Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3751_Библиотеки_им_академика_М_И_Перельмана
.pdf
III.Access
Infrapopliteallesionscanbeapproached fromthe contralateral andipsilateral femoralartery,withthe
majorityofstenoticinfrapopliteallesionsapproachedfromthecontralateralfemoralartery.Accessfrom
the contralateral femoral artery is the preferred approach when treating inflow disease and in the
morbidly obese, given the propensity of the sheath to become kinked in the groin with an antegrade
approach.A5-Fror6-Frcrossoversheathisintroducedintothecontralateralarteryandadvancedtothe
distalipsilateraliliacartery.Antegradeaccessfromtheipsilateralcommonfemoralarteryispreferred
whentreatingcomplexinfrapoplitealdiseaseintheabsenceofinflowdisease.Antegradeaccessinthe
common femoral artery allows for better wire guide ability and good “pushability” of the catheter
balloons,giventhecloseproximityoftheaccesssitetothelesions.11Whenusingacrossoverapproach,
anincreasedamountofcontrastisrequiredforadequatevisualizationofthedistalcirculationgiventhe
relativelylong distance from thetip ofthe sheath to theinfrapopliteal lesion.Incaseswhenantegrade
accesscannotbeachieved,contralateralcrossoverusinga6-Frmultipurposecoronaryguidecatheterora
hydrophilic5-Fror6-Frguidesheathmaybeadvancedfromthecontralateralcommonfemoralarteryto
the distal ipsilateral superficial femoral artery or mid-popliteal artery for better maneuverability and
control.16In patientswithchronic totalocclusions(CTOs),aretrogradeapproach,withaccessvia the
pedal,peroneal,anterior,orposteriortibialartery,canbeusedaloneorincombinationwithanantegrade
orcrossoverapproach.
IV.Intervention
A.Indications
1.ThemostcommonindicationforinfrapoplitealendovascularinterventionremainsCLIwithischemic
restpain,tissueloss,andulcerationduetoperipheralarterialdisease.Beforeendovascularintervention,
thoroughclinicalevaluationofobjectivedataincludingankle branchial index ortranscutaneousoxygen
pressure measurements, assessment of the width, length, and depth of ischemic ulcers should be
performed.
10
2. Noninvasive imaging modalities such as arterial duplex ultrasound, computed tomography (CT)
angiography,magneticresonance(MR)angiographycanassistinpreproceduralplanningforbelow-thekneeinterventions.Thecurrentstandardofcareremainsballoonangioplastyforbelow-the-kneelesions.
0.014 ″ and 0.018 ″ low-profile balloon catheters are utilized to perform focal angioplasty for
infrapopliteallesions.Inourexperienceutilizingalow-profilesupportcatheterwitha0.014″guidewire
platform has beenmost successful. Selectionof0.014 ″ guidewire is based on plaquecharacteristics,
calcifications,lengthofstenosis,andtotalocclusions.Focallesionscanbecrossedwithanycommonly
used0.014″coronaryguidewireswithafloppytip.
3.However,CTOwillrequirecoronarywireswithstiffertips,suchasConfianzaorFielderXT-Abbot
Vascular.Oncethelesioniscrossedasupportcoronary-typeguidewire(ie,V-18,V-14BostonScientific)
canbereplacedtoformascaffoldingfortheintervention.
B.AngioplastyBalloons
1.Angioplastyballoonsforinfrapopliteallesionsvaryonsizebasedonthelocationofthelesion.A2.5
or 3 mm diameter ballooncanbe used for the proximalregion of the infrapopliteal artery, while 2.0-
2.5mmballoons arecommonlyusedfordistaltibialandplantararchvessels.Newgenerationoflong,
https://t.me/med1917
low-profile 0.014 ″ tapered balloons with increased balloon lengths including 120-200 mm provide
improvedremodelingofthetreatedvessel,especiallywhenemployingprolongedballooninflationtimes.
