"The public health impact of this is monstrous," Michael Farkouh, MD, MPH, director of clinical trials at Mount Sinai Heart, tells WebMD.
"Ibuprofen is relatively safe except when we give it with aspirin to people at high risk of heart attack," Farkouh says. "Only when given with aspirin do we see an excess of heart attacks."
Farkouh admits this is a controversial conclusion — and that the study, which was not designed to look at ibuprofen safety, does not prove that ibuprofen is harmful to people at high risk of heart disease.
But he says the study provides a clear warning sign that ibuprofen is risky for people who need the blood-clot-reducing effect of daily low-dose aspirin.
"Those taking aspirin in the ibuprofen arm of the study had a ninefold excess of heart attacks," Farkouh says.
Steve Nissen, MD, chairman of cardiovascular medicine at The Cleveland
Clinic and past president of the American College of Cardiology, urges caution. He notes that the findings are based on only eight heart attacks among thousands of high-risk patients taking ibuprofen and aspirin.
"The hazard ratio here is not relevant. It is not something I would trumpet," Nissen tells WebMD. "This is not to say Dr. Farkouh is not right. We have to be careful here. If we jump to conclusions, we may do more harm than good."
Farkouh says the numbers may be small but the potential risks are great. And
it would not be the first time that relatively small numbers of heart attacks caused a major change in how doctors look at pain drugs.
"The whole Vioxx thing was based on 64 heart events among 21,000 patients studied," Farkouh says. "Here we are talking about potentially a higher magnitude of impact. The interaction of ibuprofen with aspirin is a bigger public health concern than Vioxx was."
Farkouh and colleagues report their findings in the early online issue of the BMJ specialty journal Annals of the Rheumatic Diseases.
Ibuprofen vs. Naproxen vs. Prexige
The study by Farkouh and colleagues enrolled 18,325 arthritis patients. Nearly 17 percent of these patients were at high risk of heart attack and stroke.
The trial compared ibuprofen (brand names include Advil, Motrin, and Nuprin) with naproxen (Aleve, Naprosyn) and to a new pain drug sold as Prexige in the U.K. and Canada.
Prexige is a member of the stomach-friendly family of pain drugs called Cox-2 inhibitors. Celebrex is the only member of this drug class sold in the United States. Another Cox-2 drug, Vioxx, was taken off the market after people taking the drug had a suspiciously high number of heart attacks.
All of the high-heart-risk patients in the Farkouh study should have been taking low-dose aspirin. Sixty percent of them did. These patients should have had fewer heart attacks, strokes, and heart deaths than those who did not take aspirin.
But if the patients took aspirin and also took high-dose ibuprofen, they were nine times more likely to have a heart attack than were patients who took aspirin and Prexige. Patients who took ibuprofen without taking aspirin were no more likely to have a heart attack than those who took Prexige.
Farkouh and Nissen say there is strong evidence that ibuprofen blocks the blood-clot-preventing effects of aspirin. Both agree that the drugs do not interact if a person takes aspirin two hours before taking ibuprofen. But Farkouh says this approach will not work in the real world.
"The problem with that is Grandma Jones has to take a statin drug, an ACE inhibitor, and beta-blockers, too. Now you tell her to take a white pill hours before she takes the green pill — it isn't going to work," he says.
So what is a person who needs low-dose aspirin supposed to do for arthritis pain? For those at low risk of stomach ad gut side effects, Farkouh recommends taking naproxen at the lowest helpful dose — and avoiding ibuprofen.
Nissen says there's far too little evidence to advise anyone to stop taking ibuprofen. However, he recommends that patients take their low-dose aspirin two hours before taking ibuprofen.
Answers Won't Come Soon
Nissen and colleagues are conducting a clinical trial that he and Farkouh agree should answer the ibuprofen question once and for all. That trial, now enrolling 20,000 patients, will compare Celebrex, naproxen, and ibuprofen in patients at risk of heart disease.
In that trial, patients will take their aspirin two hours before taking their study medication.
The good news is the trial will, at last, provide sorely needed information on the relative heart risks of common pain relievers.
The bad news: The study won't start returning results until 2010.
By Daniel DeNoon
Reviewed by Louise Chang
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