Is There a Generation Gap of DES: Results of PRECOMBAT …

Is There a Generation Gap of DES: Results of PRECOMBAT Series

Jung-Min Ahn, MD

Heart Institute, Asan Medical Center

University of Ulsan, Seoul, Korea

BMS vs. 1st DES for LM

JACC Cardiovasc Interv. 2010 Jun;3(6):602-11

Meta-Analysis from 44 Studies and 10,342 Patients

Time DES

(N)

BMS

(N) OR (95% CI)

Death 6-12 mon 53 50 0.94(0.06-15.5)

2 yrs 1344 496 0.42 (0.28-0.62)

3 yrs 1809 736 0.70 (0.53-0.92)

MI 6-12 mon 53 50 0.64 (0.19-2.17)

2 yrs 178 109 0.16 (0.01-3.53)

3 yrs 611 238 0.49 (0.26-0.92)

TVR/TLR 6-12 mon 53 50 0.10 (0.01-0.84)

2 yrs - - -

3 yrs 1809 736 0.46 (0.30-0.69)

MACE 6-12 mon 138 114 0.34 (0.15-0.78)

2 yrs 398 333 0.31 (0.15-0.66)

3 yrs 1198 498 0.78 (0.57-1.07)

P

value

0.97

<0.05

<0.05

0.47

0.13

<0.05

<0.05

-

<0.05

<0.05

<0.05

0.12

0.01 0.1 1 10

Favor DES Favor BMS

LM PCI Guideline (IIa-IIb)

P=0.12

31.0%

0

Cum

ula

tive E

vent R

ate

(%

)

25

50

Months Since Allocation

36.9%

TAXUS (N=357) CABG (N=348)

0 12 60 24 36 48

SYNTAX-LM

0 12 24 36 0

5

10

15

20

9.3

14.7

8.0

12.7

6.3

9.7

p=0.052 p=0.15 p=0.069

Cum

ula

tive Incid

ence, %

CYPHER (N=300) CABG (N=300)

PRECOMBAT

Months Since Allocation

SES vs. PES for LM

MAINCOMPARE ISAR LM-1

Mehilli et al. J Am Coll Cardiol 2009; 53:1760-3 Lee et al. J Am Coll Cardiol 2009;54:853-9

Death, MI, or TVR

Number at risk

PES 189 153 94 31

SES 669 551 367 169

SES

PES

RR 0.99 (95% CI, 0.69-1.42), P=.96

Years after randomization C

um

ula

tive

In

cid

en

ce

, %

Death, MI or TVR

Patients at Risk

PES 302 278 250 189 160

SES 305 271 252 198 176

0

0

70

80

90

100

365 730 1095

SES

PES

Long-Rank p value = 0.90

Days after initial procedure

Eve

nt

fre

e s

urv

iva

l (%

)

0

0

20

30

40

50

1 2

10

1st vs. 2nd DES for LM PRECOMBAT-2 Study

0 180 360 540

0

5

10

15

20 SES

EES

CABG

Kapla

n-M

eie

r In

cid

en

ce

(%

)

Months

10.8

8.9

6.7

At risk

SES 327 294 275

EES 334 297 176

CABG 272 253 241

P = 0.23

MACCE

Kim YH et al. J Am Coll Cardiol Intv 2012;5:708

Hazard Ratios of EES after Adjustment

Kim YH et al. J Am Coll Cardiol Intv 2012;5:708

1st vs. 2nd DES for LM PRECOMBAT-2 Study

1st vs. 2nd DES for LM EXCELLENT registry

Park KW et al. Int J Cardiol 2013;168:2738-44

1 Year Outcome

Events Propensity Score

Adjustment

EES (N=160)

SES (N=115)

P value HR (95% CI) P value

Death/MI/TVR 12 (7.5%) 16 (13.9%) 0.117 0.43 (0.20-0.95) 0.037

Death 7 (4.4%) 8 (7.0%) 0.383 0.52 (0.18-0.51) 0.23

Death/MI 8 (5.0%) 8 (7.0%) 0.529 0.60 (0.21-0.67) 0.323

TVR 4 (2.5%) 8 (7.0%) 0.096 0.28 (0.08-0.98) 0.046

1st vs. 2nd DES for LM PCI Florence Registry

Log rank p= 0.006

84 ± 4 %

68 ± 4 %

Time (days)

Fre

edom

fro

m M

AC

E (

%)

100

90

80

70

60

0 150 300 450 600 750

MACE

EES (N=166)

PES (N=224)

