Vioxx: How it puts you at risk

Research in mice suggests that a newer class of painkilling drugs called COX-2 inhibitors could trigger a chain of events potentially harmful to the cardiovascular system.

Researchers speculate, though, that their findings might explain the outcome of a recent major trial in which patients taking a COX-2 inhibitor – the arthritis drug Vioxx – had higher rates of heart attack and othe cardiovascular complications compared with patients on naproxen.

Naproxen, used in painkillers such as Aleve, belongs to a group of drugs known as nonsteroidal anti-inflammatory drugs (NSAID’s), which includes many familiar painkillers such as aspirin and ibuprofen. Aspirin is also well known for its heart-healthy blood-thinning effects.

COX-2 inhibitors – which besides Vioxx include the arthritis drugs Celebrex, among others – are a newer type of NSAID shown to be easier on the stomach. Unlike older forms such as aspirin, they work by selectively blocking the COX-2 enzyme. Traditional NSAID’s inhibit both the COX-2 and COX-1 enzymes, and this is believed to underlie the gastrointestinal side effects that can come with the drugs.

But the new mouse research suggests that the selectivity of COX-2 inhibitors could create an imbalance that promotes blood clotting and blood vessel constriction.

COX-1 makes thromboxane A2, which promotes blood vessel constriction and “stickiness” in blood cells called platelets. COX-2 is the major source of prostacyclin, which helps prevent platelets from clumping and promotes blood vessel dilation.

The researchers hypothesized that the heart-healthy ways of prostacyclin might counter the ill cardiovascular effects of thromboxane A2 in the body – meaning that blocking only COX-2, and therefore prostacyclin, could allow thromboxane A2 to go about its business unchecked.

The researchers found that mice without a PGI2 receptor – which mimics the clinical effect of taking COX-2 inhibitors – had an enhanced vascular response to injury and showed increased thromboxane A2 formation and platelet activation. This exaggerated respone was cancelled ou in mice lacking both thromboxane A2 and PGI2 receptors.

Recently Merck& Co. Inc., the maker of Vioxx, announced that the arthritis drug’s labelling would be changed to state that it carries higher cardiovascular risks than naproxen – a move required by the US Food and Drg administration following the Vioxx-naproxen trial.

 

Dr. Hooper’s comment:

A nice move by the FDA but a little late for those who have already had the ‘cardiovascular event.’