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SelectingSuccessfulLipid LoweringTreatmentsJamesM McKenney Pharm D 天马行空官方博客 ExpertPanelonDetection Evaluation andTreatmentofHighBloodCholesterolinAdults JAMA2001 285 2486 2497 TreatmentCategories LDL CGoalsandCutpoints 100 129mg dL afterTLC considerstatin niacin orfibratetherapy TreatmentofHyperlipidemia ExpertPanelonDetection Evaluation andTreatmentofHighBloodCholesterolinAdults JAMA2001 285 2486 2497 HighLDL C TherapeuticLifestyleChange DrugTherapy TherapyofChoice Statin Alternative Resinorniacin Statins MechanismofAction LDLreceptor mediatedhepaticuptakeofLDLandVLDLremnants SerumVLDLremnants SerumLDL C Cholesterolsynthesis LDLreceptor B Ereceptor synthesis IntracellularCholesterol ApoB ApoE ApoB SystemicCirculation Hepatocyte Reducehepaticcholesterolsynthesis loweringintracellularcholesterol whichstimulatesupregulationofLDLreceptorandincreasestheuptakeofnon HDLparticlesfromthesystemiccirculation SerumIDL VLDL TheLDL C LoweringEfficacyoftheCurrentlyAvailableStatins Physician sDeskReference 55thed Montvale NJ MedicalEconomics 2001 TheTriglyceride LoweringEffectsofStatins SteinEAetal AmJCardiol1998 81 66B 69B NonfatalMIorCHDdeath ischemiceventsDownsJRetal JAMA1998 279 1615 1622 ShepherdJetal NEnglJMed1999 333 1301 1307 ScandinavianSimvastatinStudyGroup Lancet1994 344 1383 1389 SacksFMetal NEnglJMed1996 335 1001 1009 LIPIDStudyGroup NEnglJMed1998 339 1349 1357 SchwartzGGetal JAMA2001 285 1711 1718 PittBetal NEnglJMed1999 341 70 76 EndpointTrialswiththeStatins CHDRiskReductionwithStatinTherapy LaRosaJCetal JAMA1999 282 2340 2346 CrouseJRIIIetal ArchInternMed1997 157 1305 1310 PedersenTRetal AmJCardiol1998 81 333 335 Endpoints 20 35 30 25 0 5 10 15 20 RelativeRiskReduction 40 45 50 MajorcoronaryeventsCoronarydeathsCardiovasculardeathsNoncardiovasculareventsTotalmortalityStrokesIntermittentclaudicationAngina PotentialTimeCourseofStatinEffects Timecourseestablished Days Years LDL Clowered Inflammationreduced Vulnerableplaquesstabilized Endothelialfunctionrestored Ischemicepisodesreduced Cardiaceventsreduced StatinAdverseEvents CommonsideeffectsHeadache Myalgia FatigueGIintolerance Flu likesymptomsIncreaseinliverenzymesOccursin0 5to2 5 ofcasesindose dependentmannerSeriousliverproblemsareexceedinglyrareManagebyreducingstatindoseordiscontinueuntillevelsreturntonormalMyopathyOccursin0 2to0 4 ofpatientsRarecasesofrhabdomyolysisReducebyCautiouslyusingstatinsinpatientswithimpairedrenalfunctionUsingthelowesteffectivedoseCautiouslycombiningstatinswithfibratesAvoidingdruginteractionsCarefulmonitoringofsymptomsPresenceofmuscletoxicityrequiresthediscontinuationofthestatin BileAcidResins MechanismofAction NetEffect LDL C LDLReceptorsVLDLandLDLremoval Cholesterol7 hydroxylaseConversionofcholesteroltoBABASecretion BAExcretion TerminalIleum BileAcidEnterohepaticRecirculation Reabsorptionofbileacids EffectofColesevelamonLDL C DavidsonMHetal ExpertOpinInvestigDrugs2000 9 2663 2671 ReprintedwithpermissionfromAshleyPublications ChangeinLDL C Placebo 3 8g d 4 5g d N 494patientswithbaselineLDL Cof130 220mg dLandTG 300mg dL after24weeksoftherapy 0 15 18 ClinicalFeaturesofBARs Productsavailable Cholestyramine Questran 4 16g dColestipol Colestid 5 20g dColesevelam WelChol 625mgtablets 6 7tablets dReducecoronaryevents LRC CPPT AdverseeffectsGIintolerance constipation bloating abdominalpain flatulenceLacksystemictoxicityDruginteractions colestipolandcholestyramine BindothernegativelychargeddrugsImpedetheabsorptionofdrugsand orfat solublevitaminsMustgiveotherdrugs1hourbeforeor4 6hoursafter NicotinicAcid MechanismofAction Liver Circulation HDL SerumVLDLresultsinreducedlipolysistoLDL SerumLDL VLDL