After $2.5 billion in sales last year alone, the manufacturers of the popular prescription drug Vioxx have decided to withdraw the drug from the international market, resulting in the largest withdrawal of a prescription drug in history.After approval from the Food and Drug Administration in 1999, Vioxx was introduced as an anti-inflammatory drug for the treatment of acute pain and arthritis.Five-and-a-half years later, over 80 million patients in more than 80 countries have received treatment.
Now studies show that continuous therapy for a period greater than 18 months can increase risks of heart attack and stroke in patients.While some have been highly critical of the manufacturers of Vioxx (Merck & Co., Inc.), the FDA, and other international regulatory bodies for not designing trials specifically anticipating cardiovascular risks associated with Vioxx, other professionals feel that Vioxx is still a relatively safe drug and that there is not enough evidence to prove that it is the sole cause of increased risks in patients.Rofecoxib, the chemical name for Vioxx, falls into a class of drugs known as Cyclooxygenase-2 (COX-2) inhibitors, which includes such drugs as Celebrex (celecoxib).These inhibitors work by specifically targeting the COX-2 enzyme and by blocking the enzyme that produces chemical messengers responsible for the pain and swelling associated with arthritis.As a result, inflammation is reduced.
COX-2 inhibitors, in turn, are part of a larger class of drugs known as non-steroidal anti-inflammatory drugs (NSAIDs).The other NSAIDs, which include aspirin and ibuprofen (Advil, Motrin, etc.), are different from COX-2 inhibitors in that they target both COX-1 and COX-2 enzymes.When the COX-1 enzyme is blocked, the protective lining in the stomach is reduced, leading to upset stomach, internal bleeding, and possibly ulcers.Over the past few years, Merck designed studies investigating the possibilities as to whether or not Vioxx could lead to these gastrointestinal side effects.
The two clinical studies, the APPROVe (Adenomatous Polyp Prevention on Vioxx) trial and the VIGOR (Vioxx Gastrointestinal Outcomes Research) study, showed that Vioxx had a lower rate of the gastrointestinal risks that were typically associated with NSAIDs.One of the major reasons Vioxx was such a popular drug is the fact that, according to the FDA, "Vioxx is the only NSAID demonstrated to have a lower rate of these side effects."However, while the studies revealed promising information, they unexpectedly indicated something else:relatively increased risks of cardiovascular events, such as heart attack or stroke.
The results of the VIGOR study, which were released in March 2000, only showed increased cardiovascular risks when compared to naproxen (Aleve), another NSAID.However, Vioxx did not show these risks compared to placebo or other NSAIDs.
Dr. Steven Snapinn, former senior director of the Department of Biostatistics for Merck Research Laboratories, worked in cardiovascular drug development for 20 years.He is one such professional who believes that it is still not clear whether or not Vioxx causes cardiovascular events.
"It was Merck's belief that the results of VIGOR reflected a cardiovascular benefit caused by the NSAID, and not harm caused by Vioxx," Snapinn said.
The APPROVe study was a three-year trial that indicated a relatively increased risk for cardiovascular events only after the first 18 months of treatment, and was halted in late September before completion as a result.This study, which involved 2,600 patients, indicated a 3.5 percent occurrence of heart attack or stroke in patients taking Vioxx versus 1.9 percent occurrence with placebo.
"Differences like those observed in APPROVe can occur by chance alone, and previous data suggesting cardiovascular risk with Vioxx have had methodological flaws that make them difficult to interpret," Snapinn said."While some experts, such as Eric Topol of The Cleveland Clinic, have been very critical of Merck and the FDA for not acting sooner, others I have spoken to are not convinced that Vioxx is dangerous."
Topol, Chairman of the Department of Cardiovascular Medicine at The Cleveland Clinic, addressed his concerns in "Failing the Public Health--Rofecoxib, Merck, and the FDA," an article which appeared in October 21 issue of The New England Journal of Medicine.
"For the past few years, every month has seen more than 10 million prescriptions for Rofecoxib written in the United States alone...Considering the tens of millions of patients who were taking Rofecoxib, we are dealing with an enormous public health issue," Topol wrote.
"Many epidemiological studies confirmed and amplified the concern about the risk of myocardial infarction [heart attack] and serious cardiovascular events associated with rofecoxib," Topol said, adding that many such studies considered large populations of up to 1.4 million patients.
In Topol's view, Merck responded in the same manner each time a study was published:"that the study was flawed and that only randomized, controlled trials were suitable for determining whether there was any risk."
Snapinn, however, disagrees as to the time when such suggesting evidence was revealed.
"It was only after the VIGOR trial was completed that questions were raised regarding potential cardiovascular risk," Snapinn said.He added that the FDA was aware of these results, and that prescribers were alerted in Vioxx's package insert."Merck is an extremely ethical and conservative company, and withdrew Vioxx from the market based on data that strongly suggest, but do not prove, excess cardiovascular risk."
Topol blames the FDA for not acting sooner, claiming that "it never took the initiative
Read More
U.Va. loses over $60 million in federal research cuts
By Bertie Azqueta | 12 hours agoThe impacted grants include three from the NIH, seven from the NEH, one from the United States Agency for International Development and four from the State Department.
Department of Education reverses course, awards Federal Executive Institute to U.Va.
By Ford McCracken | 3 days agoThe ED had previously awarded the institute to Charlottesville City Schools.
Students reflect on the life and legacy of Pope Francis
By Bertie Azqueta | 4 days agoAt the University, students shared a range of perspectives on his legacy of reform, inclusivity and his impact on the global Catholic community.
