lipid guidelines who, what, and how 4-26-18 · lipid guidelines who, what, and how low anita...
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Lipid Guidelines Who, What, and How Low Anita Ralstin, MS, CNP Next Step Health Consultant, LLC New Mexico Heart Institute
Disclosures ! None
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.
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
Whose Guidelines? ! AHA/ACC 2013 guidelines with update 2017 for
non-statin therapy. ! http://www.onlinejacc.org/content/accj/
63/25_Part_B/2889.full.pdf ! http://www.onlinejacc.org/content/accj/
70/14/1785.full.pdf ! New guidelines expected this year.
! American Association of Clinical Endocrinologists (AACE) 2017 guidelines ! https://www.aace.com/files/lipid-guidelines.pdf
Choices, choices
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…
ACC ASCVD Risk App
10 year CV Risk Score Example
AHA/ACC 2013 Four Statin Groups Benefit Groups
Patient Group Major Recommendations Adults > 21 years with clinical ASCVD
! < 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 40-75 without ASCVD with DM and LDL 70-189
! Moderate-intensity statin ! 10 year risk > 7.5% consider
high-intensity Adults 40-75 without ASCVD, DM with LDL 70-189 and 10 year risk >7.5
! High-intensity ! 10 year risk 5-7.5% moderate
intensity
Intensity of Statin Therapy ACC/AHA 2013 Guidelines
High Moderate Low Lowers LDL > 50% Lowers LDL 30-50% Lowers LDL <30%
Atorvastatin 40-80 mg Rosuvastatin 20-40 mg
Atorvastatin 10-20 mg Fluvastatin 40 mg BID Fluvastatin XL 80 mg Lovastatin 40 mg Pravastatin 40-80 mg Rosuvastatin 5-10 mg Simvastatin 20-40 mg
Fluvastatin 20-40 mg Lovastatin 20 mg Pitavastatin 1 mg Pravastatin 10-20 mg Simvastatin 10 mg
ACC Statin Apps
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.
AHA/ACC 2013 Four Statin Benefit Groups 2017 Update
Patient Group Major Recommendations Update
Adults > 21 years with clinical ASCVD
! < 75 years, high-intensity statin (or moderate with safety concerns)
! > 75 moderate-intensity
! LDL reduction of >50% and may consider LDL <70 or non HDL < 100
! Add non-statin therapy
Adults > 21 years with LDL > 190
! High-intensity to achieve > 50% LDL reduction
! May consider combination therapy
Adults 40-75 without ASCVD with DM and LDL 70-189
! Moderate-intensity statin ! 10 year risk > 7.5%
consider high-intensity
Adults40-75 without ASCVD, DM with LDL 70-189 and 10 year risk >7.5
! High-intensity ! 10 year risk 5-7.5%
moderate intensity
ACC/AHA 2013 Guideline 2017 Update
High Moderate Low Lowers LDL > 50% Lowers LDL 30-50% Lowers LDL <30%
Atorvastatin 40-80 mg Rosuvastatin 20-40 mg
Atorvastatin 10-20 mg Fluvastatin 40 mg BID Fluvastatin XL 80 mg Lovastatin 40 mg Pravastatin 40-80 mg Rosuvastatin 5-10 mg Simvastatin 20-40 mg
Fluvastatin 20-40 mg Lovastatin 20 mg Pitavastatin 1 mg Pravastatin 10-20 mg Simvastatin 10 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
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
AACE Screening Tools
! Framingham Risk Assessment (https:// www.framinghamheartstudy.org/risk-functions/ coronary-heart-disease/hard-10-year-risk.php)
! Multi-Ethnic Study of Atherosclerosis (https://www.mesa-nhlbi. org/MESACHDRisk/MesaRiskScore/RiskScore. aspx)
! Reynolds Risk Score (http://www.reynoldsriskscore.org) ! United Kingdom Prospective Diabetes Study (UKPDS) (https://www.dtu.ox.ac. uk/riskengine)
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
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
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.
AACE Risk Categories
Risk Category Risk factors/10 year risk Extreme ! Progressive ASCVD including unstable
angina with LDL < 70 ! Established CV disease with DM, CKD 3-4
or HeFH ! History of premature ASCVD
Very High ! 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
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
Triglyceride Level Classification
TG Category TG Concentration mg/dL
Goal
Normal < 150 Borderline 150-199 < 150 High 200-499 < 150 Very High >500 < 150
Children and Adolescent LDL Levels
Category LDL, mg/dl Acceptable < 100 Borderline 100-129
High > 130
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
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 95th BMI or smoke ! Screen between 2-8 and 12-16 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
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
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
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%,
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%
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
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.
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%)
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 $14000.00/year ! Consider referral to lipid expert to evaluate and
initiate.
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
Odyssey 1 Trial alirocumab
From Highlights of Prescribing Information sanofi-adventis
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 13-17 years with HoFH ! No renal or hepatic dose adjustments
LAPLACE-2 Trial
From Highlights of prescribing Information: Repatha Amgen
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.
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
nicotinic acid/Niacin
! Side effect of flushing, itching, abd pain, hepatotoxicity
! Elevated serum glucose ! Increases uric acid levels
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.
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%
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.
Thank You ! Questions?