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New cholesterol-lowering drug could help patients unable to take statins

Discussion in 'Pharmacology' started by Valery1957, Mar 29, 2019.

  1. Valery1957

    Valery1957 Famous Member

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    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:

    1. 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
     

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  2. Valery1957

    Valery1957 Famous Member

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    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
     

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