New pain relievers may cause blood clots

A US research group which includes a senior Irish scientist has uncovered potential problems with a newly released class of pain relievers known as "super aspirin". Its work suggests cardiovascular risks including heart attack and stroke may be linked to the use of these drugs.

The group of drugs, known as COX-2 inhibitors, are a new form of non-steroidal anti-inflammatory (NSAID) pain reliever. Aspirin is the best known NSAID, but it can irritate and damage the lining of the stomach.

The COX-2 inhibitors were designed as a replacement which offered the pain-relieving benefits without the side-effects. The University of Pennsylvania Medical Centre group, however, has just published results which suggest that COX-2 inhibitors could cause increased risk of blood clotting. A report on the study appears in the current issue of the Proceedings of the National Academy of Science.

Dr Garret A. FitzGerald, chairman of the Department of Pharmacology at the University of Pennsylvania, was senior author of the study. He is a UCD medical graduate.

While initial clinical trials assessing the use of COX-2 inhibitors in treating arthritis did not show any evidence of a cardiovascular risk, the study size was too small to draw definite conclusions, he said.

"They would have been roughly an order of magnitude too small in their sample sizes to detect what we see as a possible problem associated with the use of these drugs. So, the question hangs out there for future experience: will a cardiovascular risk emerge over time as the COX-2 inhibitors reach more and more patients?"

Dr FitzGerald and colleagues found that these drugs suppressed prostacyclin, an enzyme which helps to slow blood-clotting. This in turn would be expected to increase the risk of clotting, which can result in heart attacks and strokes.

Aspirin also suppresses pro stacyclin, but in common with other current NSAIDs it also reduces the blood's ability to clot. It therefore counteracts its tendency to suppress prostacyclin.

"One option may be for patients who are at particular risk of adverse cardiovascular events to combine COX-2 therapies with low-dose aspirin. But this is a strategy that would need to be tested in clinical trials," Dr FitzGerald said.

The lead author on the study is Dr B.F. McAdam. In addition to Dr FitzGerald other authors include Dr F. Catella-Lawson, Dr I.A. Mardini, Dr S. Kapoor and J.A. Lawson. Funding for the study was provided by G.D. Searle and Co, whose COX2 product, Celebrex, was approved for sale by the US Food and Drug Administration on December 31st, 1998. Celebrex was the COX-2 product used in the study.

Dr FitzGerald pointed out that the potential risk factor identified in his laboratory was also found in a similar study on Vioxx, a COX2 inhibitor from Merck & Co, and was therefore not unique to Celebrex.