Five year clinical follow-up of the PASSION-trial Five year clinical follow-up of the PASSION-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 Laarman on behalf of the PASSION investigators OLVG Hospital, Amsterdam, The Netherlands ACC/i Late-breaking clinical trial session, March 16, 2010

Disclosure information Maarten A. Vink, M.D.: Nothing to disclose

Background 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 PCI

Background HORIZONS-AMI showed similar rates of stent thrombosis with DES and BMS at one year 1. However, concern has arisen about the occurrence of (very) late stent thrombosis after implantation of DES 2. Available data suggest a higher rate of (very) late stent thrombosis after the use of DES in primary PCI, compared to stenting for stable angina 3. 1 Stone et al N Engl J Med 2009; 2 Pfisterer et al J Am Coll Cardiol 2006; 3 Leibundgut 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 Background DES and stent thrombosis in primary PCI

PASSION 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-trial Prospective, two-center, randomized, single-blind trial Enrollment March 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 criteria Cardiogenic shock prior to randomization Mechanical ventilation

Procedure Stent diameter and length decided before randomizationStent diameter and length decided before randomization Randomization to:Randomization to: paclitaxel-eluting stent (Taxus/Express2) or bare metal stent (Express2 or Liberté) Additional stents according to assigned stent typeAdditional stents according to assigned stent type Thrombus aspiration and direct stenting at the discretion of the operatorThrombus aspiration and direct stenting at the discretion of the operator

Concomitant medication GP IIb/IIIa receptor blocker at the discretion of the operatorGP IIb/IIIa receptor blocker at the discretion of the operator Post-PCI:Post-PCI: –Clopidogrel 300 mg, followed by 75 mg od for at least 6 months –Aspirin 100 to 500 mg, followed by mg od indefinitely

Baseline Clinical Characteristics PES N=310 BMS N=309 Age (years)61 ± 1261 ± 13 Male (%)7478 Diabetes Mellitus (%)1012 Hypertension (%)3132 Hypercholesterolemia (%)2328 Family History of CAD (%)4036 Smoking (%)5350 Previous MI (%) Symptom to balloon (hours)3.0 ST segment elevation (mm)11

Baseline Angiographic and Procedural Characteristics PES N=310 BMS N=309 Infarct related artery (%) LAD50 Cx610 RCA4238 TIMI flow 0/1 (%)7478 Multivessel disease (%)4247 Visible thrombus (%)6966 Stent size (mm) Stent length (mm)19 Thrombus aspiration (%)50 GP IIB/IIA receptor blockers (%)7374 Procedural success (%)9396

Clinical Outcome at 1 year PES N=310 BMS N=309 HR (95% CI)P Composite of cardiac death, re-MI, or TLR no. (%) 27 (8.8)39 (12.8)0.69 ( )0.12 Cardiac death no. (%)12 (3.9)19 (6.2)0.63 ( )0.20 Recurrent MI no. (%)5 (1.7)6 (2.0)0.83 ( )0.74 TLR no. (%)16 (5.3)23 (7.8)0.69 ( )0.23 Laarman et al N Engl J Med 2006

Long-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, Recurrent MI, or TLR

Cardiac death

Recurrent myocardial infarction

Target-lesion revascularization

PES N=310 BMS N=309 HR (95% CI)P Definite10 (3.6%)5 (1.7%)1.98 ( )0.20 Definite or probable11 (3.9%)10 (3.4%)1.09 ( )0.85 Possible20 (6.8%)19 (6.7%)1.03 ( )0.93 Stent Thrombosis Incidences were estimated from the Kaplan-Meier curves

PES N=310 BMS N=309 HR (95% CI)P Definite ST 30 days – 1 year1 (0.3%)0 (0.0%) 1 year – 5 years7 (2.5%)2 (0.7%) Total8 (2.9%)2 (0.8%)3.95 (0.81 – 18.61)0.06 Definite or Probable ST 30 days – 1 year2 (0.7%)0 (0.0%) 1 year – 5 years7 (2.5%)3 (1.1%) Total9 (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

Conclusions 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-up PES 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). Conclusions PASSION 5-year follow-up PES compared to BMS in primary PCI

Conclusions 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: 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