Valenti et al. JACC 2012;60(14):1217-1222

1st vs. 2nd DES for LM PCI Florence Registry

7.1

0.5

13.4

4.8

1.2

4.2

0

5

10

15

20

25

30

35

40

Cardiac Death MI TVR

PES EES

P=0.35 P=0.40 P<0.001

Valenti et al. JACC 2012;60(14):1217-1222

1st vs. 2nd DES for LM ESTROFA-LM registry

De la Hernandez JM et al. Am J Cardiol 2013;111:676-83

3 Year Event Free Survival

Events

PES (N=415)

EES (N=355)

P value

Death and MI 86% 87% 0.50

Cardiac Death and MI 92% 91% 0.90

TLR 96% 94% 0.10

All revascularization 84% 86% 0.10

Death, MI, and TLR 84% 82% 0.60

ISAR-LEFT MAIN 2 Trial

650 patients with uLMCA lesions pre-treated with 600 mg clopidogrel

Angiographic follow-up at 8

months in 73% (N=237)

Zotarolimus-eluting stent

(Endeavor Resolute)

N= 324

Everolimus-eluting stent

(Xience)

N= 326

Angiographic follow-up at 8 months

in 69% (N=226)

Clinical follow-up at 12 months in

100% (N=324)

Clinical follow-up at 12 months in

100% (N=326)

Mehilli et al. J Am Coll Cardiol 2013;62:2075-82

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 Months after randomization

Cum

ula

tive incid

ence,

%

RR 1.26 (95% CI 0.85-1.85)

P=0.25

17.5%

14.3%

Resolute Integrity (ZES)

Xience-V (EES)


MACE at 1 Year

2nd DES for LM ISAR Left Main 2 (n=650)

5.6

2.8

11.7

21.5

0.6

5.6

1.2

9.4

16.8

0.6

0

5

10

15

20

25

30

35

40

Death MI TLR AngiographicRestenosis

Definite ST

R-ZES EES

P=0.24 P=0.98

ISAR Left Main 2 (n=650) Outcomes at 1 Year

P=0.98 P=0.16 P=0.35


PCI with

Cypher N=300

CABG

N=300

Primary Endpoint (MACCE):

2-year death, MI, Stroke, and ischemic driven TVR

Randomization

PRE-COMBAT

for unprotected left main disease

Multi-centers in Korea

Treated with

Xience V

Stent

Pts randomizable

in the

PRECOMBAT

N=300

PRE-COMBAT-2

for unprotected

left main disease

Treated with

Promus

Element stent

Pts randomizable

in the

PRECOMBAT

N=300

PRE-COMBAT-3

for unprotected

left main disease

PRECOMBAT Series New DES Evaluation !

Treated with

Resolute

Integrity

Pts randomizable

in the

PRECOMBAT

N=300

PRE-COMBAT-4

for unprotected

left main disease

PRECOMBAT-3 Trial

Design

• DESIGN: a prospective, single arm, registry

• OBJECTIVE: To evaluate the outcomes of PCI with everolimus-

eluting PROMUS ELEMNT (PtCr-EES) stents for patients with

ULMCA stenosis, the results were compared with those of patients

receiving SES, CoCr-EES and CABG in the PRECOMBAT trial

• PRINCIPAL INVESTIGATOR

Seung-Jung Park, MD, PhD, Asan Medical Center, Seoul, Korea

Purpose of PRECOMBAT-3

• To evaluate the safety and efficacy of PCI using platinu

m chromium everolimus-eluting Promus Element stent

(Boston Scientific) for patients with ULMCA stenosis.

• The results were compared with those of historical cont

rols of patients receiving PCI with Cypher, Xience V or

CABG in the PRECOMBAT-1 and 2 study

Subjects

• Between August 2010 and July 2013, 300 patients

who met the inclusion and exclusion criteria of

PRECOMBAT randomized study were entered from

330 patients undergoing ULMCA stenting with PtCr-

EES in 23 Korean cardiac centers.

Inclusion and Exclusion

• Identical to the PRECOMBAT randomized study

• In brief, patients with angiographic ULMCA stenosis

(> 50% stenosis), who did not have ST-segment

elevation MI, cardiogenic shock, other serious

comorbidity or contraindication of DES, were

included.

Procedures and Follow-up

• PtCr-EES (Promus Element) was the default stent for

all lesions with LMCA in the study period

• IVUS and other devices were used at the operator’s

discretion.

• Annually clinical follow-up to 5 years

End Points

Identical to those used in the PRECOMBAT.

• MACCE : Primary end point, a composite of death, MI,

stroke and ischemia-driven TVR.

• Death : cardiac and non-cardiac deaths.

