Presented at American College of Cardiology Scientific Sessions 2005

1. COX-2 Inhibitors After Cardiac Surgery Safety of Cyclooxygenase-2 (COX-2) inhibitors, Valdecoxib and Parecoxib, versus Placebo for Post CABG Pain Management Presented at American College of Cardiology Scientific Sessions 2005 Presented by Dr. Andrew Whelton

2. COX-2 Inhibitors After Cardiac Surgery 1,671 patients undergoing elective, primary CABG with cardiopulmonary bypass; age 18-80 years; New York Heart Association class I, II, or III or an ejection fraction of ≥ 35%; body mass index ≤ 40; and weight > 55kg 14% female, mean age 62 years, mean follow up 30 days Concomitant medications: Aspirin (75-325 mg/day) for 10 days and access to standard opioid medications IV Paracoxib 40 mg day after surgery then 20mg/day every 12 hrs/3 days + Oral Valdecoxib 20mg every 12 hrs through day 10 n=555 Placebo for entire 10 days n=560 IV Placebo every 12 hrs/3 days + Oral Valdecoxib 20mg every 12 hrs trhough day 10 n=556 • Primary Endpoints: The combined incidence of predefined adverse events in the following four categories: cardiovascular events, renal events, surgical-wound complications, and gastrointestinal (GI) complications Presented at ACC 2005

3. COX-2 Inhibitors After Cardiac Surgery Primary Composite Endpoint at 30 days (Adverse Cardiovascular or Renal Events or Surgical-Wound or GI complications) • The primary endpoint of occurrence of at least one adverse event occurred more frequently in both the paracoxib plus valdecoxib group and the placebo plus valdecoxib group. • Risk ratio [RR] 1.9, p=0.02 for each group vs. placebo paracoxib + valdecoxib placebo placebo + valdecoxib Presented at ACC 2005

4. COX-2 Inhibitors After Cardiac Surgery : Summary • Among patients undergoing CABG with cardiopulmonary bypass, short-term treatment with COX-2 inhibition for pain management was associated with an increase in overall adverse events, as well as those included in the primary composite endpoint: cardiovascular adverse events, renal events, surgical-wound complications, and GI complication compared with placebo. • Incidence of cardiovascular adverse events was significantly higher in patients treated with COX-2 inhibitors than those treated with placebo. • There was no significant difference in the incidence of the other adverse event groupings, including renal failure or dysfunction, upper GI events, or surgical-wound events. There was also no significant difference in mortality. • The authors note that patients undergoing CABG with cardiopulmonary bypass, the higher incidence of serious adverse events outweighs any analgesic benefit, and they state that selective COX-2 inhibitors should be avoided in CABG patients. Presented at ACC 2005