Jewish World Review August 28, 2001 / 9 Elul, 5761

Arthritis drugs may be linked
with increased risk of heart disease

By Robert A. Wascher, M.D., F.A.C.S. -- The Journal of the American Medical Association (JAMA) reported this week on a potentially increased risk of heart attacks associated with the use of two relatively new drugs used to treat arthritis.

Vioxx and Celebrex are anti-inflammatory drugs in a class of drugs known as COX-2 inhibitors. This class of drugs selectively inhibits the production of substances in the body known as prostaglandins, some of which are associated with inflammation. Although these drugs are no more effective anti-arthritis drugs than other classes of the so-called non-steroidal anti-inflammatiory drugs (e.g., aspirin, ibuprofen/Motrin, naproxen/Naprosyn, Voltaren, and diclofenac, among others), they are associated with fewer gastrointestinal side effects because they selectively inhibit only one of the two enzymes involved in prostaglandin synthesis (COX-1 and COX-2).

In the JAMA article, a complex retrospective analysis, known as a meta-analysis, was performed. Using this statistical method, previous studies of these two drugs were reanalyzed and compared. The meta-analysis found that just under 1% of patients taking either of the two drugs developed heart attacks compared with 0.52% of patients taking a placebo (i.e., a sugar pill). While the difference in heart attack rates between these two groups of patients is quite small, it does suggest at least the possibility that some patients might be placed at increased risk of heart attack while taking either of these drugs.

It should be noted, however, that this report is based upon a reanalysis and comparison of the results of previous studies. Moreover, some of the patients in the previous studies were taking aspirin or naproxen, both of which are associated with a decreased risk of heart attacks. Therefore, it is not clear if Vioxx and Celebrex "increase" the risk of heart attack, or whether they merely are lacking the heart protective benefits of other "non-selective" anti-inflammatory drugs used to treat arthritis. Until more data is available, patients with heart disease risk factors (e.g., age over 60, elevated total or bad cholesterol, high blood pressure, diabetes, male gender, sedentary lifestyle, and family history of heart disease) are encouraged to see their doctor if they are taking either of these two medications.

The Centers for Disease Control (CDC) is warning that hospital laboratories must carefully interpret the results of a common test used to assess the ability of blood to clot.

The CDC's warning follows the death of two patients in Philadelphia due to brain hemorrhages caused by excessive thinning of the blood. Both patients were taking a drug called Coumadin (warfarin), which is used to counteract the blood's clotting mechanisms. Patients are prescribed this drug for a variety of clotting abnormalities, including a previous history of blood clots in the veins or lungs, and in the case of certain heart rhythm disturbances that predispose to life-threatening blood clot formation.

The blood-thinning effects of Coumadin must be carefully monitored, using blood tests, as excessive thinning of the blood is associated with sometimes fatal bleeding complications, including strokes and hemorrhage in gastrointestinal tract. According to the CDC's analysis, the Philadelphia patient deaths were the result of incorrect calculations by lab technicians as they measured the clotting ability of the patients' blood, both of whom were taking Coumadin.

This resulted in an underestimation of clotting inactivation in the blood of these two patients, and in the increased dose of Coumadin prescribed. The hospital in question has subsequently begun sending blood-clotting studies out to other laboratories for analysis. Patients taking Coumadin must be monitored regularly, and adjustments in their dose of medication must be made when necessary, based upon accurate testing of the blood.

Soy-derived compounds, known as isoflavones, have been under study for their estrogen and anti-estrogen effects in humans. These so-called "phytoestrogens" have been shown to bind to special cell docking sites called estrogen receptors, much as the female sex hormone, estrogen, does. Currently, isoflavones are being evaluated as possible cancer prevention agents, and particularly with respect to breast cancer (most cases of which are known to be estrogen-dependent).

In the USA, it is estimated that 18% of infants will be fed soy-based formula, mostly due to intolerance of milk-based formulas. Due to the interactions of isoflavones with estrogen receptors in the body, there has been some speculation that exposure to the isoflavones might impact on the reproductive development of infants fed soy-based formulas. In the August 15th issue of JAMA, researchers report on their study of adult men and women who were extensively fed soy-based formulas as infants. They found no statistically significant outcome differences between 248 study participants who received soy-based formula and 563 who received cow milk-based formulas during infancy. There was a slight tendency towards longer and more uncomfortable menstrual periods in women who had received soy-based formulas.

However, no developmental differences in puberty or fertility were identified in the study. It was concluded that isoflavones in soy-based infant formulas do not appear to interfere with normal reproductive development in babies fed with these products.

JWR contributor Dr. Robert A. Wascher is a senior research fellow in molecular & surgical oncology at the John Wayne Cancer Institute in Santa Monica, CA. Comment by clicking here.


© 2001, Dr. Robert A. Wascher