New concepts and guidelines in the management of ldl c and cv risk need for early intervention
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New concepts and guidelines in the management of LDL-c and CV Risk: Need for early intervention. Prof. Ulf Landmesser University Hospital Zürich Switzerland. New concepts and guidelines in the management of LDL-C and CV Risk: Need for early intervention.

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New concepts and guidelines in the management of ldl c and cv risk need for early intervention

New concepts and guidelines in the management of LDL-c and CV Risk: Need for early intervention

Prof. Ulf Landmesser

University Hospital Zürich

Switzerland


New concepts and guidelines in the management of ldl c and cv risk need for early intervention1

New concepts and guidelines in the management of LDL-C and CV Risk: Need forearlyintervention

  • Need forimprovement in managmentofcardiovascularrisk

  • What do currentguidelinespropose ?

  • Whatneedstobeexploredbeyondcurrentguidelinerecommendations ?


New concepts and guidelines in the management of ldl c and cv risk need for early intervention

Clinical presentation of

coronary disease

First clinical presentation of coronary artery disease is frequently an acute coronary syndrome. i.e. can be the last …

Men

62 %

46 %

Women

0

20

40

60

Patients (%)

Framingham Heart Study

Murabitoet al Circulation 1993; 88: 2548-54

Courtasy of John Deanfield


New concepts and guidelines in the management of ldl c and cv risk need for early intervention

Frequency and mortality of

a first coronary event

28.9 %

9.5 %

61.6 %

  • 384,597 Individuals with first coronary event

    (Coronary death or first acute myocardial infarction – population aged 35-84)

Dudas K et al.; Circulation 2011; 123: 46-52


New concepts and guidelines in the management of ldl c and cv risk need for early intervention

Recommendationsregarding

riskestimation

European Heart Journal 2012;33:1635–1701


New concepts and guidelines in the management of ldl c and cv risk need for early intervention

Estimatedriskas a functionofhigh-densitylipoprotein-cholesterol (HDL-C) forwomen in populationsathighcardiovasculardiseaserisk

Eur Heart J 2011;32(14):1769-1818

Atherosclerosis 2011;217(1):3-46


New concepts and guidelines in the management of ldl c and cv risk need for early intervention

SCORE charts with HDL-C

For use in low risk regions:

HDL-C= 1.8 mmol/L (70 mg/dl)

SCORE charts with HDL-C

For use in low risk regions:

HDL-C= 0.8 mmol/L (32 mg/dl)

Eur Heart J 2011;32(14):1769-1818

Atherosclerosis 2011;217(1):3-46


New concepts and guidelines in the management of ldl c and cv risk need for early intervention

Intervention strategies as a functionof total CV riskand LDL-C level

Eur Heart J 2011;32(14):1769-1818

Atherosclerosis 2011;217(1):3-46


New concepts and guidelines in the management of ldl c and cv risk need for early intervention

Recommendationsforlipidanalysesastreatmenttarget in thepreventionof CVD

Eur Heart J 2011;32(14):1769-1818

Atherosclerosis 2011;217(1):3-46


European guidelines on cardiovascular disease prevention in clinical practice version 2012

European Guidelines on cardiovascular disease prevention in clinicalpractice (version 2012)

Eur Heart J 2012;33:1635-1701


New concepts and guidelines in the management of ldl c and cv risk need for early intervention

Recommendationsforgenetictesting

European Heart Journal 2012;33:1635–1701


Comparison of different imaging and circulating biomarkers for cardiovascular risk estimation

Comparisonof different imagingandcirculatingbiomarkersforcardiovascularriskestimation

Yeboah J et al.; JAMA. 2012 Aug 22;308(8):788-95

  • - Multi-Ethnic Study ofAtherosclerosis (MESA) analysis

  • FRS >5%-<20%: 1330 intermediate risksubjects (from 6814 subjects),

  • 7.6 yearsoffollow-up

  • 6 markers:

    • coronaryarterycalcium,

    • carotidintima-mediathickness,

    • ankle-brachial index,

    • brachial flow-mediateddilation,

    • high-sensitivity C-reactiveprotein (CRP),

    • familyhistoryofcoronaryheartdisease (CHD)

  • Conclusions: Coronaryarterycalcium, ankle-brachial index, high-sensitivity CRP, andfamilyhistorywereindependentpredictorsofincident CHD/CVD in intermediate-risk individuals.

