Safety of Cyclooxygenase-2 (COX-2) inhibitors, Safety of Cyclooxygenase-2 (COX-2) inhibitors, Valdecoxib and Parecoxib, versus Placebo for Post Valdecoxib and Parecoxib, versus Placebo for Post

CABG Pain ManagementCABG Pain Management

Safety of Cyclooxygenase-2 (COX-2) inhibitors, Safety of Cyclooxygenase-2 (COX-2) inhibitors, Valdecoxib and Parecoxib, versus Placebo for Post Valdecoxib and Parecoxib, versus Placebo for Post

CABG Pain ManagementCABG Pain Management

Presented atPresented atAmerican College of Cardiology American College of Cardiology

Scientific Sessions 2005Scientific Sessions 2005

Presented by Dr. Andrew WheltonPresented by Dr. Andrew Whelton

COX-2 Inhibitors After Cardiac SurgeryCOX-2 Inhibitors After Cardiac SurgeryCOX-2 Inhibitors After Cardiac SurgeryCOX-2 Inhibitors After Cardiac Surgery

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 SurgeryCOX-2 Inhibitors After Cardiac SurgeryCOX-2 Inhibitors After Cardiac SurgeryCOX-2 Inhibitors After Cardiac Surgery

Presented at ACC 2005Presented 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

www. Clinical trial results.org

COX-2 Inhibitors After Cardiac SurgeryCOX-2 Inhibitors After Cardiac SurgeryCOX-2 Inhibitors After Cardiac SurgeryCOX-2 Inhibitors After Cardiac Surgery

7.4% 7.4%

4.0%

0.0%

2.0%

4.0%

6.0%

8.0%

%

7.4% 7.4%

4.0%

0.0%

2.0%

4.0%

6.0%

8.0%

%

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 2005Presented 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 + valdecoxibplacebo + valdecoxib

placeboplacebo

www. Clinical trial results.org

• Among patients undergoing CABG with cardiopulmonary bypass, short-term Among patients undergoing CABG with cardiopulmonary bypass, short-term treatment with COX-2 inhibition for pain management was associated with an 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 increase in overall adverse events, as well as those included in the primary composite endpoint: cardiovascular adverse events, renal events, surgical-wound composite endpoint: cardiovascular adverse events, renal events, surgical-wound complications, and GI complication compared with placebo. complications, and GI complication compared with placebo.

• Incidence of cardiovascular adverse events was significantly higher in patients Incidence of cardiovascular adverse events was significantly higher in patients treated with COX-2 inhibitors than those treated with placebo. treated with COX-2 inhibitors than those treated with placebo.

• There was no significant difference in the incidence of the other adverse event There was no significant difference in the incidence of the other adverse event groupings, including renal failure or dysfunction, upper GI events, or surgical-groupings, including renal failure or dysfunction, upper GI events, or surgical-wound events. There was also no significant difference in mortality.wound events. There was also no significant difference in mortality.

• The authors note that patients undergoing CABG with cardiopulmonary bypass, The authors note that patients undergoing CABG with cardiopulmonary bypass, the higher incidence of serious adverse events outweighs any analgesic benefit, 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.and they state that selective COX-2 inhibitors should be avoided in CABG patients.

COX-2 Inhibitors After Cardiac Surgery : COX-2 Inhibitors After Cardiac Surgery : SummarySummary

COX-2 Inhibitors After Cardiac Surgery : COX-2 Inhibitors After Cardiac Surgery : SummarySummary

Presented at ACC 2005Presented at ACC 2005