Vioxx heart risks confirmed in long-term study

Oct 14 2008

A long-term study has confirmed the risks associated with the arthritis drug Vioxx.

The study, an analysis of people who took the arthritis drug carried out by Dr. Robert Bresalier of the M.D. Anderson Cancer Center at the University of Texas, has found Vioxx doubles the risk of strokes and heart attacks.

Dr. Bresalier says other drugs in the same class of painkillers known as Cox-2 inhibitors may also cause similar harm, but the data suggests that the risk is not permanent and does not persist.

In 2004 preliminary safety data from this same study raised concern that Vioxx increased the risks of heart attacks and stroke, prompting drug maker Merck to withdraw the popular painkiller from the market - the research initially set out to determine whether Vioxx could prevent polyps that raise the risk of colon cancer.

At the time, before it was withdrawn from the market, Vioxx had generated sales of $2.5 billion a year.

Last year Merck agreed to a $4.85 billion deal to settle 50,000 pending lawsuits concerning claims of heart attacks, strokes and deaths allegedly caused by the drug.

An analysis in 2005 by the same researchers published in the New England Journal of Medicine suggested that it took 18 months for the drug to increase the risk of heart attacks and strokes, which became an important issue in Merck's legal defense of Vioxx.

The new analysis, by independent statisticians, however suggests the risk occurs early and persists, and Dr. Bresalier says this data shows that precisely determining the timing of the risk cannot be done, but he suggest it appears to start relatively early.

The study, 'Approve' tracked 84% of the more than 2,500 patients from the trial who had been divided into two groups, one taking daily doses of rofecoxib, and the other dummy pills with no active ingredients and it examined the effects of three years of treatment.

It looked particularly for any signs of "cardiovascular toxicity" such as non-fatal or fatal heart attacks or strokes occurring during the year after treatment stopped.

The patients were checked for side effects while on the drug and two weeks after they stopped and the study included a one-year follow-up data on patients who stopped taking the drug because of heart side effects and Bresalier says, in essence, the relative risk remained the same - about double the risk of having a heart attack or stroke than those who took a placebo.

According to Merck the overall findings were consistent with the original study, but noted not all patients were able to be followed after they stopped taking the drug and the analysis was not able to take into account other heart risks.

The company says the study is using limited data from a prematurely terminated study which needs to be interpreted very cautiously and in the context of the rest of the data from the extensive clinical development program for Vioxx.

Dr. Bresalier says a number of studies since the initial safety warning on Vioxx suggest other Cox-2 inhibitors, including Pfizer Inc's Celebrex, or celecoxib, and non-steroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen, also carry a higher risk of heart trouble.

Cox-2 drugs were designed to be safer replacements for NSAIDS, including aspirin and naproxen, which can cause gastrointestinal bleeding but Dr. Bresalier says there seems to be an increased risk for most, if not all non-steroidal anti-inflammatory drugs which we need to be aware of.

Pfizer's Celebrex remains on the market.

The study appears in the journal the Lancet.