A team of scientists based in the UK think they have discovered why COX-2 inhibitor painkillers may cause heart attacks and strokes.
Published in the December issue of the Federation of American Societies for Experimental Biology journal, a study conducted by researchers from Imperial College London and Queen Mary’s School of Medicine and Dentistry, claims that while the COX-2 inhibitors such as the withdrawn Vioxx (rofecoxib) do indeed block the COX-2 enzymes that are expressed in inflamed parts of the body, they also inhibit the COX-1 enzyme within the endothelial cells that line all blood vessels.
COX-1 in these cells makes prostacyclin, which thins the blood and where this is inhibited there is a greater chance of blood clotting, which, if the drugs are used on a regular basis, may increase the risk of heart attacks and strokes.
Prior to the study, the authors note that many in the scientific community thought the side effects of COX-2 inhibitors were caused by inhibiting COX-2 in the endothelium and that this was reducing the production of blood-thinning agents. However, the researchers found no evidence for the existence of COX-2 in the endothelium and suggest that drugmakers can now work on developing therapies which still target COX-2 but which do not have the adverse affect on COX-1 in endothelial cells.
Furthermore, the researchers found that the COX-2 inhibitors only had a significant adverse effect on COX-1 in the endothelium and not in other areas such as platelets in the blood. This had lead them to believe that there is something about the cellular environment in the endothelium that makes COX-1 in that area vulnerable to the COX-2 inhibitors.
Professor Jane Mitchell, one of the authors of the study from the National Heart and Lung Institute at ICL, said: “COX-2 inhibitors can have great benefits for patients suffering from conditions such as arthritis. However, the problem is that their use appears associated with an increased risk of heart attacks. Our new research is exciting because it means we can work on developing better COX-2 inhibitors that don’t pose the same risks.”
Professor Tim Warner, from the William Harvey Research Institute at Queen Mary’s, added: “It is essential that we have a true understanding of their sites of action so that we can produce new safe and effective drugs for years to come.”