A transatlantic discussion on the new LDL-C guidelines: What are the - PowerPoint PPT Presentation

A transatlantic discussion on the new LDL-C guidelines: What are the key differences? Christie M. Ballantyne, MD Center for Cardiometabolic Disease Prevention Baylor College of Medicine Houston, Texas

Christie M. Ballantyne, MD Financial Disclosure • Grant/Research Support: Abbott Diagnostic, Akcea, Amgen, Esperion, Novartis, Regeneron, Roche Diagnostic, NIH, AHA, ADA (all paid to institution, not individual) • Consultant: Abbott Diagnostic, Akcea, Amarin, Amgen, Astra Zeneca, Boehringer Ingelheim, Corvidia, Denka Seiken, Esperion, Intercept, Janssen, Matinas BioPharma Inc, Merck, Novartis, Novo Nordisk, Regeneron, Roche Diagnostic, Sanofi-Synthelabo • Provisional patent: “ Biomarkers to Improve Prediction of Heart Failure Risk ” (patent no. 61721475) filed by Baylor College of Medicine and Roche

Common Themes across Guidelines — 1: Aggressive Treatment of Patients with Established ASCVD • High intensity statins as the “ first-line therapy” for these high -risk patients • Goal at least 50% LDL-C reduction Guideline Recommendation AHA/ACC 2018 guidelines I A ESC/EAS 2019 guidelines I A Grundy SM et al. J Am Coll Cardiol 2019;73:e285 – e350.

Common Themes across Guidelines — 2: Aggressive Treatment of Patients with Primary LDL- C ≥190 mg/ dL: Initiate statin therapy without calculating a risk score! Guideline Recommendation AHA/ACC 2018 guidelines I B-R ESC/EAS 2019 guidelines I C Grundy SM et al. J Am Coll Cardiol 2019;73:e285 – e350.

Common Themes across Guidelines — 3: Aggressive Treatment of Patients with Diabetes Guideline Recommendation AHA/ACC 2018 guidelines I A ESC/EAS 2019 guidelines I A Grundy SM et al. J Am Coll Cardiol 2019;73:e285 – e350.

Common Themes across Guidelines — 4: Short- and Long-Term CVD Risk Calculation to Inform Risk Discussion Guideline Recommendation AHA/ACC 2018 guidelines (Pooled cohort equation) I B-NR ESC/EAS 2019 guidelines (SCORE- region specific) I C Grundy SM et al. J Am Coll Cardiol 2019;73:e285 – e350.

Common Themes across Guidelines — 5: Use of Follow-up LDL-C as Either Target of Therapy or to Monitor Response/Adherence with specific recommendations for changes in therapy based upon LDL-C levels Guideline Recommendation AHA/ACC 2018 guidelines I A ESC/EAS 2019 guidelines I A Grundy SM et al. J Am Coll Cardiol 2019;73:e285 – e350.

Shared Concepts in 2018 AHA/ACC and 2019 ESC/EAS Guidelines 1. Atherogenic lipoproteins play a causal role in the development, progression, and clinical events of ASCVD 2. Target of therapy is to lower atherogenic lipoproteins; the most important of these for a population is LDL 3. Clinical approach: levels for screening and goals or thresholds based on measurement of LDL-C or non-HDL- C (cholesterol in all atherogenic lipoproteins) and more support for measurement of apo B and Lp(a)

LDL-C: Target, Goals, and Thresholds for Nonstatin Therapy • LDL-C target: the target of therapy is reduction in atherogenic lipoproteins assessed by levels of LDL-C • LDL-C goal: number that is used to assess success of therapy • LDL-C threshold: % reduction or number to evaluate potential net ASCVD benefit in conjunction with absolute risk of the individual patient Jacobson TA, et al. J Clin Lipidol. 2015;9(2):129-69. Stone NJ, et al. J Am Coll Cardiol. 2014;63(25 Pt B):2889-934.

Differences between 2018 AHA/ACC and 2019 ESC/EAS Guidelines: Risk assessment 1. Definition of risk groups – ESC guidelines do not confine very high risk to secondary prevention, 2. Recommendation that Lp(a) be checked once in everyone in ESC versus as a risk enhancer in AHA/ACC 3. Stronger support for apo B measurement in risk assesment 4. Although both recommend Coronary Artery Calcium Scores as risk enhancers, ultrasound is only recommended by ESC/EAS

Differences between 2018 AHA/ACC and 2019 ESC/EAS Guidelines: Treatment 1. Goals vs thresholds: Very high risk patients with threshold of 70mg/dl versus a target of <55/mg/dl 2. Levels of LDL-C and non-HDL-C used as goals vs thresholds differ for “high risk primary prevention” 3. More information on apoB goals (< 80 mg and <65 mg/dl) in various risk groups in ESC/EAS guidelines 4. Recommendations for combination therapy with PSCK9 inhibitors is broader as definition of high risk is broader than in ACC/AHA for high risk primary prevention

Differences between 2018 AHA/ACC and 2019 ESC/EAS Guidelines: Treatment 1. For patients with ASCVD and second event within 2 years on maximally tolerated statin rx, LDL-C goal of <1.0 mmol/L ( 40 mg/dl) IIb-B 2. In high risk or above patients with TG between 1.5 - 5.6 mmol?l (135-499 mg/dl) despite statin rx, n-3 PUFAs (icosopent ethyl 2 x 2 g/d) should be considered in combination with statin rx IIa- B

Grundy SM et al. J Am Coll Cardiol 2019;73:e285 – e350.

