The controversy first arose a few years ago with the VIGOR trial, a study whose primary goal was to show that rofecoxib was indeed less likely to produce gastointestinal side effects than naproxen. The study confirmed the reduced incidence of GI problems, but a subanalysis also showed a 4-fold increase in heart attacks in patients treated with rofecoxib (0.1% vs. 0.4%). The most common explanation offered for this apparent increase in cardiovascular events is that the COX-2 drugs can make platelets "stickier," and thus more likely to form clots in blood vessels.
This statistically significant (but still very small) increase in the risk of heart attack has caused many doctors to avoid using COX-2 inhibitors in patients with an increased risk of cardiovascular disease. Other doctors explain the apparent increased risk with rofecoxib as an illusion - the real explanation, they postulate, is a protective effect from naproxen.
Since the VIGOR trial, several other attempts have been made to shed more light on the question of whether COX-2 inhibitors increase cardiovascular risk. A study reported earlier this year in Rheumatology suggested an increased risk of strokes, but not of heart attacks, with COX-2 inhibitors. Another study appearing in the Archives of Internal Medicine showed no increase in any cardiovascular events with COX-2 drugs. Yet another study showed an increase in the risk of heart attack with high-dose rofecoxib (50 mg/day) but not with more standard doses.
The latest report from the American Heart Journal describes no increase in cardiovascular events in over 5000 patients treated with rofecoxib, and furthermore no increase in such events in a pooled analysis of over 14,000 patients treated with this drug in 23 prior studies.
One editorial accompanying this new report begs to differ, describing the new study (co-authored by one clinican and three employees of Merck, the manufacturer of rofecoxib,) as "company propaganda". Another editorial finds the new study to be at least somewhat convincing.
All parties, however, agree that in order to settle the issue once and for all, we should stop massaging retrospective data, and instead conduct a large, prospective randomized trial. Some point out that the drug companies might even be persuaded to take a pinch of their $5 billion annual revenue from the COX-2 drugs to fund such a study.
DrRich Comments
Until this issue is settled by prospective, randomized data, the safest assumption would seem to be that the COX-2 drugs may indeed pose an increased risk of heart attack or stroke. As usual, there is no free lunch. If an anti-inflammatory drug is needed, we will have to choose between those that are more likely to cause gastrointestinal side effects (which can be fairly severe) or those that may cause more cardiovascular problems. The "right" decision will vary from patient to patient, and will require an informed patient as well as an informed doctor.Finally, if a COX-2 inhibitor is to be used, your doctor should try to get by with "standard" doses instead of using high doses, since there is at least some data suggesting an increased cardiovascular risk, if present, is related to high doses of the COX-2 drugs.
