Original
article
Two-year
outcome
after
treatment
of
severely
calcified
lesions
with
newer-generation
drug-eluting
stents
in
acute
coronary
syndromes
A
patient-level
pooled
analysis
from
TWENTE
and
DUTCH
PEERS
Jennifer
Huisman
(MD)
a,
Liefke
C.
van
der
Heijden
(MD)
a,
Marlies
M.
Kok
(MD)
a,
(J.)Hans
W.
Louwerenburg
(MD)
a,
Peter
W.
Danse
(MD,
PhD)
b,
Gillian
A.J.
Jessurun
(MD,
PhD)
c,
Frits
H.A.F.
de
Man
(MD,
PhD)
a,
Marije
M.
Lo¨wik
(PhD)
a,
Gerard
C.M.
Linssen
(MD,
PhD)
d,
Maarten
J.
IJzerman
(PhD)
e,
Carine
J.M.
Doggen
(PhD)
e,
Clemens
von
Birgelen
(MD,
PhD)
a,e,*
aDepartmentofCardiology,ThoraxcentrumTwente,MedischSpectrumTwente,Enschede,TheNetherlands b
DepartmentofCardiology,RijnstateHospital,Arnhem,TheNetherlands
c
DepartmentofCardiology,TreantZorggroep,Emmen,TheNetherlands
d
DepartmentofCardiology,ZiekenhuisgroepTwente,AlmeloandHengelo,TheNetherlands
e
HealthTechnologyandServicesResearch,MIRA–InstituteforBiomedicalTechnology,andTechnicalMedicine,UniversityofTwente,Enschede, TheNetherlands
Introduction
Percutaneous coronary interventions (PCI) in patients with severelycalcifiedlesionsareassociatedwithanincreasedriskof
suboptimalproceduralresultsandadverseclinicalevents[1].In thesettingofacutecoronarysyndromes(ACS),whichareknownto beassociatedwithanincreasedthrombogenicity,lesion calcifica-tionis frequentlypresentandmayhave aparticularlynegative impactonoutcome[2].Asisshowninalargepooledanalysisof patients with ACS and calcified target lesions, treatment with (mostly) first-generation drug-eluting stents (DES) significantly reducedtheneedforrepeatrevascularization[3],ascomparedto bare metal stents [2,4]. Newer-generation permanent polymer-coated DESwere developed to increase biocompatibility[5–7].These
ARTICLE INFO Articlehistory:
Received25March2016
Receivedinrevisedform24June2016 Accepted30June2016
Availableonlinexxx Keywords:
Calcifiedcoronarylesion
Newergeneration/secondgeneration drug-elutingstent
Percutaneouscoronaryintervention Acutecoronarysyndrome
ABSTRACT
Background: Dataonmedium-termoutcomeofpatientswithacutecoronarysyndrome(ACS),treated
withnewer-generationdurablepolymerdrug-elutingstents(DES)inseverelycalcifiedcoronarylesions,
arescarce.Weaimedtoassesstheimpactofseverecoronarylesioncalcificationonclinicaloutcomeof
patientswithACS,treatedwithnewer-generationDES.
Methods:TheTWENTEandDUTCHPEERSrandomizedtrialscomprise1779ACSpatients,whowere
categorizedintopatientswithversuswithoutseveretargetlesioncalcification.Weperformeda
patient-levelpooledanalysistoassess2-yearoutcome,includingtargetvesselfailure(TVF),acompositeof
cardiacdeath,targetvessel-relatedmyocardialinfarction(MI),ortargetvesselrevascularization(TVR).
Results:Patientswithseveretargetlesioncalcification(n=340,19.1%)wereolder(66.810.6yearsvs.
62.811.5years,p<0.001)andhadmoreoftendiabetes(22.1%vs.16.8%,p=0.02)and
hypercholesterol-emia(51.5%vs.42.9%,p=0.005)thanotherpatients(n=1439,79.9%).InadditiontheyshowedahigherTVF
rate(12.4%vs.7.0%,p=0.001),mainlyrelatedtoadifferenceinTVR(6.8%vs.3.3%,p=0.003).Therewasa
borderlinesignificantbetween-groupdifferenceincardiacdeath(3.6%vs.1.8%,p=0.05),butnotintarget
vesselMI(3.8%vs.2.6%,p=0.23)anddefinitestentthrombosis(0.9%vs.0.6%,p=0.71).Multivariateanalysis
demonstratedthatseverelesioncalcificationwasanindependentriskfactorofTVF(adjustedHR;1.58,95%
CI:1.23–2.03;p<0.001).
