A Theory of Why COX-2 Inhibitors Affect the Heart and Raise Heart Attack Risk   

In May 2005 it was reported that medical researchers affiliated with the University of Pennsylvania School of Medicine have completed a study which may help doctors understand why the so-called "COX-2 inhibitors" — such as Vioxx, Bextra, and Celebrex — can cause an increased risk of heart attack in patients who were previously at a low risk of developing cardiovascular problems.

Specifically, the University of Pennsylvania researchers looked at the effect of COX-2 inhibitors on the muscular wall of blood vessels. In so doing, these researchers found that a COX-2-derived fatty acid called prostacyclin controls the blood vessel response to stressors such as high blood pressure.  These researchers posit that, by inhibiting COX-2, one’s use of Vioxx, Bextra, or Celebrex impairs the ability of their blood vessels to react normally to high blood pressure.

Earlier research has shown that the use of COX-2 inhibitors, by suppressing prostacyclin production, can predispose patients to high blood pressure which, in turn, aggravates atherosclerosis — a condition in which the arteries gradually become clogged with plaque deposits. When the additional factor of impaired blood vessel response — the new finding from this recent University of Pennsylvania study — is combined with the earlier research, doctors may better understand why COX-2 inhibitors raise a patient’s heart attack risk.   

Until last year, COX-2 inhibitors such as Vioxx, Bextra, and Celebrex were some of the most popular prescription drugs for arthritis and pain relief. In September 2004, however, Vioxx was voluntarily removed from U.S. market after a study linked Vioxx to an increased risk of heart attack.  Thereafter, in April 2005, Bextra was voluntarily recalled on the grounds that the risk of serious side effects associated linked with Bextra — namely, heart attacks and strokes, as well as serious skin reactions — outweighed the benefits of Bextra use.  Celebrex, the other COX-2 inhibitor widely prescribed in the U.S., has been linked to an increased risk of heart attacks and strokes, also.  As such, it seems that the cardiovascular side effect problems, at least, which have been associated with Vioxx, Bextra, and Celebrex are a "class effect" of the COX-2 inhibitors.

(Posted by: Tom Lamb)