B4 Pharm Exam 1
How hyperlipidemia leads to heart failure - hyperlip --> athero --> CHD (ie. angina, MI)
and/or HTN --> heart failure
Classes of Antihyperlipidemic Drugs - - HMG-CoA reductase inhibs (statins)
- Bile acid sequestrants
- Chol absorp inhibs
- Fibrates
- Niacin
- Others incl PCSK9 inhibs, HDL elevs, HoFH
Lipoprotein - transp form of lipids made up of lipids+prots since lipids insol in plasma
Chylomicrons - lipoprot synth in intest made of dietary (exog) TGs+chol; most imp
apoprot = ApoB-48
VLDL - lipoprot synth in liver made up of endog/hep TGs; most imp apoprot = ApoB-100
IDL - lipoprot synth from VLDL catab made up of chol esters+endog TGs; most imp
apoprot = ApoB-100
LDL - lipoprot synth from VLDL catab expr in liver+intest, made up of chol esters; most
imp apoprot = ApoB-100
HDL - lipoprot synt in intest, liver, plasma made up of phospholips+chol esters; most
imp apoprot = ApoA
LDL structure - core of chol esters + outer layer of ApoB-100, phospholipids, free chol
mols
Relationship of Lipoprotein xSize x& xDensity x- xlargest xlipoprot x(chylomicrons) xhas
xlowestxdensity; xhighest xdens x= xLp(a) x& xHDL
Exogenous xPathway xof xLipid xMetabolism x- x1). xDiet xTGs+chol xincorp xinto xlarge
xchylomicxlipoprots
2). xChylomics xhydr xby xLPL xon xendoth xsurf xadip+musc, xcleaving xFAs xfrom
xTGsx3). xChylomic xenters xcirc xas xpredom xchol x(chylomic xremnant)
4). xChylomic xremnant xinto xliver xby xrec-med xendocyt
Endogenous xPathway xof xLipid xMetabolism x- x1). xLiver xsecr xTGs+chol xin
xVLDL xform,xmetab xby xLPL x--> xIDL
2). Chol xdens xin xIDL xincr xuntil xLDL xform
3). LDL xinto xliver/periph xtiss xby xLDLR xor xaccum xin xBVs x(athero)
4). HDL xprom xchol xrem xfrom xperiph xcells, xtx xto xapoprot x--> xdeliv xback xto
xliver xforxmetab/excr
,B4 Pharm Exam 1
Pathogenesis xof xAtherosclerosis x- xLDL xmigr xinto xBV xintima, xbind
xproteoglycans x-->xoxid/glycosylated x--> xaldehyde xintermeds xfragmenting
xApoB-100
- endoth xdam x--> xmac xinvasion x--> xendoth+mac xGFs xstim xsm xmusc xmigr xto xtun
xint x(sm xmusc xhyperpl) x--> xoxLDL xaccum xin xmacs x(foam xcells)+musc xcells x-->
xcoll+el xfibs xinto xCTxmatrix xforming xsubendoth xfibr xplaque
Role xof xHyperlipidemia xin xCVD x- xmajor xCHD xRF xincl xac xMI, xac+chron xIHD,
xanginaxpectoris, xathero xCVD
- gen+EVRal xfacs xincr xserum xlipoprot xlev
- athero x= xpredom xMI xcause xby xturb xbl xflow xaround xcor xart xplaque xprod xoccl
xthrombus
Antihyperlipidemic xDrugs xfor xTreatment xof xHypercholesterolemia x- x- xHMG-CoA
xReductase xInhibs x= xAtorvastatin, xLovastatin, xPravastatin, xSimvastatin, xFluvastatin,
xPitavastatin, xRosuvastatin
- Bile xAcid xSequestrants x= xColestipol, xCholestyramine, xColesevelam
- Chol xAbsorp xInhibs x= xEzetimibe
Antihyperlipidemic xDrugs xfor xTreatment xof xHyperTG x- x- xFibrates x= xGemfibrozil,
xFenofibrate, xFenofibric xAcid
- Niacin
Statins xin xorder xfrom xleast xLDL-lowering xto xgreatest xLDL-lowering x- x- xFluvastatin