DecreaseshepaticproductionofVLDLandofapoB VLDLsecretion ApoB Hepatocyte SystemicCirculation MobilizationofFFA TGsynthesis VLDL EffectofNiacinonLipoproteins AdaptedfromKnoppRH NEnglJMed1999 341 498 511 1999MassachusettsMedicalSociety Allrightsreserved 01g d2g d3g d Baseline 15 12 5 25 30 HDL CwithNiaspan TGwithNiaspan TGwithcrystallineniacin LDL CwithNiaspan LDL Cwithcrystallineniacin 35 HDL Cwithcrystallineniacin ClinicalFeaturesofNicotinicAcid Productsavailable dailydose Immediate release 2 4g dExtended release Niaspan 1 2g dOTCproducts sustained release 2g dBestagenttoraiseHDL CReducescoronaryevents CoronaryDrugProject AdverseeffectsFlushing itching headache immediate release Niaspan Hepatotoxicity GI sustained release ActivationofpepticulcerHyperglycemiaandreducedinsulinsensitivityContraindicationsActiveliverdiseaseorunexplainedLFTelevationsPepticulcerdisease ProgressionofDrugTherapyforLDL CLowering ExpertPanelonDetection Evaluation andTreatmentofHighBloodCholesterolinAdults JAMA2001 285 2486 2497 Visit1 Visit2 Visit3 F UVisits Startstatinorbileacidresinornicotinicacid Considerhigherdoseofthestatinoraddabileacidresinornicotinicacid 6wks InitiateLDL loweringdrugtherapy 6wks q4 6mo IfLDLgoalnotachieved intensifyLDL loweringtherapy IfLDLgoalnotachieved drugtherapyorrefertoalipidspecialist Monitorresponseandadherencetotherapy IfLDLgoalhasbeenachieved treatotherlipidriskfactors SimvastatinAloneandwithColesevelam PercentChangeinLDL C KnappHHetal AmJMed2001 110 352 360 ReprintedwithpermissionfromExcerptaMedicaInc MeanPercentChange PlaceboSimvastatin10mgSimvastatin20mgColesevelam2 3g Simvastatin20mgColesevelam3 8g Simvastatin10mg n 258patientswithbaselineLDL C160 220mg dL treatedfor6weeks 4 p 0 05vsplacebo 26 34 42 42 WolfeMLetal AmJCardiol2001 87 476 479 TheEffectofAddingNiaspan toaStableDoseofaStatin PercentChange 1gramdaily 2gramsdaily LDL C HDL C TG LDL C HDL C TG 27 23 30 8 24 24 BrownBGetal AmJCardiol1997 80 111 115 Triple DrugRegimen Lovastatin40mg d Niaspan2g d Colestipol20g d TargetsforTherapyafterLDL CGoalinPatientswithTG 200mg dL ExpertPanelonDetection Evaluation andTreatmentofHighBloodCholesterolinAdults JAMA2001 285 2486 2497 TreatmentofMixedHyperlipidemia ExpertPanelonDetection Evaluation andTreatmentofHighBloodCholesterolinAdults JAMA2001 285 2486 2497 HighLDL CandTGs TherapeuticLifestyleChange DrugTherapy AchievetheLDL Cgoal 1 STEP Achievethenon HDL CgoalIncreaseLDL CloweringorAddafibrate niacinorfishoils 2 STEP ChangeinLDL CandNon HDL CbyStatinsafter54WeeksofTherapy BallantyneCMetal AmJCardiol2001 88 265 269 MeanDose AveragebaselineLDL C 178mg dLAveragebaselinenon HDL C 216mg dL 24mg 62mg 52mg 31mg 23mg Atorvastatin n 1 888 Fluvastatin n 474 Lovastatin n 472 Pravastatin n 461 Simvastatin n 462 42 38 29 26 36 32 28 26 36 32 LDL C Non HDL C PercentChange PravastatinandNiacinAloneandTogether DavignonJetal AmJCardiol1994 73 339 345 LDL C230mg dL PercentChange TG170mg dL HDL C46mg dL 16 33 42 11 14 35 12 13 16 NiacinXL0 5 1 0gbidPravastatin40mghsCombination FishOils FibricAcidDerivatives EffectsofFenofibrateonPlasmaLipids Double Blind Multicenter 24 WeekStudyinPatientswithPrimaryHypercholesterolemiaorMixedHyperlipidemia HPL p0 10 BrownWVetal Arteriosclerosis1986 6 670 678 1999LippincottWilliams W TrialsofFibrates EffectsonCardiacEvents FrickMHetal NEnglJMed1987 317 1237 1245 ManninenVetal Circulation1992 85 37 45 BIPStudyGroup Circulation2000 102 21 27 RubinsHBetal NEnglJMed1999 341 410 418 PosthocanalysisofsubgroupwithTG 200mg dLandHDL C 42mg dL PosthocanalysisofsubgroupwithTG 200mg dLandHDL C 35mg dL DifferencebetweenplaceboandRxforprimaryendpointwasstatisticallysignificant p 0 05 CHDDeath NonfatalMI RxPlacebo 2 7 4 1 2 7 8 0 13 6 15 0