Hard on the heels of the COX-2 debacle, the US Food and Drug Administration, which somehow seems to have developed a conscience, has recently issued a Public Health Advisory targeting all non-steroidal anti-inflammatory drugs (NSAIDs) as worthy of investigation.
It started when the FDA poked its nose into studies of Vioxx, and unearthed evidence indicating a risk of fatal heart attack and stroke so damning that manufacturer Merck was forced to yank the best-selling arthritis drug off the market overnight (see WDDTY vol 15 no 10, Viewpoint, page 5). This situation prompted the regulatory agency to begin studying clinical trials of other COX-2 drugs, such as Celebrex (celecoxib) and Bextra (valdecoxib). These, too, demonstrated an increased risk of serious cardiovascular events, particularly among patients taking the drugs for long periods of time or in a high-risk situation (say, after heart surgery).
The FDA has now announced that it is requiring a new review of all studies where Celebrex and Bextra were used just-in-case, to prevent arthritis from developing, to ensure that adequate precautions were taken.
The agency is also insisting that local institutional review boards examine and reevaluate the studies, in light of all the breaking evidence showing a causal link with heart attack or stroke.
A further blow arrived in the form of preliminary results (from the first three years) of a long-term clinical trial showing that veteran NSAID naproxen (Naprosyn or Aleve, among others) may also be associated with a greater risk of cardiovascular disease.
After making these alarming findings about what have been the best-selling drugs of all time, the FDA now thinks it prudent to look more closely at other types of NSAIDs, many of which are now sold over the counter.
With this latest advisory (an interim measure to alert the public while the FDA continues to review the data), the agency also recommends that only patients at high risk of gastrointestinal bleeding (the most common side-effect of ordinary NSAIDs) be candidates for the remaining COX-2s. It is also recommending that doctors always consider the individual risks of heart attack and cardiovascular events when prescribing any NSAID.
Most interestingly, the FDA now advises the public not to use OTC NSAIDs for more than 10 days without consulting a doctor.
It's wise to remember that aspirin is an NSAID and that, only a few years ago, the entire medical profession was handing out aspirin to all comers as a daily long-term preventative medicine for cardiovascular events and stroke. Indeed, doctors embraced this dubious theory despite the reviews of aspirin trials that showed no clear benefit with this habit (BMJ, 2000; 321: 1170-1).
Even back when the Antithrombotic Trialists' Collaboration was first waxing lyrical on low-dose daily aspirin as a stroke preventative, accompanying reports showed serious flaws in trial methodology and an increase in deaths when used after a heart attack. Now, at last, we know why.
Nevertheless, it's well to keep in mind that this is a clear case of the FDA closing the barn door after the horse has bolted. How many hundreds of thousands of heart attacks may have been caused by aspirin and COX-2 'prevention' is anybody's guess.
Until the FDA and the Committee on Safety of Medicines insist on tighter controls and longer-term drug studies, and rely less on the enthusiasms and whims of the medical profession, it won't be just the drug companies and doctors who have blood on their hands.