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Vioxx was withdrawn in 2004. The arthritis painkiller was approved by the FDA in 1999.
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New data obtained by NPR show that patients who took Vioxx even for short periods were at higher risk of heart problems and strokes. An estimated 20 million Americans took the painkiller before Merck & Co. stopped selling it in 2004.
In a confidential report to the Food and Drug Administration (FDA) last week, Merck gave new details about a large Vioxx study known by the acronym APPROVe. Results from this study led Merck to pull Vioxx from the market in 2004, and were later published in the New England Journal of Medicine (NEJM).
The new report details more heart problems. Several of the new events occurred in Vioxx patients soon after they started taking the drug.
Clinical trial expert Curt Furberg of Wake Forest University reviewed the new report for NPR. He says it shows short-term users of Vioxx were at greater risk of heart problems than previously described in the NEJM paper.
The data in that paper indicated "it takes about 18 months to see an increase in risk," said Furberg. "With the new information, the risk appears to be present from the beginning, and it increases gradually over time."
This point is worth billions of dollars to Merck. Thousands of patients, who suffered heart problems, are suing the company. Many took Vioxx for less than 18 months.
Merck has long said there's no evidence that Vioxx caused those problems. It says the published APPROVe data show that most of the risk of heart problems was in patients who were on the drug for much longer than 18 months.
And it says the new data from the APPROVe study do not change that.
"The new APPROVe data do not establish that the risk for Vioxx starts earlier than had previously been reported.''
Furberg says Merck's way of analyzing the study is faulty.
"It's not proper scientifically to start slicing up the experience in a three-year study, and look at it after nine months or 18 or 22. It's not the way it should be done. You look at the total experience and pass judgment on the total experience,'' he said.
If you do that, Furberg says, the results show that the risk of cardiac events on Vioxx is almost twice as high over the entire study, including in the early months.
Cardiologist Steven Nissen of the Cleveland Clinic, who also reviewed the report for NPR, agrees that it gives additional evidence that Vioxx is risky from the start.
"Why should a drug have no adverse effect for 18 months and then all of a sudden these events would begin to occur? It never made good biological sense,'' Nissen said.
Merck's new report also has detailed data on heart problems that patients had after they stopped taking Vioxx. Merck released the bare bones of those findings last week. The company said the data did not show that Vioxx patients were at greater risk of heart problems after they stopped the drug.
Both Nissen and Furberg disagreed with that interpretation last week. Now they say the detailed information Merck gave the FDA confirms their opinion that the risks from Vioxx persist even one year after patients stop taking the drug. They also say the risks are almost as large as when patients are on the drug.
Cardiologist Nissen says this understanding of Vioxx's risks has important practical consequences, for patients formerly on the drug, particularly the elderly.
As a protective measure, Nissen is advising his elderly patients who had previously taken Vioxx, to regularly take a low-dose of aspirin, which is known to reduce the risk of cardiovascular events.
He adds there's no telling when or if Vioxx patients ever lose the disadvantage of having taken the drug. He says Merck should continue to follow patients in this study to find out.