O. Hlinomaz

ICRC, St. Anne Univ. Hosp., Brno, Czech Rep.Bulgarian Cardiac Institute, Varna, BulgariaBulgarian Cardiac Institute, Varna, Bulgaria

•• neointimalneointimal hyperplasiahyperplasia•• neointimalneointimal hyperplasiahyperplasia

•• 2020--35%35% afterafter BMS, 5BMS, 5--10%10% afterafter DESDES•• 2020--35%35% afterafter BMS, 5BMS, 5--10%10% afterafter DESDES

•• treatmenttreatment-- locallocal aplicationaplication ofof antiproliferativeantiproliferative•• treatmenttreatment-- locallocal aplicationaplication ofof antiproliferativeantiproliferativedrugsdrugs::

-- drugdrug--elutingeluting stentsstents (DES)(DES)-- drugdrug--elutingeluting stentsstents (DES)(DES)

-- drugdrug--elutingeluting baloonsbaloons (DEB)(DEB)

OcclusiveOcclusive

4.2014 1 BMS8.2014 POBA9.2014 1 DES9.2014 1 DES4.2015 1 DES, DEB9.2015 1 DES, DEB4.2016 2 DEB2.2017 2 DES, DEB2.2017 2 DES, DEB

stststst

•• eeffectffect ofof BMSBMS--ISRISR treatmenttreatment by PEBby PEB againstagainst•• eeffectffect ofof BMSBMS--ISRISR treatmenttreatment by PEBby PEB againstagainst11stst generationgeneration DES provedDES proved

•• PEPCAD II:PEPCAD II: signifsignif ↓ 6 M LLL, ↓ 6 M LLL, tendencytendency toto↓↓binarybinary restenosisrestenosis and MACEand MACE againstagainst PESPES

•• 22ndnd generationgeneration DESDES withwith sirolimussirolimus derivatesderivateslikelike everolimuseverolimus (EES) more(EES) more efficientefficient ininlikelike everolimuseverolimus (EES) more(EES) more efficientefficient inintreatmenttreatment ofof dede--novonovo lesionslesions

•• RandomizedRandomized,, prospectiveprospective trialtrial•• RandomizedRandomized,, prospectiveprospective trialtrial

•• AimAim::•• AimAim::

To compare the treatment of inin--BMstentBMstent restenosisrestenosis bydrug-eluting balloon catheters using paclitaxel (PEBPEB)drug-eluting balloon catheters using paclitaxel (PEBPEB)with 2nd generation drug-eluting stents usingeverolimus (EESEES)

InclusionInclusion criteriacriteria::InclusionInclusion criteriacriteria::

•• PtsPts treatedtreated forfor BMSBMS--ISR inISR in oneone center 2012center 2012--1414

•• BMSBMS--ISR ˃50% DSISR ˃50% DS

•• InformedInformed consentconsent signedsigned

ExclusionExclusion criteriacriteria::ExclusionExclusion criteriacriteria::

•• PrognosisPrognosis < 12< 12 monthsmonths

•• LimitedLimited possibilitypossibility toto performperform controlcontrol angioangio afterafter 12 M12 M•• LimitedLimited possibilitypossibility toto performperform controlcontrol angioangio afterafter 12 M12 M((advancedadvanced renalrenal failurefailure etcetc))

•• LongLong--termterm dualdual antiplateletantiplatelet treatmenttreatment notnot possiblepossible•• LongLong--termterm dualdual antiplateletantiplatelet treatmenttreatment notnot possiblepossible

•• 136136 ptspts withwith BMSBMS--ISRISR•• 136136 ptspts withwith BMSBMS--ISRISR

• 2 groups

iopromideiopromide--coatedcoated PEB (PEB (SequentSequent PleasePlease))

vs.vs.

everolimuseverolimus--elutingeluting stent (EES;stent (EES; PromusPromus,, PtPt//CrCr))