4
Inaddition,theover-the-wireplatformandlowcomplianceoftheseballoonsallowsthemosteffective
tracking and pushing characteristics. In our practice, the Ultraverse Bard dilation catheters are well
designedfortibialangioplasty.
2. Cutting balloons and scoring balloons additionally have facilitated below-the-knee endovascular
revascularization.TheAngioSculptballoon(AngioScoreInc.)isascoringballoonwithanover-the-wire
semicompliantballoonsurroundedbyanitonalcagewiththreerectangularspiralstruts.Fonescaetal,in
aprospectivemulticenterEuropeanregistryshoweda90.3%successrateandadissectionrateof10.7%.
7
There wasnoneed forfurthertherapyofthetreatedlesions.Ourexperienceusingscoringandcutting
balloonsismainlyutilizedforheavilycalcifiedlesionstoimproveluminalgain.Theprimaryconceptis
toprovideintimaldisruptionandeffectivedilationrequiringlesswalltension.
6
C.Atherectomy
Thebasisofatherectomyunderlines debulkingmaterialratherthandisplacement,thusdecreasingdistal
embolization.Peripheralcalciumtendstobeasignificantimpedimenttoachievingrevascularization,and
studiesshowthatcalciumnegativelyimpactsoutcomes.8TheDiamondbackOrbitalAtherectomySystem
(Cardiovascular Systems, Inc, St. Paul, MN) has compared below-the-knee revascularization with
standard angioplasty with positive results. In a small patient study, there was increased target lesion
revascularization and decreased stenosis. The system utilizes a diamond-coated crown to achieve a
mechanicalsandingofthevesselwalltodifferentiallytreathardplaquewhileminimizingdamagetothe
media,unlikeadirectionaldevice.Thelow-profiletechnologyallowstreatmentofdistaltibiallesions,
which was previously inaccessible. Our center has used this type of atherectomy device in heavily
calcifiedlesionsthatareunabletobecrossedbyconventionalcrossingcatheters/wires.
D.Drug-CoatedBalloons
Drug-coatedballoonshaveshownpromisingresultsinsingle-centerstudies;however,thesecouldnotbe
replicated in large multicenter trials. A recent meta-analysis looked at 5 trials (DEBATE-BTK,
DEBELLUM,BIOLUX P-II Trial, IN.PACT DEEPTrial, IDEAS Trial), in which patientswere treated
withdrug-elutingballoonangioplastyinarandomizedtrial.Themajorityofpatients,99.6%,hadcritical
limbischemiawithlesionlengthintheintermediaterangeof121mm.At12monthfollow-up,TLRrate
was 23.6%indrug-eluting balloonangioplasty versus18.3%(RR0.71;95%CI 0.47-1.09;P =0.12).
Theclinicallydriventotallesionrevascularizationratedidnotdifferbetweenmodalities,andtherewas
comparable riskfor amputations andmajor adverse events. Thus, no clinical superiority was notedin
drug-eluting balloon angioplasty compared with plain old balloon angioplasty in the below-the-knee
region.17FutureresultsoftheLutonixbelow-the-kneedrug-coatedballoonrandomizedtrialarecurrently
underway.Theroleofdrug-elutingballoonsinbelow-the-kneerevascularizationremainsunclear,witha
needforfurtherinvestigation.
5
E.Treatment
Infrapoplitiealarteriesremaindifficulttotreatduetosmallcalibervessel,lengthofdisease,andoverall
calcificationburden.Baremetalstentinghasbeentraditionallyreservedasa“bailout”techniqueforthe
treatment of hemodynamically significant flow-limiting dissections post intervention along with
significantelastic recoil. Siablis andcolleagues showed 6 month primary patencyratesat 68.1%in a
small nonrandomizedsingle center trial.14Drug-eluting stents appear tobe promising for treatment of
https://t.me/med1917
below-the-knee arterial disease.2 Three major trials since 2012, ACHILLES, YUKON-BTX, and
DESTINY, have shown significantly improved vessel patency compared with angioplasty alone.
