That’s according to a new analysis that shows there was an association between the Merck drug and cardiovascular risk as early as December 2000. Vioxx, you may recall, was withdrawn in September 2004, after mounting debate about heart risks linked to the painkiller. The analysis appears in the Archives of Internal Medicine.

The researchers reviewed 30 randomized, placebo-controlled trials that enrolled a combined 20,152 individuals, lasted from four weeks to four years and assigned a range of 17 to 2,586 participants to take 12.5 milligrams to 50 milligrams of Vioxx. As of December 2000, 21 of these trials, or 70 percent, had been completed and the risk of a cardiovascular event or death was greater among subjects assigned to Vioxx, according to the analysis.

Data subsequently collected through June 2001 shows Vioxx was associated with a 35 percent increased risk of a cardiovascular thromboembolic adverse event or death. Moreover, the association strengthened as additional data became available - as of April 2002, the pooled analysis showed a 39-percent increased risk, and as of September 2004, a 43-percent increased risk (here is the analysis).

In a statement, Merck says the authors used “unreliable methods and reached incorrect conclusions.” The drugmaker maintains it ran “regularly updated analyses of a large body of data from randomized clinical trials, conducted in consultation with outside experts and with regulatory agencies, (which) did not demonstrate an increased risk of thrombotic events when Vioxx was compared to placebo” while the painkiller was on the market.

The authors note that, in November 2004, former Merck ceo Ray Gilmartin, testified before a U.S. Senate committee that until the halted trial, combined data from all randomized controlled clinical trials showed no difference in the risk of confirmed heart events between patients taking rofecoxib and those taking placebo.

“Physicians and the public deserve to be in a position to make informed choices about risks and benefits, and the disclosure and dissemination of information about potential risk immediately after its recognition is absolutely essential,” write the researchers, who were led by Joseph Ross of Mount Sinai School of Medicine.

“Our study provides insight into what should have been known about the risks of rofecoxib,” write the authors. “If we are to detect harms early and protect the public’s health, while ensuring the availability of new, clinically effective therapeutics, a system must be established that makes full use of all existing evidence.”

[The journal reports the analysis wasn't supported by any external grants or funds, although David Madigan is a consultant for plaintiffs in litigation against Merck concerning Vioxx in Australia and was previously a consultant in litigation in the US. All other authors - Joseph Ross, David Egilman, Harlan Krumholz, Kevin Hill and Yongfei Wang - were previously consultants for plaintiffs in litigation against Merck related to rofecoxib in the US. The bottom of the journal piece has more about affiliations.]