient

34 Pharmacologic Therapy! HMG-CoA reductase inhibitors (statins)! Reduce LDL 21-55%, up regulation of hepatic LDL receptors! Cholesterol absorption inhibitors (ezetimibe)! LDL reduction 10-18% alone! With statin LDL reduction 34-61%! PCSK9 (alirocumab/praluent, evolocumab/ Repatha)! LDL reduction 48-71%,

35 Pharmacologic Therapy cont d! Fibric acid derivatives: (gemfibrozil, fenofibrate, fenofibric acid)! TG reduction 20-35%, fenofibrate reduces LDL and TC 20-25%! Niacin currently out of favor! Bile acid sequestrants (cholestyramine, colestipol, colesevelam! LDL reduction 15-25%

36 Statin Therapy! Refer to ACC/AHA statin intensity chart! Check LFTs prior to starting and as clinically indicated! Evaluate for myalgias and muscle weakness! Drug-drug interaction with some! CYP450 3A4, warfarin, cyclosporine protease inhibitors! Simvastatin 80 mg no longer recommended! Simvastatin 20 with amlodipine or ranolazine! Rosuvastatin plasma levels may be higher in Asian! New onset DM risk; monitor patients with metabolic syndrome

37 Statin Therapy! 1 year of statin use can see a 20-25% reduction in global CV risk. Those at higher risk have more benefit.! Safety! Myalgia: rhabdomyolysis extremely rare! Hemorrhagic stroke: odds ratio of 1:1.2! Diabetes: overweight, glucose intolerance, metabolic syndrome! Cost! Generic statin $48-120/year.! If followed 2013 AHA/ACC guidelines 12.3 million additional statin eligible would have a gain of 183,000 quality adjusted life years and save the US $3.8 billion in healthcare dollars.

38 Ezetimibe (Zetia)! Inhibits intestinal absorption of cholesterol! Dose: 10 mg daily! Rare myopathies! Most effective when co-administered with statin. (LDL reduction of 34-61%)

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40 PCSK9! Monoclonal antibodies that target and inactivate proprotein convertase subtilisin kesin 9, a liver protein. This results in reducing LDL receptor degradation and increased LDL clearance.! alirocumab/praluent and evolocumab/repatha! Similar benefits and minimal SE! Both SQ administration! Costly $ /year! Consider referral to lipid expert to evaluate and initiate.

41 alirocumab/praluent! 75 mg SQ every 2 weeks; max dose 150 mg every 2 weeks! Alternative 300 mg every 4 weeks! Check LDL 4-8 weeks! Missed dose! Within 7 days take, longer than 7 days wait till next scheduled dose.! Refrigerate! No data on pregnancy/lactation! No renal or hepatic dosing adjustments! No change in statin dose

42 Odyssey 1 Trial alirocumab From Highlights of Prescribing Information sanofi-adventis

43 evolocumab/repatha! 140 mg SQ every 2 weeks or 420 mg once a month! Indicated for ASHD, HoFH and HeFH! Check LDL 4-8 weeks post initiation! Missed dose! Within 7 days take, longer than 7 days wait till next scheduled dose.! Refrigerate! No pregnancy/lactation data! Small study with 10 youth years with HoFH! No renal or hepatic dose adjustments

44 LAPLACE-2 Trial From Highlights of prescribing Information: Repatha Amgen

45 Non-Statin Cost Effectiveness! Ezetimibe brand name $2600/ year.! To be cost effective would need an 80% reduction in cost of brand ($575/ year)! Generic has not been researched and costs $550-$2550/year! PCSK9! Not cost effective at current $14,000 per year.! Would need to be in the $4000-$6000 to be cost effective.! Consider for the extremely high risk individual.

46 Fibric Acid Derivatives! gemfibrozil may increase LDL 10-15%, increase risk of myalgias! fenofibrate or fenofibric acid:! Several dosing amounts! Indicated for hypertriglyceridemia, hypercholesterolemia, mixed dyslipidemia! Usually well tolerated! Reduce dose for mild to moderate GFR impairment.! Contraindicated for GFR <30

47 nicotinic acid/niacin! Side effect of flushing, itching, abd pain, hepatotoxicity! Elevated serum glucose! Increases uric acid levels

48 Bile Acid Sequestrants! cholestyramine, colestipol, colesevelam! Action: bind cholesterol rich bile acids and eliminate in stool.! Side effects of GI complaints! Bind other drugs and reduce absorption! Reduce absorption of fat soluble nutrients! Use as an alternative to ezetimibe.

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50 MTP inhibitor! lomitapide (Juxtapid) indicated only for adults with homozygous familial hypercholesterolemia (HoFH)! Prescriber certification required! Prior authorization required! Dose capsules 5mg to 60 mg! CYP3A4 drug-drug interaction! Hepatotoxicity! High number of GI side effects reported! High cost! Single arm, uncontrolled study of 29 patients LDL reduction of 45%

51 Follow up and Monitoring! AACE: Reassess lipid status 6 weeks after initiation and at 6 week intervals until treatment goal reached.! Check LFTs before starting and at 3 months post initiation. Repeat periodically.! AHA/ACC: follow up in 4-12 weeks with lipid panel until goal reached.! Complex patients: consider referral to lipid specialist.

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53 Thank You! Questions?