Coronary Stents

CoronaryStentsLookingForwardScotGarg,MB,CHB,PatrickW.Serruys,MD,PHDRotterdam,theNetherlandsDespiteallthebenefitsofdrug-elutingstents(DES),concernshavebeenraisedovertheirlong-termsafety,withparticularreferencetostentthrombosis.Inanefforttoaddresstheseconcerns,newerstentshavebeendevel-opedthatinclude:DESwithbiodegradablepolymers,DESthatarepolymerfree,stentswithnovelcoatings,andcompletelybiodegradablestents.Manyofthesestentsarecurrentlyundergoingpre-clinicalandclinicaltrials;however,earlyresultsseempromising.Thispaperreviewsthecurrentstatusofthisnewtechnology,togetherwithothernewcoronarydevicessuchasbifurcationstentsanddrug-elutingballoons,aseffortscontinuetodesigntheidealcoronarystent.(JAmCollCardiol2010;56:S43–78)©2010bytheAmericanCollegeofCardiologyFoundationPart1hashighlightedtheimpressiveclinicalbenefitsseenfollowingtheintroductionofdrug-elutingstents(DES);however,inparallel,italsoservestohighlightthesafetyconcernsassociatedwiththeiruse,whichhavepredomi-nantlycenteredaroundstentthrombosis(ST)(1–3).ThecauseofSTisclearlymultifactorial,andinadditiontopatientandlesionfactors,aportionofblamehasbeenattributedtothestentpolymer(4),whichhassubsequentlybecomeafocalareafornewresearchandstentdevelopment.Thesecond-generationDEShavemorebiocompatiblepolymers,andalthoughtheyhavealreadydemonstratedimpressivesafetyresultsatmedium-termfollow-up(5–7),additionalimprovementsareanticipatedfromthenewermetallicdurablepolymerDESthathavebeendeveloped.Despitethis,however,concernspersistoverthepresenceofanonerodablepolymer,whichremainsexposedtothecoronaryarteryenvironmentlongafteritsusefulfunctionhasbeenserved.Theseconcernsappearjustifiedinlightofevidencefromanimalandhumanstudies,whichsuggestthatthesenonerodablepolymerscancausepersistentarterialwallinflammationanddelayedvascularhealing,bothofwhichmaysubsequentlyhavearoleinprecipitatingSTanddelayedrestenosis(8–11).Thefindingsfromthesestudiesacceleratedthedevelop-mentofDEScoatedwithbiodegradablepolymers.Thesestentsoffertheattractivecombinationofcontrolleddrugelutioninparallelwithbiodegradationofthepolymerintoinertmonomers.Therefore,afterbiodegradationiscom-plete,onlyabare-metalstent(BMS)remains,therebyreducingthelong-termrisksassociatedwiththepresenceofapermanentpolymer(12).Inrecenttimes,anextensionofthisconcepthasbeenthedevelopmentofDESthatarecompletelyfreeofpolymer,andofBMScoatedinnovelcoatings.Finally,completelybiodegradablemagnesiumandpolymericstentshavebeendeveloped,whichcompletelydisappearoncevascularheal-inghastakenplace.InPart2,thisnewstenttechnology,togetherwithothercoronarydevicessuchasbifurcationstentsanddrug-elutingballoonsthatareallcurrentlyundergoinginvestigationinpre-clinicalandclinicaltrials,isreviewed.Thisnewstenttechnologyencompassesawiderangeofdevices,andalthoughnotadefinitiveclassification,devicesinthefol-lowingdiscussionhavebeengroupedtogetheralongsimilartypesofpolymer.Itmustbeacknowledged,however,thatthisclassificationdoesnotcaterforallpossibilities.MetallicDESWithDurablePolymersNumerousnewdurablepolymermetallicDESareunderdevelopment.Thesestentsbuildontheknowledgeandexperiencesgainedfromthefirst-andsecond-generationDESdescribedinPart1,whileutilizingnewpolymertechnology,antiproliferativeagents,andmetalstentplat-formsinabidtoimproveclinicaloutcomesandsafety(Table1)(13–17).Newpolymertechnology:EndeavorResolute.TheEn-deavorResolutezotarolimus-elutingstent(ZES)(Medtronic,SantaRosa,California)isthenextversionoftheEndeavorZESandiscurrentlyundergoingclinicalevaluation.ThisZESconsistsoftheDrivercobaltchromiumstentplatformandaBiolinxpolymer—ablendof3differentpolymers:thehydro-phobicC10polymertocontroldrugrelease;thebiocompatibleandhydrophilicC19polymer;andpolyvinylpyrrolidonetoFromtheDepartmentofInterventionalCardiology,Thoraxcenter,ErasmusMedicalCenter,Rotterdam,theNetherlands.Drs.GargandSerruysreportthattheyhavenorelationshipstodisclose.ManuscriptreceivedDecember9,2009;revisedmanuscriptreceivedJune1,2010,acceptedJune15,2010.JournaloftheAmericanCollegeofCardiologyVol.56,No.10SupplS,2010©2010bytheAmericanCollegeofCardiologyFoundationISSN0735-1097/$36.00PublishedbyElsevierInc.doi:10.1016/j.jacc.2010.06.008allowanearlyburstofdrugrelease(18).Thepolymerallowsdelayeddrugrelease,suchthatatleast85%ofthezotarolimusisreleasedwithin60days,withtheremainderbeingreleasedwithin180days(Fig.1)(18,19).Ultimately,thisdelayedreleaseisintendedtomatchthedelayedhealingtimesseenincomplexlesions.Evalua-tionofthestentinthe139-patientmulticenter,nonrandomized,first-in-man(FIM)RESOLUTE(Evaluationofthenewgenerationzotarolimus-elutingcoronarystentsystem)studydemonstratedanangiographicin-stentlatelossof0.22mmat9-monthsfollow-upandrespectiveratesofmajoradversecardiovascularevents(MACE),targetlesionrevascu-larization(TLR),andanydefi-nite/probableSTof8.6%,0.7%,and0.0%at12-monthfollow-up,and11.6%,1.6%,and0.0%at3-yearfollow-up(13,20,21).FurtherevaluationoftheReso-lutestenthastakenplaceintheRESOLUTEAll-Comerstrial,whichenrolled2,300patientswhowererandomizedina1:1ratiototreatmentwitheithertheResoluteZESortheXienceV(Abbot