• MI : Q-MI within 48 hours after procedure and

spontaneous MI thereafter.

• TVR : ischemia-driven revascularization.

Statistics

• Analysis among as-treated groups

• ANOVA and t-test for continuous variables

• Chi-square and Fisher-exact for categorical variables

• Censoring at 2 years (720 days) or events

• Log-rank for survival analysis

• Multivariate Cox analysis to adjust different baseline

characteristics

Baseline Characteristics

SES

(N=327)

CoCr-EES

(N=334)

PtCr-EES

(N=300)

CABG

(N=272)

P

value

Age, years 62.0±10.0 62.9±10.4 64.3±10.3 62.5±9.4 0.026

Male sex 249 (76.1) 236 (70.7) 231 (77.0) 209 (76.8) 0.19

Diabetes mellitus 109 (33.3) 116 (34.7) 94 (31.3) 82 (30.1) 0.63

Hypertension 176 (53.8) 189 (56.6) 191(63.7) 140 (51.5) 0.018

Hyperlipidemia 139 (42.5) 149 (44.6) 155 (51.7) 107 (39.3) 0.021

Current smoker 97 (29.7) 75 (22.5) 70 (23.3) 74 (27.2) 0.13

Previous PCI 42 (12.8) 27 (8.1) 51 (17.0) 34 (12.5) 0.009

Previous MI 16 (4.9) 13 (3.9) 15 (5.0) 17 (6.3) 0.62

Previous heart failure 0 4 (1.2) 11 (3.7) 2 (0.7) 0.001

Baseline Characteristics

SES

(N=327)

CoCr-EES

(N=334)

PtCr-EES

(N=300)

CABG

(N=272)

P

value

Chronic renal failure 3 (0.9) 4 (1.2) 15 (5.0) 2 (0.7) < 0.05

Peri. vascular disease 15 (4.6) 6 (1.8) 18 (6.0) 7 (2.6) 0.02

Chronic lung disease 8 (2.4) 4 (1.2) 9 (3.0) 7 (2.6) 0.46

ACS 155 (47.4) 151 (45.2) 151 (50.3) 147 (54.0) 0.16

Ejection fraction, % 61.5±8.4 61.1±8.2 59.0±9.9 60.8±8.4 <0.05

EuroSCORE 2.8±1.9 2.9±2.0 3.4±2.4 2.9±2.0 <0.05

Multivessel disease 231 (70.6) 191 (57.2) 198 (66.0) 205 (75.4) < 0.05

LM bifurcation 219 (67.0) 240 (71.9) 207 (69.0) 163 (59.9) < 0.05

SYNTAX Score 23.8±9.5 21.1±8.8 21.0±9.6 26.8±10.4 <0.05

Procedures

SES

(N=327)

CoCr-EES

(N=334)

PtCr-EES

(N=300)

CABG

(N=272)

P

value

Total stent N. in left main 1.6±0.8 1.8±0.9 1.7±0.8 <0.05

Total stent N. per patient 2.6±1.4 2.3±1.3 2.3±1.2 <0.05

IVUS 294 (89.9) 302 (90.4) 270 (90.0) 0.83

Two-stent technique 112 (34.3) 88 (26.3) 81 (27.0) 0.049

Angiographic follow-up 249 (76.1) 203 (60.8) 121 (40.3) < 0.05

N. of conduits 2.7±0.9

N. of arterial conduits 2.1±0.9

Off-pump surgery 166 (61.0)

Use of LIMA 254 (93.4)

