GETTYSBURG MEDICAL NEWS
  THE CLINICAL VIEW
  by Phillip Hoffsten, M.D.
  13 APRIL 2005

FIRST VIOXX, NOW BEXTRA - GONE

            After all of these years, I should know better; but I never cease to be amazed at how something so simple can get so complicated.  Recently, a very effective pain and arthritis pill called Vioxx was taken off of the market voluntarily by the Merck drug company because there was a slight associated increase in heart attacks.  This caused a great deal of concern among arthritis sufferers because Vioxx was a very effective medication.  Many of these arthritis sufferers then turned to Bextra as a second choice. Now Bextra has been taken off the market because it causes a skin rash problem.  These were two very similar medications taken off the market for very different reasons.  Looking at data regarding other arthritis pills, the public is now very suspicious of the whole family of “non-steroidal anti-inflammatory drugs”.  What is a person with arthritis to do now?

            To understand the problem, I think it best to go back to the beginning.  Aspirin was our first arthritis pill, introduced in 1895 by the Bayer company.  It was the first “non-steroidal anti-inflammatory drug.”  In the late 1960s, Dr. John Vane received the Nobel Prize for his discovery of how Aspirin works.  He discovered that Aspirin blocked a chemical system in the body called cyclooxygenase or (COX).  He didn’t know it at the time, but it was subsequently shown that there were two different COX systems in the body.  These were called COX-1 and COX-2.  These two systems had very different functions.

            The COX-1 system has very important body functions including regulation of blood pressure, blood clotting, protection of the stomach, and excretion of salt.  These are called constitutive functions that are critical to body well-being.

            The COX-2 system was devoted to inflammation.  When the COX-2 system is activated, the person develops inflammatory changes such as arthritis and the soreness and pain that occurs after injuries or surgeries.

            Blocking the COX-1 system is bad.  People get ulcers, high blood pressure, and salt retention.  Blocking the COX-2 system is sometimes good by stopping pain and discomfort from arthritis and injuries.

            By definition, a “nonsteroidal anti-inflammatory drug” was one that blocks the COX-2 system.  Unfortunately, all of the nonsteroidal anti-inflammatory drugs on the market through the mid-1990s blocked both the COX-1 system and the COX-2 system although to varying degrees.  Because of great individual variations, some people could tolerate large doses of Aspirin to effectively treat their arthritis without getting ulcers, fluid retention, or high blood pressure.  In other individuals Aspirin had little impact on their arthritis, but they developed stomach irritation, high blood pressure, and salt retention when they used large doses of Aspirin.  To make the situation more complicated, we have now learned that one out of four people have little beneficial effect from Aspirin.  In addition, we know that group of people in whom Aspirin does not work have a much higher rate of heart attack and stroke than the group that is sensitive to Aspirin.

            Years ago as this information was accruing, the Pfizer drug company and the Merck drug company began studying how to make a drug that would block the COX-2 system, but not block the COX-1 system.  If that could be achieved, there would be the advantage of stopping arthritis pain, but not causing high blood pressure, salt retention, or ulcers.  The first drug on the market in this group was Vioxx.  It was quickly followed by Celebrex and then Bextra.  Vioxx was by far the most effective medication of the three, but unfortunately, it still retained the side effect of causing high blood pressure and salt retention.  The drug was marketed and promoted because of the decreased incidence of ulcers and gastric irritation.  It was in fact a very effective medication for stopping arthritis pain and post-operative pain.

            Completely unexpected and not predictable was the observation that Vioxx had a slight increase in the rate of heart attack among people using the drug. The reason for this increased rate of heart attack is unknown.  It could be that people who take Vioxx are more vigorous and active because they don’t hurt so much. By being more active, they might strain their hearts more than people who don’t take Vioxx.  Alternatively, it could be that people who take Vioxx use less Aspirin.  Vioxx has no heart protection capability whereas Aspirin does.  But if someone is using Vioxx to stop pain, they are less likely to use Aspirin and thereby lose the Aspirin heart protection.  These are speculations and the answer to why Vioxx may have a slight increase in heart attack rate remains unknown at this point.  The FDA has recently suggested that Vioxx be brought back to the market, but with appropriate warnings.  The Merck pharmaceutical company is still considering whether this is what they want to do.

            The Bextra problem is brand new and also unpredicted and unexpected.  Details regarding the drug withdrawal are not available other than to say that the FDA recommended that it be removed from the market because of problems with skin rashes.  There were also speculations that it might cause an increased rate of heart attack just as Vioxx did, but that data is inconclusive at this point.

            So what is a poor arthritis sufferer to do as this seemingly never ending story goes on and on.  First, I recommend that anyone who can tolerate it, use 5 grains of adult Aspirin daily.  This is clearly heart protective and more so than the low dose of 81mg Aspirin per day.  Second, the old non selective non-steroidal anti-inflammatory drugs such as Ibuprofen, Naprosyn, Voltaren, Orudis, Indocin, etc., are still available for those individuals who can tolerate the drugs.  These medications should be avoided in elderly patients with heart problems and high blood pressure.  Third, Celebrex is the last COX-2 inhibitor still on the market.  It is relatively less effective than Vioxx or Bextra were, but seems to work very well for some individuals.  The biggest disadvantage of Celebrex is the very high price compared to the other nonselective NSAIDs mentioned above.

            As a last consideration, rather than use the non-steroidal anti-inflammatory drugs, the elderly arthritic patient might better be served with a pure pain medication.  Using products such as propoxyphene (Darvon) or tramadol (Ultram) does provide a non-narcotic way of treating arthritic pain used only when the pain occurs.  These medications do not need to be used all of the time, although they could be if needed.  The side effect profile from these medications is much less than from the non-steroidal anti-inflammatory drug group.  If Darvon and Ultram are not effective enough, I personally recommend the use of narcotics to stop the pain and allow the person some relief.  The dose of narcotic drugs can be adjusted to provide pain relief while still not causing side effects.  In this situation, the risk of “addiction” is a non-consideration if the person can just be provided some pain relief.

            There are new COX-2 inhibitors that are being considered on the market at this time.  What the future holds is not clear and probably will get more complicated yet.  But relief for the arthritis sufferer today is available through your local clinics and individual attention to the specific concerns of the individual patient and a personalized pain relief program.