Two British doctors, writing in Lancet, note that the theories of cardiovascular risk attributable to COX-2s (e.g., Vioxx) are equally applicable to the over-the-counter NSAIDs (e.g., ibuprofen) on the market. After all, NSAIDs are also COX-2 inhibitors; the main difference between the two classes of drugs are that the COX-2 selective drugs do not inhibit COX-1, and thus have a gastrointestinal advantage. Drs. Warner and Mitchell theorize that NSAIDs and COX-2 inhibitors have identical cardiovascular risk profiles—a theory, one notes, that is consistent with Dr. David Graham's own dataset in his Lancet paper, though he made wild accusations about Vioxx despite the inconsistency with his own dataset's showing a lack of a statistically significant difference between COX-2s and NSAIDs's cardiovascular risk profile. (Timothy D Warner & Jane A Mitchell, COX-2 selectivity alone does not define the cardiovascular risks associated with non-steroidal anti-inflammatory drugs, Lancet 2008; 371: 270�73.) (h/t J.C.)
If so, the panic over Vioxx may well have taken a safer drug off the market while exposing consumers to worse health risks. Recall that serious ulcerations have increased 21% since Vioxx has been withdrawn from the market. The trial lawyers will still collect at least $2 billion for their role in this fiasco, but those who would have benefited from Vioxx and were injured by the substitution of an NSAID will not have a cause of action.
Thus, it is important to understand that NSAIDs and COX-2 selective drugs do not differ by their ability to inhibit COX-2�in fact, this is one of their few common properties. NSAIDs are COX-2 inhibitors; if inhibition of COX-2 by COX-2-selective drugs precipitates thrombotic events then we must accept the same to be true for traditional NSAIDs. If there is a difference in thrombotic risk, this could only be explained by differential effects on COX-1 or by mismatched, high doses of COX-2-selective drugs (table 1 and table 2). This understanding should inform therapeutic decision making in the use of NSAIDs and COX-2-selective drugs. In particular, we must guard against the increasingly prevalent idea that traditional NSAIDs have inherently lower cardiovascular risks than do COX-2-selective drugs.