lipid management 2018 - memorial hospital€¦ · •increased rate (3.0% versus 2.4%) of physician...
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Lipid Management2018
C. Samuel Ledford, MD
Interventional Cardiology
Chattanooga Heart Institute
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Disclosures
No Financial Disclosures
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Disclosures
• I am an Interventional Cardiologist
• I put STENTS in for a living
• My greatest allies are Fast Food and Cigarettes
• I dislike the phrase….“Plaque Regression”
• because they work…..I HATE STATINS
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Objectives
• Objective #1:
• Discuss Historical and Most Recent Recommendations in Lipid Management
•
• Objective #2:
• Review Role of Nonstatin Agents including PCSK9 Inhibitors
•
• Objective #3
• Present data related to medication safety including resulting ultralow LDL levels PCSK9 inhibitors
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Circulation. 2014 Jun 24;129(25 Suppl 2):S46-8.
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• The Expert Panel did not find evidence to support the use of specific LDL-C or non–high-density lipoprotein cholesterol (nHDL-C) target levels.
Although many clinicians use target levels (e.g., LDL-C levels less than 70 mg per dL for secondary prevention and less than 100 mg per dL for primary prevention)
• The Expert Panel did not find evidence to support the use of non-statins for the reduction of ASCVD events.
2013 ACC/AHA Guidelines for Lipid Management
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! A Meta-Analysis of Statin TrialsVery Low Levels of Atherogenic Lipoproteins and the Risk for
Cardiovascular Events
• 38,153 patients
• >40% of patients assigned to high-dose
statin therapy did not reach an LDL-C
target <70 mg/dl.
• large interindividual variability in the
reductions of LDL-C, non-HDL-C, and
apoB achieved with a fixed statin dose.
• patients who achieve an LDL-C level
<50 mg/dl are at lower CVD risk than
are those achieving an LDL-C level 75 to
<100 mg/dl.
- Boekholdt SM et al. JACC. 2014;64(5):485-494
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Endocr Practice. 2017;23(4):479-497
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87 Recommendations
2017 AACE Lipid Guidelines
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Treatment Goals are based on Risk Factors and Long Term Risk
ESC and AACE Lipid Guidelines
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• Determine ASCVD 10-year risk (high, intermediate, or low) using one or more of the following:
• Framingham Risk Assessment Tool
• MESA 10-year ASCVD Risk with Coronary Artery Calcification Calculator
• Reynolds Risk Score, which includes hsCRP and family history of premature ASCVD
• UKPDS risk engine to calculate ASCVD risk in individuals with T2DM
ESC and AACE Lipid- Recommendation
- Endocr Practice. 2017;23(4):479-497; Eur Heart J 2016;37:2999-3058
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ASCVD 10-year risk Calculator Framingham Heart Study
- Framinghamheartstudy.org
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ASCVD 10-year risk Calculator Reynolds Heart Risk Score
- reynoldsriskscore.org; JAMA 2007;297:611-619
Designed for Healthy, Nondiabetics
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ASCVD 10-year risk Calculator ESC SCORE Chart
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• Rule Out Secondary Causes of Dyslipidemia
2017 AACE Lipid- Recommendation
- Endocr Practice. 2017;23(4):479-497
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! Secondary Causes of Dyslipidemia• Medications
Corticosteroids
Antihypertensives (thiazide diuretics and beta blockers [except Coreg])
Oral Estrogen/Progestin, contraceptives
Anabolic steroids
Protease Inhibitors for HIV
Amiodarone
Cyclosporine
• Renal Disease
Nephrotic syndromes, CKD
• Thyroid Disease
Hypothyroidism
• Diabetes Mellitus
• Liver Disease
Cholestatic diseases/cirrhosis
• Pregnancy
• Excessive Alcohol Intake
• Dysgammaglobulinemia (SLE, Myeloma)
- Endocr Practice. 2017;23(4):479-497
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Which Screening Tests Should Be Used
2017 AACE Lipid Guidelines
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• Screening Tests• Fasting Lipid Panel
• LDL-C, HDL-C and Triglycerides
• Non HDL-C (calculated) especially if Triglycerides significantly elevated.
