Paclitaxel-eluting Stents vs Brachytherapy for In-stent Restenosis (TAXUS V ISR) Trial

1. TAXUS V ISR Trial Paclitaxel-eluting Stents vs Brachytherapy for In-stent Restenosis (TAXUS V ISR) Trial Presented at The American College of Cardiology Scientific Session 2006 Presented by Dr. Gregg W. Stone

2. TAXUS V ISR Trial: Study Design 396 patients > 18 years with stable or unstable angina or inducible ischemia undergoing percutaneous coronary intervention (PCI) of a single bare-metal in-stent restenosis (ISR) lesion in a native coronary artery. Randomized. 34% female, median age 63 years, mean follow-up 9 months Angiography (Baseline) PCI with paclitaxel-eluting stents n=195 VBT using a beta-source radiation n=201 Repeat Angiography (9 months) 170 in VBT group and 172 in Paclitaxel group • Primary Endpoint: Ischemia-driven target vessel revascularization at 9 months Presented at ACC 2006

3. TAXUS V ISR Trial: Baseline Median time since bare-metal stent (BMS) implantation (days) p=0.43 Target lesion location left anterior descending (LAD) (%) p=0.23 percent target lesion LAD median time since BMS implantation (days) • Stenosis at baseline was approximately 68% in each group, with a median lesion length of approximately 15 mm. Presented at ACC 2006

4. TAXUS V ISR Trial: Restenosis Pattern Restenosis pattern of target lesion: diffuse vs focal (%) p=0.006 p=0.02 • A diffuse pattern of restenosis occurred less often in the VBT group than the paclitaxel group (47.0% vs 60.8%; p=0.006) • A focal pattern of restenosis occurred more often in the VBT group than the paclitaxel group (29.0% vs 18.6%; p=0.02) Presented at ACC 2006

5. TAXUS V ISR Trial: Primary Endpoint Ischemic Target Vessel Revascularization at 9 months (%) p=0.046 • The primary endpoint of ischemic target vessel revascularization was higher in the VBT group compared with the paclitaxel group at 9 months (17.5% vs 10.5%; p=0.046) Presented at ACC 2006

6. TAXUS V ISR Trial: 9 month Clinical Results Ischemic Target Lesion Revascularization at 9 months (%) p=0.01 • Ischemic target lesion revascularization was higher in the VBT group compared with the paclitaxel group at 9 months (13.9% vs 6.3%; p=0.01) Presented at ACC 2006

7. TAXUS V ISR Trial: 9 month Clinical Results Nonischemic TVR and TLR (%) p=0.01 for both • Both nonischemic TVR and TLR were lower among the paclitaxel group (6.7% vs 1.6% in both cases; p=0.01) Presented at ACC 2006

8. TAXUS V ISR Trial: 9 month Clinical Results Any TVR and TLR (%) • Any incident of TVR was greater among the VBT group (23.7% vs 12.0%; p=0.003) • Any incident of TLR was greater among the VBT group (20.1% vs 7.9%; p<0.001) p=0.003 p<0.001 Presented at ACC 2006

9. TAXUS V ISR Trial: 9 month Clinical Results Target Vessel Thrombosis (cumulative to 9 months) (%) p=0.72 There was no differences in Target Vessel Thrombosis Presented at ACC 2006

10. TAXUS V ISR Trial: Composite of MACE Composite of Any Major Adverse Cardiac Event (MACE) (%) p=0.02 • The composite of any major adverse cardiac event was greater in the VBT group compared with the paclitaxel group (20.1% vs 11.5%; p=0.02) and was primarily driven by the reduction in TVR • There was no difference in death (n=1 vs n=0) or MI (4.6% vs. 3.7%; p=0.63) Presented at ACC 2006

11. TAXUS V ISR Trial: 9 month Angiography Late Loss at 9 months (mm) p=0.08 Minimum Lumen Diameter at 9 months (mm) p<0.001 Late loss (mm) MLD (mm) • A trend toward greater late loss was present in the VBT group (0.22 mm vs 0.13 mm; p=0.08) • A smaller MLD was present in the VBT group in the analysis segment (1.55 mm vs 1.99 mm; p<0.001) Presented at ACC 2006

12. TAXUS V ISR Trial: 9 month Angiography Binary Restenosis at 9 months (%) p<0.001 Final post-procedure diameter stenosis in the analysis segment (%) p<0.001 Diameter stenosis (%) Binary restenosis (%) • A higher rate of binary restenosis was present in the VBT group (31.2% vs 14.5%; p<0.001) • The final post-procedure diameter stenosis in the analysis segment was greater for the VBT group (29.3% vs 20.6%; p<0.001) Presented at ACC 2006

13. TAXUS V ISR Trial: Limitations • Future studies should take a closer look at the role of brachytherapy in the treatment of in-stent restenosis of drug-eluting stents. • Future trials need to consider the long-term durability of drug-eluting stents for the treatment of in-stent restenosis. Presented at ACC 2006

14. TAXUS V ISR Trial: Summary • Among patients with restenotic coronary lesions, treatment with paclitaxel-eluting stents was associated with a reduction in ischemic driven target vessel revascularization at 9 months compared with vascular brachytherapy. • Intravascular brachytherapy is the only currently approved treatment for in-stent restenosis. However, brachytherapy is complicated to perform and is only performed at a limited number of sites. While not approved for ISR, drug-eluting stents have been used for the treatment of ISR and the present study is now the second large-scale randomized trial to show superiority with drug-eluting stents over VBT for treatment of ISR. • The SISR study evaluated brachytherapy compared with sirolimus-eluting stents for ISR treatment, and showed a reduction in target vessel failure with sirolimus-eluting stents. Presented at ACC 2006