Merck's Vioxx Pain Lingers

Early Warnings

Gurkipal Singh, an adjunct professor of medicine at Stanford University, believes that Vioxx looked risky even before regulators approved it for public use. During November's Senate hearing, Singh portrayed Vioxx as a drug that -- by its very design -- can lead to blood clotting and, thus, cardiac problems.

Many over-the-counter painkillers, such as Ibuprofen and Aleve, block enzymes that trigger inflammation. But those enzymes help protect the body as well. The first, COX-1, shields the stomach lining and can prevent ulcers from forming. The second, COX-2, defends blood vessels against clotting and potential heart attacks.

Drugs like Vioxx focus on blocking COX-2 and, some feel, leave the heart without one of its major protectors in the process.

Singh claims that scientists understood the biology behind this threat as early as 1996. He says that small studies, carried out each of the three years after that, caused additional reasons for concern. And he adds that a major study, known as Vigor, soon "proved conclusively" that Vioxx could trigger heart problems.

When defending his company, however, Gilmartin told the Senate last month that past trials showed that Vioxx posed no greater cardiac risks than other popular painkillers or even placebos. Still, medical experts immediately attacked the design -- and the very intent -- of those Merck-ordered studies.

"It appears ... that in early 1997, Merck scientists were exploring study designs that would, in fact, exclude people who may have a weak heart ... so that the heart attack problem would not be evident," Singh told the Senate. "We need to know how a drug behaves in people who are going to take it -- even if it, I quote [from an alleged Merck document], 'kills the drug.' It is better to kill a drug than kill a patient."