FAST (Femoral Artery Stenting Trial) Final Results Hans Krankenberg (on behalf of the FAST Investigators) Hamburg University Cardiovascular Center Prof. Schofer, Prof. Mathey & Partners Hamburg, Germany Hans Krankenberg (on behalf of the FAST Investigators) Hamburg University Cardiovascular Center Prof. Schofer, Prof. Mathey & Partners Hamburg, Germany

Institution Investigators Enrollment Berlin, Germany H. Steinkamp 60 Bad Krozingen, Germany T. Zeller 57 Hamburg, Germany H. Krankenberg 39 Leipzig, Germany D. Scheinert 28 Berlin, Germany K.L. Schulte 18 Tübingen, Germany G. Tepe 4 Vienna, Austria E. Minar 14 Bonheiden, Belgium P. Peeters 13 Dendermonde, Belgium M. Bosiers 5 Mirano, Italy B. Reimers 4 Bern, Switzerland F. Mahler 3 Institution Investigators Enrollment Berlin, Germany H. Steinkamp 60 Bad Krozingen, Germany T. Zeller 57 Hamburg, Germany H. Krankenberg 39 Leipzig, Germany D. Scheinert 28 Berlin, Germany K.L. Schulte 18 Tübingen, Germany G. Tepe 4 Vienna, Austria E. Minar 14 Bonheiden, Belgium P. Peeters 13 Dendermonde, Belgium M. Bosiers 5 Mirano, Italy B. Reimers 4 Bern, Switzerland F. Mahler 3 FAST Participating Centers

FAST Purpose To assess the efficacy of nitinol stent implantation (Bard ® Luminexx ® 3 Vascular Stent [C.R. Bard, Inc.]) vs. stand-alone balloon angioplasty (PTA) in patients with superficial femoral artery (SFA) disease : Binary restenosis (>50% stenosis on duplex ultrasound) at 12 months Primary Endpoint: Binary restenosis (>50% stenosis on duplex ultrasound) at 12 months To assess the efficacy of nitinol stent implantation (Bard ® Luminexx ® 3 Vascular Stent [C.R. Bard, Inc.]) vs. stand-alone balloon angioplasty (PTA) in patients with superficial femoral artery (SFA) disease : Binary restenosis (>50% stenosis on duplex ultrasound) at 12 months Primary Endpoint: Binary restenosis (>50% stenosis on duplex ultrasound) at 12 months The The Bard ® Luminexx ® 3 Vascular Stent is not available in the U.S.

FAST Hypothesis Assumptions: 12-month restenosis rate in the PTA arm: 45% 12-month restenosis rate in the nitinol stent arm: 25% (relative reduction by 44%) To establish this difference (45% vs. 25%) with statistical significance (2-sided  error of 0.05, 80% power) and assuming a 15% drop-out rate, a total of 244 patients (122 per arm) would be required. Assumptions: 12-month restenosis rate in the PTA arm: 45% 12-month restenosis rate in the nitinol stent arm: 25% (relative reduction by 44%) To establish this difference (45% vs. 25%) with statistical significance (2-sided  error of 0.05, 80% power) and assuming a 15% drop-out rate, a total of 244 patients (122 per arm) would be required.

FAST Key Inclusion Criteria Clinical: Rutherford classification ≥ 2 Angiographic: Single de novo SFA lesion ≥ 1 cm from origin Target lesion length 1–10 cm (visual estimate) Target lesion stenosis 70–100% (visual estimate) Popliteal artery patent At least one infrapopliteal artery patent (for distal run-off) Clinical: Rutherford classification ≥ 2 Angiographic: Single de novo SFA lesion ≥ 1 cm from origin Target lesion length 1–10 cm (visual estimate) Target lesion stenosis 70–100% (visual estimate) Popliteal artery patent At least one infrapopliteal artery patent (for distal run-off)

FAST Trial Profile 244 Patients PTA (n = 121) R Intention-to-Treat Analysis PTA (n = 108) Stent (n = 136) Crossover (n = 13 [11%]) On-Treatment Analysis Luminexx® 3 (C.R. Bard) Stent (n = 123) 12/03–3/05:

