1. 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 COX-2 Inhibitors After Cardiac Surgery

2. www. Clinical trial results.org 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 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 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 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 COX-2 Inhibitors After Cardiac Surgery Presented at ACC 2005 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 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 Placebo for entire 10 days n=560 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 IV Placebo every 12 hrs/3 days + Oral Valdecoxib 20mg every 12 hrs trhough day 10 n=556

3. www. Clinical trial results.org COX-2 Inhibitors After Cardiac Surgery Primary Composite Endpoint at 30 days (Adverse Cardiovascular or Renal Events or Surgical- Wound or GI complications) Primary Composite Endpoint at 30 days (Adverse Cardiovascular or Renal Events or Surgical- Wound or GI complications) Presented at ACC 2005 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 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 paracoxib + valdecoxib placebo + valdecoxib placebo

4. www. Clinical trial results.org 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. 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. 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. 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. 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. COX-2 Inhibitors After Cardiac Surgery : Summary Presented at ACC 2005