New concepts and guidelines in the management of ldl c and cv risk need for early intervention
Download
1 / 21

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


  • 107 Views
  • Uploaded on

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.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'New concepts and guidelines in the management of LDL-c and CV Risk: Need for early intervention' - calvin


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
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 CV Risk: 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 CV Risk: 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

Recommendations CV Risk: regarding

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

Estimated CV Risk: riskas 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 CV Risk:

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 CV Risk: 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

Recommendations CV Risk: forlipidanalysesastreatmenttarget 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 CV Risk: 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

Recommendations CV Risk: forgenetictesting

European Heart Journal 2012;33:1635–1701


Comparison of different imaging and circulating biomarkers for cardiovascular risk estimation
Comparison CV Risk: of 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 CV Risk: 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 CV Risk: 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 CV Risk: 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 CV Risk: 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

    Recommendations CV Risk: fortreatmenttargetsfor 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

    Comparison CV Risk: 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 CV Risk:

    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 CV Risk: 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