tetra randomized european direct stenting study (trends) keith d. dawkins, m. j. suttorp, leif...

Tetra Randomized European Direct Stenting Study

(TRENDS)

Tetra Randomized European Direct Stenting Study

(TRENDS)Keith D. Dawkins, M. J. Suttorp, Leif Thuesen, Edouard Benit, Armando Bethencourt, Ursula Morjaria, Susan

Veldhof, Bernard Chevalier, on behalf of the TRENDS investigators

Direct Stenting Trials (n=4297)Direct Stenting Trials (n=4297)

Patients (n) Stent Type

BET 338 Tenax

CONVERTIBLE 202 BeStent 2

DIRECT 107 Multilink Duet

DIRECTO 151 NIR Primo

DIRECTOR I + II 520 R-Stent

DISCO 416 Various

DISTANCE - S7

PREDICT 400 S670SLIDE 362 Multilink DuetSWIBAP 400 NIRTRENDS 1000 Multilink TetraVELVET II 401 Bx Velocity

Direct Stenting Trials (n=4297)Direct Stenting Trials (n=4297)

Patients (n) Stent Type

BET 338 Tenax

CONVERTIBLE 202 BeStent 2

DIRECT 107 Multilink Duet

DIRECTO 151 NIR Primo

DIRECTOR I + II 520 R-Stent

DISCO 416 Various

DISTANCE - S7

PREDICT 400 S670SLIDE 362 Multilink DuetSWIBAP 400 NIRTRENDS 1000 Multilink TetraVELVET II 401 Bx Velocity

TRENDSTRENDS

To define the medium term performance of a no pre-dilatation strategy for elective stent implantation using the Multilink Tetra™ Stent

TRENDSTRENDS

Multicenter, prospective clinical trial1:1 randomization to stent implantation with or without pre-dilatation1000 patient enrolment over a period of one year at 46 sites in Europe and South America

1000 patients

TRENDS Trial DesignTRENDS Trial Design

Diagnostic catheter(Randomisation 1:1)

Direct Stent(501 pts)

Pre-dilatation(499 pts)

Angiographic follow-up(6 months)

A Direct stenting strategyA Direct stenting strategy

Possible Advantages Shorter procedure

duration Less radiation Less contrast Reduced resource

utilisation Less embolization Less unprotected

barotrauma

Potential Disadvantages

Failure to cross lesionLoss of stentIncomplete stent deploymentIncrease in guide traumaUndersizing of stent (diameter & length)Poor visualisationError in stent positioning

117

1327

2

128

14475

52

82

133

116

35

41

35

TRENDSTRENDS

Total Patients:1000

Pre-dilatation: 499Direct stent: 501

TRENDSTRENDS

Multilink Tetra™ Coronary Stent SystemStent diameters: 2.75, 3.0, 3.5, 4.0 mmStent lengths: 8, 13, 18, 23 mm

TRENDS Primary EndpointTRENDS Primary Endpoint

Major Adverse Cardiac Events at 30 daysDeath

Myocardial infarction (Q and non-Q)CABG, or re-PCI (TVR)

TRENDS Secondary EndpointsTRENDS Secondary Endpoints

Use of multiple stents at each target lesionTotal procedure timeRadiographic screening timeContrast volumeTechnical successProcedural resource analysisDuration of hospital stayMACE at 6 monthsBinary angiographic restenosis per lesion at 6 months

Symptomatic anginaPlanned de novo single lesions, or restenotic lesions (previous POBA) in native coronary arteriesMVD may be treated, one lesion per vesselTarget vessel diameter ≥2.75 mm to ≤4.25 mm, length ≤18 mm (visual)Target lesion ≥70% stenosis, TIMI flow ≥1

TRENDS Inclusion Criteria*TRENDS Inclusion Criteria*

* Selected

Acute MI within the last 24 hoursUnprotected left main stem lesionLesion involving a significant side branch (>2 mm diameter)Evidence of severe calcificationUse of IVUS before stentingChronic total occlusion

