1. Treatment of In-Stent Restenosis by Paclitaxel Coated PTCA Balloons Presented at The American Heart Association Scientific Session 2006 Presented by Dr. Bruno Scheller PACCOCATH ISR

2. www. Clinical trial results.org PACCOCATH ISR: Background Treatment of coronary in-stent restenosis is hampered by high incidence of recurrent in-stent restenosis.Treatment of coronary in-stent restenosis is hampered by high incidence of recurrent in-stent restenosis. Multiple studies have shown the benefit of drug-eluting stents in preventing restenosis in de novo lesions, but only one randomized trial, ISAR-DESIRE, has been conducted for patients with pre-existing lesions.Multiple studies have shown the benefit of drug-eluting stents in preventing restenosis in de novo lesions, but only one randomized trial, ISAR-DESIRE, has been conducted for patients with pre-existing lesions. While the ISAR-DESIRE trial showed a reduction in restenosis for drug- eluting stents compared with bare metal stents, the stent-in-stent approach for treating restenosis may not be optimal or feasible for all patients.While the ISAR-DESIRE trial showed a reduction in restenosis for drug- eluting stents compared with bare metal stents, the stent-in-stent approach for treating restenosis may not be optimal or feasible for all patients. The goal of this trial was to assess the efficacy and safety of a paclitaxel eluting balloon catheter compared with a non-eluting balloon catheter among patients with coronary in-stent restenosis.The goal of this trial was to assess the efficacy and safety of a paclitaxel eluting balloon catheter compared with a non-eluting balloon catheter among patients with coronary in-stent restenosis. Treatment of coronary in-stent restenosis is hampered by high incidence of recurrent in-stent restenosis.Treatment of coronary in-stent restenosis is hampered by high incidence of recurrent in-stent restenosis. Multiple studies have shown the benefit of drug-eluting stents in preventing restenosis in de novo lesions, but only one randomized trial, ISAR-DESIRE, has been conducted for patients with pre-existing lesions.Multiple studies have shown the benefit of drug-eluting stents in preventing restenosis in de novo lesions, but only one randomized trial, ISAR-DESIRE, has been conducted for patients with pre-existing lesions. While the ISAR-DESIRE trial showed a reduction in restenosis for drug- eluting stents compared with bare metal stents, the stent-in-stent approach for treating restenosis may not be optimal or feasible for all patients.While the ISAR-DESIRE trial showed a reduction in restenosis for drug- eluting stents compared with bare metal stents, the stent-in-stent approach for treating restenosis may not be optimal or feasible for all patients. The goal of this trial was to assess the efficacy and safety of a paclitaxel eluting balloon catheter compared with a non-eluting balloon catheter among patients with coronary in-stent restenosis.The goal of this trial was to assess the efficacy and safety of a paclitaxel eluting balloon catheter compared with a non-eluting balloon catheter among patients with coronary in-stent restenosis. Presented at AHA 2006

3. www. Clinical trial results.org PACCOCATH ISR : Study Design  Primary Endpoint: Angiographic late lumen loss at 6 months  Secondary Endpoint: Rates of restenosis; major adverse cardiac events (MACE)  Primary Endpoint: Angiographic late lumen loss at 6 months  Secondary Endpoint: Rates of restenosis; major adverse cardiac events (MACE) Paclitaxel-Eluting Balloon Catheter (3 µg paclitaxel/mm 2 ) n=26 n=26 Non-Eluting Balloon Catheter (same balloon design without drug) (same balloon design without drug)n=26 Non-Eluting Balloon Catheter (same balloon design without drug) (same balloon design without drug)n=26 52 Patients with single in-stent restenosis in a coronary artery with a diameter stenosis of > 70%, 70%, < 25mm length, and vessel diameter of 2.5 mm to 3.5 mm; stable or unstable angina or a positive functional study. Randomized. Double-Blind. Parallel. 29% female, mean age 64 years, mean follow-up: 12 months 52 Patients with single in-stent restenosis in a coronary artery with a diameter stenosis of > 70%, 70%, < 25mm length, and vessel diameter of 2.5 mm to 3.5 mm; stable or unstable angina or a positive functional study. Randomized. Double-Blind. Parallel. 29% female, mean age 64 years, mean follow-up: 12 months Presented at AHA 2006

4. www. Clinical trial results.org PACCOCATH ISR : Primary Endpoint In-segment late lumen loss was smaller in the paclitaxel group than the bare balloon group (0.03+/- 0.48 vs. 0.74 +/- 0.86, p=0.002).In-segment late lumen loss was smaller in the paclitaxel group than the bare balloon group (0.03+/- 0.48 vs. 0.74 +/- 0.86, p=0.002). Minimum lumen diameter at 6- months was larger in the paclitaxel group than the bare balloon group (2.22 mm vs 1.57 mm, p=0.005).Minimum lumen diameter at 6- months was larger in the paclitaxel group than the bare balloon group (2.22 mm vs 1.57 mm, p=0.005). In-segment late Lumen Loss (mm) mm P=0.002 0.03 ± 0.48 0.740 ± 0.86 Presented at AHA 2006

