assessment and primary prevention of cad - seton.net · – modest benefit in cv event reduction...
TRANSCRIPT
Objectives
• IdentifyriskfactorsforCVdisease• Identifypopulationsthatlikelybenefitfromcholesterolloweringmedicationsandassesstreatmentgoals
• Selectappropriatetherapiesforlipidlowering• Identifyadditionalriskstratificationtools• “Powerslide”
BMI<25
<130/80
1-800-QUIT-NOW
40”,3-4x/weekWeighttraining
PLANT-basedLowsugar,saltLowsaturatedfat
HbA1c<6.5-7%
21+yo
ScreenCVriskfactors,checklipids(LDL)
ClinicalCVD(SecondaryPrevention)
Highintensitystatin(<75y.o.)
LDL190+(+FH)
Highintensitystatin
Age40-75,LDL70-189
Non-DM(PRIMARYPREVENTION)
10-yrRiskcalculation
7.5-20%:Shareddecision-making;Modintensitystatin(IIb)
>20%:Highintensitystatin(I)
5-7.5%:Shareddecision-making;*Consideradd’ltesting
DM-1/2
Mod-highintensityStatin
*LDL>160mg/dL*hs-CRP>2mg/L,HighLp(a),ApoB>130mg/dL*ABI<0.9*+FHx(M<65,F<55)*SouthernAsianancestry*Comorbidities(Metabolicsx,CKD,HIV,Rheumatologicd/o,prematuremenopause**CAC>100or75th%tile
2018ACC/AHAGuideline
Otherpopulations
• Noformalrecommendations:– ESRD(maintenanceHD)– Non-IschemicCHF(NYHAII-IV)– Primarypreventionpatientsage>75(noclinicalASCVD)
Lipidmanagement
• SecondarycausesofelevatedLDL• Diet:Saturatedortransfats• Drugs:Thiazidediuretics,BBl,cyclosporine,Amiodarone,Gluco-andandrogenicsteroids,proteaseinhibitors• Diseases:Nephroticsyndrome,Biliaryobstruction,hypothyroidism,obesity,pregnancy
Lipidmanagement
• ContinuedfocusonuseofHMGCo-Areductaseinhibitors(aka–statins)
• Highintensity:LowersLDL50%+– Rosuvastatin(Crestor)20-40mg– Atorvastatin(Lipitor)40-80mg
• Moderateintensitystatin:LowersLDL30-50%– Simvastatin20-40mg– Pravastatin40-80mg
Caveats• Ifunabletotoleratehighintensity
• Examples– Previousstatinintolerance– Severecomorbidities:Severehepaticorrenalimpairment– Asianpopulation– UnexplainedLFTS>3xULN– Concomitantuseofdrugs(CytP450)effectingstatinmetabolism
– >75y.o.• Defaulttomoderateintensityorlowesttolerabledose
Non-statinmedications• Lowerisbetter:CTTdata
– Ezetimibe[Zetia]• Additional20%reductioninLDL(-16mgdL)• *Within30daysofACS
– ModestbenefitinCVeventreduction(MI,CVA)– Nochangein10yrall-causemortality
• Usedincombinationwith–statins(unclearutilityasmono-therapy)• PCSK-9MonoclonalAbs
*IMPROVE-IT
PCSK-9Inhibitors• MonoclonalAbsagainstPCSK-9protein
– Alirocumab[Praluent]orEvolocumab[Repatha]:SCinjection• Nodoseadjustmentinmild-moderaterenal/hepaticimpairment
– Adversereactions:Localinjectionsitereaction• Nomuscleorhepatictoxicity(ie:myalgias)
– Clinicalbenefit• PCSK-9inhibitor+statin:Additional60%reductioninLDLvs.statinalone
• StatisticallysignificantreductioninMIandCVA• Mortalitybenefitsuggestedbymeta-analysis
