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  • Coronary artery calcium score may have a role in stratifying short-term risk in patients with familial hypercholesterolaemia...
  • Evolocumab reduces lipoprotein levels but not arterial wall inflammation...
  • High lipoprotein(a) concentra-tions and high risk of mortality...
  • EWTOPIA75: Ezetimibe prevents the development of the first cardiovascular events in the elderly...
  • Top 10 Take-Home Messages to Reduce Risk of Atherosclerotic Cardiovascular Disease Through Cholesterol Management ...
  • Updated AHA/ACC cholesterol guidelines focus on more personalized risk assessment...
  • 2018 US Cholesterol Guidelines: what has changed after 5 years?...
  • REDUCE-IT: Pure Fish Oil Lowers CVD Risk...
     

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      NSC «The M.D.Strazhesko Institute of Cardiology NAMS of Ukraine»
      European Atherosclerosis Society (EAS)
      International Atherosclerosis Society (IAS)
      Ukrainian Antihypertensive Society

     
    Coronary artery calcium in familial hypercholesterolaemia
        

    Coronary artery calcium (CAC) score may have a role in stratifying short-term risk in patients with familial hypercholesterolaemia (FH, inherited high cholesterol), according to a new study. The authors suggest that this noninvasive approach may have value in targeting treatment with a PCSK9 inhibitor to those patients at highest risk.

    Individuals with FH are considered at very high risk of atherosclerotic cardiovascular disease ( ASCVD) events due to the burden of elevated LDL cholesterol levels from birth. As FH is common, affecting about one in 200 to 250 people worldwide (1), early identification and treatment are essential to avoid the consequences of accelerated ASCVD. Regrettably, this is not the case for most patients with FH (2). Yet, despite the burden of life-long elevated LDL cholesterol levels it is also recognized that ASCVD risk among individuals with FH is heterogeneous (3,4). Therefore, additional screening that may help to identify those individuals at highest risk of cardiovascular events, and who may benefit from additional LDL cholesterol lowering therapy with a PCSK9 inhibitor, is needed.

    Investigators from Brazil reported data from 206 individuals with FH (mean age 45 years, 36% men, mean baseline and on-treatment LDL cholesterol 260 mg/dL and 150 mg/dL, respectively), who underwent CAC measurement and were followed for a median of 3.7 years (interquartile range 2.7-6.8 years). With the exception of one patient with an APOB mutation, all had LDLRmutations. At baseline, the majority (69%) were receiving a statin.

    Over the follow-up period, there were 15 ASCVD events (defined as fatal or nonfatal myocardial infarction or stroke, unstable angina requiring coronary revascularization, elective coronary revascularization because of symptoms, abnormal stress test results, or obstructive coronary artery disease on computed tomographic angiography). CAC assessment identified 101 (49%) individuals with a CAC score of 0; none of these experienced cardiovascular events over follow-up. In those individuals with a CAC score of 1-100 (n=62) and >100 (n=43), annualized event rates were 26% and 44%, respectively. The latter individuals were significantly older compared with those with CAC scores of 0.

    On the basis of their results, the authors suggest a role for CAC score as a non-invasive approach to risk stratification in FH, to enable PCSK9 inhibition to be targeted to individuals at highest risk of ASCVD events, consistent with a personalized approach to management. They do, however, acknowledge that longer follow-up is required to corroborate their findings.

    References:

    1. Benn M, Watts GF, Tybjaerg-Hansen A, Nordestgaard BG.
      Mutations causative of familial hypercholesterolaemia: screening of 98 098 individuals from the Copenhagen General Population Study estimated a prevalence of 1 in 217.
      Eur Heart J 2016;37:1384-94. PUBMED https://www.ncbi.nlm.nih.gov/pubmed/26908947
    2. Nordestgaard BG, Chapman MJ, Humphries SE et al.
      Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society.
      Eur Heart J 2013;34:3478-90a. https://www.ncbi.nlm.nih.gov/pubmed/23956253
    3. Santos RD, Gidding SS, Hegele RA, et al.
      Defining severe familial hypercholesterolaemia and the implications for clinical management: a consensus statement from the International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel.
      Lancet Diabetes Endocrinol 2016;4:850–61. https://www.ncbi.nlm.nih.gov/pubmed/27246162
    4. Besseling J, Hovingh GK, Huijgen R et al.
      Statins in familial hypercholesterolemia: consequences for coronary artery disease and all-cause mortality.
      J Am Coll Cardiol 2016;68:252–60. PUBMED https://www.ncbi.nlm.nih.gov/pubmed/27417002

