Five year clinical follow-up of the Five year clinical follow-up of the PASSIONPASSION-trial-trial

Five Year Follow-up after Primary PCI with a Paclitaxel-Eluting Stent versus a Bare-Metal Stent in

Acute ST-Elevation Myocardial Infarction

Maarten A. Vink, Maurits T. Dirksen, Maarten J. Suttorp, Jan G.P.

Tijssen, GertJan Laarmanon behalf of the PASSION investigators

OLVG Hospital, Amsterdam, The Netherlands

ACC/i2 2010 Late-breaking clinical trial session, March 16, 2010

Disclosure information

Maarten A. Vink, M.D.:

Nothing to disclose

BackgroundBackground

• Several RCTs showed a variable reduction in the need for repeat revascularization of infarct-related artery in favour of DES.

• No differences in survival rates or recurrent MI

Laarman et al N Engl J Med 2006; Kastrati et al Eur Heart J 2007; Stone et al N Engl J Med 2009

DES in primary PCIDES in primary PCI

BackgroundBackground

• HORIZONS-AMI showed similar rates of stent thrombosis with DES and BMS at one year1.

• However, concern has arisen about the occurrence of (very) late stent thrombosis after implantation of DES2.

• Available data suggest a higher rate of (very) late stent thrombosis after the use of DES in primary PCI, compared to stenting for stable angina3.

1Stone et al N Engl J Med 2009; 2Pfisterer et al J Am Coll Cardiol 2006; 3Leibundgut e al Am Heart J 2009;

DES and stent thrombosis

• In the absence of long-term outcome of RCTs, this issue remains unresolved.

• Therefore, guidelines do not uniformly support the use of DES in primary PCI for STEMI.

• ACC/AHA 2009 IIa B indication• ESC 2008 not defined

BackgroundBackground

DES and stent thrombosis in primary PCIDES and stent thrombosis in primary PCI

PASSION 5-year clinical follow-upPASSION 5-year clinical follow-up

• Clinical follow-up at 5 years

• To elucidate a possible sustained benefit of DES in the occurrence of MACE

• To address the concern of late and very late stent thrombosis

PASSION-trialPASSION-trial• Prospective, two-center, randomized, single-blind trial

• Enrollment March 2003 - December 2004 – OLVG Hospital, Amsterdam, The Netherlands– St. Antonius Hospital, Nieuwegein, The Netherlands

• 619 consecutive patients with STEMI, eligible for primary PCI with stenting

• Representative of real world population owing to limited exclusion criteria

• No routine angiographic follow-up

• Clinical follow-up at: 6, 12, 24, and 60 months

Limited exclusion criteriaLimited exclusion criteria

• Cardiogenic shock prior to randomization

• Mechanical ventilation

ProcedureProcedure

• Stent diameter and length decided before Stent diameter and length decided before randomizationrandomization

• Randomization to: Randomization to: paclitaxel-eluting stent (paclitaxel-eluting stent (Taxus/Express2Taxus/Express2) or) orbare metal stent (bare metal stent (Express2Express2 or or LibertLibertéé))

• Additional stents according to assigned stent typeAdditional stents according to assigned stent type

• Thrombus aspiration and direct stenting at the Thrombus aspiration and direct stenting at the discretion of the operatordiscretion of the operator

Concomitant medicationConcomitant medication

• GP IIb/IIIa receptor blocker at the discretion of the GP IIb/IIIa receptor blocker at the discretion of the operatoroperator

• Post-PCI: Post-PCI:

– Clopidogrel 300 mg, followed by 75 mg od for at Clopidogrel 300 mg, followed by 75 mg od for at least 6 monthsleast 6 months

– Aspirin 100 to 500 mg, followed by 80-100 mg od Aspirin 100 to 500 mg, followed by 80-100 mg od indefinitelyindefinitely

Baseline Clinical CharacteristicsBaseline Clinical CharacteristicsPESN=310

BMSN=309

Age (years) 61 ± 12 61 ± 13

Male (%) 74 78

Diabetes Mellitus (%) 10 12

Hypertension (%) 31 32

Hypercholesterolemia (%) 23 28

Family History of CAD (%) 40 36

Smoking (%) 53 50

Previous MI (%) 4.5 5.8

Symptom to balloon (hours) 3.0 3.0

∑ST segment elevation (mm) 11 11

Baseline Angiographic and Procedural CharacteristicsBaseline Angiographic and Procedural Characteristics