FAST Lesion Characteristics Lesion length (visual estimate) p = Prevalence of stenoses vs. total occlusions % stenosis of non-occluded lesions p = 0.133

FAST 12-Month Results Binary Restenosis (1 ry End Point) p = 0.554p = /10132/10134/9037/112

0.70 ( ) 0.94 ( ) 0.53 ( ) FAST 12-Month Results – ITT Impact of treatment modality on 12-month restenosis in patient/lesion subgroups Women Men Normal cholesterol Hyperlipidemia Smoker (ex/current) Hypertension Nondiabetics Diabetics baseline Total baseline Lesion length ≤50mm Lesion length >50mm No distal vessel occluded ≥1 distal vessels occluded Stent betterPTA better 1.52 ( ) 0.59 ( ) 0.43 ( ) 1.00 ( ) 0.97 ( ) 0.52 ( ) 0.48 ( ) 0.84 ( ) 0.51 ( ) 0.73 ( ) 0.73 ( ) 0.93 ( ) 0.50 ( ) OR (95% CI) No calcification Calcification

FAST Difference in Restenosis 12 Months Absolute reduction in restenosis rate (RR) con- ferred by stenting in selected patient subgroups -40% -30% -20% -10% 0% 10% 20% 30% RR [Stent] – RR [PTA] MenWomenDiabeticsSmokers Total Occlusions Mod./sev. Calcification ≥1 dist. ves. occluded RR [PTA]43.4% (76)24.0% (25)38.7% (31)40.3% (72)45.5% (22)44.4% (45)36.1% (36) RR [Stent]31.2% (61)32.5% (40)23.1% (39)26.2% (65)29.7% (37)29.6% (44)22.0% (41) Point estimate with 95% CI -15.6% -12.3% +8.5% -14.1% -15.7% -14.9% -14.2%

FAST 12-Month Results – ITT Stent fractures X-ray in 83/101 stent patients in whom restenosis was 12 months 10 stent fractures Stent fractures X-ray in 83/101 stent patients in whom restenosis was 12 months 10 stent fractures p = 0.719

FAST 12-Month Results Target Lesion Revascularizations p = 0.479p = /11517/11419/10219/127 –19%

FAST 12 Month Results – ITT Absolute walking distance and ankle-brachial index at rest in patients who were able to undergo treadmill testing at both baseline and 12-month follow-up p=0.936p=0.089p= p=0.007p=0.386p= FAST 12 Month Results – ITT

Absolute walking distance in patients who were able to undergo treadmill testing at both baseline and 12-month follow-up FAST 12 Month Results – ITT p=0.936p=0.089p= FAST 12 Month Results – ITT *medians and interquartile ranges

FAST 12 Month Results – ITT Change in Rutherford Category from baseline to 12 months in patients who were able to undergo treadmill testing at both baseline and 12-month follow-up *negative numbers denote improvement

FAST 12 Month Results – OT Change in Rutherford Category from baseline to 12 months in patients who were able to undergo treadmill testing at both baseline and 12-month follow-up *negative numbers denote improvement

FAST Conclusions The Femoral Artery Stenting Trial failed to demonstrate the hypothesized difference in 12- month restenosis between Luminexx ® nitinol stenting and stand-alone PTA in the treatment of patients with short superficial femoral artery lesions. However, stent implantation was associated with a tendency towards markedly lower restenosis rates in a wide variety of patient subgroups. Prospective randomized trials in specific patient cohorts, such as diabetics, patients with total occlusions, or patients with impaired distal run- off, are warranted. The Femoral Artery Stenting Trial failed to demonstrate the hypothesized difference in 12- month restenosis between Luminexx ® nitinol stenting and stand-alone PTA in the treatment of patients with short superficial femoral artery lesions. However, stent implantation was associated with a tendency towards markedly lower restenosis rates in a wide variety of patient subgroups. Prospective randomized trials in specific patient cohorts, such as diabetics, patients with total occlusions, or patients with impaired distal run- off, are warranted.