The COX-2 story is continuing to thrash around, as it will for some time. The latest news has Pfizer's second-generation compound, Bextra, linked to possible cardiovascular risks. This is data from patients who have undergone open-heart surgery, so we can argue about how applicable this is to the general population, but it's still not good news. The whole drug class didn't need any more clouds over it.

At the same time Pfizer has announced a large cardiac trial of Celebrex. Pfizer's positioning this as a trial to look for cardiovascular benefits, actually, but it's going to be hard to shake the impression that they're looking for risks. It'll be interesting to see how quickly they can enroll patients in that one, although odds are we're not going to be able to find that out.

And over at Merck, they've presented data from a study of their own second-generation drug, Arcoxia. In a trial against diclofenac (a classic antiinflammation drug), Arcoxia didn't seem to show an increased risk of heart attack or stroke. But what it did show was a correlation with slightly increased blood pressure, and that's not what Merck or anyone else wanted to hear. You could, in a pessimistic mood, link increased blood pressure to long-term cardiac effects, although there's no way to know if that's what's going on yet.

Remember, the Vioxx problems didn't really show up until the drug had been on the market for some time. You'd think, to read some of the stories (or to hear some of the ads from law firms) that the drug was just mowing down its patients, but that's not what happened. Vioxx's side effects might never have been noticed in the normal course of use - although severe, they're too uncommon to pick up for sure except in a large sample. Patients had to take the drug for over a year to show any problems at all, for one thing.

Without trials specifically designed (and statistically powered) to look for them, the side effects of other COX-2 medications might be invisible. But invisibility isn't an option.