The COX-2 Dilemma: Risking Heart Problems To Ease PainMar 2, 2005 | USA TODAY When she was just 18 months old, Melissa Hafeli was diagnosed with rheumatoid arthritis.
When she was just 12 years old, she was diagnosed with a stomach ulcer. Her doctor blamed it on the aspirin and naproxen she had been taking for her arthritis.
When she was 26, Hafeli switched to a new drug called Celebrex. Her doctor said it would be safer for her stomach.
Now 32, Hafeli isn't sure what to think about her arthritis medication, one of the so-called COX-2 inhibitors facing intense scrutiny by the Food and Drug Administration. "Sometimes," says Hafeli, of Nashville, "I choose not to think about it."
Last month, an FDA advisory panel unanimously concluded that Celebrex and its cousins, Bextra and Vioxx, significantly raised the risk of heart attack and stroke. Still, a slim majority recommended that the drugs could still be sold, even Vioxx, whose maker, Merck, took it off the market last September because of the safety concerns.
The panelists also noted that little is known about the long-term safety of many older drugs taken for arthritis pain and inflammation.
Patients and their doctors are left trying to figure out the new math of arthritis medications: With COX-2 inhibitors, is an increased risk of cardiovascular problems worth the possibility of fewer stomach complications? If not, is the risk of stomach problems from older drugs such as ibuprofen plus their generally unknown effect on the cardiovascular system worth the pain relief they provide?
Staying on drugs despite risk
"This is a wake-up call for all of us," says Sara Walker, a doctor with the Missouri Arthritis Rehabilitation Research and Training Center. "There are many problems that a simple pill can't or won't fix. We have to individualize every case."
Apparently, many patients and doctors already have calculated that the risks from taking COX-2 inhibitors or older prescription anti-inflammatory pain relievers outweigh their benefits. A recent report from IMS Health, a market research firm, shows that the U.S. market for COX-2 inhibitors and the older prescription anti-inflammatory pain relievers had dropped 9% by the end of last year. Meanwhile, total sales of non-prescription arthritis drugs in the last quarter of 2004 were up 8% compared with the last quarter of 2003, according to ACNielsen.
Bextra fan Rosie Shiver, 47, bristles at the suggestion that she could do just as well on an over-the-counter arthritis drug.
Shiver says she tried naproxen for her spondylolisthesis, a type of arthritis of the spine, but after a few weeks it was like taking a sugar pill. Eventually, she says, a hiatal hernia gave her chronic heartburn, which made COX-2 inhibitors attractive.
Vioxx left her nauseated, and Celebrex didn't relieve her symptoms, says Shiver, a resident of Lake Placid, Fla., who had to give up teaching years ago because of her health problems. She went on Bextra in October of 2002.
"It worked right out of the chute," she says. Sure, Bextra makes her ankles swell, Shiver says, but she doesn't necessarily believe it's bad for her heart.
Hafeli, a state employee, says she has no options other than a COX-2 inhibitor for her "pretty severe" arthritis. A year ago, though, Hafeli decided to cut her daily 400-milligram dose of Celebrex in half. "I don't like to take a lot of medication," she explains.
The 200-milligram dose appears to be safe, the FDA advisory panel concluded. But in mid-December, Hafeli says, she began having chest pain. "The tests were all negative. We're just not sure what that was."
Concerned about her heart, Hafeli tried taking 200 milligrams of Celebrex every other day. That lasted about two weeks, she says. "Those off days were too much."
Her experiment proved that Celebrex worked, Hafeli says, "but it was kind of disheartening that I couldn't get off of it.
"It's just hard to gauge whether the risks outweigh the real pain alleviation it provides."
COX-2 inhibitors may remain the best choice for rheumatoid arthritis patients who require medication for pain and inflammation on a daily basis, says Walker, a professor of internal medicine at the University of Missouri.
But the new information about cardiovascular risk "will cause us to look very hard at our patients with osteoarthritis," whose disease usually does not involve inflammation, Walker says. For those patients, the best choice might be non-drug options, such as glucosamine, exercise or weight loss, she says, noting that a drop of just 10 or 15 pounds can relieve the pain of osteoarthritis in weight-bearing joints.
Are any COX-2s safe?
Those non-drug alternatives wouldn't much help Eileen Lacijan, who has osteoarthritis in her thumbs. She began taking Vioxx in March of 2000 and, because it bothered her stomach, switched to Celebrex the following June.
"I was pain-free for a long time," says Lacijan, 57, an Arnold, Md., nurse who directs a hospice program. "My grandson was born in May and I started knitting him a sweater." By last July, though, the Celebrex had stopped working, so Lacijan switched to Bextra.
A month later, she had a heart attack. Her blood pressure and cholesterol were fine, and a catheterization after her heart attack found no blockage.
"I don't really know if that's what caused the heart attack," Lacijan says of her more than four years on COX-2s. "I don't know if I will ever know."
After her heart attack, Lacijan switched to Mobic, now the fastest-growing prescription arthritis drug that, some scientists say, is more like a COX-2 inhibitor than not.
Lacijan told her story to the FDA panel. As she parked before speaking at the meeting, she heard a radio news report about FDA scientist David Graham's report to the panel that morning. His analysis of California Medicaid patients suggested that Mobic might be as risky for the heart as Vioxx.
"Awww, great," Lacijan recalls thinking. "I've got to talk to my rheumatologist and see what she thinks."