Faculty Bibliography

Both Vioxx and Celebrex are members of the class of drugs known as Cox-2 inhibitors, which act against an enzyme that causes inflammation but theoretically spare another that protects the stomach lining. The drugs had been promoted as stomach-safe, and heavy advertising had helped Celebrex become the top-selling arthritis drug in the country (although its stomach-protective benefits have never been proved). More than 20 million prescriptions were written for Celebrex last year alone, according to IMS Health, a pharmaceutical information company. It was true that the National Institutes of Health had just suspended an Alzheimer's prevention study after it was discovered that study participants taking naproxen (Aleve) for three years appeared to have a 50% increased risk of heart disease. This was still no reason that a patient couldn't take an occasional Aleve or its prescription counterpart. I tried to explain that daily use of nonsteroidal anti-inflammatory drugs -- be they the Cox-2 inhibitors or the more common ibuprofen or naproxen -- could put stress on the heart after several months or years by causing the organ to retain fluids and by raising blood pressure. But my patient no longer seemed to be listening. He'd been convinced by the drug representative to use Celebrex to replace Vioxx, and he'd even reported on how well it had worked. But now, disappointed by the sudden news, he no longer had faith in the earlier sales pitch. With Vioxx banned and Bextra, Celebrex and now Aleve seemingly down for the count, I instructed my office staff to beware of the Mobic representative. (Mobic is a nonsteroidal drug that has some of the properties of Celebrex but is not a full-fledged Cox-2 inhibitor.)

What isn't clear to the public is that drugs like Celebrex are largely safe when taken for shorter periods at lower doses, which is the way they're generally intended to be used for common joint inflammation. The increased risk to the heart is due to taking them at high doses over a prolonged period of time. Celebrex diminishes an enzyme that prevents clotting, which is associated with heart attacks. The prolonged use of Aleve, and perhaps all non-steroidal anti-inflammatory drugs, can lead to fluid retention and elevated blood pressure, itself a risk factor to the heart. Yet these drugs are being overprescribed by doctors and overused by patients who consider them safe and effective. Public expectation regarding Celebrex and Vioxx was ramped up by direct-to-consumer advertising, a process that is not adequately overseen by the Food and Drug Administration. The public was told that these so-called Cox 2 inhibitors protect the stomach in a way that other non- steroidal drugs, all of which can cause bleeding ulcers or gastritis, don't. Thinking of Celebrex as a wonder drug, the public naturally feels betrayed now that it understands that the stomach- sparing qualities, though they may exist, were not actually proven, and now that it knows about the elevated heart risk, which FDA scientists suspected from the outset. The FDA that engages in that analysis will have to be a much stronger and more effective agency than the one in place now. In an editorial in the Nov. 30 issue of the Journal of the American Medical Association, deputy executive editor Phil Fontanarosa discussed the creation of a new office of drug safety to ensure a more independent and extensive evaluation of drugs than the FDA can provide. It would seem that a better first step would be to try to strengthen the FDA itself, to make it a more effective regulatory agency less dependent on drug company money and political appointments

Siegel comments on the shortage of flu vaccines after the Centers for Disease Control announced that 50 million influenza vaccines from the British manufacturer Chiron won't be available in the US this year because of possible contamination. Among other things, he cites that the main reason of the shortage is that drug manufacturers are not eager to produce vaccines. Without a patent to insure high prices, the profit margins for 'generic' vaccines is narrow

Most of my patients will do fine without one, but knowing that there's a scarcity has clouded people's reason. The flu is blamed for approximately 36,000 deaths every year and 200,000 hospitalizations, but most of these patients are very sick to begin with. Among those who are hospitalized for the flu, it is pneumonia or bronchitis, not the flu, that more than half the time makes patients the sickest and can kill them. My usual flu vaccine supply, like that of most of New York's private practitioners, originates with Chiron Corp., the company whose license was suspended in Britain for having contaminated stock. Most of the remaining vaccine (from Aventis) went to corporations, hospitals and supermarket chains. Health is seeking submissions from physicians for its Doctor Files column, a monthly feature that explores the art of medicine. The column seeks to illuminate the human aspect of medicine, including the doctor-patient relationship. Submissions, which should be 700 to 800 words in length, can be sent by e-mail to health@latimes.com, or by regular mail to Doctor Files, Health, Los Angeles Times, 202 W. 1st St., Los Angeles, CA 90012. Submissions cannot be returned