• Apo B- consider in patients at target LDL, but with addl risks not addressed in risk calculators (family hx, DM, Metabolic syndrome)
• hsCRP- consider in those with borderline or intermediate risk and low LDL
• Subfraction Analysis and Homocysteine NOT Recommended
2017 AACE - Recommendations
- Endocr Practice. 2017;23(4):479-497
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! 2017 AACE Lipid Guidelines
2016 ESC Lipid Guidelines
- Endocr Practice. 2017;23(4):479-497; Eur Heart J 2016;37:2999-3058
ASCVD Risk Categories and Treatment Goals
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ASCVD Risk Categories and LDL-C Treatment Goals
2017 AACE Lipid GuidelinesRisk
categoryRisk factors/10-year risk
Treatment goals
LDL-C
(mg/dL)
Non-HDL-C
(mg/dL)
Apo B
(mg/dL)
Extreme riskAACE
‒ Progressive ASCVD including unstable angina in
individuals after achieving an LDL-C <70 mg/dL
‒ Established clinical cardiovascular disease in
individuals with DM, stage 3 or 4 CKD, or HeFH
‒ History of premature ASCVD (<55 male, <65 female)
<55 <80 <70
ECS No Recommendations - - -
Very high
risk
AACE
‒ – Established or recent hospitalization for ACS,
coronary, carotid or peripheral vascular disease, 10-
year risk >20%
‒ – DM or stage 3 or 4 CKD with 1 or more risk factor(s)
‒ – HeFH
<70 <100 <80
ESC
‒ - Established ASCVD
‒ Severe CKD (GFR <30)
‒ DM with target organ damage or major risk factor
<70 <100 <80
High risk
AACE‒ – ≥2 risk factors and 10-year risk 10%-20%
‒ – DM or stage 3 or 4 CKD with no other risk factors<100 <130 <90
ESC‒ Diabetes, moderate CKD (GFR 30-50),
‒ 10 year risk 5-10%,
‒ Familial Hyercholesterolemia
<100 <130 <100
Moderate
risk
AACE ≤2 risk factors and 10-year risk <10% <100 <130 <90
ECS 10 -year risk 1-5% <115 - -
Low risk AACE 0 risk factors <130 <160 NR
ECS 10-year risk <1% <115 - -
- Endocr Practice. 2017;23(4):479-497; Eur Heart J 2016;37:2999-3058.
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ASCVD Risk Categories and Treatment Goals
2017 AACE Lipid Guidelines
- Endocr Practice. 2017;23(4):479-497
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Treatments
2017 AACE Lipid Guidelines
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Questions Regarding Statin Use
2017 AACE Lipid Guidelines
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• Case series and 2 small, 6 month RCTs with statins raised concern regarding cognitive deficits
• In 2012 FDA added risk of adverse cognitive effects to label on all statins
• Analysis from large scale RCTs do not support findings
• 2014 Statin Cognition Safety Task Force concluded that statins are not associated with cognitive side effects
- Journal of Clinical Lipidology (2014) 8, S5–S16
Statin Safety - Cognition
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• 2008 JUPITER (17,802 patients) • Increased rate (3.0% versus 2.4%) of physician diagnosed DM2 in Rosuvastatin
treatment group compared to placebo.
• 2011 meta-analysis (32,752 patients) • Increased incidence DM2 with intensive statin therapy compared to moderate
statin therapy. • 2 additional case per 1000 patient-years (NNH = 448) • 6.5 fewer CVD events per 1000 patient-years (NNT = 155)
• 2012 - FDA added a statement to the labels of statin medications indicating that increases in glycated hemoglobin (HbA1C) and fasting glucose levels have been reported with statin use.
- NEJM 2008;359(21):2195 ; JAMA. 2011;305(24):2556
Statin Safety - Diabetes
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• 2014 - Statin Diabetes Safety Task Force• “the available clinical evidence for changes in insulin sensitivity induced by statin therapy is
mixed, with no clear evidence of worsening or improvement with statin therapy. No firm conclusions can be drawn at present regarding the potential mechanistic link between statin therapy and increased risk for diabetes mellitus.”
• Statin-therapy CVD benefit exceeds DM2 risk • Discussion with patient regarding risk/benefit
Statin Safety - Diabetes
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! Non-statin Treatment- Niacin
• 2011- AIM HIGH 3,414 patients; 4 year f/u
• No incremental benefit from adding niacin to statin therapy in patients with ASCVF and LDL-C <70mg/dl
• 2014- Heart Protection Study2-THRIVE 25,673 patients; 3.9 yr f/u
• Niacin + statin in patients with ASCVD did not reduce the risk of major vascular events but did increase the risk of adverse events; despite additional lowering of LDL.
