Analog SFF, September 2010 by Dell Magazine Authors

News
    Another reason why medical research goes wrong falls under the category of “What's good for one part of the body may be bad for another."
    The rise and fall of cyclooxygenase-2 (COX-2) inhibitors, a class of medications introduced in the late 1990s, illustrates this principle. COX-2 inhibitors are one type of a larger class of medications called NSAIDs ("nonsteroidal anti-inflammatory drugs"). NSAIDs are used to treat arthritis and inflammation, and include such commonly used medicines as aspirin, ibuprofen (Motrin), and naproxen (Naprosyn). These and some other NSAIDs inhibit both the COX-1 and COX-2 receptors present to varying degrees in most tissues in the body.
    Inhibiting COX-2 receptors reduces inflammation—a beneficial effect. However, inhibiting COX-1 receptors can lead to irritation, inflammation, and ulceration of the lining of the stomach and other parts of the gastrointestinal tract. These adverse effects can cause bleeding and other complications. NSAIDs designed to selectively inhibit COX-2 receptors were developed with the idea that this would maximize their good effects (e.g. reducing inflammation and joint pain) and minimize bad ones, such as damaging the stomach.
    Two selective COX-2 inhibitors, rofecoxib (Vioxx) and celecoxib (Celebrex), were approved by the FDA in the late 1990s and a third, valdecoxib (Bextra), in 2001. For several years they were widely prescribed for treatment of arthritis. Some studies, including the C elecoxib L ong-term A rthritis S afety S tudy (CLASS) and the VI oxx G astrointestinal O utcomes R esearch (VIGOR) study, reported that selective COX-2 inhibitors were indeed associated with a lower incidence of gastrointestinal side effects than other types of medications used to treat arthritis.[9], [10]
    However, VIGOR and later studies found that COX-2 inhibitors were also associated with an increased risk of myocardial infarction, stroke, heart failure, and high blood pressure.[11] Although the exact mechanisms for some of these increased risks are still debated, they may include increased chance of a blood clot (thrombus) forming, as well as excessive retention of sodium and water. Based on these reported adverse cardiovascular effects, rofecoxib was withdrawn from the U.S. market in 2004 and valdecoxib in 2005.
    Celecoxib remains available by prescription. However, current guidelines state that it should be used for treatment of arthritis only if less risky medications have failed; duration of treatment should be as short as possible and at the lowest effective dose; and it should be used with special caution or not at all in patients at highest risk of cardiovascular events. That includes those with prior myocardial infarction or otherwise known to have or to be at high risk of having coronary artery disease (one or more blockages in the arteries of the heart).
    Interestingly, this research also indicated that older NSAIDs that produce a milder degree of selective COX-2 inhibition, such as ibuprofen, might also be associated with increased risk of cardiovascular events, but not as much as rofecoxib and similar medications. These older NSAIDs should also be used with caution in patients with known or suspected cardiovascular disease.
    The COX-2 inhibitors aren't alone in initially appearing to be reasonably effective and benign, only to be found when used in larger numbers of patients to have unexpected bad effects on other parts of the body besides those being treated. In the 1990s, a medication that combined fenfluramine and phentermine (Fen-Phen) was marketed as an aid to weight loss. As use of this medication became more widespread, however, its use was found to be associated with serious and even fatal cardiovascular problems—development of increased pressure in the arteries of the lungs (pulmonary hypertension), and abnormalities of heart valves such as increased thickening and leaking.[12], [13]
    In 1997, the FDA recommended that medications containing