I am writing regarding the article “BC only province not paying for painkillers,” which appeared in the Vancouver Province 13 October 2002.
The subtitle, “Older drugs have stomach ripping side-effects” implies the newer non-steroidal anti-inflammatory drugs (NSAIDs), celecoxib (Celebrex) and rofecoxib (Vioxx) are safer; sadly, the report is misleading the public and increasing patient demand for these expensive prescription drugs. True, the VIGOR study published in the New England Journal of Medicine found the incidence of intestinal bleeding and perforation was 1% with naproxen (an older, cheaper generic drug) and 0.4% with rofecoxib. However, the full trial data reported to the Food and Drug Administration (FDA) was not published by the clinical investigators. The FDA version found an incidence of serious cardiovascular clotting of 0.7% with naproxen and 1.7% with rofecoxib, an incidence of serious adverse effects of 7.8% with naproxen and 9.3% with rofecoxib, and a heart attack rate of 0.1% with naproxen and 0.4% with rofecoxib. There was no difference in death rate. In terms of efficacy (pain relief and decreased joint swelling), there was no clinical difference.
In the CLASS study published in the Journal of the American Medical Association, ibuprofen (Motrin, Advil, generic) or diclofenac (Voltaren, generic) was compared with celecoxib. The full trial data submitted to the FDA (but not published in JAMA) found celecoxib did not demonstrate a statistical or clinical difference in lower intestinal bleed or perforation rates, death, or serious and total adverse effects. Furthermore, two pooled data analyses reveal increased risk of thrombotic events (heart attacks and strokes) with the newer coxibs versus the older NSAIDs; most likely because the older NSAIDs exert a protective effect by thinning the blood the same way the commonly used drug acetylsalicylic acid (Aspirin) does.
The Arthritis Research Centre of Canada claims the newer coxib drugs could reduce the 1900 deaths caused each year by the older drugs by 50%. Based on the FDA data, the newer drugs will not reduce the death rate and may even be harmful by promoting clots. The arthritis consumer experts believe coxibs “save suffering and lives.” I wish this were true.
Given the lack of demonstrated clinical and safety superiority and substantial difference in drug cost, the literature does not support recommending the coxib class as first line therapy for arthritis treatment.
Every public dollar wasted on drug therapy with no documented net benefit is a dollar not available for proven therapy for other patients. This is truly a shame when our public health care system is financially strained and starting to ration care.
I hope an informed general public and physicians use this information wisely when discussing drug therapy options for arthritis.
—Anthony Taddei, PharmD
Department of Pharmacy Services
Fraser North Area,
Fraser Health Authority
When offering a critical appraisal, it is always wise to look to the medical literature. However, it is not wise to “cherry pick” that literature.
There are many publications[1-4] regarding the new cyclooxygenase II-selective nonsteroidal anti-inflammatory agents (coxibs), other than the CLASS and VIGOR trials. Although some of the criticisms of Dr Taddei regarding the CLASS and VIGOR trials are accurate, he has not balanced this with other commentary. While he does not reference the two “pooled data analyses” alluded to in his letter, at least one of these pooled noncomparable databases offers no contribution to our knowledge.
There are a number of other studies that consistently demonstrate a reduction in serious upper gastrointestinal events with these agents. Moreover, there are at least two cost-benefit analyses in favor of the use of these agents in selected risk groups.[6,7]
The question of the causation of the increased cardiovascular events in the VIGOR study is open to debate.[8,9] There is a reasonable body of opinion that this was the result of a cardioprotective effect of naproxen, not a toxicity of rofecoxib.
Should the coxibs be used for all individuals requiring nonsteroidal anti-inflammatory drugs? Of course not. However, in those over the age of 70, those with a history of peptic ulcer disease in the past 5 years or with a history of complicated peptic ulcer disease, those on anticoagulants, those with severe rheumatoid disease, and those on chronic corticosteroid therapy, there is demonstrable benefit, both to the patient and to health care costs.
Since the vast majority of patients are paying out of their own pocket for the coxibs that they take, the use of these agents can scarcely be construed as a drain on the public purse. It would be worth Dr Taddie’s consideration that many patients not in a risk group, after being presented with the alternative of a coxib versus a nonselective agent, and with the relatively small risk-benefits if they are not in a risk group, select the coxib, despite the fact that this means user-pay. They take the attitude that, likely being hit by a train, it does not matter that the risk was small if you are the one being hit. Not a sensible choice? In that case, wearing a seatbelt and having air bags is not sensible, since the majority of automobile accidents will not result in significant injury, even if a seatbelt is not worn, and these are costly additions to our automobiles (as well as being associated with some side effects). It is unclear why the health care bureaucracy continues to recommend “good enough treatment” for the population when, in so many other parts of our society, we expect maximum safety and effectiveness.
—Barry Koehler, MD
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Halpern SD, Ubel PA, Caplan AL, Marion DW, Palmer AM, Schiding JK, et al. Solid-organ transplantation in HIV-infected patients. N Engl J Med. 2002;347:284-7.
About the ICMJE and citation styles
The ICMJE is small group of editors of general medical journals who first met informally in Vancouver, British Columbia, in 1978 to establish guidelines for the format of manuscripts submitted to their journals. The group became known as the Vancouver Group. Its requirements for manuscripts, including formats for bibliographic references developed by the U.S. National Library of Medicine (NLM), were first published in 1979. The Vancouver Group expanded and evolved into the International Committee of Medical Journal Editors (ICMJE), which meets annually. The ICMJE created the Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals to help authors and editors create and distribute accurate, clear, easily accessible reports of biomedical studies.
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