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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 ?
slide3

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

slide4

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

slide5

Recommendationsregarding

riskestimation

European Heart Journal 2012;33:1635–1701

slide6

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

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

Atherosclerosis 2011;217(1):3-46

slide7

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

slide8

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

slide9

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

slide11

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.
slide13

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

slide17

Recommendationsfortreatmenttargetsfor LDL-C

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

Atherosclerosis 2011;217(1):3-46

slide19

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)

slide20

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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