Endovascularinterventionswithdrug-elutingstentsmayimproveoverallcost-effectivenessandimproved
qualityoflifeoutcomesinthefuture.
2
V.Complications
Procedural complications include vasospasms, no-reflow, thrombosis, perforation, and flow-limiting
dissection. Prevention and treatment of vasospasms may be achieved through the use of intra-arterial
nitratesandcalcium channel antagonists.Thecauseofno-reflow is oftenmultifactorial and may result
from distal embolization, vasospasm, andskeletal muscle edema.13 When attempting to determine the
causeofno-reflow,occultdissection,andthrombosismustbeconsidered.Thrombosisthatoccursduring
infrapoplitealinterventionmustbepromptlyaddressedwithcatheter-based,mechanicalthrombectomy.If
thrombosis persists despite performing catheter-based mechanical thrombectomy, thrombolytic therapy
should be considered if there are no contraindications.13 Perforations and flow-limiting dissections
commonly occurwhentreating long occludedsegmentsor whenusingatherectomydevices.Prolonged
balloon inflations are typicallysufficient toachieve hemostasis. For limb-threatening perforations not
controlledwithballooninflation,deploymentofacoronarycoveredstentmaybeconsidered.
13
References
1.AllieDE,PatlolaRR,MitranEV,IngraldiA,WalkerCM.Criticallimbischemia.In:FogartyT,WhiteR,eds.Peripheral
EndovascularInterventions.3rded.NewYork,NY:Springer;2010:305-316.
2.AltitR,GrayWA.Newinnovationsindrug-elutingstentsforperipheralarterialdisease.CurrCardiolRep.2017;19:117.
3.BrodmannM.Theangiosomeconceptinclinicalpractice.EndovascularToday.2013;60-61.
4.CasserlyIP,SacharR,YadavJS.ManualofPeripheralVascularIntervention.2nded.Philadelphia:LippincottWilliams&Wilkins;
2011.
5.CasseseS,NdrepepaG,liistroF,etal.drug-coatedballoonsforrevascularizationofinfrapoplitealarteries:ameta-analysisofrandomized
trials.JACCCardiovascinterv.2016;9:1072-1080.
6.EngelkeC,MorganRA,BelliAM.Cuttingballoonpercutaneoustransluminalangioplastyforsalvageoflowerlimbarterialbypassgraft:
feasibility.Radiology.2002;223:106-114.
7.FonsecaA,CostaJR,AbizaidA,etal.IntravascularultrasoundassessmentofthenovelAngioSculptscoringballooncatheterforthe
treatmentofcomplexcoronarylesions.JInvasiveCardiol.2008;20:21-27.
8.FitzgeraldPJ,PortsTA,YockPG.Contributionoflocalizedcalciumdepositstodissectionafterangioplasty.Anobservationalstudyusing
intravascularultrasound.Circulation.1992;86(1):64-70.
9.Gerhard-HermanMD,GornikHL,BarrettC,etal.2016AHA/ACCGuidelineonthemanagementofpatientswithlowerextremity
peripheralarterydisease:areportoftheAmericanCollegeofCardiology/Americanheartassociationtaskforceonclinicalpractice
guidelines.Circulation.2017;135(12):e726-e779.doi:10.1161/CIR.0000000000000471.
10.GotI.Transcutaneousoxygenpressure(TcP02):advantagesandlimitations.DiabetesMetab.1998;24:379-384.
11.HigashimoriA.Angiographyandendovasculartherapyforbelow-the-kneearterydisease.In:YokoiY,ed.Angiographyand
EndovascularTherapyforPeripheralArteryDisease.Rijeka,Croatia:InTech;2017.doi:10.5772/67179.
12.KinlayS.Managementofcriticallimbischemia.CircCardiovasInterv.2016;9:e001946.
13.SilverM,AnselG.Infrapoplitealintervention.In:PracticalPeripheralVascularIntervention.2nded.Philadelphia,PA:Lippincott
Williams&Wilkins;2011:265-277.