    Read the article here:
    Miname MH, Bittencourt MS, Moraes SR et al.
    Coronary Artery Calcium and Cardiovascular Events in Patients With Familial Hypercholesterolemia Receiving Standard Lipid-Lowering Therapy.
    J Am Coll Cardiol Img 2018; doi: 10.1016/j.jcmg.2018.09.019.
    https://www.ncbi.nlm.nih.gov/pubmed/30448145

     
    Evolocumab Reduces Lipoprotein Levels but Not Arterial Wall Inflammation
        

    Subjects with lipoprotein(a) [Lp(a)] elevation have increased arterial wall inflammation and cardiovascular risk. In patients at increased cardiovascular risk, arterial wall inflammation is reduced following lipid-lowering therapy by statin treatment or lipoprotein apheresis. However, it is unknown whether lipid-lowering treatment in elevated Lp(a) subjects alters arterial wall inflammation. We evaluated whether evolocumab, which lowers both low-density lipoprotein cholesterol (LDL-C) and Lp(a), attenuates arterial wall inflammation in patients with elevated Lp(a).

    In the multicentre, randomized, double-blind, placebo-controlled study, 129 patients {median [interquartile range (IQR)]: age 60.0 [54.0-67.0] years, Lp(a) 200.0 [155.5-301.5] nmol/L [80.0 (62.5-121.0) mg/dL]; mean [standard deviation (SD)] LDL-C 3.7 [1.0] mmol/L [144.0 (39.7) mg/dL]; National Cholesterol Education Program high risk, 25.6%} were randomized to monthly subcutaneous evolocumab 420?mg or placebo. Compared with placebo, evolocumab reduced LDL-C by 60.7% [95% confidence interval (CI) 65.8-55.5] and Lp(a) by 13.9% (95% CI 19.3-8.5). Among evolocumab-treated patients, the Week 16 mean (SD) LDL-C level was 1.6 (0.7) mmol/L [60.1 (28.1) mg/dL], and the median (IQR) Lp(a) level was 188.0 (140.0-268.0) nmol/L [75.2 (56.0-107.2) mg/dL]. Arterial wall inflammation [most diseased segment target-to-background ratio (MDS TBR)] in the index vessel (left carotid, right carotid, or thoracic aorta) was assessed by 18F-fluoro-deoxyglucose positron-emission tomography/computed tomography. Week 16 index vessel MDS TBR was not significantly altered with evolocumab (-8.3%) vs. placebo (-5.3%) [treatment difference -3.0% (95% CI -7.4% to 1.4%); P=0.18].

    Evolocumab treatment in patients with median baseline Lp(a) 200.0?nmol/L led to a large reduction in LDL-C and a small reduction in Lp(a), resulting in persistent elevated Lp(a) levels. The latter may have contributed to the unaltered arterial wall inflammation.


    Source:
    https://www.ncbi.nlm.nih.gov/pubmed/30561610

     
    High Lipoprotein(a) Concentrations and High Risk of Mortality
        

    Plasma lipoprotein(a) [Lp(a)] concentration is related to risk of cardiovascular disease. The defining protein component of Lp(a) particles, apolipoprotein(a) [apo(a)], is encoded by the LPA gene. Apo(a) is extremely heterogeneous in size due to a common copy number variation, leading to a variable number of kringle-IV type 2 (KIV2)-like domains. Alleles with fewer KIV2 repeats, encoding smaller apo(a) isoforms, are associated with higher plasma Lp(a) concentrations. Two principal methods to detect variation in KIV2 repeat number are electrophoresis with immunoblotting to detect apo(a) protein isoforms or pulse-field electrophoresis of unamplified genomic DNA to detect the variation of the LPA gene.