Conclusions: InpatientswithACS,treatmentofseverelycalcifiedlesionswithnewer-generationDES
wasassociatedwithanoverallhigherclinicaleventrisk–relatedinparticulartoahigherTVRrate,while
theriskofMIwaslow.
ß2016JapaneseCollegeofCardiology.PublishedbyElsevierLtd.Allrightsreserved.
* Correspondingauthorat: ThoraxcentrumTwente & Universityof Twente, MedischSpectrum Twente (MST),Department of Cardiology, Postbus50.000, 7500KAEnschede,TheNetherlands.Tel.:+31534872105;fax:+31534872107.
E-mailaddress:c.vonbirgelen@mst.nl(C.vonBirgelen).
ContentslistsavailableatScienceDirect
Journal
of
Cardiology
j our na l ho me pa g e : w ww . e l se v i e r . com / l oca t e / j j cc
http://dx.doi.org/10.1016/j.jjcc.2016.06.010
devicesdemonstratedafavorablesafetyprofileandhighefficacyin study populations with mild-to-moderate cardiovascular event risks [8–11] as well as in broad, greatly unrestricted patient populations[12–18].Nevertheless,severelycalcifiedtargetlesions maystillimpairdeliveryandexpansionofnewer-generationDES and may represent a serious challenge to polymer coatings [19]. While the treatment of severelycalcified coronary lesions with newer-generation DES may still be associated with an increasedriskofadverseevents–in particularinthe settingof ACS–only limiteddataareavailable.TheTWENTEand DUTCH PEERStrialsaretwoprospectiverandomizedclinicalstudiesthat assessednewer-generation zotarolimus-eluting and everolimus-elutingstentsinbroadpatientpopulations,whichreflectroutine clinicalpracticeandcomprisemanyhigh-riskpatientswithACSand severetargetlesioncalcification[15,16].Inthepresentpatient-level pooledanalysisofthesetwotrials,weevaluatedtheimpactofsevere targetlesioncalcificationon2-yearoutcomeofPCIwith newer-generationpermanentpolymer-coatedDESinthesettingofACS. Methods
Amongall1779patientswithanACSintheTWENTE(The Real-World Resolute Versus Xience V Drug-Eluting Stent Study in Twente;NCT01066650)andDUTCHPEERS(TWENTEII)(Durable Polymer-BasedStentChallenge ofPromus Elementvs. Resolute Integrity;NCT01331707)trials[15,16],weassessedtheimpactof severetargetlesioncalcificationon2-yearclinicaloutcome.Both trialswereapprovedbytheaccreditedMedicalEthicsCommittee Twenteand the institutionalreview boards of all participating centersandcompliedwiththeDeclarationofHelsinki.Allpatients providedwritteninformedconsent.
DetailsoftheTWENTEandDUTCHPEERS(TWENTEII)trials [15,16]andthe2-yearclinicalfollow-upofbothtrialshavebeen reported[20,21].Inbrief,thetwostudiesareinvestigator-initiated, patient-blinded,randomizedtrialsinwhichrespectively1391and 1811 patients with stable or ACS were enrolled. After 1:1 randomization,patients inthe TWENTEtrialweretreated with theResolutezotarolimus-elutingstent(MedtronicVascular,Santa Rosa,CA,USA)ortheXienceVeverolimus-elutingstent(Abbott Vascular,SantaClara,CA,USA).PatientsintheDUTCHPEERStrial were randomized to treatment with the Resolute Integrity zotarolimus-eluting stent (Medtronic Vascular, Santa Rosa, CA, USA) or the Promus Element everolimus-eluting stent (Boston Scientific,Natick,MA,USA).Forthepurposeofthepresentanalysis, patientspresenting withanACSwerecategorizedinto patients withversuswithoutseveretargetlesioncalcification.
