An important meta-analysis has appeared in the BMJ.
When COX-2 inhibitors appeared they were seen as an answer to one of the real problems of pain relief. For years gastroenterologists have been plagued by hospital admissions for haematemasis (bleeding from the stomach) following treatment with non-steroidal anti-inflammatory drugs (NSAIDs). Drugs like Vioxx and Celebrex seemed to reduce the risk of bleeding. Alas, they also increased the risk of clotting. Vioxx, in particular has been blamed for causing heart attacks.
The meta-analysis looks at the thrombotic risk of COX-2 inhibitors compared to placebos and also old fashioned NSAIDs.
Sure enough there is a risk for all COX-2 inhibitors. Compared to placebos the risk of myocardial infarction went from 0.3% per year to 0.6% per year - an increased risk of 86% (confidence interval 33% to 159%). However, the striking thing was that compared to old fashioned NSAIDs there was no statistically significant increased risk.
This should not be too surprising. We know that the old fashioned NSAIDs inhibit both COX1 and COX2 to varying degrees. In fact, diclofenac (volterol or diclomax or motifene or arthrotec) is a very good COX-2 inhibitor. Even ibuprofen, widely available over-the-counter in various guises, carries the same risk. What stands out is that one particular NSAID seems to carry no increased risk of thrombosis. Naproxen (naprosyn or synflex or napratec) is an excellent COX1 inhibitor. Unfortunately, it seems to be the NSAID with the worst reputation for bleeding from the stomach.
What should we learn from this?
First, that the media hype and the compensation culture, directed at Vioxx was an over-reaction. For a start half the myocardial infarctions that occurred on Vioxx would have occurred if a placebo had been given, and as many would have happened if a standard over-the-counter pain killer had been used. It is also hard to blame a drug company for Vioxx if similar problems have been going unnoticed with the old fashioned NSAIDs for more than 20 years.
Second, we may ask why there has not been a similar outcry against the use of NSAIDs causing stomach hemorrhage.
Third, we are going to have to be more circumspect in our use of these drugs in future. I take ibuprofen in 800mg doses for my arthritis, but only once or twice a week. An editorial in the BMJ is entitled "Life without COX2 inhibitors" spells out the risk.