    Both methods are technically challenging, laborious, and time consuming. Here, report a rapid method to determine the number of KIV2 repeats in LPA from genomic DNA using quantitative real-time polymerase chain reaction (qPCR). With qPCR, found KIV2 repeat number was correlated with both apo(a) isoform size as determined by immunoblotting (r(s) = 0.50, P < 1 x 10(-6)) and with plasma Lp(a) concentration (r(s) = 0.30, P < 1 x 10(-6)). The qPCR technique permits rapid evaluation of apo(a) size from genomic DNA, and thus would provide an adjunctive genomic variable, in addition to LPA single nucleotide polymorphisms, for evaluating the genetic determinants of plasma Lp(a) concentration in genetic epidemiology studies of cardiovascular disease outcomes.

    High levels of lipoprotein(a), through corresponding low LPA KIV-2 number of repeats rather than through high cholesterol content were associated with high risk of mortality. These findings are novel.

    * "kringle" domain, or "double loop" domain, is a conservative element of the secondary structure of proteins in which the polypeptide chain was formed in the form of a characteristic double loop ("loop in a loop") involving three disulfide bonds.


    Source:
    https://academic.oup.com/eurheartj/advance-article-abstract/doi/10.1093/eurheartj/ehy902/5273475?redirectedFrom=fulltext

     
    EWTOPIA75: Ezetimibe prevents the development of the first cardiovascular events in the elderly
        

    According to a report at the ANA session (Chicago, 2018), ezetimibe was ahead of the onset of the first cardiovascular event (sudden cardiac death, myocardial infarction (MI), stroke, and need for coronary revascularization) - more than just a diet in the 75- to 104-year-old Japanese patients with elevated LDL cholesterol and the second risk factor following a randomized trial.

    Treatment with ezetimibe at a dose of 10 mg / day, which reduces cholesterol absorption from the intestine plus diet, has led to a decrease in the rate of this combined cardiovascular outcome over 5 years compared with the mono-diet option.

    These results are the first evidence that primary prevention of atherosclerotic cardiovascular events with lipid-lowering therapy is possible in elderly patients over the age of 75 with statin intolerance.

    From 2009 to 2016, 3796 patients randomized to the EWTOPIA75 trial received 10 mg/day ezetimibe plus diet in accordance with Guideline for Prevention of ASCVD from the Japan Atherosclerosis Society or diet alone. Patients aged 75 years and over with LDL cholesterol are at least 140 mg/dL (3.62 mmol/l) and with one or more of seven risk factors (type 2 diabetes, hypertension, smoking, low HDL cholesterol, high levels of triglycerides , peripheral arterial disease, or documented history of cerebral infarction) were observed for 3-5 years.

    Output demographic characteristics were as follows: the average age was 80.7 ± 4.8 years; body mass index 23,4 ± 3,6; about 74% of the surveyed were women in both groups; hypertension - 78.0%; diabetes - 22.8%. Despite the high incidence of concomitant hypertension, systolic and diastolic blood pressure was well controlled (136.1 ± 15.9 mm Hg and 74.1 ± 10.5 mm Hg respectively).

    The basic characterization of lipids was similar in two groups. Cholesterol LDL cholesterol decreased in 1 year from 162 mg/dl (4.19 mmol/l) to 126 mg/dl (3.26 mmol/l) in the intervention group and to 144 mg/dl (3.72 mmol/l) in control group and then gradually decreased to 120 mg/dL (3.10 mmol/l) in the group of ezetimibe and 131 mg/dl (3.39 mmol/l) in the control group after 5 years. During the observation, no significant differences were found in the groups between HDL cholesterol levels or triglycerides.

    The incidence of the first combined outcome (sudden cardiac death, MI, coronary revascularization, and stroke) was significantly lower in the group receiving ezetimibe plus diet than in the diet alone group. However, it is noted that Japanese people may have genetic differences that make them hypersensitive to the mechanism of action of ezetimibe and it is unclear whether patients outside of Japan on the background of therapy with ezetimibe demonstrate similar results.

    It is claimed that statins have proven survival benefits in elderly patients with elevated levels of LDL, since EWTOPIA has not been shown to have a beneficial effect on reducing cardiovascular and total mortality. It is obvious that these positive results of ezetimibe hypolipidemic therapy can be considered proven for older 75+ Japanese women with normal body weight and intolerance to statins.


