Science News from research organizations New cholesterol-lowering drug could help patients unable to take statins Date: March 13, 2019 Source: Imperial College London Summary: A new class of oral cholesterol-lowering drug could help patients unable to take statins due to side effects. Share: Materials provided by Imperial College London. Original written by Ryan O'Hare. Note: Content may be edited for style and length. Journal Reference: Kausik K. Ray, Harold E. Bays, Alberico L. Catapano, Narendra D. Lalwani, LeAnne T. Bloedon, Lulu R. Sterling, Paula L. Robinson, Christie M. Ballantyne. Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol. New England Journal of Medicine, 2019; 380 (11): 1022 DOI: 10.1056/NEJMoa1803917
Management of Blood Cholesterol Francis J. Alenghat, MD, PhD; Andrew M. Davis, MD, MPH Summary of the Clinical Problem Pharmacologically lowering low-density lipoprotein cholesterol (LDL-C) consistently reduces ASCVD events (myocardial infarc- tion, stroke, and cardiovascular death), and the principle that lower LDL-C is better was reaffirmed by trials that added ezetimibe or pro- protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to statin therapy. 1,2 The 2013 guideline removed specific LDL-C treatment tar- gets, but high-quality trials since offered the opportunity to rein- troduce such goals based on risk gradations. Characteristics of the Guideline Source This guideline was developed by the AHA and ACC in partnership with other professional societies, 3 with a writing committee notable for wide scope of practice and lack of conflicts of interest, using an independent formal systematic review of recent large outcome trials of nonstatin lipid-modifying agents. 2 The overall quality of this guideline is high (eTable in the Supplement ). Evidence Base The new guideline does not recommend or prefer that lipid profiles be obtained while fasting in the initial evaluation of patients be- cause nonfasting test results are sufficient for assessing prognosis. 4 Nonfasting calculated LDL-C is adequate unless triglycerides are greater than 400 mg/dL, which requires a repeat test while fast- ing. Ascertainment of lipid pro- files is suggested for adults re- quiring ASCVD risk estimation and for children with obesity or family history of early ASCVD. In all individuals of all ages, emphasizing a heart-healthy lifestyle remains a strong recommendation. Pharmacologic lipid management remains strongly recom- mended, even without risk calculation, in patients with clinical ASCVD, LDL-C of 190 mg/dL or higher, or diabetes. Stratified LDL-C goals have been reintroduced for patients with clinical ASCVD. First, reduce LDL-C by greater than 50% using high-intensity statins. Higher-intensity statin use (atorvastatin 40 mg/d or rosuvasta- tin 20 mg/d) resulting in a greater than 50% reduction in LDL-C has yielded greater reduction of major vascular events (composite cardiovascular death, myocardial infarction, and stroke) vs lower- intensity treatment. 1,5 For patients with very high-risk ASCVD ( Figure ), a second goal is to reduce LDL-C to less than 70 mg/dL. If this cannot be done with a maximally tolerated statin, the guide- line recommends ezetimibe next and, if needed, a PCSK9 inhibitor. Earlier trials supported an LDL-C target of less than 70 mg/dL, and recent nonstatin trials support even lower LDL-C levels in very high- risk patients. When added to intensive statin therapy, ezetimibe re- sulted in a median LDL-C of 54 mg/dL, whereas it was 48 mg/dL and Editorial Supplemental content Figure. Major Recommendations for Management of Blood Cholesterol Secondary prevention Very high-risk ASCVD >18 High ≥50 <70 ≥50 High >18 All other ASCVD Clinical Status a Age Range, y Statin Intensity b Goal LDL-C Reduction, % Goal LDL-C Level, mg/dL c Primary prevention LDL-C ≥190 mg/dL 20-75 40-75 High ≥50 <100 ≥30 Moderate Moderate Select cases d Diabetes, LDL-C ≥70 mg/dL 40-75 ≥50 High High risk, LDL-C ≥70 mg/dL 40-75 ≥30 Intermediate risk, LDL-C ≥70 mg/dL d All others (low-borderline risk, LDL-C <70 mg/dL, or outside age range) ASCVD indicates atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein cholesterol. a Very high-risk ASCVD: multiple major ASCVD events (acute coronary syndrome in past year, prior myocardial infarction or cerebrovascular accident, peripheral artery disease with symptoms or procedure) or 1 major ASCVD event and multiple high-risk conditions (aged 65 years, diabetes, hypertension, chronic kidney disease, heart failure, smoking, prior coronary artery bypass graft surgery/percutaneous coronary intervention, persistent LDL-C 100 mg/dL). Using 10-year ASCVD risk calculator in primary prevention, high = 20%; intermediate = 7.5%-19.9%; borderline = 5%-7.4%; and low = <5%. b High intensity: atorvastatin, 40-80 mg/d; rosuvastatin, 20-40 mg/d. Moderate intensity: atorvastatin, 10-20 mg/d; rosuvastatin, 10 mg/d; simvastatin, 20-40 mg/d; pravastatin or lovastatin, 40 mg/d. Consider high-intensity statin in diabetes for patients aged 50 to 75 years with multiple high-risk conditions. c Reduction of LDL-C level is a secondary goal after reduction of LDL-C percentage is achieved. Consider additional agents (ezetemibe before PCSK9 inhibitors) if LDL-C goals are not met using maximum tolerated statin therapy. d Discuss risk enhancers such as family history of premature ASCVD, chronic inflammatory conditions, metabolic syndrome, South Asian ancestry, elevated lipoprotein(a), etc, as well as coronary artery calcium testing in select intermediate- and borderline-risk patients to potentially reclassify risk. GUIDELINE TITLE 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol DEVELOPERS American Heart Association (AHA) and American College of Cardiology (ACC) RELEASE DATE November 10, 2018 PRIOR VERSION 2013 FUNDING SOURCES AHA/ACC TARGET POPULATION Patients with or at risk of developing atherosclerotic cardiovascular disease (ASCVD) Clinical Review & Education JAMA Clinical Guidelines Synopsis jama.com (Reprinted) JAMA Published online February 4, 2019 E1 © 2019 American Medical Association. All rights reserved. Downloaded from jamanetwork.com by guest on 02/04/2019