5. www. Clinical trial results.org PACCOCATH ISR : Secondary Endpoint PACCOCATH ISR : Secondary Endpoint Binary restenosis occurred less frequently in the paclitaxel-eluting group than the bare balloon group (5% vs. 43%, p=0.002).Binary restenosis occurred less frequently in the paclitaxel-eluting group than the bare balloon group (5% vs. 43%, p=0.002). Binary Restenosis (%) p=0.002 Presented at AHA 2006

6. www. Clinical trial results.org PACCOCATH ISR : Secondary Endpoint PACCOCATH ISR : Secondary Endpoint At 12 months, the rate of major adverse cardiac events was 31% in the bare balloon group and 4% in the coated-balloon group (p=0.01).At 12 months, the rate of major adverse cardiac events was 31% in the bare balloon group and 4% in the coated-balloon group (p=0.01). This difference was primarily due to the need for target lesion revascularization in six patients in the bare balloon group (p=0.02).This difference was primarily due to the need for target lesion revascularization in six patients in the bare balloon group (p=0.02). Rate of Major Adverse Cardiac Events (%) p=0.01 Presented at AHA 2006

7. www. Clinical trial results.org PACCOCATH ISR: Limitations The scale of the trial does not justify clinical application or regulatory approval of the drug-coated balloons.The scale of the trial does not justify clinical application or regulatory approval of the drug-coated balloons. Although the core laboratory was not aware of study-group status, the coated balloons have a faintly white color, a difference that might have unblinded the clinical investigators.Although the core laboratory was not aware of study-group status, the coated balloons have a faintly white color, a difference that might have unblinded the clinical investigators. Larger clinical trials should be conducted in order to determine whether the results of this trial can be replicated.Larger clinical trials should be conducted in order to determine whether the results of this trial can be replicated. This trial does not evaluate whether paclitaxel eluting balloons would be efficacious in the treatment of de novo lesions as opposed to in-stent restenosis.This trial does not evaluate whether paclitaxel eluting balloons would be efficacious in the treatment of de novo lesions as opposed to in-stent restenosis. The scale of the trial does not justify clinical application or regulatory approval of the drug-coated balloons.The scale of the trial does not justify clinical application or regulatory approval of the drug-coated balloons. Although the core laboratory was not aware of study-group status, the coated balloons have a faintly white color, a difference that might have unblinded the clinical investigators.Although the core laboratory was not aware of study-group status, the coated balloons have a faintly white color, a difference that might have unblinded the clinical investigators. Larger clinical trials should be conducted in order to determine whether the results of this trial can be replicated.Larger clinical trials should be conducted in order to determine whether the results of this trial can be replicated. This trial does not evaluate whether paclitaxel eluting balloons would be efficacious in the treatment of de novo lesions as opposed to in-stent restenosis.This trial does not evaluate whether paclitaxel eluting balloons would be efficacious in the treatment of de novo lesions as opposed to in-stent restenosis. Presented at AHA 2006

8. www. Clinical trial results.org PACCOCATH ISR: Summary In this pilot study, treatment with a paclitaxel-eluting balloon catheter was associated with lower late lumen loss at 6 month angiography compared with a bare balloon catheter among patients with coronary in-stent restenosis.In this pilot study, treatment with a paclitaxel-eluting balloon catheter was associated with lower late lumen loss at 6 month angiography compared with a bare balloon catheter among patients with coronary in-stent restenosis. The study also showed that treatment of coronary in-stent restenosis with paclitaxel-coated balloon catheters significantly lowered the incidence of adverse events.The study also showed that treatment of coronary in-stent restenosis with paclitaxel-coated balloon catheters significantly lowered the incidence of adverse events. The findings suggest that the inhibition of restenosis by local drug delivery may not require the implantation of stents and the prolonged release of a drug.The findings suggest that the inhibition of restenosis by local drug delivery may not require the implantation of stents and the prolonged release of a drug. In this pilot study, treatment with a paclitaxel-eluting balloon catheter was associated with lower late lumen loss at 6 month angiography compared with a bare balloon catheter among patients with coronary in-stent restenosis.In this pilot study, treatment with a paclitaxel-eluting balloon catheter was associated with lower late lumen loss at 6 month angiography compared with a bare balloon catheter among patients with coronary in-stent restenosis. The study also showed that treatment of coronary in-stent restenosis with paclitaxel-coated balloon catheters significantly lowered the incidence of adverse events.The study also showed that treatment of coronary in-stent restenosis with paclitaxel-coated balloon catheters significantly lowered the incidence of adverse events. The findings suggest that the inhibition of restenosis by local drug delivery may not require the implantation of stents and the prolonged release of a drug.The findings suggest that the inhibition of restenosis by local drug delivery may not require the implantation of stents and the prolonged release of a drug. Presented at AHA 2006