Common Painkillers Increase Stroke Risk

Common painkillers that have been linked to an increased risk of heart attack may also elevate risk of stroke, a new study suggests.

Researchers found that among nearly 38,000 Taiwanese adults who suffered a stroke over one year, the use of a non-steroidal anti-inflammatory drug (NSAID) in the prior month may have elevated their stroke risk.

The increases linked to individual NSAIDs were generally modest, the investigators report in the medical journal Stroke. And the findings do not prove that the medications themselves led to some people's strokes.

NSAIDs are a group of painkillers that include over-the-counter medications like aspirin, ibuprofen (Advil, Motrin, and other brands), and naproxen (Aleve), as well as prescription arthritis drugs known as COX-2 inhibitors.

The COX-2 inhibitors were first linked to an increased risk of heart attack and other cardiovascular problems, and two of the drugs — rofecoxib (Vioxx) and valdecoxib (Bextra) — were pulled from the market in 2004 and 2005, respectively; a third COX-2 inhibitor, celecoxib (Celebrex) remains on the market.

But subsequent studies also raised concerns about the possible heart risks of some of the older, over-the-counter NSAIDs, including ibuprofen and diclofenac (Voltaren).

These latest findings suggest that the "concern may also extend to the risk of stroke," said Dr. Elliott Antman, a professor of medicine at Harvard Medical School and Brigham and Women's Hospital in Boston who was not involved in the study.

The new results do underscore the general recommendation that, to limit any cardiovascular risks, people should use NSAIDs at the lowest dose and for the shortest time necessary to relieve their pain, added Antman, who is also a spokesman for the American Heart Association (AHA).

For the current study, researchers led by Dr. Chia-Hsuin Chang of National Taiwan University Hospital used information from Taiwan's national health insurance database. They identified nearly 38,000 adults age 20 or older who had suffered a stroke in 2006, then looked at the patients' NSAID use in the month before the stroke and compared it to use in the prior three to six months.

The specific medications included celecoxib, ibuprofen, naproxen, diclofenac, and other oral NSAIDs, as well as ones sometimes given by IV or injection, such as ketorolac (Toradol).

In general, the study found that use of any NSAID in the 30 days before the stroke was linked to an increased risk — of anywhere from 20 percent to 90 percent for most of the oral NSAIDs, depending on the drug. Oral ketorolac was linked to the greatest risk increase of 2.6-fold.

Antman urged caution in interpreting the last result because it was based on a small number of patients: only 131 had used oral ketorolac in the month before their strokes.

The pattern was seen in patients with cardiovascular risk factors and those without, the researchers say.

While the risk increases may sound big, Chang's team describes them as "small."

It's important to keep in mind, Antman said, that the figures represent relative increases in risk; the absolute risk to any one NSAID user may well be quite small.

For example, the National Institute of Neurological Disorders and Stroke estimates that adults in their 50s who are free of the major stroke risk factors — including high blood pressure, established heart disease, diabetes, and smoking — have about a 1 percent to 3 percent chance of suffering a stroke in the next 10 years.

So, even a doubling of such a person's short-term stroke risk would still yield a very low absolute risk.

Limiting use of NSAIDS is nevertheless a good idea, said Antman, and especially important for people with established heart disease or its risk factors, such as high blood pressure.

In guidelines published in 2007, the AHA recommended that people first try to ease their aches and pains with acetaminophen (Tylenol), which is not an NSAID, or aspirin — which, although it is an NSAID, is known to be protective against heart attacks.

Among nonaspirin over-the-counter NSAID products, Antman said, naproxen has so far been shown to be the safest as far as heart risks.

The bottom line, according to Antman, is that even common over-the-counter medications are "real drugs that do have risks." He noted that people should not continue to take NSAIDs beyond the period of time recommended on the label without talking with their doctor first.

It's thought that NSAIDs other than aspirin may contribute to heart problems or stroke for a few reasons, including effects that may make blood clots more likely to form or may create spikes in blood pressure.