14.SiablisD.KraniotisP,JarnabatidisD,etal.Sirolimus-elutingversusbarestentsforbailoutaftersuboptimalinfrapoplitealangioplastyfor
criticallimbischemia:6-monthangiographicresultsfromanonrandomizedprospectivesingle-centerstudy.JEndovascTher.2005;12:685-
695.
15.ShisheborM,WhiteC,BruceG,etal.Criticallimbischemia.JACC.2016;68(18):2002-2015.doi:10.1016/j.jacc.2016.04.071.
16.WardC,GamberdellaJ,Mena-HurtadoC.Endovasculartreatmentofbelow-the-kneearteries.In:LanzerP,ed.PanVascular
Medicine.3rded.SpringerBerlinHeidelberg;2015:3195-3203.doi:10.1007/978-3-642-37078-6_912.
17.VandenBergJC.Drug-elutingballoonsinbelowthekneetreatment.JCardiovascSurg.2016;57:811-816.
18.VaruV,HoggM,KibbeM.Criticallimbischemia.JVascSurg.2010;51(1):230-241.
https://t.me/med1917
C H A P T E R 1 2
Drug-CoatedTherapies
MadhanShanmugasundaramMD,FACC,FSCAI
I.Introduction
II.RationaleforDrug-CoatedDevices
III.DrugsUsedinDrug-ElutingStentsandDrug-CoatedBalloons
IV.DesignofDrug-ElutingStentsandDrug-CoatedBalloons
A.DESElements
B.DCBElements
V.Drug-ElutingStent
A.Drug-ElutingStentforFemoropoplitealDisease
B.Drug-ElutingStentsinBelowKneeDisease
C.UnansweredQuestionsinDrug-ElutingStentArena
VI.Drug-CoatedBalloon
A.Drug-CoatedBalloonsforFemoropoplitealDisease
B.Drug-CoatedBalloonsinBelowKneeDisease
C.Drug-CoatedBalloonsforinStentRestenosis
VII.FutureDirections
VIII.Conclusion
KeyPoints
Endovascularinterventionsforperipheralarterydisease(PAD)havebecomethecornerstoneof
therapy.
■TheprognosisandtreatmentstrategyforPADisdependentonthemodeofpresentationof
eachpatientthatincludesintermittentclaudicationandacuteorchroniclimbischemia.
■Even though PADreferstoinvolvementofvesselsoutsidecoronary territory, most ofthe
diseaseislocalizedtothefemoropoplitealtract.
■PAD involving femoropopliteal tract has unique characteristics including diffuse long
stenosis,heavycalcification,andcrossingjointlinesmakingstentimplantationsuboptimal.
■Traditionallysurgery wasconsidered goldstandard forlowerextremityPAD,butthere is
significantlylessmorbidityandfasterrecoverytimeswithendovasculartherapiesespecially
inpatientswithmultiplemedicalcomorbidities.
■Majorcriticismofendovasculartherapyhasbeenthelowlong-termpatencyrateespecially
https://t.me/med1917
for infrainguinal interventions, and the evolution of drug-coated therapy is aimed at
increasingthepatencyratesofendovasculartechnologies.
■The drug-eluting stent (DES) typically consists of a scaffold, polymer matrix, and drug.
Paclitaxel is the most commonly used drug in these devices and is cytotoxic, inhibiting
cellularproliferationandmitosis.
■Thedrug-coatedballoon(DCB)isthenewadditiontothisarenaandconsistsofstandard
PTAcatheter,excipientthathelpsreleasethedrugrapidlyassoonasitcomesincontactwith
thevesselwallandthedrugitself.
■Comparedwithbare-metalstentsorstandardballoonangioplasty,bothDESandDCBhave
shown to have better primary patency, lower binary restenosis, and lower target vessel
revascularizationupto2years.
