New results from a large scientific study show that the risk of heart problems from the painkiller Vioxx are long-lasting: the risk remains up to one year after patients stop taking the drug.
Preliminary results from a Merck study of its painkiller Vioxx show that the risk of heart attacks and strokes remains elevated long after people stop taking the drug.
"The reality here, the hard cold fact is that the risk just didn't go down when the drug was stopped; it continued, at least for the first year," said Dr. Steven Nissen, the interim chair of the Department of Cardiovascular Medicine at the Cleveland Clinic in Ohio.
Nissen spoke with NPR about the consequences of this latest Vioxx study for patients:
NPR: How big is this risk?
Nissen: These risks are not small. I must tell you it was very surprising to me. I thought the risk would fairly rapidly diminish. It suggests that perhaps the drug Vioxx was doing more than just promoting clotting, that there were other sources of damage to the arteries — produced by the drug — that would have more long-lasting effects.
NPR: Do the data show that Vioxx was an even bigger public health problem than previously thought?
Nissen: I think you can conclude that. Many of us believed that after the drug was stopped, after it was taken off the market, that very quickly the excess risk would very quickly go away. This study shows that the excess risk does not go away. So we have more people at continuing risk than any of us previously believed.
These new results are from a study called APPROVe. Participants were given either Vioxx or a placebo for three years.
The study was stopped in 2004 just before it was to end, after scientists saw that Vioxx patients were almost twice as likely to have cardiovascular problems as those on the placebo. Those findings prompted drugmaker Merck & Co. to take Vioxx off the market.
But scientists tracked the patients who completed the APPROVe study for one more year. At that point, none of the patients was on Vioxx. Researchers found that the group that had taken the placebo developed 16 heart problems. The former Vioxx patients developed 28.
"It was very surprising to me,'' says Steven Nissen, acting chief of cardiovascular medicine at Ohio's Cleveland Clinic. "I had always assumed that if you stop taking the drug, the risk would go away.''
Nissen says this data shows that's not true.
"What it shows us is that you can stop taking Vioxx, and based upon this study, for the next year, you're still at increased risk. And, in fact, the amount of increase is almost exactly the same as we saw during the three years that people were actually taking the drug,'' Nissen said.
Vioxx patients were 74 percent more likely to develop heart problems in the year after they went off the drug. In the three years they were taking Vioxx, they were at 90 percent higher risk of heart problems.
Nissen says the study suggests that Vioxx raises the risk of cardiovascular problems by doing long-lasting damage to the arteries, perhaps by increasing the buildup of plaque in them.
In a press release, Merck, which faces some 11,500 product-liability lawsuits from Vioxx patients and their families, portrayed the results as good news. The company pointed out the number of cardiovascular problems in the year after patients stopped taking Vioxx was so small that the cardiovascular problems could have been due to chance.
Clinical-trial expert Curt Furberg of Wake Forest University says it's true the numbers are small. But, he says, they show a clear trend, and he's worried.
"I think they should not hide behind technicalities. My take-home message is that there is persisting risk with Vioxx, at least for a year," says Furberg. "Does it continue for another couple of years or beyond that? No one knows, and I'm not sure we'll ever know."
Merck's press release says the company does have data on some patients in the study who were followed for almost three years after they stopped taking Vioxx.
The company did not provide details.
By one expert estimate, Vioxx may have caused more than 138,000 heart attacks and 58,000 deaths.
Nissen says these new results suggest the toll on American public health may be greater than previous estimates.
"If all the risk goes away when you stop the drug, then you know taking the drug off the market makes this public-health problem disappear. But this study demonstrates that the risk does not go away, that it continues. So we have more people at continuing risk than any of us previously believed,'' Nissen said.
Merck says the results will have no effect on its strategy of defending each product liability case in court. Six cases have gone to trial so far. The company has won three and lost three.