TRENDS Exclusion Criteria*TRENDS Exclusion Criteria*

* Selected

TRENDS Baseline Demographics (I)TRENDS Baseline Demographics (I)

Pre-dilatationn=499 (%)

Direct stentn=501 (%)

Age (years) 59.4(range 32-84)

59.9(range 31-84)

Male 78 78

Diabetes 18 15

Hypercholesterolemia

58 63

Hypertension 49 53

Family history 36 40

p=ns

TRENDS Baseline Demographics (II)TRENDS Baseline Demographics (II)

Pre-dilatationn=499 (%)

Direct stentn=501 (%)

Current smoker 27 25

Previous smoker 46 43

Previous MI 37 38

Previous CABG/PCI 8 8

History of angina 97 98

p=ns

TRENDS Lesion Characteristics (I)TRENDS Lesion Characteristics (I)

Pre-dilatation Direct stent

Procedure:

Single vessel 91% 93%

Two Vessel 8% 7%

Three vessel 1% 0%

p=ns

TRENDS Lesion Characteristics (II)TRENDS Lesion Characteristics (II)

Pre-dilatation Direct stent

Vessel:

LAD 42% 40%

LCx 20% 25%

RCA 36% 34%

p=ns

TRENDS Lesion Characteristics (III)TRENDS Lesion Characteristics (III)

Pre-dilatation Direct stent

ACC/AHA Class:

Type A 17% 17%

Type B1 44% 40%

Type B2 38% 42%

Type C 1% 1%

p=ns

TRENDS Lesion Characteristics (IV)TRENDS Lesion Characteristics (IV)

Pre-dilatation Direct stent

TIMI Flow:

Grade 0 0% 0%

Grade 1 2% 2%

Grade 2 5% 5%

Grade 3 93% 93%

p=ns

TRENDS Quantitative Coronary ArteriographyTRENDS Quantitative Coronary Arteriography

Pre-dilatationmean ± SD

(n = 472)

Direct stentmean ± SD

(n = 469)

Pre-procedure DS (%) 63.9 ± 11.2 64.7 ± 10.4

Pre-procedure MLD (mm) 1.07 ± 0.36 1.06 ± 0.36

Pre-procedure reference vessel diameter (mm)

2.99 ± 0.50 3.03 ± 0.56

Lesion length (mm) 12.4 ± 4.87 12.3 ± 4.89

Post-procedure MLD (mm) 2.95 ± 0.44 2.91 ± 0.49

Post-procedure DS (%) 7.95 ± 8.30 8.93 ± 9.73

p=ns

0

10

20

30

40

50

Predilatation Direct Stent

TRENDS Stent Deployment PressureTRENDS Stent Deployment Pressure

<10 10-12 13-14 15-16 17-18 19-20 >20

Perc

ent

(%)

Maximum pressure (Atm)

TRENDS Procedural Data (I)TRENDS Procedural Data (I)

Pre-dilatation Direct stentMaximum pressure 13.0 Atm 13.7 AtmBalloon-Artery Ratio 1.14 ± 0.51 1.14 ± 0.55Post implant dilatation

13.3% 15.9%

Additional stent implant

6.4% 6.7%

p=ns

TRENDS Procedural Data (II)TRENDS Procedural Data (II)

Pre-dilatation Direct stentAdditional Stent implant:

Inflow dissection 13 11

Outflow dissection 8 10

Failure to cover original target lesion

7 10

Lesion at distant site 6 3

Thrombotic lesion 0 1

Unknown 0 1

p=ns

TRENDS Procedural Data (III)TRENDS Procedural Data (III)

Pre-dilatation Direct stentScreening time (mins)

8.7 8.6

Procedure time (mins)

37.5 34.3*

Contrast volume (mls)

186 175#

Hospital stay (days) 3.6 3.4

*p=0.01, #p=0.05 (Fisher’s Exact Test)

TRENDS Procedural Data (IV)TRENDS Procedural Data (IV)

Pre-dilatation Direct stent

Technical Success 100% 100%

p=ns

Technical Success: Ability to access the lesion, deploy the stent or remove the delivery system in the event of failure to cross the lesion without stent loss, balloon rupture or general device failure.