■CombiningtherapiessuchasatherectomyandDCBhavetheoreticaladvantagesandappear
attractiveasatreatmentstrategybutremainstobestudied.
I.Introduction
Catheter-based revascularization strategies have rapidly evolved in the past few years and are the
standardofcareforpatientswithlowerextremityperipheralarterydisease(PAD).EventhoughPADin
general refers to involvement of any noncoronary vessel, the majority of lesions are located in the
femoropopliteal tract.1Historicallysurgical intervention was the treatment of choice for patientswith
lifestyle-limitingclaudication,criticallimbischemia(CLI)oracutelimbischemia,butwiththeadventof
endovasculartechnology,thelandscapeoftherapeuticstrategieshavechanged.Thereissignificantlyless
morbidity and faster recovery times with endovascular therapies especially in patients with multiple
medicalcomorbidities.However,oneofthemajor criticisms ofendovasculartherapy hasbeenapoor
long-term patencyrateespeciallyfor infrainguinal vasculature. However,most of this evidencecomes
fromthepercutaneoustransluminalangioplasty(PTA)andbare-metalstent(BMS)era.Theevolutionof
drug-coatedtherapyaimedatincreasingthelong-termpatencyratesofendovascularinterventions.Most
oftheinnovationsinthe PADarenafor thepast5 years werein the development of an“ideal” drugcoatedtherapytomimicthesuccessofthesetherapiesinthecoronaryvasculature.Onecouldarguethat
thismilestoneisyettobeachieved,butneverthelesstheexplosionofcardiovasculartechnologiesinthis
area cannotbe ignored. Theobjective ofthis chapteris to provide abasic understanding of thedrugcoatedtechnologiesinthePADworldandtheircurrentclinicalimplications.
II.RationaleforDrug-CoatedDevices
Even though the initial success ratesofendovascular revascularizationinthe femoropopliteal territory
have improved with betterment of dedicated devices,2 the long-term patency remains suboptimal.
3
RestenosisafterendovasculartherapyforPADhasbeenthemajorlimitationforBMSsandPTA.4Itis
importanttounderstandthemechanismofrestenosistoexpandthehorizonofinterventionaltherapiesand
toimproveitsdurability. There are not a lot of pathophysiologic studies examining the mechanismof
restenosisinPAD,butonecanextrapolatetheworkdoneinthecoronaryrealm.Itiswellrecognizedthat
the principal mechanism of restenosis is by neointimal hyperplasia.5 The mechanical injury from
angioplastyorstentimplantationincitesafibroproliferativereactioninitiallyinvolvingthesmoothmuscle
cells,followedbyaccumulationofextracellularmatrixthatresultsinneointimalthickeningandeventually
restenosis.
5,6
ThisprocesshasbeentheAchilles’heelofendovasculartherapyingeneral.Moreoverin
https://t.me/med1917
thePADarena,femoropopliteal(FP)territoryhasincreasedbiomechanicalstressthatresultsinhigherinstentrestenosiswithBMSs.7Apartfrom patientcentricfactors,there arenumerous anatomic factorsin
PADthatpredictsin-stentrestenosisandhenceworselong-termoutcomes.CLIisusuallyassociatedwith
diffuselongsegmentFPlesions,belowkneedisease,ormultilevelstenosesthatportendhigherrestenosis
rates.
8,9
The constant search for endovascular therapies with better long-term outcomes by reducing
restenosis have resultedinthe evolution of drug-coatedtherapies including drug-elutingstents (DESs)
anddrug-coatedballoons(DCBs).