    Sources:
    www.medscape.com/viewarticle/905525#vp_1
    www.abstractsonline.com/pp8/#!/4682/presentation/59405

     
         Top 10 Take-Home Messages to Reduce Risk of Atherosclerotic Cardiovascular Disease Through Cholesterol Management
      

    1. In all individuals, emphasize a heart-healthy lifestyle across the life course. A healthy lifestyle reduces atherosclerotic cardiovascular disease (ASCVD) risk at all ages. In younger individuals, healthy lifestyle can reduce development of risk factors and is the foundation of ASCVD risk reduction. In young adults 20 to 39 years of age, an assessment of lifetime risk facilitates the clinician–patient risk discussion (see No. 6) and emphasizes intensive lifestyle efforts. In all age groups, lifestyle therapy is the primary intervention for metabolic syndrome.
    2. In patients with clinical ASCVD, reduce low-density lipoprotein cholesterol (LDL-C) with highintensity statin therapy or maximally tolerated statin therapy.The more LDL-C is reduced on statin therapy, the greater will be subsequent risk reduction. Use a maximally tolerated statin to lower LDLC levels by >=50%.
    3. In very high-risk ASCVD, use a LDL-C threshold of 70 mg/dL (1.8 mmol/L) to consider addition of 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 the LDL-C level remains >=70 mg/dL (1.8 mmol/L). In patients at very high risk whose LDL-C level 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.
    4. In patients with severe primary hypercholesterolemia (LDL-C level >=190 mg/dL [4.9 mmol/L]), without calculating 10-year ASCVD risk, begin high-intensity statin therapy without calculating 10-year ASCVD risk. If the LDL-C level remains >=100 mg/dL (2.6 mmol/L), adding ezetimibe is reasonable. If the LDL-C level 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.
    5. In patients 40 to 75 years of age with diabetes mellitus and LDL-C >=70 mg/dL (1.8 mmol/L), start moderate-intensity statin therapy without calculating 10-year ASCVD risk. In patients with diabetes mellitus at higher risk, especially those with multiple risk factors or those 50 to 75 years of age, it is reasonable to use a high-intensity statin to reduce the LDL-C level by >=50%.
    6. In adults 40 to 75 years of age evaluated for primary ASCVD prevention, have a clinician–patient risk discussion before starting statin therapy. Risk discussion should include a review of major risk factors (e.g., cigarette smoking, elevated blood pressure, LDL-C, hemoglobin A1C [if indicated], and calculated 10-year risk of ASCVD); the presence of risk-enhancing factors (see No.8); the potential benefits of lifestyle and statin therapies; the potential for adverse effects and drug–drug interactions; consideration of costs of statin therapy; and patient preferences and values in shared decisionmaking.
    7. In adults 40 to 75 years of age without diabetes mellitus and with LDL-C levels >=70 mg/dL (1.8 mmol/L), at a 10-year ASCVD risk of >=7.5%, start a moderate-intensity statin if a discussion of treatment options favors statin therapy. Risk-enhancing factors favor statin therapy (see No.8). If risk status is uncertain, consider using coronary artery calcium (CAC) to improve specificity (see No.9). If statins are indicated, reduce LDL-C levels by >=30%, and if 10-year risk is >=20%, reduce LDL-C levels by >=50%.
    8. In adults 40 to 75 years of age without diabetes mellitus and 10-year risk of 7.5% to 19.9% (intermediate risk), risk-enhancing factors favor initiation of statin therapy (see No.7).Risk enhancing factors include family history of premature ASCVD; persistently elevated LDL-C levels >=160 mg/dL (4.1 mmol/L); metabolic syndrome; chronic kidney disease; history of preeclampsia or premature menopause (age < 40 years); chronic inflammatory disorders (e.g., rheumatoid arthritis, psoriasis, or chronic HIV); high-risk ethnic groups (e.g., South Asian); persistent elevations of triglycerides >=175 mg/dL (1.97 mmol/L); and, if measured in selected individuals, apolipoprotein B >=130 mg/dL, high-sensitivity C-reactive protein >=2.0 mg/L, ankle-brachial index <0.9 and lipoprotein (a) >=50 mg/dL or 125 nmol/L, especially at higher values of lipoprotein (a). Risk-enhancing factors may favor statin therapy in patients at 10-year risk of 5-7.5% (borderline risk).
    9. In adults 40 to 75 years of age without diabetes mellitus and with LDL-C levels >=70mg/dL-189mg/dL (1.8-4.9 mmol/L), at a 10-year ASCVD risk of >=7.5% to 19.9%, if a decision about statin therapy is uncertain, consider measuring CAC.If CAC is zero, treatment with statin therapy may be withheld or delayed, except in cigarette smokers, those with diabetes mellitus, and those with a strong family history of premature ASCVD. A CAC score of 1 to 99 favors statin therapy, especially in those >=55 years of age. For any patient, if the CAC score is >=100 Agatston units or >=75th percentile, statin therapy is indicated unless otherwise deferred by the outcome of clinician–patient risk discussion.
    10. Assess adherence and percentage response to LDL-C–lowering medications and lifestyle changes with repeat lipid measurement 4 to 12 weeks after statin initiation or dose adjustment, repeated every 3 to 12 months as needed. Define responses to lifestyle and statin therapy by percentage reductions in LDL-C levels compared with baseline. In ASCVD patients at very high-risk, triggers for adding nonstatin drug therapy are defined by threshold LDL-C levels

