The cardiovascular risks associated with rofecoxib (Vioxx) would have been apparent in 2001, more than 3 years before the drug was withdrawn from the market, had data from unpublished trials been disclosed, according to a report.
The data “have only now become available through litigation” against Merck & Co., the manufacturer of Vioxx, said Dr. Joseph S. Ross of Mount Sinai School of Medicine, New York, and his associates.
“These findings are particularly compelling because as early as the late 1990s there were concerns about cardiovascular risk that emerged in the drug development process,” the investigators noted (Arch. Intern. Med. 2009;169:1976-85).
Merck & Co. disavowed the research. “We believe the analysis published in Archives used flawed methods and reached incorrect conclusions,” Merck spokesman Ron Rogers said in an interview. The study notes that all of the study authors are or were consultants for plaintiffs in litigation against Merck regarding rofecoxib.
The researchers analyzed data from 30 randomized clinical trials that had already been completed by September 2004, when the APPROVe (Adenomatous Polyp Prevention on Vioxx) trial was terminated and rofecoxib was voluntarily withdrawn from the market, in response to reports of adverse cardiovascular effects.
Dr. Ross and his colleagues assessed only studies that compared a daily dose of 12.5 mg or more of rofecoxib with placebo in adults who were treated for at least 4 weeks. A total of 17,256 subjects were included.
Six of these trials were unpublished and came to light only as a result of litigation. “Therefore, data representing 36% of patients studied in placebo-controlled trials prior to APPROVe” had never been disclosed or included in safety analyses, the investigators said.
If all these data had been analyzed, the use of rofecoxib would have been seen to be associated with a 43% increase in risk of a cardiovascular thromboembolic event or death, according to the investigators.