III.DrugsUsedinDrug-ElutingStentsandDrug-Coated
Balloons
Itisimportanttohaveabasicunderstandingofthedrugsusedtocoatthestentsandballoonsforbetter
therapeuticdecisions.Theidealdrugwouldhavealongtissueretentiontime,widetherapeuticwindow,
andlipophilicnaturetoincreasetissueconcentration.Traditionallytherehavebeentwoclassesofdrugs
thatsatisfiedthesecriteriaandhavebeenusedinthetreatmentofCAD.TheseincludetheRapamycin(limus) family and paclitaxel. In PAD, paclitaxel is more commonly used. Rapamycin is a macrolide
antibiotic that binds to the cellular FK-binding protein to inhibit the mammalian target of rapamycin
(mTOR).Thisinturninhibitstheproteincomplexes responsible forprogression ofcellsfromG1toS
phasehence blockingsmoothmuscle cellmigrationandproliferation.10However,rapamycindoes not
causecelldeath.Paclitaxelontheotherhandbindstotheβ-subunitoftubulinheterodimerinhibitingthe
proteinkinaseessentialformicrotubuledepolymerization.Thisresultsintheunstablemicrotubulesthat
inhibitcellproliferationandmitosis.11Higherdosesofpaclitaxelcanresultincelldeath.Themannerin
whichthesedrugsareincorporatedintothestentplatformandballoonsisuniquelydifferentandexplains
therationaleoftheircurrentclinicaluse.
IV.DesignofDrug-ElutingStentsandDrug-CoatedBalloons
A.DESElements
The DES comprises of three basic elements: a metallic scaffold (typically nickel-titanium, platinumchromium alloy, or stainless steel), polymer matrix that binds the drug (silicone, polyurethane, and
celluloseesters),andthedrugitself.Therateatwhichthedrugelutesisproportionaltothedegradation
ofthepolymermatrix,thuscreatingasubtledifferenceinthewayvariousdrug-coatedtherapiesareused.
Aftertheinitial success ofDES,there were numerousissuesnotedwiththepersistenceofthe polymer
that creates a source of delayed intimal hyperplasia and lack of endothelialization of stent surface
resultinginlatestentthrombosis.12Thedruginthenewer generationDESisincorporateddirectlyinto
the metallic scaffold,avoiding polymer-relatedlong term issues.A varietyof biodegradable materials
suchaspolycarbonatesandpolyestershavebeenusedtomakepolymersandscaffoldsbutcurrentlyare
notavailableintheUnitesStates.
13
B.DCBElements
DCBsontheotherhandaremadeofastandardPTAballooncatheter(semicompliantornoncompliant),
drug(paclitaxel),andanexcipient(ureaoriopramide).UnliketheDES,inDCBsonlypaclitaxelisused,
because the–limusclass ofdrugs are susceptible tooxidation hence unstable onDCBs. Paclitaxel is
lipophilic,isresistanttooxidation,andhasprolongedtissueretention.14Thehydrophilicexcipientforms
https://t.me/med1917
animportantcomponentofDCB,asithasbeenshowntoincreasethetransferofthedrugintothetissue
fromthesurfaceoftheballoon.9Withouttheexcipient,paclitaxelreleasefromtheballooniserraticand
tendstoremainadheredtotheballoonsurface.Oncetheballoonisinflatedandcomesincontactwiththe
vesselwall,duetothehydrophilicproperties,theexcipientreleasesthedrugintothetissue,whichinturn
due toitslipophilic properties bindstothevesselwall. Thisisshown in Fig. 12.1. There areseveral
advantages of DCB over DES, such as its utility intreating disease in“nostent zones” (bifurcations,
diffuselydiseasedsegments)anditsabilitytoavoidstent-relatedlong-termproblems,suchasrestenosis
or thrombosis, stent fracture, and stent-related biomechanical stress, and to be used to treat in-stent
restenosisandallowmorehomogenousdistributionofthedrug.
FIGURE12.1 Drug-coatedballoon(DCB)technology.
Reproducedwithpermissionfrom
PetersonS,HasenbankM,SilvestroC,RainaS.IN.PACTAdmiraldrug-coatedballoon:durable,consistentandsafetreatmentforfemoropopliteal
peripheralarterydisease.AdvDrugDelivRev.2017;112:69-77.