Angiographic analysts of Thoraxcentrum Twente,blinded to randomization and patient outcome, performed the qualitative and quantitative coronary angiographic analyses of all cases according to current standards, using the software Qangio XA (Version 7.1 and 7.2, Medis, Leiden, The Netherlands). The angiographic analysts of the core lab prospectively classified target lesion calcification in analogy with previous studies [4,9]. The presence of target lesion calcification was defined as readilyapparentdensitiesorX-rayabsorbingmasses,notedwithin theapparentvascularwallatthesiteofthetargetlesionpriorto anycontrastinjection;inaddition,severetargetlesioncalcification wasnotedwithoutcardiacmotionbeforecontrastinjectionand generallycompromisedbothsidesofthearterialwall.
Interventional procedureswereperformedaccordingto stan-dardtechniques, routineclinicalprotocols, andcurrent medical guidelines.Lesionpreparation(e.g.useofrotationalatherectomy orcuttingballooninflation),stentpostdilatation,andthe applica-tion of concomitant medication were left to the operator’s discretion. Medical treatment did not differ between the two trials. Unfractionated heparin was usually administered as
anticoagulant duringPCI, and dual anti-platelettherapy, which consistedofaspirin andclopidogrel orticagrelor,wasgenerally prescribed for 12 months [15,16]. Electrocardiograms and laboratorytestsweresystematicallyperformed.
An external clinical research organization (Diagram, Zwolle, The Netherlands), performed the monitoring independently. Clinical follow-up data were obtained at visits to outpatient clinicsor,ifnotfeasible,bytelephoneand/ormedical question-naire. In both trials, processing of clinical outcome data were performedbyindependentclinicalresearchorganizations (Cardi-alysis,Rotterdam,TheNetherlands).Independentclinicalevents committees, blinded tothe assigned treatment, adjudicated all majoradverseclinicalevents.
TheclinicalendpointsweredefinedaccordingtotheAcademic ResearchConsortium(ARC),includingtheaddendumon myocar-dialinfarction[22,23],andhavepreviouslybeendescribedindetail [15,16].Inbrief,deathwasconsideredcardiac,unlessanevident non-cardiaccausecouldbeestablished,andmyocardialinfarction (MI)wasdefinedby anycreatine kinaseconcentration of more thandoubletheupperlimitofnormalwithelevatedvaluesofa confirmatorycardiac biomarker. Atarget vessel-relatedMIwas related to thetarget vesselor could not berelated toanother vessel, and a periprocedural MI was defined as target vessel-relatedMIwithin48hafterPCI.Stentthrombosiswasclassified accordingtotheARCdefinitions.
The composite clinical endpoint target vessel failure (TVF), whichat1-yearwastheprimaryendpointofboththeTWENTEand DUTCHPEERStrials,isdefinedasa compositeofcardiacdeath, targetvesselMI,orclinicallydriventargetvesselrevascularization (TVR). TVR and target lesion revascularization (TLR) were considered clinically indicated if the angiographic diameter stenosiswas70%,or50%inthepresenceofischemicsignsor symptoms.Thecompositeendpointtargetlesionfailureisdefined as a composite of cardiac death, target vessel-related MI, and clinicallyindicatedTLR;majoradversecardiaceventsisacomposite ofall-causedeath,anyMI,emergentcoronarybypasssurgery,or clinicallyindicatedTLR;apatient-orientedcompositeendpointisa compositeofall-causemortality,anyMI,andanyrepeat (target-andnon-targetvessel)revascularization.
Data were reported as frequencies and percentages for dichotomous and categorical variables, and as meanstandard deviation (SD) or median with interquartile range (IQR) for continuous variables. Dichotomousandcategoricalvariableswere assessed using Chi-square tests and Fisher’s exact tests, and continuous variables were assessed using Student’s t tests, the Wilcoxonrank-sumtestsorMann–WhitneyUtest,asappropriate. TheKaplan–Meiermethodwasusedtocalculatethetimetoclinical endpointandthelog-rank testwas appliedtocompare between-groupdifferences.Allp-valuesandconfidence intervalswere two-sided andp-values <0.05were consideredsignificant. Parameters wereconsideredaspotentialconfoundersifinunivariateanalyses associationswerefoundwithap-value<0.15.AmultivariateCox regressionmodelwasthenusedtoadjustforpotentialconfounders. Data analysis was performed with SPSS (version 17.0, SPSS Inc., Chicago,IL,USA).
