Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery.
BACKGROUND
Valdecoxib and its intravenous prodrug parecoxib are used to treat postoperative pain but may involve risk after coronary-artery bypass grafting (CABG). We conducted a randomized trial to assess the safety of these drugs after CABG.


METHODS
In this randomized, double-blind study involving 10 days of treatment and 30 days of follow-up, 1671 patients were randomly assigned to receive intravenous parecoxib for at least 3 days, followed by oral valdecoxib through day 10; intravenous placebo followed by oral valdecoxib; or placebo for 10 days. All patients had access to standard opioid medications. The primary end point was the frequency of predefined adverse events, including cardiovascular events, renal failure or dysfunction, gastroduodenal ulceration, and wound-healing complications.


RESULTS
As compared with the group given placebo alone, both the group given parecoxib and valdecoxib and the group given placebo and valdecoxib had a higher proportion of patients with at least one confirmed adverse event (7.4 percent in each of these two groups vs. 4.0 percent in the placebo group; risk ratio for each comparison, 1.9; 95 percent confidence interval, 1.1 to 3.2; P=0.02 for each comparison with the placebo group). In particular, cardiovascular events (including myocardial infarction, cardiac arrest, stroke, and pulmonary embolism) were more frequent among the patients given parecoxib and valdecoxib than among those given placebo (2.0 percent vs. 0.5 percent; risk ratio, 3.7; 95 percent confidence interval, 1.0 to 13.5; P=0.03).


CONCLUSIONS
The use of parecoxib and valdecoxib after CABG was associated with an increased incidence of cardiovascular events, arousing serious concern about the use of these drugs in such circumstances.
Nussmeier
Nancy A
NA
Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, TX 77225-0345, USA. nnussmeier@heart.thi.tmc.edu
Whelton
Andrew A
AA
Brown
Mark T
MT
Langford
Richard M
RM
Hoeft
Andreas
A
Parlow
Joel L
JL
Boyce
Steven W
SW
Verburg
Kenneth M
KM
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000401:mortality; D001026:Coronary Artery Bypass / Q000401:mortality; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007555:Isoxazoles / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010149:Postoperative Pain / Q000188:drug therapy*; D013449:Sulfonamides / Q000009:adverse effects* / Q000627:therapeutic use; D000096926:Benzenesulfonamides
D016861:Cyclooxygenase Inhibitors; D007555:Isoxazoles; D013449:Sulfonamides; C406224:valdecoxib; D000096926:Benzenesulfonamides; C409945:parecoxib