•• PrimaryPrimary endend--point:point: 12 M late lumen loss (LLL)•• PrimaryPrimary endend--point:point: 12 M late lumen loss (LLL)

•• SecondarySecondary endend--pointspoints::

12 months binary restenosis12 months binary restenosis

MACE (CV death/nonfatal MI/TVR)

•• nonnon--inferiority studyinferiority study•• nonnon--inferiority studyinferiority study

•• ClinicalClinical 66 monthsmonths and 12and 12 monthsmonths visitvisit

•• 1212 monthsmonths angioangio withwith QCAQCA

PEBPEB EESEES ppPEBPEB EESEES pp

PatientPatientss,, nn 6868 6868

ISRISR llesionsesions,, nn 7474 7474ISRISR llesionsesions,, nn 7474 7474

MMalesales//FemalesFemales 4343 ((63,2463,24%)%) // 2525 ((36,7436,74%)%) 4646 ((67,6567,65%)%) // 2222 ((32,3532,35%)%) 0,5890,589 ⃰⃰

Age,Age, yearsyears 65,665,6 ±±10,910,9†† 65,565,5 ±±10,610,6†† 0,9300,930††Age,Age, yearsyears 65,665,6 ±±10,910,9†† 65,565,5 ±±10,610,6†† 0,9300,930††

EjeEjectionction fractionfraction,, %% 49,7449,74 ±±11,9511,95††//50,050,0‡‡ 49,5749,57±± 11,4411,44††//50,050,0‡‡ 0,9560,956♯♯

Diabetes mellitusDiabetes mellitus 1717 ((25,0025,00%)%) 1818 ((26,4726,47%)%) 0,8440,844 ⃰⃰Diabetes mellitusDiabetes mellitus 1717 ((25,0025,00%)%) 1818 ((26,4726,47%)%) 0,8440,844 ⃰⃰

RenRenalal insufficiencyinsufficiency 22 ((2,942,94%)%) 77 ((10,2910,29%)%) 0,1650,165§§

2VD2VD//3VD3VD 3838 ((55,8855,88%)%) 4141 ((60,2960,29%)%) 0,6020,602 ⃰⃰2VD2VD//3VD3VD 3838 ((55,8855,88%)%) 4141 ((60,2960,29%)%) 0,6020,602 ⃰⃰

Multi ISRMulti ISR 44 ((5,885,88%)%) 55 ((7,357,35%)%) 1,0001,000§§

† mean ± SD; ‡ median

PEBPEB EESEES pp--valuevalue

ACSACS (STEMI/NSTEMI)(STEMI/NSTEMI) 4545 ((66,1866,18%)%) 5050 ((73,5373,53%)%)ACSACS (STEMI/NSTEMI)(STEMI/NSTEMI) 4545 ((66,1866,18%)%) 5050 ((73,5373,53%)%)0,3500,350 ⃰⃰

SStabtablele APAP 2323 ((33,8233,82%)%) 1818 ((26,4726,47%)%)

LesionLesion typetype B2/CB2/C 5151 ((68,9268,92%)%) 47 (47 (63,5163,51%)%) 0,4870,487 ⃰⃰

SStenttent diameterdiameter,, mmmm 3,183,18 ±±0,430,43/3,0/3,0‡‡ 3,203,20 ±±0,410,41††//3,03,0‡‡ 0,6090,609♯♯

StentStent lengthlength,, mmmm 22,6522,65 ±±11,7011,70††//19,019,0‡‡ 19,3919,39 ±±9,279,27††//16,016,0‡‡ 0,0770,077♯♯StentStent lengthlength,, mmmm 22,6522,65 ±±11,7011,70††//19,019,0‡‡ 19,3919,39 ±±9,279,27††//16,016,0‡‡ 0,0770,077♯♯

† mean ± SD; ‡ medianmean ± SD; median

PEB EES p

ACS,ACS, STEMI/NSTEMISTEMI/NSTEMI 2424 ((35,2935,29%)%) 2525 ((36,7636,76%)%) 0,0980,098 ⃰⃰

TimeTime ofof ISRISR,, mmonthsonths 12,1012,10±±8,478,47††//9,09,0‡‡ 16,5116,51±±9,499,49††//24,024,0‡‡ 0,0090,009♯♯