Results
Atotalof1779patientswithACSwereassessed,ofwhom340 (19.1%)patients weretreated forat leastoneseverely calcified targetlesion.Thesepatientsweresignificantlyolder,moreoften haddiabeteswithmoreantidiabetictreatment,andahistoryofMI. In addition they had significantly lower levels of low-density lipoproteincholesterol,andhigherlevelsofhigh-density lipopro-teincholesterol(Table1).The4differentstenttypeswereequally distributed between patientswithversuswithoutsevere target
lesioncalcification.Therateofrenalfailurewassimilarinboth groups (3.2%vs. 2.6%, p=0.55). Patients withseverely calcified targetlesionsmoreoftenunderwenttreatmentofmultiplevessels (24.7%vs.17.3%,p=0.002)andaorto-ostiallesions(12.4%vs.6.4%, p<0.001),andmorelesionpreparationwasrequired.Inaddition, patients withseverely calcified lesionsweresignificantly more oftentreatedforlonglesions(25.3%vs.15.5%,p<0.001;Table2). Duringthefirstyearoffollow-up,3patientswithdrewconsent. Of allother 1776 patients (99.8%),2-year follow-up data were available.Atime-to-eventanalysisofTVFrevealedasignificantly highereventrateinpatientswithseverelycalcifiedtargetlesions (12.4%vs.7.0%,p=0.001;Fig.1).Oftheindividualcomponentsof TVF,onlyTVRandcardiacdeathshowedsignificantlyhigherrates inpatientswithseverelycalcifiedlesions(6.8%vs.3.3%,p=0.003, and3.6%vs.1.8%,p=0.05;Table3,Fig.2).However,therewasno significantbetween-groupdifferenceintargetvesselMI(3.8%vs. 2.6%,p=0.23)ordefinitestentthrombosis(0.9%vs.0.6%,p=0.71; Table3).
MultivariateanalysisforTVFdemonstratedthat,after adjust-ment for potential confounders (i.e. diabetes mellitus, insulin treatment, cholesterol levels, previous myocardial infarction, lesionlengthmorethan27mm,anduseofcuttingballoon),the presenceofseverelycalcifiedtargetlesionswasanindependent
predictorofTVFat2-yearfollow-up(adjustedHR;1.58,95%CI: 1.23–2.03;p<0.001).
Discussion
In this patient-level pooleddataanalysis fromTWENTE and DUTCHPEERS(TWENTEII),patientswithACS,whoweretreated withnewer-generationzotarolimus-elutingand everolimus-elut-ing stents for severely calcified coronary lesions, showed significantlyhigherratesofthecompositeclinicalendpointTVF at 2-year follow-up (12.4% vs.7.0%). A multivariate analysis confirmedseveretargetlesioncalcificationtobeanindependent predictor of TVF (adjusted HR 1.58). Insulin treatment and cholesterollevels(low-densitylipoproteincholesteroland high-densitylipoproteincholesterol)werenoindependentpredictorsof TVF.TheoverallhigherriskofclinicaleventsinACSpatientswith severelycalcifiedtargetlesionswasprimarilyrelatedtoahigher incidence of TVR(6.8% vs. 3.3%),which is first and foremost a parameteroftreatment efficacy.Thefactthat theMIand stent thrombosisrateswerelowmaybeinterpretedasasafetysignalfor thetreatmentofACSpatientswithseveretargetlesions calcifica-tion using newer-generation DES. The early (periprocedural) increase in MIinboth patients withand withoutseveretarget
Table1
Baseline characteristics ofall study patients comparing patients with versus withoutseveretargetlesioncalcification.
