As many as 140,000 cases of serious coronary heart disease may have been caused by the now-withdrawn arthritis drug Vioxx since it hit the US market in 1999, a report contends. And up to 40% of those cases may have been fatal, the study author claims.
The courts recently supported this conclusion when they ruled in favor of the widow of a man who died after taking Vioxx, in the first lawsuit against Merck & Co., the drug's manufacturer.
The study was led by Dr. David Graham, associate director for science at the US Food and Drug Administration's (FDA) Office of Drug Safety. He has been a long-standing critic of Vioxx, a Cox-2 inhibitor drug that was pulled from the market in September 2004 by Merck, after studies showed that it could lead to an increased risk of heart attack and stroke.
Graham and his colleagues looked specifically at the side effects associated with Vioxx and with two other nonsteroidal anti-inflammatory drugs (NSAIDs) —Celebrex and naproxen, the active ingredient in Aleve-in 1.4 million people who were enrolled in a managed-care plan in California and used NSAIDs from the beginning of 1999 through September 2004.
After reviewing the data, the researchers concluded that people taking Vioxx had a 59% higher risk of coronary heart disease than those taking Celebrex. People taking a lower dose of Vioxx had a 47% increased risk; those taking a higher dose had a 360% increased risk.
People taking naproxen experienced a 14% increased risk of coronary heart disease. This is contrary to previous studies, which had suggested that naproxen protected against coronary heart disease.
The study found no increased risk of heart disease with Celebrex use.
Dr. Eric Topol, chairman of cardiovascular medicine at the Cleveland Clinic and a critic of Cox-2 drugs, says Graham's conclusion seems very reasonable.
"It's an important analysis," he says. "It has a big base of patients. It is a very strong new piece of supportive information that this can occur very early, that the risk does not appear to be time-dependent and it's confirmed now in the largest population ever."
The researchers report that heart problems with Vioxx tended to became apparent soon after people started taking the drug.
Nearly 107 million Americans received prescriptions for Vioxx while it was available in the marketplace.
Graham's study could have implications not only for people who had been taking Vioxx but also for those currently taking other Cox-2 inhibitors or other drugs in the wider NSAID category.
First, Do No Harm
The study was to have been published on November 17, 2004, a day before Graham testified before Congress on what he said were the FDA's shortcomings in monitoring drugs for safety. The paper was withdrawn on November 16.
At the time, Graham said the FDA threatened him with "serious consequences" if he proceeded with the publication of the study. "The FDA did everything in its power to suppress (the findings and keep them from public view," Graham contends.
FDA officials later granted Graham permission to resubmit the paper.
Graham says he published his research so the medical community and the public would see the consequences of the FDA's failure to protect the general population. The FDA reportedly knew of the heart disease risks associated with Vioxx prior to its withdrawal.
"People can now begin to focus seriously on what I believe is a major public health and policy question that faces Congress and faces the American people-are we going to do anything to ensure that what happened with Vioxx doesn't happen again?" Graham says.
"The FDA is on record as saying that all of its decisions about Vioxx were appropriate and that, basically, faced with the same information again, the FDA would make the same decision," he adds.