Upload
goldfishx
View
230
Download
0
Embed Size (px)
Citation preview
7/25/2019 Lipid Guideline Controversies
1/43
Lipid Guideline Controversiesin 2014: The Decision is Yours
Carl E. Orringer !D "#CC"$L#
7/25/2019 Lipid Guideline Controversies
2/43
O%&ectives
To provide an overvie' o( the #)ericanCollege o( Cardiolog*+#)erican ,eart#ssociation and the $ational Lipid#ssociation lipid )anage)entapproaches (or #-CD prevention
To identi(* the si)ilarities and di/erences
%et'een the t'o approaches To provide the in(or)ation needed to
decide 'hich approach to use and 'hen
7/25/2019 Lipid Guideline Controversies
3/43
T'o #-CD revention #pproaches
T'o Di/erent erspectives
Eternal revie'er #uthor
7/25/2019 Lipid Guideline Controversies
4/43
US age-standardized death rates
attributable to CVD, 2000 to 2010
Go A S et al. Circulation. 201412!"e2#-e2!2
Copyright American Heart Association, Inc. All rights reserved.
elease o( $CE#T 333 elease o( $CE
#T 333 pdate
7/25/2019 Lipid Guideline Controversies
5/43
Mean age-adjusted LDL-C trends 20012011in theUnited States: Analysis of 105 illion!atient re"ords
fro a single national diagnosti" la#oratory
10.1561+&ournal.pone.0075417
7/25/2019 Lipid Guideline Controversies
6/43
3s There a $eed (or a Dra)atic Changein #pproach to #-CD revention8
CC-3#-
E#-+E-C9#-$3CE$L#
Changes in:
Evidence %aseCentral (ocusLipid goalsse o( nonstatinsis; calculator
#CC+#,#
7/25/2019 Lipid Guideline Controversies
7/43
The ules
The topic 'ill %e identi
7/25/2019 Lipid Guideline Controversies
8/43
Evidence =ase
ACC$A%A
ando)i>ed
controlled trials?CT@ o( statintherap*
!etaanal*ses o(CT
&LA
CT o( statins andnonstatin drug
therap*
!etaanal*ses o( CT
O%servationalepide)iologic studies
Genetic studies
!eta%olic studies
!echanistic studies
7/25/2019 Lipid Guideline Controversies
9/43
ando)i>ed Controlled Trials ?CT@
-*ste)aticall* test e/ect?s@ o( an interventionon prespeci
7/25/2019 Lipid Guideline Controversies
10/43
O%servational Epide)iologic -tudies
orld'ide in scope and )a* assess#-CD ris; across populations
Cohort studies evaluate )ortalit* and
)or%idit* 'ithin populations Con(ounding )a* occur even a(ter
)atching strati
7/25/2019 Lipid Guideline Controversies
11/43
O%servational Epide)iologic Cohort -tud* o(2147 atients 'ith ", and no C,D at =aseline
ers)issen 9 et al =!9 200B 556: a2425
7/25/2019 Lipid Guideline Controversies
12/43
Genetic -tudies
Genetic epide)iolog* reduces theli;elihood o( con(ounding %* (ocusing on
single varia%les: genetic )utations 3denti
7/25/2019 Lipid Guideline Controversies
13/43
Data De)onstrating Genetic
ariants #/ecting #-CD is;
-euence variants in the gene
encoding (or C-F resulting in loss o((unction )utations are associated'ith 2H reduction in LDLC an Hreduction in C,D ris; and provide
support (or the value o( long ter) lo'LDLC in pro)oting C,D ris; reduction
9 Cohen et al. $ Engl 9 !ed 2007B5I4:127462
7/25/2019 Lipid Guideline Controversies
14/43
'(iden"e )ase: Suary
#CC+#,# =* li)iting the scope to CT o( statins and
)etaanal*ses o( CT onl* the highest level o(evidence on statins in de
7/25/2019 Lipid Guideline Controversies
15/43
Central "ocus o( Guideline
ACC$A%A
3denti
7/25/2019 Lipid Guideline Controversies
16/43
#CC+#,# -tatin =ene
7/25/2019 Lipid Guideline Controversies
17/43
,igh and !oderate3ntensit*Dail* -tatin Therap*
,igh 3ntensit*?Lo'ers LDLC I0H@ Ator(astatin 0-30
g
4osu(astatin 20-40 )g
!oderate 3ntensit*?Lo'ers LDLC 50
I0H@ Ator(astatin 10 ?20@
g
4osu(astatin ?I@10
g Si(astatin 200
g
Si(astatin 30 g 6ra(astatin 0 ?0@
g
Lo(astatin 0 g "luvastatin NL 0 )g 7lu(astatin 0 g
28$day
Bold = ested in !C and
revie"ed #y $%pert &anel'ello"=(ot tested in !Crevie"ed #y $%pert &anel
7/25/2019 Lipid Guideline Controversies
18/43
EPcac* o( 3ntensive Lo'ering o( LDLC in -u%&ects 'ith Lo' =aseline LDLC
!etaanal*sis o( CTAs o( Q1000 participantsand M2 *ears treat)ent duration o( )oreversus less intense statin trials involving
1715 su%&ects The )a&or vascular event reduction a)ong in
those 'ith %aseline LDLC R66)g+dL per(urther 5 )g+dL reduction 'as 2H ?H C3
24 pS0.006@B in those 'ith %aseline LDLCR60 )g+dl si)ilar reduction in LDLCcontinued to de)onstrate !E reduction ?0.75 H C3 0.410.I pS0.004@.
