A Tale of Technology, Risks, and Unintended Consequences
Invited Post by John Nail, Ph.D.
Modern pharmaceutical drugs, along with other medical technologies, have doubled life expectancies during the past 100 years. There is a real possibility that the news media, politicians, lawyers and gullible jurors will put an end to these advances. The news media appears to enjoy reports of ‘dangerous products’ that the politicians embrace as it gives them a way of diverting attention from their own lack of competence. Trial lawyers earn their living by convincing gullible jurors that the ‘big companies’ are to blame for anything adverse that occurs when someone uses their product. Often, the result of the media and political orgy is that useful products are removed from the market. This is the story of a drug that was removed due to safety reasons and the possible unintended consequences of its removal. Before we proceed, we should note that 1) ALL technologies have unintended adverse consequences, 2) It is not possible to know what these consequences will be until large numbers of people start using (and abusing) the product, and 3) Decisions have unintended consequences, including often making a situation worse when trying to make it better.
Vioxx (generic name rofecoxib) was a prescription drug for the treatment of pain from osteoarthritis (this is the type of arthritis that occurs when bones are rubbing against each other). Vioxx was approved for use by the US Food and Drug Administration on May 20, 1999; it was discontinued on September 30, 2004, due to concerns regarding cardiovascular problems (heart attacks and strokes) in patients that used the drug.
A considerable amount of testing is required before the FDA will approve the use of a new prescription drug. One of the pre-approval tests involving Vioxx was the ‘VIGOR’ study – a double-blind test in which one group of participants (the study group) was given Vioxx and the other, (the control group) naproxen, a non-prescription pain reliever. This trial found that the Vioxx group members who had pre-existing heart attack risk factors were four times more likely to have a heart attack than were the participants of the naproxen group with pre-existing heart heart attack risk factors. One interpretation of this result is that Vioxx causes heart attacks in people with heart disease risk factors; the other interpretation is that naproxen prevents heart attacks in people with heart disease risk factors. We know that aspirin prevents heart attacks, so it is reasonable to assume that naproxen prevents heart attacks. Interestingly, there was no difference between the two groups in regards to deaths from heart attacks, nor was there a difference between heart attack rates between the two groups in people who did not have heart attack risk factors. Thus, if a person has heart attack risk factors and should be taking a ‘baby’ aspirin each day, that person’s chance of a heart attack is four times higher if the person is taking Vioxx instead of naproxen.
APPROVe was another Vioxx clinical study in which the ‘control’ group was given a placebo (sugar pill). During this study, it was found that, after 18 months, the participants who were being given Vioxx were almost twice as likely to have a heart attack than were the participants who were being given sugar pills. However, the heart attack deaths (mortalities) were equivalent between the two groups. Thus, as in the VIGOR study, the rate of heart attacks were greater in the Vioxx group, but the rate of heart attack deaths were identical between the two groups. The APPROVe results and the resulting media uproar resulted in Vioxx being withdrawn from sale.
Bextra and Celebrix were Vioxx’s competitors. Bextra was withdrawn due to increased heart attack and stroke risks in patients who were taking Bextra while recovering from heart surgery. Celebrix is still being marketed, however, it has a ‘black box warning’ that it should be used only as a last resort on patients who have heart disease or a risk of developing heart disease.
One of the arguments for why Vioxx and Bextra should no longer be sold was that “osteoarthritis patients have other options for relieving their pain” – these other options are over the counter pain relievers (aspirin, naproxen, acetaminophen, ibuprofen, etc.), and opioids such as codeine, demerol and morphine. While opioids are among the most effective of all pain relievers, they have unintended effects such as narcosis (sleep inducement) and physical and psychological addition. Rush Limbaugh allegedly became psychologically addicted to opioids.
Recently, a study determined that switching osteoarthritis patients from Vioxx or Bextra to opioids has resulted in a fourfold increase in falls and broken bones in elderly osteoarthritis patients. A quote from an article in The Journal of Higher Education that discussed this increase in falls and broken bones,
“Somebody should have thought more carefully about the elderly before making these recommendations” (switching elderly osteoarthritis patients from drugs such as Vioxx to drugs such as codeine to control their pain), says Bruce N. Cronstein, a professor of medicine at New York University’s Langone Medical Center. “Falls in an elderly population can be very dangerous, leading to long hospitalizations and even death.” ….”We don’t have wonderful alternatives for treating chronic pain”… Long treatment with aspirin or ibuprofen, for instance, often irritates and damages the digestive system…Falling down seems like one of the most obvious adverse effects, says Dr. Cronstein. “That’s not rocket science,” he notes. “The elderly are more frail. They have a host of factors that could lead to falls. If you add something that makes you a little unsteady, it increases the risk”
Thus, the choices for people with osteoarthritis are (and were) over the counter drugs such as aspirin and ibuprofen, that can cause digestive damage from long-term use, prescription narcotics that increase a person’s risk of falling by fourfold, or prescription drugs such as Vioxx that, in people with heart attack risks, increased their risk of heart attacks, however, these did not increase their risk of dying from a heart attack. The media and political storm that resulted in Vioxx and Bextra being removed from the market appears to have resulted in either more pain in osteoarthritis sufferers due to their not treating the pain, or the possibility / reality of digestive system damage, or increased use of opioid drugs which has produced an increase in falls and broken bones.
Elderly patients also don’t have the best of memories. This sometimes leads to accidental overdoes of opioid (and other drugs) due to a patient’s forgetting that they had already taken their pain pill for that day. It is also known that people often develop tolerances to opioid drugs, making these increasingly less effective.
I leave you with a comment uploaded to the discussion section from The Journal of Higher Education article:
‘“In addition to the danger of increased falls, the removal of Vioxx and Bextra from the market meant increased arthritis pain for millions of people (including me). The possibility of heart problems for some won out over the reality of pain for millions. I hope that not all medical decisions are made this way” John C.’
Unfortunately, this is how medical decisions are made during a media generated crisis. The next time that there is a media uproar about ‘dangerous medical products’, remember that the unintended consequences from the product’s alternatives may be worse than the product’s unintended consequences.
DR. NAIL is Chair of the Chemistry Department at Oklahoma City University