Tuesday, December 21, 2004
The problem is that we must stop and think for a minute, something which the FDA has not done. We know quite a bit about NSAIDs and the risk of vascular events. The only COX inhibitor proven to reduce the risk of myocardial infarction is aspirin. That was confirmed by The Antithrombotic Trialist Collaboration (BMJ 2002) which reviewed many studies including 5 randomized trials of more than 60,000 men and women. Aspirin reduced the risk of first myocardial infarction by 32%. The VIGOR study included 8000 patients with rheumatoid arthritis randomized between rather high doses of rofecoxib and naproxen. Rates of MI were 4 times as high in the Vioxx group as with naproxen. Then we were told that naproxen had some vascular protective effects and that a better comparison would be rofecoxib vs. Ibuprofen (nicer for the drug company). Naproxen has more effects on COX-1 and platelets than Ibuprofen does, and several studies suggest weak anti-thrombotic naproxen effects, but naproxen has never been proven to reduce the risk of vascular events compared to placebo. The recent TARGET study compared the incidence of various problems, including cardiovascular events in 9156 patients age 50 years or older randomized to lumiracoxib (another Cox-2 inhibitor) 400 mg QD, naproxen 500 mg twice daily (4754), or ibuprofen 800 mg three times daily (4415) in two identical sub studies. The primary cardiovascular endpoint was non-fatal and silent myocardial infarction, stroke, or cardiovascular death. Here are the results:
Confirmed/probable cardiac or Cerebrovascular events:
Lumiracoxib (85/9117 or 0.93%) both NSAIDs 75/9127 (0.82%)
All myocardial infarction:
Lumiracoxib 23 (0.25%) both NSAIDs 17 (0.19%)
L’coxib vs. Ibuprofen 5 (L) & 7 (I)
L’coxib vs. Naproxen 18 L (0.38) & 10 N (0.21%)
None of these differences are statistically significant. This big prospective study shows that naproxen is at least as good as Ibuprofen in terms of cardiovascular events. Therefore if the FDA is to suggest that naproxen be used for no more than 10 days, they must do the same for Ibuprofen.
This is lunacy. The FDA and the DOD are under fire, bobbing and weaving with hasty daily press releases. The heads of both agencies should be put on notice: think before you open your mouth. It was reasonable to stop the Alzheimer study. It was unreasonable to suggest that Naproxen increases the risk of cardiovascular disease for the general population.
I think that it’s clear that all selective Cox-2 inhibitors modestly increase the risk of MI and stroke; they should not be taken off the market; they should not be used in persons above age 40, which still leaves a significant group of patients with migraine, connective tissue diseases, etc below 40. Patients above age 40 without any cardiovascular risk factors can take Ibuprofen or Naproxen, but shouldn’t push them to high doses. They should use physical therapy and acupuncture to help control joint pain. Patients with definite cardiovascular risk factors should take aspirin and generic omeprazole, which costs less than the brand name COX-2 inhibitors, and has no higher incidence of GI bleeding. We must get away from this idea of miracle drugs and pay much more attention to diet and exercise. Physicians must be more skeptical about drug company promotions and gifts and must individualize treatment to particular patients. There isn’t going to be a magic bullet for all humans in pain – the tremendous effects of age and genetic heterogeneity guarantee this.
....I own no drug company stocks, I can supply a list of 18 references to any interested parties.
And Precision Blogger asks what doses were used in the studies. That's a good question. The Celebrex study used dosages that were twice the normal dose used for arthritis. I don't know what doses were used in the narpoxen study.
posted by Sydney on 12/21/2004 08:49:00 PM 0 comments