Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most prescribed medications in the U.S. for pain arising from conditions like arthritis, tendonitis, and less serious conditions causing pain. The most common ones are aspirin, ibuprofen, and naproxen, and they’re taken by as many as 23 million people, according to the American Heart Association. Yet, many of them, including the most common ones, have the potential to harm the heart. So researchers have been looking to alternatives, finding a possible alternative in a new study.

Many NSAIDs work by inhibiting the enzymatic pathway COX-2, which produces enzymes that cause inflammation. The researchers’ new study builds on a previous one that found that rather than inhibiting the pathway as a whole, deleting only one of the enzymes, called mPGES-1, could slow the progression of atherosclerosis — a buildup of plaque and hardening of the arteries — in mice with heart disease.

However, in order to slow the progression, the researchers found that they had to target a specific type of cell in which mPEGS-1 appeared. If they targeted and deleted mPGES-1 in macrophages, immune system cells that clear out pathogens but also contribute to inflammation, then the mice’s arteries hardened more slowly. The same thing did not occur when they targeted vascular cells, which line the entire circulatory system.

The findings provide new insights into possible alternatives, as they avoid some of the harmful side effects that come with taking regular NSAIDs. “While deletion or inhibition of COX-2 in mice elevates their blood pressure and predisposes them to clotting and hardening of the arteries due to suppressing the cardioprotective lipid prostacyclin, deleting mPGES-1 avoids these effects and even restrains the development of atherosclerosis,” said Dr. Garret FitzGerald, director of the Institute for Translational Medicine and Therapeutics and senior author of the study, in a press release.

COX-2 inhibitors like Celebrex, Vioxx, and Bextra are used to treat different forms of arthritis. But as evidence mounts that NSAIDs may be detrimental to heart health, scientists have been rushing to find alternatives. Targeting only MPGES-1 could be one way to avoid these problems. The FDA announced in February that there isn’t enough data proving that naproxen was safer on the heart than other painkillers. The panel that came to this conclusion advised anyone taking the meds that they should take the “lowest dose and for the shortest period necessary to control symptoms” if they aren’t able to undergo alternative treatments.