  • Coronaryarterycalciumprovidedsuperiordiscriminationandriskreclassificationcomparedwithotherriskmarkers.


  • New concepts and guidelines in the management of ldl c and cv risk need for early intervention

    Recommendations on managementofhyperlipidaemia

    European Heart Journal 2012;33:1635–1701


    Is there evidence for a benefit of statin therapy in people at low risk of vascular disease

    Is there evidence for a benefit of statin therapy in people at low risk of vascular disease ?

    Interpretation:

    In individuals with 5-year risk of major vascular events lower than 10%, each 1 mmol/L reduction in

    LDL cholesterol produced an absolute reduction in major vascular events of about 11 per 1000 over 5 years. This benefit greatly exceeds any known hazards of statin therapy.

    Under present guidelines, such individuals would not typically be regarded as suitable for LDL-lowering statin therapy. The present report suggests, therefore, that these guidelines might need to be reconsidered.

    Cholesterol Treatment Trialists' (CTT) Collaborators; Lancet. 2012 Aug 11; 380(9841):581-90


    Is there evidence for a benefit of statin therapy in people at low risk of vascular disease1

    Is there evidence for a benefit of statin therapy in people at low risk of vascular disease ?

    Cholesterol Treatment Trialists' (CTT) Collaborators; Lancet. 2012 Aug 11; 380(9841):581-90


    Major vascular events avoided in different cardiovascular risk cohorts categories

    Major vasculareventsavoided in different cardiovascularriskcohortscategories

    Cholesterol Treatment Trialists' (CTT) Collaborators; Lancet. 2012 Aug 11; 380(9841):581-90


    New concepts and guidelines in the management of ldl c and cv risk need for early intervention

    Recommendationsfortreatmenttargetsfor LDL-C

    Eur Heart J 2011;32(14):1769-1818

    Atherosclerosis 2011;217(1):3-46


    New concepts and guidelines in the management of ldl c and cv risk need for early intervention

    JAMA. 2012 Mar 28;307(12):1302-9


    New concepts and guidelines in the management of ldl c and cv risk need for early intervention

    Comparison HPS2-THRIVE

    and Aim-High trial

    HPS2-THRIVE trial

    AIM-HIGH trial

    (N Engl J Med 2011)

    • Pre-randomisation phase with niacin (1.5/2g) exclusion: 20.1 %

    • Aiming to have similarly low LDL-C in both treatment groups

      • LDL: - 5.5 %, HDL: + 13.2 %

      • More patients on high-dose statin

      • or ezetimibe in control-group

  • Randomization (n): 1718 vs. 1696 patients

  • Mean FU - 3 years (556 events)

    • Pre-randomisation phase with ER-niacin (2g)/

    • laropiprantexclusion: 25.4 %

    • No further adjustment of LDL-C levels after randomization

      • LDL: -20 %; HDL + 17 %

    • Addition of laropiprant

    • (Antagonist of PGD2receptor DP1)

    • Randomization (n): 12838 vs. 12835 patients

    • Mean FU - 4 years (? events)

    HPS2-THRIVE clinical outcome data

    (presentation expected in 2013)


    New concepts and guidelines in the management of ldl c and cv risk need for early intervention

    Lipid-targeted Therapies

    What should be added to statins

    in patients with high vascular risk ?

    Statin

    therapy

    HDL-C

    Further

    LDL-C

    Combined

    LDL-C

    HDL-C

    • Reconstituted HDLs

    • ApoA1 modulation

    • NPC1L1 (Ezetimibe*)

    • PCSK9 inhibition

    • (Monoclonal Ab*)

    • ApoB-100 Antisense oligonucleotides

    • Niacin/Laropiprant*

    • CETP inhibition

    • (Anacetrapib*,Evacetrapib*)

    *Clinical outcometrialsongoing


    Hdl metabolism hdl c can be increased by several mechanisms

    HDL metabolism – HDL-C canbeincreasedbyseveralmechanisms

    (2) apoA-I

    (lipid-free)

    (3) ABCA-1 expression

    (4) SR-BI inhibition

    (1) CETP inhibition

    Besler C et al. & Landmesser U. EMBO Mol Med 2012; 4(4):251-68


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