    Full text in PDF. p.5-6

    Source : www.ahajournals.org/doi/10.1161/CIR.0000000000000625
    Grundy SM, et al., 2018 Cholesterol Clinical Practice Guidelines, Page 5 - 6

     
    Updated AHA/ACC cholesterol guidelines focus on more personalized risk assessment
        

    More personalized risk assessments and new cholesterol-lowering drug options for people at the highest risk for cardiovascular disease (CVD) are among the key recommendations in the 2018 cholesterol guidelines from the American Heart Association (AHA) and the American College of Cardiology (ACC).

    “The updated guidelines reinforce the importance of healthy living, lifestyle modification and prevention. They build on the major shift we made in our 2013 cholesterol recommendations to focus on identifying and addressing lifetime risks for cardiovascular disease,” said Ivor Benjamin, M.D., FAHA, president of the A merican Heart Association. “Having high cholesterol at any age increases that risk significantly. That’s why it’s so important that even at a young age, people follow a heart-heathy lifestyle and understand and maintain healthy cholesterol levels.”

    “High cholesterol treatment is not one size fits all, and this guideline strongly establishes the importance of personalized care,” said Michael Valentine, M.D., FACC, president of the American College of Cardiology. “Over the past five years, we’ve learned even more about new treatment options and which patients may benefit from them. By providing a treatment roadmap for clinicians, we are giving them the tools to help their patients understand and manage their risk and live longer, healthier lives.”

    A special report simultaneously published as a companion to the cholesterol guidelines provides a more detailed perspective about the use of quantitative risk assessment in primary prevention for cardiovascular disease. The risk calculator introduced in the 2013 guidelines remains an essential tool to help health care providers identify a patient’s 10-year risk for CVD.

    Because the calculator uses population-based formulas, the guidelines now urge doctors to talk with patients about “risk-enhancing factors” that can provide a more personalized perspective of a person’s risk, in addition to traditional risk factors. Risk-enhancing factors include family history and ethnicity, as well as certain health conditions such as metabolic syndrome, chronic kidney disease, chronic inflammatory conditions, premature menopause or pre-eclampsia and high lipid biomarkers, now also including Lp(a) and apoB. This additional information can make a difference in what kind of treatment plan a person needs.

    In primary and secondary prevention, when high cholesterol can’t be controlled by diet or exercise, the first line of treatment remains statins. For people at high risk for another CV event and whose LDL-C levels are not adequately lowered by statin therapy, the guidelines now recommend the select additional use of other cholesterol-lowing drugs. The guidelines recommend a stepped-approach of ezetimibe, available as a generic, in addition to the statin for these patients. If that combination doesn’t work well enough, a PCSK9 inhibitor could be added, specifically for people who are at very high risk.

    Once treatment is started, whether only lifestyle modifications are prescribed or if medication therapy is added, adherence and effectiveness should be assessed at 4 to 12 weeks with a fasting lipid test, then retested every 3-12 months based on determined needs.

