Randomized Angioplasty Beta Blocker Intracoronary Trial II (RABBIT II)

1. RABBIT II Trial Randomized Angioplasty Beta Blocker Intracoronary Trial II (RABBIT II) Presented at The American Heart Association Scientific Session 2006 Presented by Dr. Barry F. Uretsky

2. RABBIT II Trial: Background • The goal of this trial was to evaluate intracoronary administration of the beta-blocker propranolol among patients undergoing percutaneous coronary intervention (PCI) also being treated with glycoprotein IIb/IIIa inhibitors. Presented at AHA 2006

3. RABBIT II Trial: Study Design 400 patients undergoing elective or urgent PCI excluding those who had an MI within 24 hours of procedure, cardiogenic shock, NYHA class III or IV heart failure, severe renal failure, second planned intervention within 30 days, or allergy to propranolol Placebo controlled. Randomized. 36% female, mean age 59 years, mean follow-up 1 year (30 days reported to date), Intracoronary (IC) propranolol + GP IIb/IIIA Inhibitors n=200 Intacoronary (IC) saline + GP IIb/IIIA Inhibitors n=200 • Primary Endpoint: Post-PCI MI; composite of death, MI, or ischemic driven target vessel revascularization (TVR) at 30 days • Secondary Endpoint: Composite of death, MI, or ischemic driven target vessel revascularization (TVR) at 1 year Presented at AHA 2006

4. RABBIT II Trial: Primary Endpoint Post-Procedure MI (% patients) p=0.016 • The primary endpoint of post-procedure MI (creatine kinase-myocardial band [CK-MB] elevation) occurred less frequently in the propranolol arm than in the placebo arm (12.5% vs. 21.5%, p=0.016). • Baseline characteristics were similar between treatment groups. Heart rate and blood pressure did not change after IC injection of propranolol or placebo. Presented at AHA 2006

5. RABBIT II Trial: Co-Primary Composite Endpoint Co-Primary Composite Endpoint of Death, Post-Procedural MI, Clincal MI, or Ischemic Driven TLR at 30 days (% patients) p=0.01 • The co-primary composite endpoint of death, post-procedural MI, clinical MI, or ischemic driven TLR at 30 days was lower in the propranolol treatment group (13.5% vs. 22.5%, p=0.01), driven by the reduction in • post-procedure MI. Presented at AHA 2006

6. RABBIT II Trial: Co-Primary Composite Endpoint (cont.) • There were no deaths in either arm, and no differences in clinical MI (2.5% for propranolol vs. 1.0% for placebo) or TLR (1.0% for propranolol vs. 1.5% for placebo). • Results were similar across a variety of subgroups, including those on oral beta-blockers at baseline. • The reduction in post-PCI MI occurred only in patients without mechanical complications during the PCI; in the small cohort who had mechanical complications, there was no difference between treatment groups. Co-Primary Composite Endpoint of Death, Post-Procedural MI, Clincal MI, or Ischemic Driven TLR at 30 days (% patients) p=NS p=NS Presented at AHA 2006

7. RABBIT II Trial: Limitations • Results of the present study are very similar to those of an earlier study by the same group that was conducted without mandatory administration of GP IIb/IIIa inhibitors. • The results were most successful in patients without mechanical complications during the PCI. • Larger, multicenter trials of this low-cost, promising therapy are warranted to confirm the findings beyond this single center, as well as to evaluate clinical outcomes. Presented at AHA 2006

8. RABBIT II Trial: Summary • Among patients undergoing PCI also treated with glycoprotein IIb/IIIa inhibitors, intracoronary administration of the beta-blocker propranolol was associated with a reduction in the frequency of post-PCI MI compared with intracoronary saline administration. Presented at AHA 2006