Non-statinmedications• Completestatinintolerance• CombinationRxinpatientswithinadequateresponse– Highrisk(secondaryprevention):IfLDL>70mg/dL– +FH:IfLDL>100
• Notclinicallybeneficial– ^Niacin:NoCVeventriskreduction
• TrendtowardMSK/GIevents,infection,ischemicCVA,bleeding
– *Fibrates:Nomortalitybenefit
^AIM-HIGH,HPS-2-THRIVE
*VA-HIT,HelsinkiHeart,FIELD,ACCORD-Lipid
BeyondLDL• Hypertriglyceridemia
– SecondarytargetinCVriskprevention• Treatsecondarycauses
– DM/metabolicsyndrome– EtOHabuse– CKD/ESRD/nephroticsyndrome– Hypothyroid– Meds(similartoLDLmedicationculprits)
• Primaryprevention– 500+mg/dLèTreattopreventPancreatitisbeforeuseofLDLlowering
medication(Ic)– *>150-199:O-3Fishoil
• *Secondaryprevention– >150-199èO-3Fishoil(PureEPA;Vascepa)– ReductionofMACE
*REDUCE-IT
BeyondLDL
• LowHDL:M<40mg/dL,F<50mg/dL– Stronglydeterminedbygenetics– *NoclinicalbenefittoraisingHDLwithexistingpharmacotherapies• Cholesterylestertransferprotein(CETP)inhibitors• Niacin
*Heartwire(Medscape),7/2014
BeyondLDL• LowHDLè*LifestyleRx!
– Diet• Oliveoil(polyphenolshigherinEVOO)• Coconutoil(2Tdaily;incorporatedindiet)• Red/purplevegetables(anthocyaninsandanti-oxidantsineggplant,red
cabbage,blueberries/blackberries)• Fattyfish(Omega-3fawith4x/wkconsumption:Salmon,herring,sardines,
mackerel)• Lowercarbohydratediet(“Ketogenic”particularlyinpre-existingDM,Obese,
andMetabolicsyndrome)• AVOIDartificialtrans-fats(“partiallyhydrogenated”)
– Exercise(particularlyhighintensityexercise)– Quittobacco(potentialbenefitofsimplyswitchingtovaporcigarettes)– Weightloss(viaseveralmethodsofwtloss)
*Heartwire(Medscape),7/2014
Follow-up• RecheckFLP4-12weeksfollowinginitiation– Routineq3-12monthreassessment
• Follow-upvisits– Assesseffectivenessoftreatment
– Assesscompliance/adherence– Reinforcementtool– Up-titrationifnecessary– Assess/addressothersecondarycauses/lifestylechanges
– Assesssideeffects
Follow-up
• CheckLFT’satbaseline– Noroutinecheckthereafter(unlesssignsofhepaticdysfunction)
• CKnotroutinelychecked(unlessmusclesymptoms)
Statinsafety• MAINconcern:Drug-druginteractions
– NOTmetabolizedbyCytP450• Pravastatin• Pitavastatin[Livalo]
– Simva,Atorva,Lova-statin:CYP3A4• Avoidwith:
– Trytoavoid/LOWdosewithDiltiazem,Verapamil(non-DHP)– HIVPI– -azole(antifungals)– -mycin(MacrolideAbx)– Gemfibrozil– Grapefruitjuice
– Simvastatin– Maxdose10mg:Non-DHPCCB(Diltiazem,Verapamil)– Maxdose20mg:Amiodarone,Ranolazine
Statinsafety• Safetyinpregnancy
– CategoryX:Recommenddiscontinuationpriortoconception– Notrecommendedduringbreast-feeding
• Myopathy*– Myalgiasreported:5-29%%– Myositis0.5%– Rhabdomyolysis<0.1%– Highestrisk:Renaldysfunction,hypothyroidism,liverdysfunction,concomitantmeds– MeasurementofCK(ifmusclesymptoms)