    Another new aspect of the guidelines is the recommendation of coronary artery calcium (CAC) measurements for people in some risk categories, when their risk level isn’t clear and treatment decisions are less certain. A CAC score of zero typically indicates a low risk for CVD and could mean those people can forego or at least delay cholesterol-lowering therapy as long as they are non-smokers or don’t have other high-risk behaviors or characteristics. This measurement of calcified plaque is a non-invasive heart scan that should be done by a qualified provider in a facility offering the most current technology.

    Recognizing the cumulative effect of high cholesterol over the full lifespan, identifying and treating it early can help reduce the lifetime risk for CVD. Selective cholesterol testing is appropriate for children as young as two who have a family history of heart disease or high cholesterol. In most children, an initial test can be considered between the ages of nine and 11 and then again between 17 and 21. Because of a lack of sufficient evidence in young adults, there are no specific recommendations for that age group. However, it is essential that they adhere to a healthy lifestyle, be aware of the risk of high cholesterol levels and get treatment as appropriate at all ages to reduce the lifetime risk of heart disease and stroke.

    This lifespan approach to reducing CVD risk should start at an early age. Kids may not need medication but getting them started on healthy behaviors when they’re young can make a difference in their lifetime risk. When high cholesterol is identified in children, that could also alert a doctor to test other family members who may not realize they have high cholesterol, because awareness and treatment can save lives.

    The guidelines offer more specific recommendations for certain age and ethnic groups, as well as for people with diabetes, all important for the comprehensive and individualized provider-patient discussion.

    Source: www.pace-cme.org

     
    2018 US Cholesterol Guidelines: what has changed after 5 years?
    New US Cholesterol Guidelines: worth waiting for?
        

    In 2013, the US lipid management guidelines reverted to guidelines for cholesterol management (1). These guidelines were predominantly based on evidence from randomized controlled trials (RCTs); some queried this approach without leeway for clinician-based judgement. The new Guideline on the Management of Blood Cholesterol discussed Saturday provides a more sensible approach for clinicians. As in the 2013 Cholesterol Guidelines, the primary source of evidence is RCTs with statins the first-line treatment; however, the guidelines have also moved on with consideration of RCT evidence for ezetimibe (2), and most recently, the PCSK9 inhibitors evolocumab and alirocumab (3,4). These nonstatin therapies feature as add-on treatments to statins in high and very high-risk patients who are inadequately controlled with maximally tolerated statin therapy using a stepped approach, with ezetimibe the first choice, followed by a PCSK9 inhibitor.

    While the primary goal is ?50% reduction in baseline LDL cholesterol, thresholds have crept in for consideration of add-on nonstatin therapy. In patients with clinical atherosclerotic cardiovascular disease (ASCVD) considered at very high risk, i.e. with a history of multiple major ASCVD events or one major ASCVD event with multiple high-risk conditions (i.e. age ?65 years, heterozygous familial hypercholesterolaemia [FH, inherited high cholesterol], history of prior coronary artery bypass s urgery or percutaneous coronary intervention, diabetes, hypertension, chronic kidney disease, smoking and/or a history of congestive heart failure), the addition of nonstatin therapies are considered in a stepped approach. If LDL cholesterol is >=70 mg/dL or 1.8 mmol/L despite maximally tolerated statin therapy, ezetimibe should be considered first, with a PCSK9 inhibitor added if LDL cholesterol is still >=70 mg/dl or 1.8 mmol/L on maximally tolerated statin plus ezetimibe. A similar stepped approach is used in patients with primary severe hypercholesterolaemia (LDL cholesterol >=190mg/dL or 4.9 mmol/L) if LDL cholesterol remains >=100 mg/dL or 2.6 mmol/L despite intensive statin therapy. These LDL cholesterol thresholds also serve to reinforce the importance of monitoring response to statin (and subsequently, ezetimibe) therapy. Consideration of a stepped approach to nonstatin therapy is broadly consistent with the practical recommendations of a European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) Task Force, although this group was somewhat more conservative in their approach as they lacked the data from ODYSSEY OUTCOMES (5).

