It seems that nonsteroidal anti-inflammatory drugs (NSAIDS), which include everything from ibuprofen and aspirin to more selective medications, are increasingly gaining a reputation for causing harm. In a new study from researchers at Aarhus University, selective NSAIDS known as COX-2 inhibitors were found to increase risk of death from stroke.

The drugs are commonly prescribed to treat pain, swelling, and fever, as well as more severe conditions like arthritis, colorectal polyps, and menstrual cramps. Some people also take them daily to prevent serious heart conditions. But growing evidence suggests that people taking the drugs may be putting themselves at risk — the Food and Drug Administration has even warned the 20 percent of U.S. adults taking aspirin every day or every other day to be wary of side effects.

Selective NSAIDS are different from others because they target specific enzymes that cause pain and inflammation. Whereas aspirin and ibuprofen target both COX-1 and COX-2, which are responsible for producing the chemical messengers for pain and inflammation, known as prostaglandins, Celebrex only targets COX-2. This allows COX-1, which is present in tissue and protects the stomach’s lining, to remain active.

For the study, the researchers examined hospital records from 100,243 people who experienced their first stroke in Denmark between 2004 and 2012. They then looked into how many people had been taking NSAIDS up to two months before the stroke (taking note of long- and short-term users), and how many had died up to a month after it. Overall, stroke deaths were 19 percent higher in those who were taking the COX-2 inhibitors than among those who took nothing at all. Even worse, those who had just started taking the older COX-2 inhibitors, such as Voltaren, were 42 percent more likely to die. But by far, patients taking etodolac (Lodine) were 53 percent more likely to die from stroke.

“While newer versions of these COX-2 inhibitors drugs have been pulled off shelves, older ones are still frequently prescribed,” study author Dr. Morten Schmidt said in a press release. Our study provides further important evidence solidifying the risks of certain arthritic pain relievers and death from stroke.”

The research echoes previous findings about various types of NSAIDS. One study, for example, found that nonselective NSAIDS could increase stroke and heart attack risk because of sodium added to the pills to improve absorption. Meanwhile, another study published in the journal Circulation, found that heart attack survivors who used over-the-counter NSAIDS were at an increased risk of having a second heart attack. With over 23 million people taking these pills regularly, that’s a lot of risk.

Scientists are already in the process of righting these wrongs. In a study from April, researchers wrote about how they were able to inhibit an enzyme in the COX-2 pathway, known as mPGES-1, rather than the pathway as a whole. In doing so, the pain-relieving properties of the drug could be utilized without the risk of cardiovascular issues. However, with these developments still in their early stages, most people will just have to consult their doctors to assess risk and look for better options.

Source: Schmidt M, Sørensen H, Petersen K, et al. Preadmission use of nonaspirin nonsteroidal anti-inflammatory drugs and 30-day stroke mortality. Neurology. 2014.