Painkiller panic

Posted: Dec 30, 2004 12:00 AM

 Depending on which of two recent studies you may have read about, you might suppose the pain reliever Alleve (naproxen) will either reduce or increase the risk of heart attacks.

 On Dec. 13, The Financial Times reported, "Widely used anti-inflammatory drugs such as ibuprofen and naproxen could help reduce the risk of heart attacks, while abruptly halting the usage increases the risks, according to a large UK study." On Dec. 21, The Washington Post dished out the opposite advice, noting that, "federal officials announced that naproxen, a painkiller sold by prescription and also over the counter as Aleve, might increase people's risk of having a heart attack."

 Between those dates, my periodontist prescribed naproxen. What the press described as a "quick review of the data" in the United States may have suggested to equally hasty readers that I should stop using naproxen or risk a heart attack. But the larger British study said to stop taking naproxen would risk a heart attack. So, I decided to take a closer look at the U.S. version.

 It turns out that in a study of about 2,400 older people, 70 of those using naproxen had experienced some "cardiovascular event," such as a stroke or heart attack, though only two or three died. The number 70 was said to be twice the rate among those taking a placebo. Press reports promptly ascribed that minor difference (1.5 percent) to the added risk of taking a large daily dose of naproxen for three years.

 For all we know, the difference might be because those taking naproxen ate fatter foods than most other participants, exercised less, were older, had worse family histories or smoked more cigarettes. Nobody said these other risk factors were properly taken into account, so the quick review lacks statistical credibility.

 Even in the case of Vioxx, nobody claims it is dangerous if the normal 25 mg dose is taken for only a couple of weeks, as I would still like to do for an arthritic big toe on vacations (because I'm allergic to Celebrex).

 I am now denied the opportunity to use Vioxx responsibly, not to eliminate even the slightest health risk (which is impossible), but in the hope of reducing litigation risk. Typing "Vioxx" into Google generates about 14 million hits, mostly ads inviting people to share in the fabulous riches from class-action suits. One says, "Vioxx lawsuit is the easiest way to make you a millionaire."

 Mass tort lawyers must love David Graham, an associate director in the FDA's Office of Drug Safety. Graham became an instant media darling when he testified against the FDA at a November hearing of the Senate Finance Committee. Yet Graham's testimony was not so much about blowing whistles as it was about tooting horns.

 "During my career," he began, "I believe I have made a real difference for the cause of patient safety. ... I have recommended the market withdrawal of 12 drugs. Only two of these remain on the market today -- Accutane and Arava." He went on to recommend banning several other FDA-approved medications.

 Graham's urge to banish risk reflects the mindset of aspiring regulatory czars. The fewer drug choices left to doctors and patients, the better job Graham imagines he has done. Yet if zero risk from new drugs was really ideal, then it would be best to simply ban all new drugs. The FDA does not go quite that far, but the agency has certainly slowed the introduction of many drugs that could have saved or improved many lives had they been made available more promptly. A classic example was beta-blockers, which an American Heart Association study says "lengthen the lives of people at risk of sudden death due to irregular heart beats." Beta-blockers were available in Europe in 1967, yet the FDA banned them until 1976.

 Graham went on to say: "The FDA, as currently configured, is incapable of protecting America against another Vioxx. We are virtually defenseless." From his standpoint, the only sure way of "protecting America against another Vioxx" is to greatly increase the regulatory cost and time involved in bringing new drugs to market.

 But every day in which a lifesaving drug is delayed for further testing is a day in which the FDA approval process may kill more people. Suffering with acute or chronic pain is not death, to be sure, but it can be horrible enough to warrant taking major health risks (as with codeine or morphine).

 Graham noted that a single drug -- thalidomide -- was the reason the FDA first began its dangerous campaign to stall or thwart the introduction of new drugs: "In 1962, Congress enacted the Kefauver-Harris Amendments," he testified, "in response to the thalidomide disaster in Europe. Oversees, between 1957 and 1961, an estimated 5,000 to 10,000 children were born with thalidomide-related birth defects."

 Even in this difficult case, however, the understandable impulse to ban risky drugs still needs to weigh costs against benefits. After the thalidomide ban was finally eased for research, the once-infamous drug has shown considerable promise in the treatment of multiple myeloma, leprosy and AIDS. Like two other drugs Graham wants to ban (Accutane and Arava), thalidomide should never be taken by pregnant women. But pregnancy is a condition that affects women infrequently and men not at all.

 Contingent risks, such as those associated with pregnancy or allergy, are best handled with warning labels. Food processing companies should develop clearer warning labels for children with peanut allergies, who risk death from anaphylactic shock. But nobody suggest we should ban peanuts. When it comes to far less dangerous risks from pharmaceutical products, however, those afflicted with the regulatory mindset are far too eager to ban drugs that offer important benefits to many people.

 If a warning label is adequate protection against rat poison, it surely should suffice for side effects from overused painkillers. Yet Graham's testimony about Vioxx made that product sound far more dangerous than rat poison. He speciously described murky statistical probabilities of cardiovascular events as equivalent to specific numbers of certain deaths. And his rhetoric was hysterically hyperbolic, to a degree that made sense only if he saw this as an opportunity to launch a career as an expert witness.

 He spoke of "the enormity of the Vioxx debacle" and the "Vioxx catastrophe." He exclaimed, "We are faced with what may be the single greatest drug safety catastrophe in the history of this country or the history of the world." If true, that would make Vioxx more dangerous than, say, hydrochloride of diacetylmorphine -- marketed as Bayer's cough medicine from 1898 to 1913 under its familiar trademark, Heroin.

 The hullabaloo about questionable risks from chronic overuse of such beneficent drugs as Celebrex and Alleve may yet result in truly serious health risks if it ends up contributing to the FDA's terrifying bureaucratic urge to deny doctors and their patients timely access to vital drugs.