- Lovastatin
- Pravastatin
- Simvastatin
- Pitavastatin
- Atorvastatin
- Rosuvastatin
MOA x& xPharm xConsequences xof xHMG-CoA xReductase xInhibitors x- x- xMOA x= xinhib
xHMG-xCoA xreduc xconv xHMG-CoA xto xmevalonic xac xin xchol xbiosynth x(rate-lim xstep)
- inhib xHMG-CoA xred x--> xdecr xchol xsynth xw/in xcell x--> xupreg xLDLR xsynth x-->
xincr xuptakexLDL xfrom xbl, xdecr xserum xLDL, xdecr xVLDL xsecr xby xliver xby xlack xraw
xmats xfor xVLDL xsynth
Overall xPharmacological xEffects xof xStatin xTreatment xon xLipids x- x- xdecr xLDL-C
- decr xVLDL-C
- incr xHDL-C xin xsome xpts xby xincr xApoA-1 xsynth
- decr xserum xTG xby xdecr xVLDL-C
- Atorv, xLova, xPrava, xSimva x--> xdecr xfat+non-fat xCHD xev, xdecr xstroke, xdecr xtotal
xmort
Mode xof xexcretion xfor xmost xstatins x- xbiliary/fecal xexcr
Examples xof xlong-acting xstatins x- x- xAtorvastatin x(t1/2 x= x14 xhr x--> xonce-daily xdose)
- Rosuvastatin x(t1/2 x= x19 xhr x--> xonce xdaily xdose)
- Pitavastatin x(t1/2 x= x12 xhr)
,B4 Pharm Exam 1
Why xdoes xPravastatin xpresent xwith xless xAEs xand xDIs xthan xother xstatins? x- xlow
xprot xbinding x& xdoes xNOT xreq xCYP450 xenz xfor xmetab x--> xlow xint xw/ xother
xdrugs/body xprots x&xexcr xlargely xunchanged xfrom xparent xcomp
Beneficial xCV xEffects xof xStatins x- x- xendoth xfunc ximprov
- incr xathero xplaque xstab x(ie. xbefore xsurg)
- anti-infl
- lipoprot xoxid xinhib
- anticoag xby xplt xaggreg+plt xthrombi xinhib
Statins xw/ xgreatest xeffects xon xTGs x(used xfor xMixed xHyperlipidemia) x- x- xAtorvastatin
- Rosuvastatin
Use xof xAtorvastatin+Amlodipine x(Caduet) x- xAmlodipine x= xCa2+ xchann xblocker
x(vasodil)
- combo xfor xHTN/angina x+ xhyperchol
Statins xfor xtreatment xof xchildren xw/ xHeterozygous xFamilial xHypercholesterolemia
x(LDLRxdefect) x- x- xAtorvastatin
- Lovastatin
- Simvastatin
- Pravastatin
Potential xnon-CV xuses xof xstatins x- x- xClin xTrials x= xmaybe xprot xag xosteop, xcancer
- recent xfindings xthat xboost xerec xfunc
AEs x& xCIs xof xStatins x- x- xAEs x= xGI x(cramps, xconstip, xdiarr, xheartburn) xmost
xcomm; xliverxtox; xRHABDOMYOLYSIS x= xpot xfat xstat-ind xmyop xby xcell xmemb
xcomp x+ xelec xprops xalterations x--> xdiscont xstatin xif xoccurs
- CIs x= xpreg+nursing xwomen xb/c xchol xsynth xnec xfor xfet xgrowth
DIs xof xStatins x- x- xcaution xw/ xfibric xac xderivs xb/c xcan xalso xcause xmyops
- Erythromycin x& xItraconazole x--> xinhib xstatin xmetab x--> xincr xAEs xlike xmyop
- decr xmetab/incr xlevels xof xCYP450 xsubstrates x(Warfarin)
Effects xof xStatin-Induced xRhabdomyolysis xon xKidneys x- xstatins xalter xmusc xcell
xmembxcomp x--> xweak xmyocytes x--> xmusc xprot xleak x--> xdecr xelec xprops x&
xlodging xprots xin xkidney x--> xac xkidney xfail
Examples x& xMOA xof xBile xAcid xSequestrants x(binding xresins) xfor
xHypercholesterolemia x-xincl xCholestyramine, xColestipol, xColesevelam
