Prescription For Trouble

<B>Ed Bradley</B> Reports On The Painkiller Vioxx

When the pharmaceutical giant Merck pulled its blockbuster pain medication Vioxx off the market last fall, it was the largest prescription drug recall in history.

The company said it had taken immediate action after new studies had shown that Vioxx doubled the risk of heart attacks and strokes in some patients.

Just over a week ago, a jury in Texas found that Merck had concerns that Vioxx could cause cardiovascular problems long before it was pulled off the market. It held Merck liable for the death of a man who took Vioxx, and awarded the family more than $250 million in damages.

Much of the evidence the jury heard was reported last November on 60 Minutes by correspondent Ed Bradley. Today, Merck is facing thousands lawsuits that have been filed on behalf of patients alleging that Vioxx was a prescription for trouble.

When it first hit the market under a barrage of TV commercials, Vioxx was hailed by Merck as a miracle drug. It was one of a new class of drugs called COX-2 inhibitors that could reduce all kinds of pain, especially arthritis, without causing serious gastrointestinal discomfort and bleeding, a risk seen in older drugs like aspirin, Aleve and Advil.

With annual sales of about $2.5 billion, Vioxx was one of the most successful new drugs ever.

It was prescribed to people like 39-year-old Janet Huggins, who had been diagnosed with early-stage rheumatoid arthritis.

According to her medical records, Huggins was in otherwise excellent health. But that was until Sept. 25, 2004, when she died of a sudden heart attack, less than a month after she started taking Vioxx. She was buried the day Merck took Vioxx off the market. Huggins' husband, Monty, is suing Merck, holding the company responsible for her death.

"The morning of her funeral, I had just gotten dressed and my sister walked in and told me that she had just seen on the news that Vioxx had been pulled from the market. And when she told me that, I can't explain what hit me," Monty Huggins says. "I dropped straight to the floor. It was just a shock, because this is a 39-year-old female that's in good shape and is healthy and she's got a heart attack."

He says that if the drug had been taken off the market a month earlier, "I believe my wife would be here."

Merck says it believes that many of the deaths being attributed to Vioxx could be explained by any number of other causes. The company insists it has acted responsibly, saying it withdrew Vioxx as soon as it received what it says was surprising data from a clinical trial it was conducting, called the APPROVe (Adenomatous Polyp Prevention on VIOXX) study, designed to determine if Vioxx could prevent colon polyps.

Instead, Merck found something potentially worse: Patients taking Vioxx for longer than 18 months were twice as likely to suffer a heart attack or stroke than those taking a placebo.

Merck declined a request from 60 Minutes for an on-camera interview, but CEO Raymond Gilmartin explained the company's decision in a news conference Sept. 30, 2004: "We're taking this action because we believe it best serves the interest of patients. We believe it would have been possible to continue to market Vioxx with labeling that would incorporate these new data. However, given the availability of alternative therapies, and the questions raised by the data, we concluded that a voluntary withdrawal is the responsible course to take."

Merck maintains that the APPROVe study provided the first clear evidence that Vioxx was linked to heart attacks and strokes. But attorney Andy Birchfield is spearheading an all-out legal assault against Merck.

Birchfield met in November 2004 with hundreds of plaintiffs' lawyers from across the country to coordinate their efforts in lawsuits they planned to file against Merck on behalf of more than 10,000 people who, it's claimed, were harmed or killed by Vioxx.

"Merck knew, even before this drug went on the market, that there could be significant increase in cardiovascular risk. To say that the APPROVe study was the first indication that they had of a risk is absolutely untrue," Birchfield says. "You know, they had warning sign after warning sign, study after study, that suggested a significant, a substantial increase in risk."

Birchfield says Merck ignored the studies because it needed a blockbuster drug because it had several that were coming off patent and Merck was looking for another big revenue source.

Merck denies that profits would come before patient safety. In 1999, Merck conducted its biggest clinical trial of Vioxx, a study of 8,000 people called the VIGOR (VIOXX Gastrointestinal Outcomes Research) study. It was designed to determine if Vioxx was safer on the stomach than an older pain medication called Naproxen.

While the VIGOR study found that Vioxx caused fewer gastrointestinal side effects than Naproxen, Vioxx users also had a nearly five-fold increase in heart attacks. Merck attributed the increase to what it believed was Naproxen's ability to protect the heart, not to any problem with Vioxx.

However, an internal Merck e-mail written by the company's research president in March 2000 (the day he learned about the results of the VIGOR study, and nearly a year after the drug came on the market) said that heart problems "are clearly there." And he said: "It is a shame, but it is a low incidence and it is mechanism-based as we worried it was." "Mechanism-based" refers to the molecular structure of the drug.

Plaintiff's attorneys cite that and other Merck internal memos and e-mails as far back as 1996, which they say show some Merck scientists anticipated a higher rate of heart problems. Merck says those e-mails reflect only hypothetical concerns, and that there was not enough evidence at the time to prove that Vioxx increased the risk of heart problems.

Dr. Eric Topol, chief of cardiovascular medicine at the Cleveland Clinic, was Merck's first and most persistent critic. In 2001, he conducted a statistical analysis of all the available data about Vioxx. His study was published in the Journal of the American Medical Association.

What did his study — which came out after the VIGOR study — find?

"That study, which looked at all the data available for both the medicines of these COX-2 inhibitors and all other medicines, including aspirin, that were available, showed a very substantial worrying risk of heart attacks and strokes — across the board — from the VIGOR trial and about Vioxx," says Topol.

Topol examined data from a 1998 Merck clinical trial called Study "090", which was never published. Among 978 patients studied, serious cardiovascular events, including heart attack and stroke — were found about six times more often in patients taking Vioxx than in patients taking another arthritis drug or a placebo.