Patientcharacteristics Allpatients(n=1779) Severe calcification (n=340) Nosevere calcification (n=1439) p Age(years) 66.810.6 62.811.5 <0.001 Women 106(31.2) 405(28.1) 0.27 BMI(kg/m2 ) 27.84.4 27.74.4 0.76 Diabetesmellitus 75(22.1) 242(16.8) 0.02 Hypertension 181(53.2) 705(49.0) 0.16 Hypercholesterolemia 172(51.5) 611(42.9) 0.005 Currentsmoker 78(22.9) 462(32.1) 0.001 Familyhistoryofcoronary
arterydisease
168(49.4) 675(46.9) 0.41 Chronicrenalfailurea
11(3.2) 38(2.6) 0.55 Peripheralarterialdisease 40(11.9) 111(7.8) 0.02 Previousmyocardialinfarction 126(37.1) 393(27.3) <0.001 PreviousPCI 64(18.8) 238(16.5) 0.31 PreviousCABG 35(10.3) 103(7.2) 0.05 Clinicalsyndrome 0.33
ST-elevationMI 69(20.3) 301(20.9) Non-STelevationMI 172(50.6) 667(46.4) Unstableanginapectoris 99(29.1) 471(32.7)
Oralantidiabetics 62(18.2) 190(13.2) 0.02 Insulin 34(10.0) 78(5.4) 0.002 Statins 310(91.2) 1341(93.2) 0.20 ACEinhibitors 147(43.2) 604(42.0) 0.67 AT1-receptorantagonists 60(17.6) 228(15.8) 0.42 b-Blockers 288(84.7) 1227(85.3) 0.79 Calciumchannelblockers 80(23.5) 178(19.3) 0.08 LDL-cholesterol(mmol/l) (n=255/1102) 2.871.09 3.071.06 0.006 HDL-cholesterol(mmol/l) (n=259/1151) 1.260.38 1.170.34 <0.001 Triglycerides(mmol/l) (n=256/1130) 1.741.32 1.841.27 0.23 Hemoglobin(mmol/l) (n=315/1336) 8.451.06 8.690.94 <0.001 Creatinine(mmol/l) (n=316/1337) 83.420.2 84.129.8 0.69
Valuesaremean(SD)orn(%).BMI,bodymassindex;CABG,coronaryartery bypassgrafting;MI,myocardialinfarction;PCI,percutaneouscoronary interven-tion;ACE,angiotensin-convertingenzyme;AT1,angiotensinreceptor1;LDL, low-densitylipoprotein;HDL,high-densitylipoprotein.
a
Chronicrenalfailurewasdefinedasaserumcreatininelevel130mmol/l.
Table2
Lesionandproceduralcharacteristicsofpatientswithanacutecoronarysyndrome, comparingpatientswithseverecalcifiedlesionsversuspatientswithoutsevere calcifiedlesions.
Lesion/proceduralcharacteristics Patientswithacutecoronarysyndrome (n=1779) Severe calcification (n=340) No severe calcification (n=1439) p Multivesseltreatment 84(24.7) 249(17.3) 0.002 Twoormorelesions
treatedperpatient
127(37.4) 401(27.9) 0.001 Treatedcoronaryvessels
Rightcoronaryartery 150(44.1) 513(35.6) 0.004 Leftanteriordescending
artery
170(50.0) 699(48.6) 0.64 Circumflexartery 97(28.5) 428(29.7) 0.66 Denovolesions 307(90.3) 1303(90.5) 0.89 Atleastonechronictotal
occlusion
15(4.4) 44(3.1) 0.21 Atleastonein-stent
restenosis
14(4.1) 50(3.5) 0.57 Atleastoneostiallesion 42(12.4) 92(6.4) <0.001 Atleastonesmall-vessela
198(58.2) 806(56.0) 0.46 Atleastonelesionlength
>27mm
86(25.3) 223(15.5) <0.001 Totalstentlength 40.0(24.0–60.0) 28.0(18.0–45.0) <0.001 Numberofstentsper
patient
2.1(1.3) 1.7(1.0) <0.001 Maximalimplantation
pressurestent(atm)
15.92.75 15.32.55 <0.001 Rotablation 10(2.9) 4(0.3) <0.001 Cuttingballoon 26(7.6) 14(1.0) <0.001 Maximum%diameter
stenosisprePCI
71.6(53.8–79.1) 68.8(59.4–79.2) 0.02 Maximum%diameter
stenosispostPCI
13.2(9.5–17.1) 14.7(11.0–20.0) <0.001 Minimumlumen
diameterpostPCI
2.220.61 2.180.56 0.30 Maximum%diameter
stenosisprePCI
71.6(53.8–79.1) 68.8(59.4–79.2) 0.02 Postdilation 302(88.8) 1125(78.2) <0.001 Maximalpressure
postdilation(atm)
23.74.9 22.55.2 <0.001
Values aremean(SD),median(IQR),or n(%). PCI,percutaneouscoronary intervention.
a
lesioncalcificationwasoftennotcausedbyastentthrombosis,but itmayhavebeentheresultofprocedure-relatedembolizationof atherothromboticmaterial ortheocclusionof (very) smallside branches from predilatation, stenting, and/or postdilatation of stents.