- MOA x= xlarge xmol xwt xpolyms xbinding xgut xbile xac, xexcr xin xfeces xblocking
xenterohep xbile xac xcycling x(BAS xtoo xlarge xfor xliver xabsorp) x--> xmore xliv xchol
xused xfor xBA xsynth x--> xupregxliv xLDLR x--> xdecr xLDL-C
, B4 Pharm Exam 1
Therapeutic xUses, xAEs, xDIs xof xBile xAcid xSequestrants x- x- xUses x= xmod xeffec
xhypercholxtreatement x(red xLDL-C xbut xmay xincr xTG+VLDL), xoften xcombo xw/
xstatins; xtreatment xdiarr+itching xcaused xby xexcess xBAs x(BAs xbind xelectros xto
xabsorb xin xintest+stool)
- AEs x= xgen xwell-tol, xmild xGI xsx, xskin xrash
- DIs x= xbind xdigoxin, xthyroxin, xwarfarin; xVit xK xmalabs x--> xprolonged
xprothrombin xtimex(decr xclotting)
MOA x& xPK xof xEzetimibe x- x- xMOA x= xchol xabsorp xinhib xby xsel xinhib xNPC1L1 xchol
xtransp xprot xbrush xbord xcells, xdecr xchol xtransp xfrom xmicelles xinto xenteros xby x50%
xw/o xred xTG/fat-xsol xvit xabsorp
- single xdaily xdose x--> xdecr xLDL x15-20% x+ xTG x8%, xincr xHDL x3%
- esp xeffec xin xcombo xw/ xstatin
- PK x= xrap xabsorb xfrom xintest xafter xor xadmin, xmetab xin xintest+liver xforming
xezetimibe- xglucuronide xconjug x(highly xwater-sol xby xgluc xac, xbetter xexcr);
xenterohep xcirc xw/ xt1/2 x= x22xhrs
Therapeutic xUses x& xAEs xof xEzetimibe x- x- xUses x= xmost xcomm xnonstatin
xagent xforxlowering xLDL; xalone/combo xw/ xstatins xfor xhyperchol xtreatment
- Ezetimibe+Simvastatin x(Vytorin) x= x60% xLDL xred xfor xhomoz xfam xhyperchol
- AEs x= xgen xwell-tol xbut xsome ximpair xliv xfunc, xdyspepsia, xmyalgia, xrare xmyop, xHA
Use xof xBile xAcid xSequestrants xif xHigh xTGs x- xBA xseqs xred xLDL-C xby x15-30% xbut
xnot xabsxso xno xsyst xeffects, xbut xassoc xw/ xGI xsx x(constip) x& xcan xcause xsev
xhyperTG xif xfasting xTG x300+
Examples x& xActions xof xFibrates x(fibric xacid xderivatives) x- xincl xGemfibrozil,
xFenofibrate,xFenofibric xAcid
- xdecr xTGs x(40-50%), xdecr xLDL-C x(10%), xincr xHDL-C x(10-20%)
MOA xof xFibrates xfor xLowering xVLDL-TGs x- xbind+activ xPPAR-alpha x(peroxisome
xprolif xactiv xrec xalpha) x--> xincr xLPL xexpr, xdecr xApoC-III x(LPL xinhib) xexpr x--> xincr
xhydr+rem xVLDLxTGs x& xchylomic xTGs x--> xdecr xplasma xTGs
- also xactiv xPPAR-alpha x--> xincr xexpr xFA xoxid xenz x--> xdecr xTG xsynth
MOA xof xFibrates xfor xLowering xLDL-C x& xIncreasing xHDL-C x- xactiv xPPAR-alpha x-
-> xincrxliver xLDLR xexpr x--> xincr xLDL xuptake xby xliver x--> xdecr xLDL-C
- also xactiv xPPAR-alpha x--> xincr xFA xoxid x--> xdecr xTG xsynth x--> xdecr xVLDL xform
x--> xdecrxLDL xform x(prod xof xVLDL xby xliver)
- activ xPPAR-alpha x--> xincr xApoA-I x& xApoA-II xsynth x(HDL xcomps) x--> xincr xHDL
xform x-->xincr xHDL-C
Therapeutic xUses, xAEs, xDIs xof xFibrates x- x- xUses x= xprim xfor xhyperTG x& xHDL xdef;
xalso xforxcomb xhyperchol x& xhyperTG
- AEs x= xGI xsx, xmyops x(rhabdo), xincr xrisk xcholelithiasis
- DIs x= xcomb xw/ xstatins x(Rosuva, xPrava) xfor xcomb xhyperlip/decr xHDL