Instead of worrying about the flu, government has been busy spending millions stockpiling more than a million doses of anthrax vaccine (with no use for it in the foreseeable future) and more than 200,000 doses of smallpox vaccine (without a single case occurring here since 1949). These actions were taken so that the Department of Homeland Security can look like it takes the threat of biological agents seriously. Fearing an anthrax attack since 2001, Congress has contracted for millions of dollars in vaccine production. Since the vaccine is perishable, and there is no anthrax, most of what is produced is thrown away. Similarly, panicked over smallpox in 2002 and 2003, the government bought 291,400 doses of the antiquated live virus vaccine, which was found to have significant side effects. Ultimately, only 38,549 people were vaccinated and more than 250,000 doses were discarded. Influenza kills about 40,000 people in the United States every year and hospitalizes more than 200,000

Nervous anticipation is creating emotional and physical wrecks among some of us who live in the big cities or obsessively watch the ever-alert cable TV news shows. President Bush has pounded Sen. John Kerry as being weak on terrorism and inconsistent on Iraq. Kerry has warned voters that a second Bush term could lead to another Vietnam while reminding us that Osama bin Laden is still a haunting threat. Both candidates, via ads, speeches and the debates, are megaphoning their danger/safety messages via the media's hype apparatus. The message -- be afraid -- is getting out. A front-page headline in this newspaper last week pointed out that even the voting process is stirring fears: 'Election warning causes anxiety.' Fear traces its roots as a protective mechanism to the animal kingdom. The fear center of all animal brains, humans included, becomes activated in response to perceived danger signals. The body is thrown into a 'fight or flight' mode. Unchecked, however, this stress creates far more heart disease, stroke and suicide victims than does terrorism

This realization is a silver lining to the Vioxx recall. It gives doctors a chance to revisit the issue of pain and arthritis and to compare the actual versus the intended use of a medicine. In this patient's case, I was more concerned about the long-term effects of the drug on her kidneys and liver than her heart. With extended use, nonsteroidal drugs such as Vioxx -- along with Celebrex (a competitor to Vioxx), naproxen and ibuprofen -- are associated with gradual, progressive damage to the tubules of the kidney. Despite the patient's esophageal reflux, she didn't have proven gastritis or ulcer, so I was reluctant to automatically switch her to Celebrex. I might have done so previously, but the Vioxx recall had made me more wary of all the newest arthritis drugs, regardless of what the drug reps said to try and influence me

According to Fred Feit, director of interventional cardiology at New York University Medical School, the goal these days is to 'come with the treatment that is least invasive.' Feit said that over a recent two-day period, he catheterized 17 patients, snaking a tiny tube from the groin up into the coronary arteries. He sent only one for bypass; the rest received stents. Stents are tiny mesh cylinders are made of metal and coated these days with a drug that retards clogging. They are floated into the artery with a catheter and then snapped into place. With the latest technology, each stent appears to have less than a 10 percent chance of closing up over the first six months. Feit says stent placement is safer, with an in-hospital mortality rate of only 0.7 percent, compared with 1.4 to 2.1 percent for bypass surgery. In addition, bypass surgery poses other risks: heart attack immediately after surgery (3 percent), wound infection (3 percent), bleeding (3 to 5 percent) and heart arrhythmias (30 percent). After recommending surgery, [Craig R. Smith] had a second major decision to make: whether to operate on a beating heart. That was his initial preference because of the lower risk of complications. But after Smith opened [Bill Clinton]'s chest, he reversed his decision after discovering that one of the arteries he had to bypass was buried within a thickened heart muscle. Stopping the heart allowed him better access. Cooling and potassium-containing solution stops the heart, and the patient is kept alive by filtering the blood through a heart lung machine until the heart is restarted with a shock