ISRISR:: I (I (fofocalcal)) 3030 ((40,5440,54%)%) 2121 ((28,3828,38%)%)

0,2660,266 ⃰⃰II (II (difdiffusefuse)) 3434 ((45,9545,95%)%) 3535 ((47,3047,30%)%)

III (III (proliferativproliferativee)) 55 ((6,766,76%)%) 88 ((10,8110,81%)%)

IVIV ((occlusiveocclusive)) 55 ((6,766,76%)%) 1010 ((13,5113,51%)%)IVIV ((occlusiveocclusive)) 55 ((6,766,76%)%) 1010 ((13,5113,51%)%)

CuttingCutting predilatpredilatationation 16 (16 (21,6221,62%)%) 55 ((6,766,76%)%) 0,0100,010 ⃰⃰

ISR; PEB/EESISR; PEB/EES diametdiameterer,, mmmm 3,323,32 ±±0,390,39/3,5/3,5‡‡ 3,313,31 ±±0,430,43††//3,53,5‡‡ 0,9890,989♯♯ISR; PEB/EESISR; PEB/EES diametdiameterer,, mmmm 3,323,32 ±±0,390,39/3,5/3,5‡‡ 3,313,31 ±±0,430,43††//3,53,5‡‡ 0,9890,989♯♯

ISR; PEB/EESISR; PEB/EES lengthlength,, mmmm 22,5322,53 ±±8,138,13††//20,020,0‡‡ 28,4728,47 ±±12,7612,76††//24,024,0‡‡ 0,0010,001♯♯

PostdilataPostdilatationtion,, atmatm 14,8414,84 ±±2,772,77††//16,016,0‡‡ 14,1114,11 ±±2,452,45††//12,012,0‡‡ 0,0930,093♯♯PostdilataPostdilatationtion,, atmatm 14,8414,84 ±±2,772,77††//16,016,0‡‡ 14,1114,11 ±±2,452,45††//12,012,0‡‡ 0,0930,093♯♯

22ndnd stent istent implantamplantationtion 11 (11 (14,8614,86%)%) 1111 ((14,8614,86%)%) 1,0001,000 ⃰⃰

† mean ± SD; ‡ median

PEBPEB EESEES pp

PreprocedurPreproceduralal pparametarametersers::PreprocedurPreproceduralal pparametarametersers::

Minimal lumen diameter, mmMinimal lumen diameter, mm 0,920,92±±0,450,45††//1,001,00‡‡ 0,790,79±±0,480,48††//0,770,77‡‡ 0,0620,062§§

Reference diameter, mmReference diameter, mm 2,642,64±±0,470,47††//2,632,63‡‡ 2,662,66±±0,450,45††//2,662,66‡‡ 0,6720,672§§

% Diameter% Diameter stenosisstenosis 71,871,8±±13,913,9††//70,070,0‡‡ 78,078,0±±13,413,4††//76,076,0‡‡ 0,0070,007§§

PostprocedurPostproceduralal pparameterarameters:s:

Minimal lumen diameter, mmMinimal lumen diameter, mm 2,182,18±±0,390,39††//2,132,13‡‡ 2,512,51±±0,380,38††//2,492,49‡‡ <<0,00010,0001§§Minimal lumen diameter, mmMinimal lumen diameter, mm 2,182,18±±0,390,39 //2,132,13 2,512,51±±0,380,38 //2,492,49 <<0,00010,0001

Reference diameter,Reference diameter, mmmm 2,792,79±±0,410,41††//2,792,79‡‡ 3,013,01±±0,400,40††//2,962,96‡‡ 0,0060,006§§