How hyperlipidemia leads to heart failure - hyperlip --> athero --> CHD (ie. angina, MI)
and/or HTN --> heart failure
Classes of Antihyperlipidemic Drugs - - HMG-CoA reductase inhibs (statins)
- Bile acid sequestrants
- Chol absorp inhibs
- Fibrates
- Niacin
- Others incl PCSK9 inhibs, HDL elevs, HoFH
Lipoprotein - transp form of lipids made up of lipids+prots since lipids insol in plasma
Chylomicrons - lipoprot synth in intest made of dietary (exog) TGs+chol; most imp
apoprot = ApoB-48
VLDL - lipoprot synth in liver made up of endog/hep TGs; most imp apoprot = ApoB-100
IDL - lipoprot synth from VLDL catab made up of chol esters+endog TGs; most imp
apoprot = ApoB-100
LDL - lipoprot synth from VLDL catab expr in liver+intest, made up of chol esters; most
imp apoprot = ApoB-100
HDL - lipoprot synt in intest, liver, plasma made up of phospholips+chol esters; most
imp apoprot = ApoA
LDL structure - core of chol esters + outer layer of ApoB-100, phospholipids, free chol
mols
Relationship of Lipoprotein xSize x& xDensity x- xlargest xlipoprot x(chylomicrons) xhas
xlowestxdensity; xhighest xdens x= xLp(a) x& xHDL
Exogenous xPathway xof xLipid xMetabolism x- x1). xDiet xTGs+chol xincorp xinto xlarge
xchylomicxlipoprots
2). xChylomics xhydr xby xLPL xon xendoth xsurf xadip+musc, xcleaving xFAs xfrom
xTGsx3). xChylomic xenters xcirc xas xpredom xchol x(chylomic xremnant)
4). xChylomic xremnant xinto xliver xby xrec-med xendocyt
Endogenous xPathway xof xLipid xMetabolism x- x1). xLiver xsecr xTGs+chol xin
xVLDL xform,xmetab xby xLPL x--> xIDL
2). Chol xdens xin xIDL xincr xuntil xLDL xform
3). LDL xinto xliver/periph xtiss xby xLDLR xor xaccum xin xBVs x(athero)
4). HDL xprom xchol xrem xfrom xperiph xcells, xtx xto xapoprot x--> xdeliv xback xto
xliver xforxmetab/excr
,B4 Pharm Exam 1
Pathogenesis xof xAtherosclerosis x- xLDL xmigr xinto xBV xintima, xbind
xproteoglycans x-->xoxid/glycosylated x--> xaldehyde xintermeds xfragmenting
xApoB-100
- endoth xdam x--> xmac xinvasion x--> xendoth+mac xGFs xstim xsm xmusc xmigr xto xtun
xint x(sm xmusc xhyperpl) x--> xoxLDL xaccum xin xmacs x(foam xcells)+musc xcells x-->
xcoll+el xfibs xinto xCTxmatrix xforming xsubendoth xfibr xplaque
Role xof xHyperlipidemia xin xCVD x- xmajor xCHD xRF xincl xac xMI, xac+chron xIHD,
xanginaxpectoris, xathero xCVD
- gen+EVRal xfacs xincr xserum xlipoprot xlev
- athero x= xpredom xMI xcause xby xturb xbl xflow xaround xcor xart xplaque xprod xoccl
xthrombus
Antihyperlipidemic xDrugs xfor xTreatment xof xHypercholesterolemia x- x- xHMG-CoA
xReductase xInhibs x= xAtorvastatin, xLovastatin, xPravastatin, xSimvastatin, xFluvastatin,
xPitavastatin, xRosuvastatin
- Bile xAcid xSequestrants x= xColestipol, xCholestyramine, xColesevelam
- Chol xAbsorp xInhibs x= xEzetimibe
Antihyperlipidemic xDrugs xfor xTreatment xof xHyperTG x- x- xFibrates x= xGemfibrozil,
xFenofibrate, xFenofibric xAcid
- Niacin
Statins xin xorder xfrom xleast xLDL-lowering xto xgreatest xLDL-lowering x- x- xFluvastatin