PESN=310

BMSN=309

Infarct related artery (%)

LAD 50 50

Cx 6 10

RCA 42 38

TIMI flow 0/1 (%) 74 78

Multivessel disease (%) 42 47

Visible thrombus (%) 69 66

Stent size (mm) 3.2 3.3

Stent length (mm) 19 19

Thrombus aspiration (%) 50 50

GP IIB/IIA receptor blockers (%) 73 74

Procedural success (%) 93 96

Clinical Outcome at 1 year

  PESN=31

0

BMSN=309

HR (95% CI) P

Composite of cardiac death, re-MI, or TLR no. (%)

27 (8.8)

39 (12.8)

0.69 (0.43-1.10)

0.12

Cardiac death no. (%) 12 (3.9)

19 (6.2)

0.63 (0.31-1.27)

0.20

Recurrent MI no. (%) 5 (1.7)

6 (2.0) 0.83 (0.13-5.34)

0.74

TLR no. (%) 16 (5.3)

23 (7.8)

0.69 (0.37-1.27)

0.23

Laarman et al N Engl J Med 2006

Long-term Follow-upLong-term Follow-up

• Complete follow-up available at 5 years:

• vital status: 98.5% (9 patients lost to FUP)

• clinical events: 95.8%

Composite of Cardiac death, Composite of Cardiac death, Recurrent MI, or TLRRecurrent MI, or TLR

Cardiac deathCardiac death

Recurrent myocardial infarctionRecurrent myocardial infarction

Target-lesion revascularizationTarget-lesion revascularization

 PES

N=310

BMSN=30

9HR (95% CI) P

           

Definite10

(3.6%)

5 (1.7%)

1.98 (0.67 - 5.79)

0.20

Definite or probable

11 (3.9%)

10 (3.4%)

1.09 (0.46 - 2.57)

0.85

Possible20

(6.8%)

19 (6.7%)

1.03 (0.55 - 1.93)

0.93

Stent ThrombosisStent Thrombosis

Incidences were estimated from the Kaplan-Meier curves

PES N=31

0

BMS N=30

9

HR (95% CI) P

Definite ST30 days – 1 year 1

(0.3%)

0 (0.0%)

1 year – 5 years 7 (2.5%)

2 (0.7%)

Total 8 (2.9%)

2 (0.8%)

3.95 (0.81 – 18.61)

0.06

Definite or Probable ST

30 days – 1 year 2 (0.7%)

0 (0.0%)

1 year – 5 years 7 (2.5%)

3 (1.1%)

Total 9 (3.2%)

3 (1.1%)

2.97 (0.80 – 12.97)

0.09

Late and Very Late Stent Thrombosis

Incidences were estimated from the Kaplan-Meier curves

Definite Stent Thrombosis

ConclusionsConclusions

• The PASSION-trial is the first RCT to report very long-term follow-up.

• No significant difference in the occurrence of the composite endpoint of cardiac death, recurrent MI, or TLR

• No significant differences in the occurrence of individual major adverse cardiac events

PASSION 5-year follow-upPES compared to BMS in primary PCI

• 5-year follow-up of the PASSION-trial confirms small risk of (very) late stent thrombosis.

• Comparable incidence of definite or probable stent thrombosis

• However, the rate of definite stent thrombosis in the PES-group was two-fold as compared to the BMS-group (P = 0.20).

ConclusionsConclusionsPASSION 5-year follow-up

PES compared to BMS in primary PCI

ConclusionsConclusions

• The risk of stent thrombosis appears to persist for several years after stent implantation.

• We have to outweigh the possible advantage of DES in TLR against the potential risk of (very) late stent thrombosis.

DES in primary PCI for STEMI

Thanks to:Thanks to:

The PASSION Investigators

MT Dirksen, MJ Suttorp, JGP Tijssen, J van Etten,T Slagboom, M Patterson, F Kiemeneij, GJ Laarman

And to all patients and co-workers of the PASSION trial at

OLVG Hospital, Amsterdam

St. Antonius Hospital, Nieuwegein