Acute gain, mmAcute gain, mm 1,251,25±±0,540,54††/1,12/1,12‡‡ 1,721,72±±0,470,47††/1,69/1,69‡‡ << 0,00010,0001§§Acute gain, mmAcute gain, mm 1,251,25±±0,540,54 /1,12/1,12 1,721,72±±0,470,47 /1,69/1,69 << 0,00010,0001

% Diameter residual% Diameter residual stenosisstenosis 19,519,5±±7,47,4††//20,020,0‡‡ 16,316,3±±5,95,9††//16,016,0‡‡ 0,0050,005§§

PEBPEB EESEES

1212--M visitM visit 6868 6868

1212--M QCAM QCA--ptspts 6363// 92,6%92,6%((95% CI: 83,7%95% CI: 83,7% --97,6%)97,6%)

62/ 91.2%62/ 91.2%(95% CI: 81.78(95% CI: 81.78––96.69)96.69)((95% CI: 83,7%95% CI: 83,7% --97,6%)97,6%) (95% CI: 81.78(95% CI: 81.78––96.69)96.69)

1212--M QCAM QCA-- lesionslesions 69/69/ 93,293,2%%((95% CI: 84,9%95% CI: 84,9% -- 97,8%)97,8%)

6868// 91,9%91,9%((95% CI: 83,2%95% CI: 83,2% -- 97%)97%)

p = 0,753p = 0,753

PEBPEB EESEES pp

Minimal lumen diameter, mmMinimal lumen diameter, mm 2,092,09±±0,570,57††//2,132,13‡‡ 2,072,07±±0,800,80//††2,232,23‡‡ 0,4810,481§§Minimal lumen diameter, mmMinimal lumen diameter, mm 2,092,09±±0,570,57††//2,132,13‡‡ 2,072,07±±0,800,80//††2,232,23‡‡ 0,4810,481§§

Reference diameter, mmReference diameter, mm 2,812,81±±0,480,48††//2,812,81‡‡ 2,962,96±±0,500,50††//2,862,86‡‡ 0,1880,188§§

% Diameter% Diameter stenosisstenosis 26,226,2±±18,018,0††//22,022,0‡‡ 30,930,9±±24,624,6††//21,521,5‡‡ 0,8160,816§§

Late lumen loss, mmLate lumen loss, mm 0,090,09±±0,440,44††//0,020,02‡‡ 0,440,44±±0,730,73††//0,190,19‡‡ 0,00040,0004 §§

BinBinaryary restenosisrestenosis (%(%DS˃50%)DS˃50%) 66 ((8,78,7%)%) 13 (13 (19,1219,12%)%) 0,0780,078♯♯

§nonparametric Mann–Whitney U test

PEBPEB EESEES pp §§

ISRISR lengthlength ˃10 mm˃10 mm LLLLLL (mm)(mm) 0,160,16±±0,500,50††//0,050,05‡‡ 0,530,53±±0,670,67††//0,260,26‡‡ 0,00020,0002

VesselVessel diameterdiameter ˂ 3 mm˂ 3 mm LLLLLL (mm)(mm) 0,120,12±±0,480,48††//0,050,05‡‡ 0,420,42±±0,630,63††//0,160,16‡‡ 0,0030,003VesselVessel diameterdiameter ˂ 3 mm˂ 3 mm LLLLLL (mm)(mm) 0,120,12±±0,480,48††//0,050,05‡‡ 0,420,42±±0,630,63††//0,160,16‡‡ 0,0030,003

Diabetes mellitusDiabetes mellitus LLLLLL (mm)(mm) 0,120,12±±0,330,33††//0,060,06‡‡ 0,480,48±±0,860,86††//0,120,12‡‡ 0,2540,254

PEBPEB EESEES pp

MACEMACE allall 7 (7 (10,2910,29%)%) 1313 ((19,1219,12%)%) 0,2130,213§§MACEMACE allall 7 (7 (10,2910,29%)%) 1313 ((19,1219,12%)%) 0,2130,213§§

