Vioxx Mechanisms Leading to Increased Cardiovascular Risks Unclear

Merck has been unable to determine exactly why its arthritis pain drug Vioxx causes increased rates of heart attacks and strokes, but the drugmaker still believes that it's premature to draw conclusions about the entire class of Cox-2 drugs.

The mechanisms for the increased risk of thrombotic cardiovascular (CV) events in the APPROVe (Adenomatous Polyp Prevention on Vioxx) study are uncertain, Merck said in background materials for the FDA's Feb. 16-18 joint advisory committee meeting, which is examining the safety of Cox-2 selective nonsteroidal anti-inflammatory drugs (NSAIDs) and related agents.

The APPROVe study found that patients who received Vioxx (rofecoxib) had twice the risk of CV events than those who received a placebo, with the risk emerging after 18 months of exposure. That finding led Merck to pull the product off the market on Sept. 30, 2004. Soon after Merck's action, safety concerns were raised about other Cox-2 inhibitor agents, a particular class of NSAID.

CV risks found in a National Cancer Institute study of Pfizer's Celebrex (celecoxib) led the firm to issue a December 2004 alert warning consumers about possible adverse events. In addition, the FDA in December 2004 announced similar concerns about naproxen, a common OTC NSAID that is marketed by Bayer under the brand Aleve. But Celebrex and naproxen products remain on the market.

Merck noted, however, that the therapeutic options for patients with arthritis and chronic pain are limited. "For the near term, NSAIDs and selective Cox-2 inhibitors are effective agents with certain benefits and risk both in absolute terms and relative to each other," Merck said. "It is premature to draw conclusions at this time on the implications of the new findings with rofecoxib, celecoxib and naproxen," the firm noted.