One by one, arthritis drugs that promised to ease pain without causing ulcers are losing their luster.
In September, Merck & Co. yanked Vioxx from the market when a trial showed that long-term use of the painkiller nearly doubled the risk of heart attack and stroke.
This week, researchers said a preliminary study indicated that Bextra — another painkiller in the same class — also more than doubled the risk of heart attacks and strokes among patients with heart disease.
Pfizer, which manufactures Bextra, said researchers made “unsubstantiated conclusions” during their presentation at the annual meeting of the American Heart Association in New Orleans. The company also said the research was “based on information that has not been published in a medical journal or subject to independent scientific review.”
Pfizer already has told regulators it will add to its packaging a black box warning, the most strident alert, to warn consumers of a potentially fatal skin reaction linked to Bextra.
Scientists renewed a call for more studies of the painkillers in patients with heart disease, the group likely to suffer the most harm from this class of drugs known as cox-2 inhibitors. For clinicians at Kaiser Permanente, which serves 8.3 million patients, the Bextra study already has prompted discussion of safer alternatives. And some pressured the Food and Drug Administration to halt advertising directed at consumers.
“Arthritis drugs are not saving people’s lives. Ironically, they’re inducing heart attacks and may be losing people’s lives,” said Dr. Eric J. Topol, a Cleveland Clinic cardiologist who was among the first to warn about heart woes associated with the new painkillers.
The FDA controls drug marketing directed at consumers, Topol said. “The reality is they could shut that down at any time.”
Kathleen Quinn, an FDA spokeswoman, could not say which actions the agency would take.
The FDA doesn’t discuss negotiations or talks with companies, she said. “We will be taking a look at the whole class of drugs.”
Quinn said the FDA has not accelerated the timing of an upcoming meeting on cox-2 inhibitors, currently planned for mid-February.
What’s a bone-weary consumer to do?
Experts give contrasting advice.
The cox-2 drugs were praised for blocking the enzyme that causes the pain and swelling of arthritis inflammation. The drugs, however, were selective in their targets, bypassing the cox-1 enzyme that helps the stomach maintain a protective lining.
John Talley, the chemist who invented the Celebrex and Bextra molecules, said the cox-2 drugs helped people who couldn’t tolerate the older generation of painkillers. “I do think these drugs have been a tremendous benefit to folks. And they’ve been extensively studied,” Talley said.
Consumers and doctors agreed, to the tune of 40 million cox-2 inhibitor prescriptions written in the first nine months of 2004, according to IMS Health, a company that tracks drug industry trends.
Whether there is a classwide problem with cox-2 inhibitors, to many, remains debatable.
“I would hate for people to go off these medications on what may turn out to be unfounded rumors,” said Dr. Elizabeth A. Tindall, incoming president of the American College of Rheumatology. “Each drug has to be carefully scrutinized. I don’t think they’ve quite done that with Bextra to the extent they did with Vioxx.”
Clinicians who are the decision-makers at Kaiser Permanente, however, are alarmed by the Bextra findings and agree that there are safer alternatives.
“These drugs are no better for control of pain than Motrin,” said David Campen, Kaiser’s medical director of pharmacy operations. And most people don’t enjoy the expensive drug’s slight benefit because they’re not at risk for stomach ulcers, Campen said.
Topol, of the Cleveland Clinic, said naproxen should be the first anti-inflammatory of choice for people with arthritis who have heart problems.
“If there’s even a potential risk for heart disease, that’s where you don’t want to err in the wrong drug class,” Topol said.
To examine heart risk associated with Bextra, a Wake Forest University School of Medicine researcher looked at studies involving some of the most vulnerable patients, those with heart disease undergoing coronary artery bypass graft surgery.
Taking Bextra more than doubled the risk of heart attacks and stroke, compared with dummy pills.
Dr. Curt Furberg, a public health sciences professor at Wake Forest, questioned the timing of Pfizer’s release of the data. The company mentioned the study in a statement in October.
“I think it’s healthy to get the information out and have a debate. I think it will probably pressure Pfizer to be more open,” said Furberg, among the academicians invited to attend the FDA’s February session on cox-2 inhibitors.