V.Drug-ElutingStent
A.Drug-ElutingStentforFemoropoplitealDisease
1. SIROCCO I and II (A Clinical Investigation of the Sirolimus Coated Cordis Smart Nitinol Self-
Expandable Stent forthe Treatment ofObstructive Superficial Femoral ArteryDisease) were the first
randomizedtrialsthatinvestigatedtheuseofDES(Sirolimus)inthetreatmentofFPdisease.SiroccoI
had36patientsfollowedfor6months,andSiroccoIIhad93patientsfollowedforatotalof24months;
bothtrialsrandomizedpatientswithFPdiseasetoeitherSirolimusorBMS,andtheprimaryoutcomewas
Dopplermeasuredin-stentrestenosis(ISR).Itwasshownthattherewasnosignificantdifferenceinthe
ISRratesortargetlesionrevascularization(TLR)at6or24months(22.6%vs30.9%,P=NSor22.9vs
21.2,P=NSrespectively).TwoproposedreasonsforthelackofdifferencewithDESwerelowerthan
expectedISRratesintheBMSarmandlatecatchupeffectrelatedtostentpolymer.
15,16
https://t.me/med1917
2.Everolimus-elutingstent(Dynalink-E,Abbott)wasstudiedinanonrandomizedtrial,STRIDES(A
Study to Evaluate the Safetyand Performance of the Dynalink-E, Everolimus Eluting Peripheral Stent
System for Treating Atherosclerotic de Novo or Restenotic Native Superficial Femoral and Proximal
PoplitealArteryLesions),thatincluded104patientswithFPdisease.The6-monthprimarypatencyrate
measuredbyDopplerwas94%±2.3%,and12-monthpatencyratewas68%±4.6%.
17
3.ZILVERPTX(EvaluationoftheZilverPTXDrug-ElutingPeripheralStent)wasthelargesttrialthat
randomized over 400 patients with FP disease to either PTA or paclitaxel DES. If there was a PTA
failure,thepatientswerethenrerandomizedtoeither BMSor DESarm.Itwasdemonstratedthatthere
wassuperiorevent-freesurvivalandpatencyat12and24monthsintheDESarmcomparedwiththePTA
orBMSarm.
18,19
These resultsaresummarizedinFig.12.2.Therewas alsoanonrandomizedarmthat
includedover700patientswhounderwentDESplacementforFPdiseasewithsimilarlong-termpatency
rates.18Table12.1summarizestheimportantDEStrials.
https://t.me/med1917
FIGURE12.2 Twelve-monthprimarysafetyoutcomes.Theblackcurveshows82.6%event-freesurvival(EFS)for
thepercutaneoustransluminalangioplasty(PTA)group,andtheredcurveshowsthesignificantlyhigher
(P=0.004)90.4%EFSfortheprimarydrug-elutingstent(DES)group.
Reproducedwithpermissionfrom
DakeMD,AnselGM,JaffMR,etal.Paclitaxel-elutingstentsshowsuperioritytoballoonangioplastyandbaremetalstentsinfemoropop liteal
disease:twelve-monthZilverPTXrandomizedstudyresults.CircCardiovascInterv.2011;4(5):495-504.
Table12.1
DESTrialsinPAD
Trial Sample
Size
Drug Territory ControlGroup PrimaryOutcome Follow-
Up
SIROCCOI/II
15,16
47 Sirolimus FP PTA 6-moISR(DUSorangio)
4.8%vs4.5%
24mo
STRIDES
17
104 Everolimus FP N/A 6and12mopatency
6mo:94%±2.3%
12mo:68%±4.6%
12mo
ZILVERPTX18479 Paclitaxel FP PTAand
PTA+BMS
Event-freesurvival:90%vs83%
(P<0.01)
Primarypatency:90%vs73%
36mo
https://t.me/med1917
(P<0.01)
YUKONBTK20161 Sirolimus BTK BMS 12-moevent-freesurvival
66%vs45%(P=0.02)
36mo
PARADISE
24
106 Sirolimusand
paclitaxel
BTK PTA 3-yamputationfreesurvival:
6%vs18%(P=0.04)
Overallsurvival:
71%vs63%(P=0.02)
36mo
DESTINY
21
140 Everolimus BTK BMS 12-moprimarypatencymeasured
85%vs54%(P<0.001)
12mo
DES,drug-elutingstent;FP,femoropopliteal;PAD,peripheralarterydisease;PTA,percutaneous
transluminalangioplasty.