Clinical Outcomes

Death

0 180 360 540 720 0

5

10

15

20

N. at risk

SES 327 324 317 315 311

CoCrEES 334 331 308 292 282

PtCrEES 300 289 273 200 119

CABG 272 265 264 262 260

5.4%

3.1% 3.3%

2.1%

P=0.18

SES CoCr-EES PtCr-EES CABG

Days Since Index Procedure

Cu

mu

lative

In

cid

en

ce

, %

Death, MI, or Stroke

0 180 360 540 720 0

5

10

15

20

N. at risk

SES 327 321 314 310 306

CoCrEES 334 331 304 287 275

PtCrEES 300 286 270 194 116

CABG 272 260 258 256 254

4.4%

5.5% 4.9%

7.9%


P=0.32


Cu

mu

lative

In

cid

en

ce, %

TVR

0 180 360 540 720 0

5

10

15

20

N. at risk

SES 327 321 298 292 284

CoCrEES 334 331 289 269 255

PtCrEES 300 287 263 188 114

CABG 272 263 260 258 255

10.2%

6.5%

8.8%

2.6%


P=0.004


Cu

mu

lative

In

cid

en

ce

, %

P=0.32

MACCE: Death, MI, Stroke, or TVR

0 180 360 540 720 0

5

10

15

20

N. at risk

SES 327 318 295 288 280

CoCrEES 334 331 286 266 253

PtCrEES 300 284 259 183 112

CABG 272 258 254 252 249

13.3%

12.4% 13.2%

7.4%


P=0.12


Cu

mu

lative

In

cid

en

ce, %

3.3

1.5

2.6

1.1

3.1

1.2

8.8

0.6

2.1 1.6

10.2

1

5.4

1.2

6.5

2

0

2

4

6

8

10

12

14

16

18

20

Death MI TVR Stroke

CABG SES CoCr-EES PtCr-EES

Pati

en

ts,

%

Clinical Outcomes at 2 Years

Cumulative KM Event Rate; log-rank P value; *Binary rates

P=0.18

P=0.96

P<0.004

P=0.47

P value among all groups

P=0.09

P=0.88

P=0.32

P=0.47

P value among DES groups

Definite Stent Thrombosis at 2 Years

0.3 0.3 0.4

0

0.5

1

1.5

2

2.5

3

Definite Stent Thrombosis

SES CoCr-EES PtCr-EES

Pati

en

ts,

%

P=0.79

Stent Deformation

0.3 0.9

4.3

0

1

2

3

4

5

6

7

8

9

10

Stent Deformation

SES CoCr-EES PtCr-EES

Pati

en

ts,

%

P<0.001

Adjusted HR for PtCr-EES Adjusted Hazard ratio 95% CI P value

Death

vs SES 1.06 0.69 - 1.63 0.78

vs. CoCr-EES 1.81 0.60 – 5.44 0.29

vs. CABG 1.33 0.54 – 3.25 0.53

Death, MI, or stroke

vs. SES 1.05 0.75 – 1.49 0.77

vs. CoCr-EES 1.40 0.69 – 2.83 0.35

vs. CABG 1.10 0.56 – 2.22 0.79

TVR

vs. SES 0.88 0.65 – 1.20 0.42

vs. CoCr-EES 0.61 0.34 – 1.11 0.10

vs. CABG 2.75 1.13 – 6.69 0.026

MACCE

vs. SES 0.99 0.79 – 1.24 0.95

vs. CoCr-EES 0.85 0.53 – 1.36 0.50

vs. CABG 1.70 0.97 – 2.95 0.062

0.1 1 10 Favor PtCr-EES Favor Others

5.1 6.6

10.3 10.6

13.8

20.7

12.7 11.8 12.8

9.9

21.5

12.1

0

5

10

15

20

25

30

35

40

45

50


Patients

, %

Intermediate (23-32) Low (≤22) High (≥33)

2-Y MACCE in SYNTAX Subgroup


P=0.38

P=0.041

P=0.32

P=0.17

4.9

11 12.8

14 13.5

9.7

14.2

11.5

0

5

10

15

20

25

30

35

40


Patients

, %

Non-Bifurcation Bifurcation

2-Y MACCE in Bifurcation


P=0.038 P=0.83

P=0.95

9.8

6.4

16.5

11.5

16.8

10.1

17.8

11.2

0

5

10

15

20

25

30

35

40


Patients

, %

Non-DM DM

2-Y MACCE in DM


P=0.54 P=0.31

12.5

2.3

8.4 7.4

5.6 6.8

15.8 16.3

13.8

6.6

16.1

12.9

4.3

9.7

13.9

18.9

0

5

10

15

20

25

30


Patients

, %

LM+1VD LM Isolated LM+2VD LM+3VD

2-Y MACCE in LM Subgroups


P=0.38

P=0.51

P=0.45

P=0.10

Conclusions

• The PRECOMBAT-3 trial demonstrated PCI for ULMCA

stenosis using PtCr-EES is safe and effective compared

with previous version of DES including SES and CoCr-

EES.

• However, the adoption of more flexible stent design was

associated with the higher rate of stent deformation.

• In addition, compared with the historical control of

CABG group in PRECOMBAT-1 trial, PtCr-EES stenting

was associated with the similar rate of the death, MI, or

stroke but the higher rate of the repeated

revascularization at 2 year follow-up.

Conclusions

• Based on the current available data, the generation gap

of DES appears to be very minimal regarding the clinical

endpoint.

• Therefore, physicians pay more attention to “how to

stent” rather than “what kind of stent”.

Documents

Is There a Generation Gap of DES: Results of PRECOMBAT …