Cholesterol Treat)ent Trialists Colla%oration. Lancet 2010B567:17601
7/25/2019 Lipid Guideline Controversies
19/43
#CC+#,# erspective on -tatinTherap*
-tatin intensit* trials sho'ed clear%ene
7/25/2019 Lipid Guideline Controversies
20/43
#CC+#,# erspective on $on-tatinLipid Drug Therap*
$onstatin drugs 'ithout de)onstrated#-CD ris; reduction )a* (avora%l* alterlipids %ut have an un(avora%le ris;+%eneeti)i%e
CET inhi%itors torcetrapi% and dalcetrapi%
The use o( nonstatin drugs should generall*%e avoided
7/25/2019 Lipid Guideline Controversies
21/43
Overvie' o( the $L#eco))endations
1. #ll preventive therap* %egins 'ith ris; assess)ent and aproviderpatient discussion o( the pros and cons o( therap*
2. Li(est*le therap* is at the %asis o( all #-CD preventivereco))endations regardless o( %aseline ris;
5.9udicious use o( evidence%ased drug therap* particularl*)oderate and highdose statins is associated 'ith opti)al#-CD ris; reduction
4. hen ecessive circulating atherogenic cholesterol ?non,DLcholesterol and LDL cholesterol@ persists a(ter
appropriate li(est*le and statin therap* the use o( nonstatin therap* )a* %e considered
I. Longter) (ollo'up (ostered %* providerpatientco))unication is essential (or opti)al #-CD prevention
7/25/2019 Lipid Guideline Controversies
22/43
$L# #-CD is; Categor* Criteria
4is Category Criteria
er* ,igh #-CD Dia%etes )ellitus ?t*pe 1 or 2@ M2 other )a&or #-CD ris;(actorsB or Evidence o( endorganda)age
,igh M5 )a&or #-CD ris; (actors Dia%etes )ellitus ?t*pe 1 or 2@ 01 other )a&or #-CD ris;(actor and no evidence o( endorganda)age
Chronic ;idne* disease -tage 5=or 4
LDLC M10 or non,DLC M220)g+dL
!oderate 2 )a&or #-CD ris; (actors "or speci
7/25/2019 Lipid Guideline Controversies
23/43
$L# #-CD is; Categories Levels (orConsideration o( Drug Therap* and Treat)ent Goals
4is Category Consider Drug9hera!y
9reatent oal
$on,DLC +LDLCGoal ?)g+dL@
$on,DLC+LDLCGoal ?)g+dL@
er*high M100
M60
R100
R60,igh M150
M100R150R100
!oderate M170M150
R150R100
Lo' M10M170
R150R100
ts with ASCVD or diabetes mellitus, consider use of moderate or highrrespective of baseline atherogenic cholesterol levels.
7/25/2019 Lipid Guideline Controversies
24/43
$L# erspective on -tatin
Therap* -tatin therap* is the )ost potent and evidence%ased approach to lo'ering atherogeniclipoproteins ?non,DLC and LDLC@
-tatin intensit* trials sho'ed clear %ene
7/25/2019 Lipid Guideline Controversies
25/43
$L# erspective on$on-tatin Lipid Drug Therap*
3( non,DLC and LDLC goals are not achieved 'ith)ai)al tolerated statin therap* the addition o(nonstatin therap* should %e considered to lo'eratherogenic cholesterol levels and to achieve goals Doctors can %e instructed not to use niacin in patients on
aggressive statin regi)ens
#s e>eti)i%e is sa(e and lo'ers atherogenic cholesterolits use )a* %e considered in selected patients 'ith
elevated non,DLC and+or LDLC esins )a* %e considered in selected patients
!etaanal*ses o(
7/25/2019 Lipid Guideline Controversies
26/43
3s ,ighDose -tatin Therap*the End o( the Line8
i %ili ( hi d
7/25/2019 Lipid Guideline Controversies
27/43
!eta anal*sis
o( statin CTinvolving 51I5 su%&ectso( 'ho) I56had 727)a&or C
events andhad %aselineand 1 *earlipids andlipoproteins
aria%ilit* o( #chieved LDLCith ,igh3ntensit* -tatin
Therap*=oe;holdt -! et al. 9 #) Coll Cardiol 2014B74: 4I4
"ro) T$T-#CL 3DE#L and
93TEde)onstratingvaria%ilit* o(LDLC lo'ering.Q40H did not achieveLDLC R60 )g+dl onatorvastatin 0 orrosuvastatin 20 )gdail*
ater(all plot o(3ndividual values
er* Lo' LDL C and $on ,DL C
7/25/2019 Lipid Guideline Controversies
28/43
er* Lo' LDLC and $on,DLCin -tatin Trials and !a&or CD
Event is;
0/22
0/510/5; 0/53
0/;2
0/,1
1/00
0/5, 0/;0
0/;20/;