TRENDS Procedural Data (V)TRENDS Procedural Data (V)

Pre-dilatation Direct stentResource utilization:

Guide wiresGuiding cathetersIVUS cathetersPTCA cathetersIABP cathetersTETRATM stentsOther stents

540554

9548

156819

543

586*

7 115#

155922

IIb/IIIa Inhibitor use 19.3% 18.8%

*p=0.02, #p=0.001 (Fisher’s Exact Test)

TRENDS Cross-over to pre-dilatationTRENDS Cross-over to pre-dilatation

Direct stent (n=541)

Cross-over to pre-dilatation:

31 (5.7%)

Stent did not cross lesion 25

Guide catheter dissection 1

Ostial location 1

Lesion occluded 1

Fear of dissection 1

Stent placement not feasible 1

Unknown 1

TRENDS QCA Analysis (6 months)TRENDS QCA Analysis (6 months)

Pre-dilatation

(n=395)

Direct stent(n=379)

Binary Restenosis (≥50%): In-stent

11.4%[95% CI 8.4%, 14.9%]

11.6%[95% CI 8.6%, 15.3%]

In-segment(stent ± 5mm)

12.2%[95% CI 9.1%, 15.8%]

13.4%[95% CI 10.1%, 17.2%]

Late Loss (In-stent) (mm) 0.88 ± 0.52[95% CI 0.83, 0.93]

0.83 ± 0.50[95% CI 0.78, 0.88]

p=ns

TRENDS MACE at 180 days*TRENDS MACE at 180 days*

Pre-Dilatation

Direct stent Difference [95% CI]

TVF (Death, MI, TLR, TVR)

11.4% 10.8% 0.64% [0.25%, 1.04%]

MACE (Death, MI, TLR) 10.8% 9.8% 1.04% [0.66%, 1.43%]

Death 1.0% 1.0% 0.00% [-0.12%, 0.13%]

Q-wave MI 0.4% 0.4% 0.00% [-0.08%, 0.08%]

Non-Q wave MI

3.0% 2.0% 1.01% [0.80%, 1.22%]

* Hierarchical Ranking

TRENDS MACE at 180 days*TRENDS MACE at 180 days*

Pre-Dilatation

Direct stent

Difference [95% CI]

TLR CABG 0.6% 0.2% 0.40% [0.31%, 0.50%]

TLR PCI 5.8% 6.2% -0.38% [-0.67%, -0.09%]

TVR CABG 0.0% 0.0% 0.00% [0.00%, 0.00%]

TVR PCI 0.6% 1.0% -0.04% [-0.49%, -0.30%]

Stent thrombosis 0.2% 0.2% 0.00% [-0.05%, 0.06%]

Bleeding ComplicationVascular Complication

2.8%0.4%

2.0%0.4%

0.81% [0.60%, 1.01%]0.00% [-0.08%, 0.08%]

* Hierarchical Ranking

95

96

97

98

99

100

0 7 14 30 60 90 120 150 180

Direct Stent

Predilatation

TRENDS SurvivalTRENDS Survival

Days

Perc

ent

Surv

ivin

g

99.0%

99.0%

Difference [95% CI] = 0.00% [-0.12%, 0.13%]

90

92

94

96

98

100

0 7 14 30 60 90 120 150 180

Direct Stent

Predilatation

TRENDS Major Adverse Cardiac Events*TRENDS Major Adverse Cardiac Events*

Days

Freedom

fro

m M

AC

E (

%)

92.94%

91.21%Difference [95% CI] = 1.04% [0.66%, 1.43%]