• Currently only recommended for treatment of severe Hypertrigylceridemia
-AHA Science Advisory, Circulation. 2017;135:e867-e884; Endocr Practice. 2017;23(4):479-497
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! Non-statin Treatment- Omega 3 FAs
Indication (Population) RecommendationClass (Strength) of
RecommendationLevel (Quality) of Evidence
Severe Hypertriglyceridemia Treatment is Reasonable IIa …
Prevention of CVD mortality in
diabetes mellitus/prediabetesTreatment is not indicated III* B-R
Prevention of CHD among
patients at high CVD riskTreatment is not indicated III*† B-R
Secondary prevention of CHD
and SCD among patients with
prevalent CHD
Treatment is reasonable IIa† A
Primary prevention of stroke
(high CVD risk [with or without
prevalent CHD])
Treatment is not indicated III* B-R
Secondary prevention of
outcomes in patients with
heart failure
Treatment is reasonable IIa B-R
-AHA Science Advisory, Circulation. 2017;135:e867-e884; Endocr Practice. 2017;23(4):479-497
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! Non-statin Treatment- Omega 3 FAs
• Omega-3 Treatment Trialists’ Collaboration
• meta-analysis of 10 Trials Involving 77, 917 Individuals
• mean of 4.4 years follow up.
• No significant effect on either of fatal CHD, nonfatal MI, stroke, revascularization events, or any major vascular events.
• No benefit in any subgroups, including prior vascular disease, diabetes, lipid levels, or statin use.
- JAMA Cardiol. Published online January 31, 2018
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! Non-statin Treatment- Ezetimibe
IMPROVE-IT: 18,144 patients. All with ACS/MI
• First trial demonstrating incremental clinical benefit when adding a non-statin agent (Ezetimibe) to statin therapy:
• Non-statin lowering LDL-C with Ezetimibereduces cardiovascular events
• Even Lower is Even Better(achieved mean LDL-C 53 vs. 70 mg/dL at 1 year)
• Confirmed Ezetimibe safety profile
• Reaffirmed the LDL hypothesis, that reducing LDL-C prevents cardiovascular events
- NEJM 2015;372:2387-97.
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! Non-statin Treatment- PCSK9 Inhibitors
• Proprotein Convertase Subtilisin Kexin 9 Inhibitor
• Monoclonal Antibody
• Injectable SQ Administration- Q2 weeks – monthly
• Indications:
Familial Hypercholesterolemia and/or CVD:
on maximal medical therapy and not at goal
intolerant to statins and not at goal on nonstatin agents
- Manufacturer’s Prescribing Information
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! PCSK9 Mechanism of Action
- Lambert G, et al. J Lipid Res 2012; 53:2515
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! Non-statin Treatment- PCSK9 Inhibitors
Adverse reactions
local injection site reactions 1.9% greater for Alirocumab vs. placebo
0.7% greater for Evolocumab vs. placebo
Influenza 1.2% greater for Alirocumab vs. placebo
0.2% greater for Evolocumab vs. placebo
Most common adverse reactions with similar rates for drug vs. placebo
Alirocumab (4-12%) Nasopharyngitis, urinary tract infections, diarrhea,bronchitis, and myalgia
Evolocumab (2-4%) Nasopharyngitis, back pain, and upper respiratory tract infection.
- Respective Manufacturer Prescribing Information
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! Non-statin Treatment- PCSK9 Inhibitors
FOURIER:
• 27,564 high risk patients with known CV disease (prior MI/CVA or symptomatic PAD)
• demonstrated incremental clinical benefit when adding a non-statin agent (Evolocumab) to statin therapy:
• Non-statin lowering LDL-C with Evolocumab reduces cardiovascular events
• Even Lower is Even Better(achieved mean LDL-C 31 vs. 90 mg/dL at 1 year)
• Confirmed Evolocumab safety profile
Reaffirmed the LDL hypothesis, that reducing LDL-C prevents cardiovascular events
- NEJM 2017;376:1713-22.
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! Non-statin Treatment- PCSK9 Inhibitors
• Prohibitively Expensive without insurance coverage or
assistance programs; ~ $14,000/yr.
• Plan to do battle with the insurance companies for approval
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! Summary
Rule Out Secondary Causes
Calculate 10 year Risk
Treat to specific Goals
Nonstatins Reduce Events
Lower is Better
Stop the Omega 3’s and Niacin
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THANK YOU
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