B.Drug-ElutingStentsinBelowKneeDisease
Typically,interventionsforbelow-the-knee(BTK)diseasearereservedforpatientswithCLI(restpain
or gangrene) or nonhealing ulcers as a limb-saving strategy. There are various percutaneous treatment
optionsthathavebeentriedforlimbsalvage,whichincludePTA,BMS,DES,andinsomecasesDCB.
1. The YUKON- BTK trial (Yukon-Drug-Eluting Stent Below-The-Knee-Prospective Randomized
Double-BlindMulticenter Study)randomized 161patientswith BTKdiseasetoeitherSirolimus-eluting
stent(SES)orBMS.Itwasshownthatevent-freesurvivalandfreedomfromTLRwerebetterintheSES
armat3-yearfollow-up.
20
2.TheDESTINY(ProspectiveRandomizedMulticenterTrialComparingtheImplantofaDrugEluting
StentvsaBareMetalStentintheCriticallyIschemicLowerLeg)trialusedEverolimusDESinpatients
withBTKdiseasetodemonstratesuperiorresultsincludingrestenosisandfreedomfromTLRcompared
withBMS.21Ameta-analysisbyAntoniouetal.thatincluded4randomizedcontroltrials(RCT)showed
improved patency rates, decreased restenosis withDES butwith nodifference inoverall mortalityor
limbsalvagerates.22Fusaroetalalso confirmedthese findingsintheirmeta-analysis.Theyconcluded
thatdespitethereductioninreintervention,therewasnodifferenceinmortalityorchangeinRutherford
classinpatientswithBTKdiseasewhohadDESplacement.
23
3.ThePARADISE(PreventingLegAmputationsinCriticalLimbIschemiawithBelow-the-KneeDrug-
ElutingStents)trialhadthelargestcohortofpatientswithCLIandBTKdiseasetreatedwithDES(Cyper
∼80%andTaxus∼20%).Thiswasa nonrandomizedstudy,buttheoutcomeswerecomparedwithan
historiccohortofsimilarpatientsfromtheBASIL(BypassvsAngioplastyinSevereIschemiaoftheLeg)
trial.ThistrialconcludedthatcomparedwithPTA,DESresultedinimprovedamputation-freesurvivalin
theseCLIpatients.24Anupdatedmeta-analysispublishedin2013,whichincludedaround4000patients
withBTKdiseasewhoreceivedvarioustherapiesincludingPTA,BMS,andDES,demonstratedsuperior
patency rates in short term (∼1 year), freedom from TLR, and improved limb salvage with DES.
However,nodifferencewasnotedbetweenBMSandPTA.
25
C.UnansweredQuestionsinDrug-ElutingStentArena
DESappears toimprove patencyrates and reduce restenosis inboth FPandBTKdiseaseinthe short
term. Long-term resultsofDES are still questionable. Focal and short lesions (<100mm) inthe BTK
territoryseemtorespondwelltoDES,butBTKdiseaseisusuallydiffuseandprogressive.Theutilityof
DEStoimprovelimbsalvageintheselonglesionsstillneedstobeexplored.Anotherlingeringquestion
is: which DES is more effective? sirolimusor paclitaxel. There is some evidencethat due toshorter
elutiontime,–limus-basedDESshavebetteroutcomescomparedwithpaclitaxel.10Optimaldurationof
dualantiplatelettherapyafterDESimplantationhasneverbeenfullyanswered.DESissubjectedtolate
https://t.me/med1917
Соседние файлы в папке Библиотека им академика М.И. Перельмана