    The Guidelines highlight the need to identify and initiate treatment as early as possible in children and adolescents with FH, a view consistent with a European Atherosclerosis Society Consensus Panel statement (6).

    These guidelines also considered the cost-effectiveness of PCSK9 inhibitor therapy; not surprisingly, the economic value of these novel agents is improved by selecting higher risk patients, consistent with a pragmatic approach of ‘highest risk highest benefit’ (7). It is, however, important to bear in mind that cost value assessments are based on mid 2018 data and thus do not take account of the actual price paid now.

    Commenting on these new guidelines, PCSK9 FORUM Editor Professor Kausik Ray (Imperial College, London UK) said: ‘These latest US Guidelines for Management of High Cholesterol are more reflective of real-world practice, with consideration of enriching factors for cardiovascular risk, as well as thresholds for considering PCSK9 inhibitor therapy. While there has not been a sea change in thinking, the guidelines are practical and sensible, and clearly relevant to real-world practice.’

    References:

    1. Stone NJ, Robinson JG, Lichtenstein AH et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63(25 Pt B):2889-934. PUBMED https://www.ncbi.nlm.nih.gov/pubmed/24239923
    2. Cannon CP, Blazing MA, Giugliano RP et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015;372:2387-97. PUBMED https://www.ncbi.nlm.nih.gov/pubmed/26039521
    3. Sabatine MS, Giugliano RP, Keech AC et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017;376:1713–1722. PUBMED https://www.ncbi.nlm.nih.gov/pubmed/26039521
    4. Schwartz GG, Steg PG, Szarek M et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med 2018;published online 7 November 2018. DOI: 10.1056.NEJMoa1801174. Available at https://www.nejm.org/doi/full/10.1056/NEJMoa1801174?query=featured_home
    5. Landmesser U, Chapman MJ, Stock JK et al. 2017 Update of ESC/EAS Task Force on practical clinical guidance for proprotein convertase subtilisin/kexin type 9 inhibition in patients with atherosclerotic cardiovascular disease or in familial hypercholesterolaemia. Eur Heart J 2018;39:1131-43. PUBMED https://www.ncbi.nlm.nih.gov/pubmed/29045644
    6. Wiegman A, Gidding SS, Watts GF et al. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J 2015;36:2425-37. PUBMED https://www.ncbi.nlm.nih.gov/pubmed/26009596
    7. Annemans L, Packard CJ, Briggs A, Ray KK. 'Highest risk-highest benefit' strategy: a pragmatic, cost-effective approach to targeting use of PCSK9 inhibitor therapies. Eur Heart J 2018;39:2546-50. PUBMED https://www.ncbi.nlm.nih.gov/pubmed/29236976

    Source: www.pcsk9forum.org

     
    Pure Fish Oil Lowers CVD Risk
        

    No doubt about it: icosapent ethyl—a purified fish oil supplement—reduced cardiac events. The stunningly positive primary endpoint slide from the REDUCE-IT trial[1] earned applause from a packed audience here at the American Heart Association (AHA) Scientific Sessions 2018 in Chicago.

    In a large multicenter randomized controlled trial, patients with high cardiovascular risk and elevated triglycerides who took 4 g of a purified eicosapentaenoic acid ethyl ester (EPA) per day vs a mineral oil placebo had a 4.5% lower risk of dying from cardiac causes or experiencing myocardial infarction, stroke, coronary revascularization, or unstable angina necessitating hospital admission.

    Strengths of REDUCE-IT include that randomization resulted in well-matched groups; the 25% relative risk reduction is robust; the active treatment reduced all components of the composite endpoint (not just softer ones like coronary revascularization); and the findings showed a consistent effect in important subgroups (eg, sex, race, high vs low levels of triglycerides, statin intensity). Finally, the 25% relative risk reduction in REDUCE-IT comports with the JELIS trial,[2] a non–placebo-controlled trial of Japanese patients that found a 19% reduction in cardiac events with a lower daily dose of EPA.

    The high-dose EPA did show a trend toward higher rates of overall bleeding, but the rate of life-threatening bleeding events was similar. An unexpected but definite 1.4% increased risk for atrial fibrillation occurred in the EPA group.

    Source: www.nejm.org

     
     
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