Complications of the COX-2 Inhibitors Parecoxib and Valdecoxib after Cardiac Surgery
February 17, 2005 07:57

Complications of the COX-2 Inhibitors Parecoxib and Valdecoxib after Cardiac Surgery

ABSTRACT

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.

Notice: Because of its potential public health implications, this article was published at www.nejm.org on February 15, 2005. It will appear in the March 17 issue of the Journal.

Cardiovascular Events Associated with Rofecoxib in a Colorectal Adenoma Chemoprevention Trial

Robert S. Bresalier, M.D., Robert S. Sandler, M.D., Hui Quan, Ph.D., James A. Bolognese, M.Stat., Bettina Oxenius, M.D., Kevin Horgan, M.D., Christopher Lines, Ph.D., Robert Riddell, M.D., Dion Morton, M.D., Angel Lanas, M.D., Marvin A. Konstam, M.D., John A. Baron, M.D., for the Adenomatous Polyp Prevention on Vioxx (APPROVe) Trial Investigators

ABSTRACT

Background Selective inhibition of cyclooxygenase-2 (COX-2) may be associated with an increased risk of thrombotic events, but only limited long-term data have been available for analysis. We report on the cardiovascular outcomes associated with the use of the selective COX-2 inhibitor rofecoxib in a long-term, multicenter, randomized, placebo-controlled, double-blind trial designed to determine the effect of three years of treatment with rofecoxib on the risk of recurrent neoplastic polyps of the large bowel in patients with a history of colorectal adenomas.

Methods A total of 2586 patients with a history of colorectal adenomas underwent randomization: 1287 were assigned to receive 25 mg of rofecoxib daily, and 1299 to receive placebo. All investigator-reported serious adverse events that represented potential thrombotic cardiovascular events were adjudicated in a blinded fashion by an external committee.

Results A total of 46 patients in the rofecoxib group had a confirmed thrombotic event during 3059 patient-years of follow-up (1.50 events per 100 patient-years), as compared with 26 patients in the placebo group during 3327 patient-years of follow-up (0.78 event per 100 patient-years); the corresponding relative risk was 1.92 (95 percent confidence interval, 1.19 to 3.11; P=0.008). The increased relative risk became apparent after 18 months of treatment; during the first 18 months, the event rates were similar in the two groups. The results primarily reflect a greater number of myocardial infarctions and ischemic cerebrovascular events in the rofecoxib group. There was earlier separation (at approximately five months) between groups in the incidence of nonadjudicated investigator-reported congestive heart failure, pulmonary edema, or cardiac failure (hazard ratio for the comparison of the rofecoxib group with the placebo group, 4.61; 95 percent confidence interval, 1.50 to 18.83). Overall and cardiovascular mortality was similar in the two groups.

Conclusions Among patients with a history of colorectal adenomas, the use of rofecoxib was associated with an increased cardiovascular risk.

Notice: Because of its potential public health implications, this article was published at www.nejm.org on February 15, 2005. It will appear in the March 17 issue of the Journal.

Jeffrey M. Drazen, M.D.

http://content.nejm.org/cgi/content/abstract/NEJMe058042
Bruce M. Psaty, M.D., Ph.D., and Curt D. Furberg, M.D., Ph.D.

FDA whistleblower Dr. David Graham delivered damning testimony on Vioxx and other cox-2 inhibitors Thursday at government hearings on the drugs.

"There's a one-in-50 chance that a male aged 65 to 74 will have a heart attack this year. Increase that fivefold with high doses [of Vioxx]," Graham testified before a standing-room-only crowd as the second of three days of Food and Drug Administration hearings continued in Washington, D.C

http://www.ajc.com/health/content/shared-auto/healthnews/artd/524062.html

http://olympics.reuters.com/newsArticle.jhtml?type=healthNews&storyID=7662883
GAITHERSBURG, Md. (Reuters) - A pain reliever called Mobic showed an "increased risk" for heart attacks in preliminary data, a veteran U.S. Food and Drug Administration scientist told an FDA advisory panel on Thursday.

http://business.bostonherald.com/businessNews/view.bg?articleid=69000
Federal regulators did a better job than the nation's best medical journals analyzing the cardiac dangers of Vioxx, but both failed to communicate the painkiller's risks to doctors and the general public, a top Harvard Medical School instructor will testify today.
U.S. Food and Drug Administration advisers are conducting hearings this week weighing the risks of the entire class of painkillers known as COX-2 inhibitors, which includes Merck & Co.'s Vioxx and Pfizer Inc.'s Celebrex.