• Hepaticdysfunction– 0.5%-3%– Dosedependent,andusuallywithinfirst4months– Hepaticfailure:Incidencenodifferentfromgeneralpopulation– 2012FDAlabeling:BaselineLFTs,withrepeatmonitoringonlyifclinicallyindicated(notroutine)– IfALT>3ULN,decreasedoseorchangestatin
• DM– AcceleratesdevelopmentofDMinpre-diabetics– Assessrisk:benefit(althoughoverallbenefitofvasculareventreductionlikelyoutweighsrisk)
• Cognition– Datanotdefinitive– Higherratesofconcernwithlipophilicstatins(atorva,simva)comparedtohydrophilic(prava,rosuva)
• CA– Nodatatosupportanincreasedrisk
*Pravastatinandfluvastatinlessintrinsicmuscletoxicity
Source:Uptodate
Pravastatin:DiminishedDMrisk
Statinsafety• -StatinsassociatedwithLOWriskofadverseeffects
– Seriousmuscleinjury<0.1%• Myalgias5-29%• 10%willdiscontinue• Incidenceofmusclesymptomsinstatinv.placebo-treated:<1%
– >50%ptsalsohadsxw/placebo*
– Serioushepatotoxicity<0.001– Newlydx’dDM0.2%/year– PotentialincreaseinhemorrhagicCVA– NOcausalrelationship:
• Cancer• Cognitivedysfxn• Cataracts,peripheralneuropathy,ED
• “…benefitofreducingCVriskwithstatintherapyfaroutweighsanysafetyconcerns.”
AHAScientificStatement,12/2018,Arteriosclerosis,Thrombosis,andVascularBiology*GAUSS-3trial
CVRiskstratification
• Asymptomaticadultscreeningexams• ForCAD(CHDriskstratification)
– Resting12-leadECG– CalciumarteryscoreCT(“HeartHealthy”CT)– ABIstudy(2ndline)– Hs-CRP(2ndline)
• ForAAA– AbdominalaorticU/S
*Stresstesting(ETT,stress-echo,stress-Nuclear)NOTrecommendedscreeningtoolinasymptomaticadults
CoronaryarterycalciumCT(“HeartHealthy”CT)
• M>40orF>45yo– 1Framinghamrisk(HTN,HLD,*FHx)– 5-20%CVeventriskbycalculator
• Cashpaystudy– Widelyavailable/accessible
*Familyhxnotincludedinriskcalculators
ManagementofCVdisease:YesorNo?
Treatment/Test1. Diet,exercise2. Lipidmgmt.3. HTNmgmt.4. DMmgmt.5. Tobaccocess6. Carotiddoppler7. AAAscreen8. PADscreen(ABI)9. Calciumscore10. Lp(a),hs-CRP,apo-B11. Stresstesting12. Aspirin
• PrimaryPrevention• ABSOLUTELYYES• YES*• YES• YES• ABSOLUTELYYES• NO• YES(>65y.o.^)• YES(riskstrat)• YES(riskstrat)• YES(riskstrat)• NO• ??
• SecondaryPrevention• ABSOLUTELYYES• ABSOLUTELYYES*• YES;ACEi,+/-BBl• YES#• ABSOLUTELYYES• Symptom-driven• YES/symptom-driven• Symptom-driven• NO• NO• Symptom-driven• YES;Rivaroxaban
^Males>65yo+smoked100+cigarettesMalesorfemales>65yowitha+FHxofAAA
*Ezetimibe,PCSK-9,O-3fishoil(TG) #SGLT-2-I,GLP-1R-A
Summary• ModifiableCVriskfactorsandhearthealthyhabits
– Assessearly,often,andencourage/treataggressivelythroughoutlife
• Identifythe4patientgroupsthatwouldbenefitfromlipidmanagement
• Stillfocuson–statinsasworkhorsemedicationinlipidRx– Ezetimibe,PCSK-9inhibitors,O-3fishoil
• ConsideradditionalCVriskstratificationtoolsinmoreambiguousclinicalscenarios(ie:CACCT)
• LipidmanagementandCVriskmanagement(similartoalltherapeuticdecisions)isneveranabsolutismè“shareddecision-makingprocess”