Lipid Management C. Samuel Ledford, MD Interventional Cardiology Chattanooga Heart Institute

Transcription

1 Lipid Management 2018 C. Samuel Ledford, MD Interventional Cardiology Chattanooga Heart Institute

2 Disclosures No Financial Disclosures

3 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

4 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

5 Circulation Jun 24;129(25 Suppl 2):S46-8.

6 2013 ACC/AHA Guidelines for Lipid Management 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 nonstatins for the reduction of ASCVD events.

7 A Meta-Analysis of Statin Trials Very 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):

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9 Endocr Practice. 2017;23(4):

10 2017 AACE Lipid Guidelines 87 Recommendations

11 ESC and AACE Lipid Guidelines Treatment Goals are based on Risk Factors and Long Term Risk

12 ESC and AACE Lipid- Recommendation 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 - Endocr Practice. 2017;23(4): ; Eur Heart J 2016;37:

13 - Framinghamheartstudy.org ASCVD 10-year risk Calculator Framingham Heart Study

14 ASCVD 10-year risk Calculator Reynolds Heart Risk Score Designed for Healthy, Nondiabetics - reynoldsriskscore.org; JAMA 2007;297:

15 ASCVD 10-year risk Calculator ESC SCORE Chart

16 2017 AACE Lipid- Recommendation Rule Out Secondary Causes of Dyslipidemia - Endocr Practice. 2017;23(4):

17 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):

18 2017 AACE Lipid Guidelines Which Screening Tests Should Be Used

19 2017 AACE - Recommendations 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 - Endocr Practice. 2017;23(4):

20 2017 AACE Lipid Guidelines 2016 ESC Lipid Guidelines ASCVD Risk Categories and Treatment Goals - Endocr Practice. 2017;23(4): ; Eur Heart J 2016;37:

21 Risk category Extreme risk Very high risk High risk Moderate risk Low risk Risk factors/10-year risk 2017 AACE Lipid Guidelines LDL-C (mg/dl) Progressive ASCVD including unstable angina in individuals after achieving an LDL-C <70 mg/dl Treatment goals Non-HDL-C (mg/dl) Apo B (mg/dl) AACE Established clinical cardiovascular disease in <55 <80 <70 ASCVD Risk Categories and LDL-C Treatment Goals individuals with DM, stage 3 or 4 CKD, or HeFH History of premature ASCVD (<55 male, <65 female) ECS No Recommendations AACE ESC AACE ESC 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 - Established ASCVD Severe CKD (GFR <30) DM with target organ damage or major risk factor 2 risk factors and 10-year risk 10%-20% DM or stage 3 or 4 CKD with no other risk factors Diabetes, moderate CKD (GFR 30-50), 10 year risk 5-10%, <70 <100 <80 <70 <100 <80 <100 <130 <90 Familial Hyercholesterolemia <100 <130 <100 AACE 2 risk factors and 10-year risk <10% <100 <130 <90 ECS 10 -year risk 1-5% < AACE 0 risk factors <130 <160 NR ECS 10-year risk <1% < Endocr Practice. 2017;23(4): ; Eur Heart J 2016;37:

22 2017 AACE Lipid Guidelines ASCVD Risk Categories and Treatment Goals - Endocr Practice. 2017;23(4):

23 2017 AACE Lipid Guidelines Treatments

24 2017 AACE Lipid Guidelines Questions Regarding Statin Use

25 Statin Safety - Cognition 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

26 Statin Safety - Diabetes 2008 JUPITER (17,802 patients) Increased rate (3.0% versus 2.4%) of physician diagnosed DM2 in Rosuvastatin treatment group compared to placebo 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) 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

27 Statin Safety - Diabetes 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

28 Non-statin Treatment- Niacin 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 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):

29 Non-statin Treatment- Omega 3 FAs Indication (Population) Recommendation Class (Strength) of Recommendation Level (Quality) of Evidence Severe Hypertriglyceridemia Treatment is Reasonable IIa Prevention of CVD mortality in diabetes mellitus/prediabetes Prevention of CHD among patients at high CVD risk Treatment is not indicated III* B-R Treatment is not indicated III* B-R Secondary prevention of CHD and SCD among patients with prevalent CHD Primary prevention of stroke (high CVD risk [with or without prevalent CHD]) Secondary prevention of outcomes in patients with heart failure Treatment is reasonable IIa A Treatment is not indicated III* B-R Treatment is reasonable IIa B-R -AHA Science Advisory, Circulation. 2017;135:e867-e884; Endocr Practice. 2017;23(4):

30 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

31 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 Ezetimibe reduces 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:

32 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

33 PCSK9 Mechanism of Action - Lambert G, et al. J Lipid Res 2012; 53:2515

34 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

35 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:

36 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

37 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

38 THANK YOU

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