Conflicting views on how to take aspirin and ibuprofen
Millions of people at risk for heart attack or stroke take a small daily dose of aspirin–it has been shown to reduce the incidence of these events by about 25 percent. Now the Food and Drug Administration wants them to watch the clock before swallowing an ibuprofen product, such as Advil or Motrin, to relieve pain. An FDA safety alert issued last week advises consumers to wait at least 30 minutes to take ibuprofen after taking aspirin, and not to take aspirin for heart benefits for at least eight hours after taking ibuprofen. If the two drugs are used too closely together, warns the FDA, the ibuprofen may cancel out the aspirin's benefits.
But the FDA's action seems unwarranted to some experts. They worry that it may discourage doctors from putting patients in pain on a cheap and effective drug. And it conflicts with several studies, the latest of which was published online this week in the Journal of the American Medical Association, which found no interaction between the two medications.
The reason for the alert, according to an FDA spokesman, was unpublished data submitted by an unnamed pharmaceutical company–determined by U.S. News to be Wyeth Consumer Healthcare, maker of Advil–that demonstrated an interaction between the drugs. The agency then reviewed published studies, some of which also showed an interaction. Aspirin reduces heart risk by interfering with the process that causes platelets to clump together and form blood clots. Ibuprofen seems to temporarily get in the aspirin's way. If the two drugs are taken closely together, some researchers say, part of the aspirin will be gone from the bloodstream by the time the effect of the ibuprofen ebbs. That leaves less protection behind.
But other investigators have found little or no interaction between ibuprofen and aspirin. Besides the JAMA study, for example, a 2003 study in the British Medical Journal of nearly 70,000 heart-attack patients age 65 and older concluded that the two drugs "did not adversely interact."
"I think [the safety alert] is much ado over no data," says Steven Nissen, chairman of the Cleveland Clinic's department of cardiovascular medicine and an expert on the heart risks of pain-relief drugs. "I don't know why the FDA did this–the whole damn thing just doesn't make any sense. It will confuse clinicians and it will confuse the public."
Nissen and others worry that patients who need heart protection but are also desperate for pain relief from arthritis and other chronic conditions may be steered away from ibuprofen. Like other nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen is already under a cloud–the FDA now requires NSAID labels to carry a warning that long-term regular use "may increase the risk of heart attack or stroke." If physicians nudge patients away from ibuprofen, that would further reduce an arsenal of pain drugs already diminished by concerns about the heart risks of Cox-2 inhibitors.
For those who take ibuprofen occasionally, the lack of conclusive evidence that it interferes with aspirin's heart-protective benefits is immaterial. It's a simple matter to space out the ibuprofen doses. Those who use it regularly at full strength for up to 10 days–the maximum approved dosage without a physician's advice–might even follow Wyeth's own recommendations, more conservative than the FDA's, based on blood tests of 47 volunteers. Ibuprofen should be taken a full hour after aspirin, and at least 11 hours should separate the last ibuprofen of the day from the next day's first aspirin, says Suman Wason, senior director, global medical affairs, of Wyeth Consumer Healthcare. "This is a very complicated situation," says Wason. "We have defined a regimen that we think can be followed with absolute safety."
Advil products now reaching the shelf already carry a warning tracking the new safety alert: Anyone taking aspirin to prevent heart attack or stroke should check with a doctor or pharmacist before using Advil "because ibuprofen may decrease this benefit of aspirin."
The final word on any tendency of ibuprofen or other NSAIDs to muck up aspirin's ability to stave off heart attack and stroke may come in 2010, when a clinical trial called PRECISION is scheduled to bear fruit. Overseen by Nissen, the trial will involve some 21,000 osteoarthritis patients in U.S. and other medical centers who will be divided into three groups, each taking a different NSAID. Each group will be further split between patients who are and are not given aspirin. And even though no current data, to Nissen's mind, proves an aspirin-ibuprofen interconnection, patients in the ibuprofen group will be instructed to wait two hours to take the drug after their aspirin dose. "It doesn't hurt," he concedes.