CVCV deathdeath 1 (1 (1,471,47%)%) 1 (1 (1,471,47%)%) 1,0001,000§§

NonfatalNonfatal MIMI 1 (1 (1,471,47%)%) 1 (1 (1,471,47%)%) 1,0001,000§§NonfatalNonfatal MIMI 1 (1 (1,471,47%)%) 1 (1 (1,471,47%)%) 1,0001,000§§

TVRTVR 55 ((7,357,35%)%) 11 (11 (16,1816,18%)%) 0,1100,110§§

DefiniteDefinite stentstent thrombosisthrombosis 1 (1 (1,451,45 %)%) 0 (0%)0 (0%) 1,0001,000♯♯DefiniteDefinite stentstent thrombosisthrombosis 1 (1 (1,451,45 %)%) 0 (0%)0 (0%) 1,0001,000♯♯

EventEvent--freefree survivorsurvivorss 61 (61 (89,7189,71%)%) 55 (55 (80,8880,88%)%) 0,1100,110§§

•• NNonon--inferiorityinferiority but also superiority of PEB vs EESbut also superiority of PEB vs EES•• NNonon--inferiorityinferiority but also superiority of PEB vs EESbut also superiority of PEB vs EES

•• 1212 monthsmonths LLL in PEBLLL in PEB groupgroup significantlysignificantly lowerlower•• 1212 monthsmonths LLL in PEBLLL in PEB groupgroup significantlysignificantly lowerlowervsvs EESEES groupgroup

•• NoNo significantsignificant differencedifference in Binaryin Binary restenosisrestenosis andand1212 monthsmonths MACEMACE1212 monthsmonths MACEMACE

•• 190190 ptspts withwith BMSBMS--ISRISR

•• iopromideiopromide--coatedcoated PEB (PEB (SequentSequent PleasePlease) vs. EES () vs. EES (XienceXience,,Co/Co/CrCr))

PEBPEB EESEES pp

Co/Co/CrCr))

•• 99--MM angioangio(QCA) and 12(QCA) and 12--MM clinicalclinical followfollow upup

PEBPEB EESEES pp

MLD, mmMLD, mm 2,01+/2,01+/-- 0,60,6 2,36 +/2,36 +/--0,60,6 p < 0,001p < 0,001

%DS%DS 25+/25+/--20%20% 13+/13+/--17%17% p < 0,001p < 0,001%DS%DS 25+/25+/--20%20% 13+/13+/--17%17% p < 0,001p < 0,001

LLL, mmLLL, mm 0,14+/0,14+/-- 0,50,5 0,04+/0,04+/-- 0,50,5 p = 0,14p = 0,14

binarybinary ISRISR 9,59,5%% 4,7%4,7% p = 0,22p = 0,22binarybinary ISRISR 9,59,5%% 4,7%4,7% p = 0,22p = 0,22

12 M12 M MACEMACE 8%8% 6%6% p = 0,6p = 0,6

•• MoreMore neoatherosclerosisneoatherosclerosis

•• TreatmentTreatment ofof DESDES--ISR:ISR: worseworse resultsresults thanthan in BMSin BMS--ISRISR

•• HabaraHabara etet alal::•• HabaraHabara etet alal::

subanalysissubanalysis –– significsignific ↑ LLL (0,18 vs. 0,05mm; p = 0,03) and ↑ LLL (0,18 vs. 0,05mm; p = 0,03) and binarybinary restenosisrestenosis (9,1 vs. 1,1%, p= 0,04)(9,1 vs. 1,1%, p= 0,04) vsvs BMSBMS--ISRISR

•• SeQuentSeQuent PleasePlease WorldWorld WideWide Registry:Registry:

significsignific ↑ TLR (9,6 vs. 3,8%; p˂0,001) and MACE (11,3 vs. ↑ TLR (9,6 vs. 3,8%; p˂0,001) and MACE (11,3 vs. 5,6%;5,6%;p˂0,001) p˂0,001) vsvs BMSBMS--ISRISRp˂0,001) p˂0,001) vsvs BMSBMS--ISRISR