2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol In patients with severe primary hypercholesterolemia (LDL- C ≥190 mg/ dL [≥4.9 mmol/L]), begin high-intensity statin therapy without calculating 10-year ASCVD risk • If LDL-C remains ≥100 mg/ dL (≥2.6 mmol/L) on statin, adding ezetimibe is reasonable • If LDL-C on statin plus ezetimibe remains ≥100 mg/ dL (≥2.6 mmol/L) and the patient has multiple factors that increase subsequent risk of ASCVD events, a PCSK9 inhibitor may be considered, although the long-term safety (>3 years) is uncertain and economic value is low at mid-2018 list prices. Grundy SM et al. J Am Coll Cardiol 2019;73:e285 – e350.

Grundy SM et al. J Am Coll Cardiol 2019;73:e285 – e350.

Risk-Enhancing Factors (I) Risk-Enhancing Factors • Family history of premature ASCVD (males, age <55 y; females, age <65 y) • Primary hypercholesterolemia (LDL-C, 160 – 189 mg/dL [4.1 – 4.8 mmol/L); non – HDL-C 190 – 219 mg/dL [4.9 – 5.6 mmol/L])* • Metabolic syndrome (increased waist circumference, elevated triglycerides [>175 mg/dL], elevated blood pressure, elevated glucose, and low HDL-C [<40 mg/dL in men; <50 in women mg/dL] are factors; tally of 3 makes the diagnosis) Chronic kidney disease (eGFR 15 – 59 mL/min/1.73 m 2 with or without albuminuria; not treated with dialysis or • kidney transplantation) • Chronic inflammatory conditions such as psoriasis, RA, or HIV/AIDS • History of premature menopause (before age 40 y) and history of pregnancy-associated conditions that increase later ASCVD risk such as preeclampsia • High-risk race/ethnicities (e.g., South Asian ancestry) Grundy SM et al. J Am Coll Cardiol 2019;73:e285 – e350.

Risk-Enhancing Factors (II) Risk-Enhancing Factors • Lipid/biomarkers : Associated with increased ASCVD risk o Persistently* elevated, primary hypertriglyceridemia (≥175 mg/dL); o If measured: ▪ Elevated high-sensitivity C-reactive protein (≥2.0 mg/L) ▪ Elevated Lp(a): A relative indication for its measurement is family history of premature ASCVD. An Lp (a) ≥50 mg/dL or ≥125 nmol/L constitutes a risk -enhancing factor especially at higher levels of Lp(a). ▪ Elevated apoB ≥130 mg/dL: A relative indication for its measurement would be triglyceride ≥200 mg/dL. A level ≥130 mg/dL corresponds to an LDL -C >160 mg/dL and constitutes a risk-enhancing factor ▪ ABI <0.9 Grundy SM et al. J Am Coll Cardiol 2019;73:e285 – e350.

Which Secondary Prevention Patients to Use Non-Statins in? Grundy SM et al. J Am Coll Cardiol 2019;73:e285 – e350.

2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol In very-high-risk ASCVD, use LDL-C threshold of 70 mg/dL (1.8 mmol/L) to consider adding nonstatins to statin therapy • Very high risk includes a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions • In very high-risk ASCVD patients, it is reasonable to add ezetimibe to maximally tolerated statin therapy when LDL- C remains ≥70 mg/dL (≥1.8 mmol/L) • In patients at very high risk whose LDL- C remains ≥70 mg/ dL (≥1.8 mmol/L) on maximally tolerated statin and ezetimibe therapy, adding a PCSK9 inhibitor is reasonable, although the long-term safety (>3 years) is uncertain and cost-effectiveness is low at mid-2018 list prices Grundy SM et al. J Am Coll Cardiol 2019;73:e285 – e350.

Very High-Risk ASCVD Patients Major ASCVD Events Recent ACS (within the past 12 mo) History of MI (other than recent ACS event listed above) History of ischemic stroke Symptomatic peripheral arterial disease (history of claudication with ABI <0.85, or previous revascularization or amputation) High-Risk Conditions Age ≥65 y Heterozygous familial hypercholesterolemia History of prior coronary artery bypass surgery or percutaneous coronary intervention outside of the major ASCVD event(s) Diabetes mellitus Hypertension CKD (eGFR 15-59 mL/min/1.73 m 2 ) Current smoking Persistently elevated LDL-C (LDL- C ≥100 mg/dL [≥2.6 mmol/L]) despite maximally tolerated statin therapy and ezetimibe History of congestive HF *Very high risk includes a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions . Grundy SM et al. J Am Coll Cardiol 2019;73:e285 – e350.