- Lovastatin
- Pravastatin
- Simvastatin
- Pitavastatin
- Atorvastatin
- Rosuvastatin
MOA x& xPharm xConsequences xof xHMG-CoA xReductase xInhibitors x- x- xMOA x= xinhib
xHMG-xCoA xreduc xconv xHMG-CoA xto xmevalonic xac xin xchol xbiosynth x(rate-lim xstep)
- inhib xHMG-CoA xred x--> xdecr xchol xsynth xw/in xcell x--> xupreg xLDLR xsynth x-->
xincr xuptakexLDL xfrom xbl, xdecr xserum xLDL, xdecr xVLDL xsecr xby xliver xby xlack xraw
xmats xfor xVLDL xsynth
Overall xPharmacological xEffects xof xStatin xTreatment xon xLipids x- x- xdecr xLDL-C
- decr xVLDL-C
- incr xHDL-C xin xsome xpts xby xincr xApoA-1 xsynth
- decr xserum xTG xby xdecr xVLDL-C
- Atorv, xLova, xPrava, xSimva x--> xdecr xfat+non-fat xCHD xev, xdecr xstroke, xdecr xtotal
xmort
Mode xof xexcretion xfor xmost xstatins x- xbiliary/fecal xexcr
Examples xof xlong-acting xstatins x- x- xAtorvastatin x(t1/2 x= x14 xhr x--> xonce-daily xdose)
- Rosuvastatin x(t1/2 x= x19 xhr x--> xonce xdaily xdose)
- Pitavastatin x(t1/2 x= x12 xhr)
,B4 Pharm Exam 1
Why xdoes xPravastatin xpresent xwith xless xAEs xand xDIs xthan xother xstatins? x- xlow
xprot xbinding x& xdoes xNOT xreq xCYP450 xenz xfor xmetab x--> xlow xint xw/ xother
xdrugs/body xprots x&xexcr xlargely xunchanged xfrom xparent xcomp
Beneficial xCV xEffects xof xStatins x- x- xendoth xfunc ximprov
- incr xathero xplaque xstab x(ie. xbefore xsurg)
- anti-infl
- lipoprot xoxid xinhib
- anticoag xby xplt xaggreg+plt xthrombi xinhib
Statins xw/ xgreatest xeffects xon xTGs x(used xfor xMixed xHyperlipidemia) x- x- xAtorvastatin
- Rosuvastatin
Use xof xAtorvastatin+Amlodipine x(Caduet) x- xAmlodipine x= xCa2+ xchann xblocker
x(vasodil)
- combo xfor xHTN/angina x+ xhyperchol
Statins xfor xtreatment xof xchildren xw/ xHeterozygous xFamilial xHypercholesterolemia
x(LDLRxdefect) x- x- xAtorvastatin
- Lovastatin
- Simvastatin
- Pravastatin
Potential xnon-CV xuses xof xstatins x- x- xClin xTrials x= xmaybe xprot xag xosteop, xcancer
- recent xfindings xthat xboost xerec xfunc
AEs x& xCIs xof xStatins x- x- xAEs x= xGI x(cramps, xconstip, xdiarr, xheartburn) xmost
xcomm; xliverxtox; xRHABDOMYOLYSIS x= xpot xfat xstat-ind xmyop xby xcell xmemb
xcomp x+ xelec xprops xalterations x--> xdiscont xstatin xif xoccurs
- CIs x= xpreg+nursing xwomen xb/c xchol xsynth xnec xfor xfet xgrowth
DIs xof xStatins x- x- xcaution xw/ xfibric xac xderivs xb/c xcan xalso xcause xmyops
- Erythromycin x& xItraconazole x--> xinhib xstatin xmetab x--> xincr xAEs xlike xmyop
- decr xmetab/incr xlevels xof xCYP450 xsubstrates x(Warfarin)
Effects xof xStatin-Induced xRhabdomyolysis xon xKidneys x- xstatins xalter xmusc xcell
xmembxcomp x--> xweak xmyocytes x--> xmusc xprot xleak x--> xdecr xelec xprops x&
xlodging xprots xin xkidney x--> xac xkidney xfail
Examples x& xMOA xof xBile xAcid xSequestrants x(binding xresins) xfor
xHypercholesterolemia x-xincl xCholestyramine, xColestipol, xColesevelam