In a histopathological study, microcalcifications within the thin fibrous capof atheromatousplaques – in particular when
>5
m
m–wererelatedtoplaquerupture[24].Inaddition,coronary calcificationisknowntoincreasewithaplaqueburden;however, thereisstillanongoingdebateonwhethercoronarycalcificationis just (or mainly) a marker of plaque burden or also indicates unstablelesionswithanincreasedriskofrupture[24,25]. Ge´ne´r-euxet al. recentlyshowedthat at least onemoderate-to-severe targetlesioncalcificationispresentin27%and38%ofpatientswith non-STelevationACSandSTEMI,respectively[2].Inthepresent study,atleastoneseveretargetlesioncalcificationwaspresentin 19%ofpatientswithACS,whichfitsintothisscope.Fig.1.Kaplan–Meiercurvesfortargetvesselfailure(TVF)andtheindividualcomponentsat2-yearfollow-up.Kaplan–Meiercumulativeincidencecurvesfor:(A)TVF,a compositeofcardiacdeath,targetvessel-relatedmyocardialinfarction,ortargetvesselrevascularization;(B)cardiacdeath;(C)targetvessel-relatedmyocardialinfarction; (D)targetvesselrevascularization.
Table3
2-yearclinicaloutcome of patients withversus withoutsevere target lesion calcification.
Patientswithacutecoronary syndrome(n=1776) Severe calcification (n=338) Nosevere calcification (n=1438) p Death 22(6.5) 45(3.1) 0.003 Cardiacdeath 12(3.6) 26(1.8) 0.046 TargetvesselMI 13(3.8) 38(2.6) 0.23 PeriproceduralMI 9(2.7) 25(1.7) 0.27 Clinicallyindicatedtargetvessel
revascularization
23(6.8) 48(3.3) 0.003 Clinicallyindicatedtargetlesion
revascularization
19(5.6) 34(2.4) 0.002 Targetvesselfailure 42(12.4) 100(7.0) 0.001 Targetlesionfailure 39(11.5) 90(6.3) 0.001 Majoradversecardiacevents 47(13.9) 113(7.9) <0.001 Patient-orientedcompositeendpoint 63(18.6) 166(11.5) <0.001 Definitestentthrombosis 3(0.9) 9(0.6) 0.71 Definiteorprobablestentthrombosis 5(1.5) 15(1.0) 0.49 Valuesaren(%).2-yearfollow-upwasavailablefor1776ofall1779patients
(99.8%).MI,myocardialinfarction. Fig.2.Adversecardiovasculareventsat2-yearfollow-up.2-yearfollow-updata wereavailablefor1776ofall1779patients(99.8%).
Directstentingofseverely calcifiedcoronarylesionsis often impossibleandinmanycasesundesirable,asthisapproachbearsa higherriskofstentunder-expansionand delayedorincomplete stent endothelialization, which may lead to stent thrombosis and/orin-stentrestenosis[26].Inaddition,manipulationswitha DES in a severely calcified coronaryvesseland/or lesionmight causedamagetothepolymercoating,whichmaylocallyimpair bothdrugdeliveryfromthecoatinganditscapacitytoprevent restenosis[19].Coronarymacro-calcification,amarkerof exten-siveatheroscleroticdisease,waspreviouslyshowntopredictan increasedriskofTLRafterstenting[2,27].Rotationalatherectomy may be used to favorably modify severely calcified lesions, facilitate stentdelivery, and improvelesion expansion and the proceduralresult[26].Asanalternative,severelycalcifiedlesions canalsobepre-treatedwithcutting-balloons.Inthepresentstudy, rotationalatherectomyorcuttingballooninflationswereusedin nomorethan11%ofpatientswithseveretargetlesioncalcification. Asthecrossing-profilesofmodernDEShavebecomeincreasingly small and flexible, stenting can be performed in many cases followingapre-dilatationwitha(non-compliant)ballooncatheter. Inaddition,stentpostdilatationathigherballoonpressures,which was frequently performed in our patients with severe lesion calcification(89%),ismosthelpfultoachievea goodprocedural resultwithadequatestentexpansionandapposition.