*MACE: Death, MI, TLR

TRENDS Diabetic statusTRENDS Diabetic status

Diabetic Diabetic (n=128)(n=128)

Non-Diabetic Non-Diabetic (n=872)(n=872)

0

5

10

15

20

25

TRENDS Diabetic subgroup (n=128)TRENDS Diabetic subgroup (n=128)Targ

et

Vess

el Fa

ilure

(%

)

Pre-Dilatation Direct Stent

*95% CI 3.92 [2.52, 5.33]TVF = Death, MI, TLR, TVR

19%19%

0

5

10

15

20

25

TRENDS Diabetic subgroup (n=128)TRENDS Diabetic subgroup (n=128)M

AC

E (%

)

*95% CI 5.59 [4.18, 6.99]MACE = Death, MI, TLR

27%27%

Pre-Dilatation Direct Stent

0

5

10

15

20

25

TRENDS Diabetic subgroup (n=128)TRENDS Diabetic subgroup (n=128)Targ

et

Lesi

on R

evasc

ula

risa

tion (%

)

*95% CI 9.31 [7.99, 10.64]TLR = CABG, Re-PCI

53%53%

0

5

10

15

20

25

TRENDS Diabetic subgroup (n=128)TRENDS Diabetic subgroup (n=128)M

AC

E (%

)

*95% CI 5.59 [4.18, 6.99]MACE = Death, MI, TLR

27%27%

Pre-Dilatation Direct Stent

J Am Coll Cardiol 2002;39:15-21

0

5

10

15

20

25

30

Direct Stenting in AMI (n=206)Direct Stenting in AMI (n=206)C

om

posi

te A

ngio

gra

phic

Endpoin

t*

(%)

*Composite angiographic endpoint = distal embolization, slow flow, no reflow

Pre-Dilatation Direct Stent

p=0.01

J Am Coll Cardiol 2002;39:15-21

0

10

20

30

40

Direct Stenting in AMI (n=206)Direct Stenting in AMI (n=206)ST-s

egm

ent

Reso

luti

on

(%)

Pre-Dilatation Direct Stent

p=0.01

J Am Coll Cardiol 2002;39:15-21

Restenosis RatesSelected Trials (uncoated stents)Restenosis RatesSelected Trials (uncoated stents)

30

25

20

15

10

5

Sirius

Music

Elutes

West II

Benestent I

Taxus I

Benestent II

Ravel

Trends

Bin

ary

Rest

enosi

s R

ate

(%

)*

Finesse II

*QCA at six month angiographic follow-upTaxus II

Taxus II

1. Direct stenting, without balloon pre-dilatation, is technically feasible in the majority of patients

2. Failure to deploy the Multilink Tetra™ stent using a direct stenting strategy in a wide variety of lesions is uncommon, occurring in only 5.8% of patients in this study

3. Resource utilization is significantly less with a direct stent approach

4. Six month QCA results were comparable between groups with a low (11.5%) in-stent binary restenosis rate

5. At six month follow-up, a direct stenting strategy resulted in a lower target vessel failure (TVF) rate, and a lower major adverse cardiac event (MACE) rate than in the balloon pre-dilatation group

6. Direct stenting may have a significant impact on the late results when using a drug eluting stent

TRENDS ConclusionsTRENDS Conclusions

A Direct stenting strategyA Direct stenting strategy

Possible Advantages Shorter procedure

duration Less radiation Less contrast Reduced resource

utilisation Less embolization Less unprotected

barotrauma

Potential Disadvantages

Failure to cross lesionLoss of stentIncomplete stent deploymentIncrease in guide traumaUndersizing of stent (diameter & length)Poor visualisationError in stent positioning

A Direct stenting strategyA Direct stenting strategy

Possible Advantages Shorter procedure

duration

Less contrast Reduced resource

utilisation? Less embolization Less unprotected

barotrauma

Potential Disadvantages

Failure to cross lesion 5.8%