- MOA x= xlarge xmol xwt xpolyms xbinding xgut xbile xac, xexcr xin xfeces xblocking
xenterohep xbile xac xcycling x(BAS xtoo xlarge xfor xliver xabsorp) x--> xmore xliv xchol
xused xfor xBA xsynth x--> xupregxliv xLDLR x--> xdecr xLDL-C
, B4 Pharm Exam 1
Therapeutic xUses, xAEs, xDIs xof xBile xAcid xSequestrants x- x- xUses x= xmod xeffec
xhypercholxtreatement x(red xLDL-C xbut xmay xincr xTG+VLDL), xoften xcombo xw/
xstatins; xtreatment xdiarr+itching xcaused xby xexcess xBAs x(BAs xbind xelectros xto
xabsorb xin xintest+stool)
- AEs x= xgen xwell-tol, xmild xGI xsx, xskin xrash
- DIs x= xbind xdigoxin, xthyroxin, xwarfarin; xVit xK xmalabs x--> xprolonged
xprothrombin xtimex(decr xclotting)
MOA x& xPK xof xEzetimibe x- x- xMOA x= xchol xabsorp xinhib xby xsel xinhib xNPC1L1 xchol
xtransp xprot xbrush xbord xcells, xdecr xchol xtransp xfrom xmicelles xinto xenteros xby x50%
xw/o xred xTG/fat-xsol xvit xabsorp
- single xdaily xdose x--> xdecr xLDL x15-20% x+ xTG x8%, xincr xHDL x3%
- esp xeffec xin xcombo xw/ xstatin
- PK x= xrap xabsorb xfrom xintest xafter xor xadmin, xmetab xin xintest+liver xforming
xezetimibe- xglucuronide xconjug x(highly xwater-sol xby xgluc xac, xbetter xexcr);
xenterohep xcirc xw/ xt1/2 x= x22xhrs
Therapeutic xUses x& xAEs xof xEzetimibe x- x- xUses x= xmost xcomm xnonstatin
xagent xforxlowering xLDL; xalone/combo xw/ xstatins xfor xhyperchol xtreatment
- Ezetimibe+Simvastatin x(Vytorin) x= x60% xLDL xred xfor xhomoz xfam xhyperchol
- AEs x= xgen xwell-tol xbut xsome ximpair xliv xfunc, xdyspepsia, xmyalgia, xrare xmyop, xHA
Use xof xBile xAcid xSequestrants xif xHigh xTGs x- xBA xseqs xred xLDL-C xby x15-30% xbut
xnot xabsxso xno xsyst xeffects, xbut xassoc xw/ xGI xsx x(constip) x& xcan xcause xsev
xhyperTG xif xfasting xTG x300+
Examples x& xActions xof xFibrates x(fibric xacid xderivatives) x- xincl xGemfibrozil,
xFenofibrate,xFenofibric xAcid
- xdecr xTGs x(40-50%), xdecr xLDL-C x(10%), xincr xHDL-C x(10-20%)
MOA xof xFibrates xfor xLowering xVLDL-TGs x- xbind+activ xPPAR-alpha x(peroxisome
xprolif xactiv xrec xalpha) x--> xincr xLPL xexpr, xdecr xApoC-III x(LPL xinhib) xexpr x--> xincr
xhydr+rem xVLDLxTGs x& xchylomic xTGs x--> xdecr xplasma xTGs
- also xactiv xPPAR-alpha x--> xincr xexpr xFA xoxid xenz x--> xdecr xTG xsynth
MOA xof xFibrates xfor xLowering xLDL-C x& xIncreasing xHDL-C x- xactiv xPPAR-alpha x-
-> xincrxliver xLDLR xexpr x--> xincr xLDL xuptake xby xliver x--> xdecr xLDL-C
- also xactiv xPPAR-alpha x--> xincr xFA xoxid x--> xdecr xTG xsynth x--> xdecr xVLDL xform
x--> xdecrxLDL xform x(prod xof xVLDL xby xliver)
- activ xPPAR-alpha x--> xincr xApoA-I x& xApoA-II xsynth x(HDL xcomps) x--> xincr xHDL
xform x-->xincr xHDL-C
Therapeutic xUses, xAEs, xDIs xof xFibrates x- x- xUses x= xprim xfor xhyperTG x& xHDL xdef;
xalso xforxcomb xhyperchol x& xhyperTG
- AEs x= xGI xsx, xmyops x(rhabdo), xincr xrisk xcholelithiasis
- DIs x= xcomb xw/ xstatins x(Rosuva, xPrava) xfor xcomb xhyperlip/decr xHDL
