By Daniel DeNoon
October 1, 2004
Oct. 1, 2004 — The phone in the office of Michael E. Farkouh, MD, hasn’t stopped ringing all day.
Most of the calls are from patients. And many of them are from other doctors wondering what to tell their arthritis patients in the wake of Merck’s stunning Vioxx withdrawal. Farkouh, associate director of the NYU cardiovascular clinical research center, is an expert on the heart side effects of Cox-2 inhibitors. That’s the class of drugs to which Vioxx belongs.
“We are getting calls from all over the country,” Farkouh tells WebMD.
Yesterday, Merck stunned the medical world when it announced it would pull Vioxx off the market. The decision was based on clinical trial results showing that Vioxx doubles a patient’s risks of heart attack and stroke. That risk is small, but with 2 million people taking the drug, it means a lot of heart disease.
Vioxx’s Link to Heart Problems No Surprise
Merck’s sudden action may have been a shock. But experts familiar with Vioxx research tell WebMD that they have been suspicious of the drug’s heart side effects for years.
“The cardiology community has known of this for four years now,” Muhammad Mamdani, PharmD, MPH, tells WebMD. Mamdani heads the drug research group at the Institute for Clinical Evaluative Sciences and is an associate professor at the University of Toronto, Ontario. He has done extensive research on heart disease and Cox-2 inhibitors.
Carl Lavie, MD, isn’t surprised either. Lavie is medical co-director of cardiac rehabilitation and preventive cardiology at New Orleans’ Ochsner Clinic Foundation.
“I have been taking heart patients off Vioxx for three or four years,” Lavie tells WebMD. “I see many patients with heart disease given Vioxx by rheumatologists and other doctors. I tell them it’s better to take ibuprofen or naproxen. And if they really need a Cox-2 drug, I have been putting them on Celebrex.”
So if they saw this coming, why did it take five years to pull Vioxx off the market?
“There will be a lot of angry consumers, a lot of angry researchers — a lot of angry people in general saying why did it take so long to take Vioxx off the market,” Mamdani says. “But to make a big decision about a drug that affects so many peoples lives, and with so much money at stake — $2.6 billion — you do need more information. When we make decisions like this, we need lots of evidence from many directions to say something really is going on. Should that have occurred faster? Yes. But much faster? I am not so sure.”
What About Other Cox-2 Drugs?
Cox-2 drugs should never be used to prevent heart disease. That’s what aspirin is for, Farkouh says. But people getting pain relief from the other U.S.-approved Cox-2 inhibitors — Bextra and Celebrex — don’t have to stop.
“What we are telling folks is one message: If a patient requires aspirin — if a patient is at any cardiovascular risk — that patient should be on aspirin, independent of whether they are on these Cox-2 drugs or not. So we are talking about, for people with heart disease risks, one baby aspirin a day. With this we believe they will be safe.”
Farkouh says he sees no problem if patients want to continue taking Celebrex or Bextra.
“If you are not at risk of heart disease by traditional guidelines, and you are taking a Cox-2 drug, I don’t believe you need aspirin,” he says. “I think these drugs are safe. If you don’t need aspirin and you take an aspirin a day anyway, you get the risk of problems — stomach erosion and so on — without getting any benefit.”
There’s always worry that problems with one drug will mean problems with other drugs in the same class. But Mamdani, a pharmacologist, says there’s reason to think the Vioxx problems don’t extend to Celebrex.
“Number one, they have different chemical structures,” he says. “Two, they are treated differently in the body. … Vioxx sticks around longer. … Three, there are many unknown things in play here. But for some reason, Celebrex [in many ways] works differently from Vioxx.”
What about Bextra and the yet-to-be-FDA-approved Prexige and Arcoxia?
“Celebrex looks clean so far,” Mamdani says. “Do we have that information on the others? No. Although the Prexige people should be commended for looking into the issue,” Mamdani says.
Farkouh leads the study of the heart-safety profile of Prexige. He says the drug isn’t giving off the same warning signals that Vioxx did.
No Lasting Vioxx Harm — Maybe
Mamdani says that he’s not convinced by Merck’s claim that those taking Vioxx for less than 18 months don’t see any heart problems. But he thinks that those who took the drug and haven’t yet suffered heart disease won’t suffer lasting harm.
“I think the effects will likely wear out once the drug is out of your system,” Mamdani says. “I don’t think it does any permanent damage to the body. But we really need to find out more about the long-term effects of Vioxx and other drugs.”
Meanwhile, what should doctors tell their patients? Here’s Mamdani’s advice:
Try Tylenol. For many patients, it offers effective pain relief.
People with no risk of heart disease, kidney disease, or stomach side effects should try ibuprofen.
People at risk of heart disease, kidney disease, and stomach side effects might try Celebrex.
Physical therapy is a nondrug option for many patients.
“If you don’t need a drug, don’t take it,” Mamdani says. “The quick fix is a part of our culture now. Maybe we need to go back to old days and say, ‘Look at the alternative that is most natural and most non-intrusive to my body.”
SOURCES: Michael E Farkouh, MD, associate director, cardiovascular clinical research center, New York University School of Medicine. Muhammad Mamdani, PharmD, MPH, head of the drug research group, Institute for Clinical Evaluative Sciences; associate professor, University of Toronto, Ontario. Carl Lavie, MD, medical co-director of cardiac rehabilitation and preventive cardiology, Ochsner Clinic Foundation, New Orleans.