DespiterecentimprovementsinDES,thepresenceofaseverely calcifiedcoronarytargetlesionstillisapredictorofworseoutcome [2,27–29].Arecentretrospectivepooledanalysisof7stenttrials that used various first- and second-generation DES for the treatment of different patient populations demonstrated that the presence of a severely calcified lesion is an independent predictor of all-cause death, myocardial infarction, and any revascularization(HR1.18;95%CI:1.01–1.39;p=0.04),butnot ofstentthrombosis[27].Inapooledanalysisofpatientstreatedfor ACS with(mostly) first-generationDES, a higherTVR rate was observed in patients with moderate-to-severe target lesion calcification(9.4%vs.7.5%,p=0.02),and amultivariateanalysis showedanindependentassociationbetweenmoderate-to-severe targetlesioncalcificationand1-yearTLR(HR1.44;95%CI:1.17– 1.78; p<0.001) [2]. In addition, in that study, patients with severelycalcified lesionshada higherrateof stentthrombosis. WhileinthesettingofACStheriskofstentthrombosisisgenerally increased[6],inourpresentstudytherateofstentthrombosiswas low.Thismaypartlybeduetothemorebiocompatiblenatureof thepolymercoatingsofthenewer-generationDESused,while,due to the systematic assessment of post-PCI cardiac markers and electrocardiographicchangesandtheavailabilityoffollow-upinas muchas99.8%ofpatients,underreportingofstentthrombosisor othervitalclinicaleventsisunlikely.
The present study is limited by its post-hoc nature, and thereforeitsfindingsshouldbeconsideredhypothesis-generating. Nevertheless,asdataonmedium-termoutcomeofpatientswith ACS treated in severely calcified coronary lesions with newer-generationDESarescarce,thefindingsmaybeofinterest.Inour currentstudythatmadenoroutineuseofintracoronaryimaging techniques,weevaluatedin arelativelylarge populationof all-comerpatientsthepresenceoftargetlesioncalcificationbasedon X-rayappearance.Previousstudieshave shownthat prognostic information on targetlesion calcification canbe obtained from angiographicassessment [27–29]. However, intravascular ultra-soundand opticalcoherence tomographyallowamoredetailed assessment ofcoronaryatherosclerosisand plaquecomposition [30–35].Thisincludesabetteridentificationandclassificationof targetlesioncalcification,asthesetechniquesaremoresensitivein detecting calcium and also reveal information on the exact location,magnitude,and distributionofcalcium(e.g.superficial versusdeeplocation)[35–39].
Inconclusion,inpatientswhopresentedwithACS,treatmentof severely calcified lesions with newer-generation permanent polymer-coated DES was associated with an overall increased riskofadversecardiovasculareventsat2-yearfollow-up–related inparticulartoahigherTVRrate–whiletheriskofMIremained low.
Fundingsources
Thisstudyreceivednogrant fromanyfundingagencyinthe public, commercial, or not-for-profit sectors. The TWENTE and DUTCHPEERS(TWENTEII)randomizedtrialsweresupportedby equalunrestrictedgrantsfromAbbottVascularandMedtronic,and fromBostonScientificandMedtronic,respectively.
Disclosures
MaartenJ.IJzermanisconsultanttoPanaxeaB.V.,andhehas received lecture fees from Roche, Pfizer, and Sanofi Aventis. ClemensvonBirgelenhasbeenconsultanttoBostonScientificand Medtronic and hasreceived lecturefeesfrom AstraZeneca.The institution has received research grants, provided by Abbott Vascular,Biotronik,BostonScientific,Medtronic,andAstraZeneca. Allotherauthorsdeclarethattheyhavenoconflictofinterest. Acknowledgements
None. References
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