This is one of the subtopic of my presentation titled “How drug company misled healthcare professionals and harm patients” during my DPIS attachment. One of the famous event happened in drug history. The story is quiet lengthy sorry i tried to summarized it already
Vioxx (rofecoxib), a selective NSAID that made a annual sales of 2.5 billion in 2003 and estimated 80 millions people were prescribed with vioxx at some time and the second famous cox 2 inhibitor next to Celebrex. (celecoxib). On the other hand, this drug also accounted to approximately 90 thousand American’s heart attacks and 38 thousand of death.
Well, although it is very scientific (I dislike to be scientific xD), I would try to explain the story in a more easy way.
The story begin in 1999 when the FDA approve vioxx, in the same year, Merck (Company of vioxx) conducted a study call vioxx gastrointestinal research study (VIGOR), this study involve 8 thousand patient to compare the safety of vioxx to naproxen in gastrointestinal.
Few months later the safety panel review that vioxx have serious heart problems and death among vioxx patients is twice as high as the naproxen group, the safety board votes to continue the trial as the effect might be because of the cardio protective effect of naproxen.
In year 2000, merck get the result of the VIGOR trial and publish it to the New England Journal of Medicine (NJEM), however, they only submitted 17 of the 20 heart attack without acknowledge NEJM the 3 extra death.
7 month later, Merck submitted the result to FDA but still didn’t submit to NEJM, so the study published in NEJM doesn’t mention the another 3 death and leave out alots of data on cardiovascular effects.
(*Note: The data were published by NEJM in 2005 after the withdrawal of vioxx, the relative risk cardiovascular event increase from 4.25 to 5%.)
Then in 2001, some researcher manage to get the data from FDA and made a meta analysis on it, the result cast a serious doubt on the hypothesis that naproxen protects the heart.
The story continue until 2004, there are several epidemiological studies shown vioxx increased cardiovascular problems, but this doesn’t affect the sales of vioxx, and it continue to rise until 2003 for its peak sales.
In 2004, merck voluntary withdraws vioxx after a study called “Approve” which shown that the drug rises the risk of heart attack after 18 months.
By the time it withdraw, it is estimated there are 20 million Americans have taken the drug, research later published in lancet which estimate that approximately 90 thousand American had heart attacks from taking vioxx, and 38 thousand of them died!
So, the next question is, how about other cox 2 inhibitor? Bextra which is marketed by Pfizer were removed from market due to the concern of possible increased risk of heart attack and strokes, which is after vioxx events. Arcoxia, which is the next generation of merck cox 2 inhibitor are not approved by FDA due to insufficient safety data provided.
Next is celecoxib, the celecoxib long term arthritis safety study (CLASS) did not present an increase in events, but however, some researcher cast a doubt on the safety of Celebrex as the CLASS trial is only range from 6 month to 13 month (Note: Vioxx rise the risk of heart attack after 18 month), so Pfizer promise to do a big, large trials for Celebrex named PRECISION trial, which begin in 2006 and completed in may 2014 which is after the Celebrex patent end.
If you goto the clinicaltrials.gov check for the PERCISION study at here http://clinicaltrials.gov/ct/show/NCT00346216?order=13 and see the progress.
References:
1. “PRECISION : Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen Or Naproxen”. ClinicalTrials.gov. National Library of Medicine. 2006-12-07.
2. Expression of Concern: Bombardier et al., “Comparison of Upper Gastrointestinal Toxicity of Rofecoxib and Naproxen in Patients with Rheumatoid Arthritis,” N Engl J Med 2000;343:1520-8. Gregory D. Curfman, M.D., Stephen Morrissey, Ph.D., and Jeffrey M. Drazen, M.D
3. Drugs.com: Arcoxia FDA Drug Approval Status
4. http://www.npr.org/templates/story/story.php?storyId=5470430
5. http://www.naturalnews.com/011401_Dr_David_Graham_the_FDA.html
My Pharmacist House 