•• DEB ~ DESDEB ~ DES

BVSBVS RestenosisRestenosis ((ScRScR))BVSBVS RestenosisRestenosis ((ScRScR))

SubanalysisSubanalysis ofof GHOSTGHOST--EU registry:EU registry:

•• 1414 ScRScR -- 3,63,6%; 60%; 60%% focalfocal, 20%, 20% diffusediffuse•• 1414 ScRScR -- 3,63,6%; 60%; 60%% focalfocal, 20%, 20% diffusediffuse

•• DueDue to:to: underexpansionunderexpansion (in(in diffusediffuse),), 1x1x geograficgeograficmissmissmissmiss

•• treatmenttreatment: 45: 45% DEB, 35% DES,% DEB, 35% DES, 15% POBA15% POBA ––NCNC postdilatationpostdilatation,, anotheranother BVSBVS (1x) 5(1x) 5%%

• High minimal lumen diameter (MLD)• High minimal lumen diameter (MLD)

• PEB similar to DES

• Different types of PEB and DES• Different types of PEB and DES

• PEB better when ≥2 stent layers

• DES better when edge disease

• OCT, IVUS• OCT, IVUS

•• MostMost trialstrials -- endpointsendpoints:: TLFTLF (CV(CV deathdeath +TV+TV--•• MostMost trialstrials -- endpointsendpoints:: TLFTLF (CV(CV deathdeath +TV+TV--MI+MI+ TLR)TLR)

•• ABSORB II :ABSORB II : TLFTLF 5%5%•• ABSORB II :ABSORB II : TLFTLF 5%5%

•• ABSORB III:ABSORB III: TLFTLF 7,4% /12M7,4% /12M -- nonnon--inferiorinferior vs.vs.EESEESEESEES

•• GHOST EU registry:GHOST EU registry: TLFTLF 2,2%2,2% -- 1M and1M and 4,4%4,4%-- 6M, 16M, 1 yearyear predictionprediction -- 1010%%-- 6M, 16M, 1 yearyear predictionprediction -- 1010%%

Adjusted ORAdjusted OR 95% CI95% CI pp

Diabetes mellitus (Diabetes mellitus (1=1=yesyes, 0=n, 0=noo)) 2,0452,045 0,6110,611 –– 6,8426,842 0,2460,246Diabetes mellitus (Diabetes mellitus (1=1=yesyes, 0=n, 0=noo)) 2,0452,045 0,6110,611 –– 6,8426,842 0,2460,246

RenRenalal insufficiencinsufficiencyy ((1=1=yesyes,, 0=n0=noo)) -- -- 0,9990,999

TypeType B2/CB2/C lesionlesion (1=(1=yesyes,, 0=n0=noo)) 1,6611,661 0,5280,528 –– 5,2245,224 0,3860,386TypeType B2/CB2/C lesionlesion (1=(1=yesyes,, 0=n0=noo)) 1,6611,661 0,5280,528 –– 5,2245,224 0,3860,386

PEB =1 / EES =2PEB =1 / EES =2 3,1323,132 1,0581,058 –– 9,2699,269 0,0390,039

VesselVessel diameterdiameter <3<3 mm (mm (1=1=yesyes,, 0=n0=noo)) 2,2832,283 0,5580,558 –– 9,3439,343 0,2510,251VesselVessel diameterdiameter <3<3 mm (mm (1=1=yesyes,, 0=n0=noo)) 2,2832,283 0,5580,558 –– 9,3439,343 0,2510,251

ISRISR lengthlength >10 mm (>10 mm (1=1=yesyes, 0=n, 0=noo)) 1,9751,975 0,5870,587 –– 6,6466,646 0,2720,272

The 2-sided 95% confidence interval for the difference betweentreatments in LLL (0,149 - 0,558) and the non-inferiority margin (0,12)treatments in LLL (0,149 - 0,558) and the non-inferiority margin (0,12)non-inferiority but also superiority of PEB vs EES