PARIS, Jan 25 (AFP) - The controversial painkiller Vioxx may have caused as many as 140,000 cases of serious coronary heart disease in the United States before it was pulled from shelves last September, according to a much-awaited study published on Tuesday.
People taking Vioxx had a 34 percent higher chance of developing this potentially fatal ailment when compared with individuals who used other medications in the same category, the study said.
The research is lead-authored by David Graham, a senior official in the US Food and Drug Administration (FDA), which vets applications for new drugs.
Graham has been at the heart of the storm over Vioxx and its maker, the US pharmaceutical giant Merck, over charges the drug not only boosted the risk of heart disease, but that this threat should have been spotted during clinical trials.
Last November, Graham, who is associate director of the FDA's Office of Drug Safety, said in testimony to Congress that he believed Vioxx had caused 139,000 cases of serious heart problems. And in January, he angrily accused his bosses at the FDA of trying to block publication of his research.
The study -- published online by the British medical weekly The Lancet -- is based on a database of six million people in California who were enrolled with the managed health care provider Kaiser Permanente.
Of the six million, 1.4 million had used a category of commonly taken painkillers, non-steroidal anti-inflammatory drugs (NSAIDs), in the period that Vioxx was marketed, from January 1999 to September 2004.
The two leading NSAIDs they took were two over-the-counter drugs. One was ibuprofen, with just under a million users, and the other, naproxen, with 435,000 users.
The other two NSAIDS were prescription-only drugs called cyclo-oxygenase 2 (COX2) inhibitor selective NSAIDs. These are prescribed by doctors for easing the symptoms of arthritis but without having the gastric side-effects of over-the-counter drugs.
Around 40,000 used the COX2 NSAID celecoxib, marketed as Celebrex, and about 27,000 used rofecoxib, the pharmaceutical name for Vioxx.
During the period under investigation, 8,143 individuals had serious coronary heart disease, of whom 1,508 died of a sudden heart attack.
Each case was compared with four "controls" -- people of the same age and sex -- to see whether there was a statistical risk between a drug and heart disease.
Overall, the risk of serious coronary heart disease was 34 percent higher among Vioxx users when compared with other NSAIDS as a whole, the authors said.
The risk was even higher when Vioxx was compared to its fellow COX-2, celecoxib.
On standard doses, coronary heart disease was 1.6 times likelier to develop with Vioxx than with Celebrex. Among high-dose users, says Graham's team, the risk was 3.6 times higher.
"An estimated 88,000-140,000 excess cases of serious coronary heart disease probably occurred in the USA over the market life of rofecoxib," Graham said.
"The US national estimate of the case fatality rate (in serious coronary heart disease) was 44 percent, which suggests that many of the excess cases attributable to rofecoxib use were fatal."
Graham's estimate is a nationwide extrapolation for the United States, and does not cover other countries. Vioxx was marketed worldwide before its sudden withdrawal.
The study also dealt a blow to previous research which said naproxen had a protective effect against cardiac disease.
In fact, according to its figures, people taken this drug had a 14-percent increased risk when compared with other NSAIDSs.
"Naproxen use does not protect against serious coronary heart disease," the study says. "... Indeed, the present data show the possibility of a small increased risk."
Last year, The Lancet said Merck should have heeded warning signs from its clinical trials that should have stopped the Vioxx from ever going to market.
Merck retorted it had been "vigilant in monitoring and disclosing the cardiovascular safety" of Vioxx and added that the company "absolutely disagrees with any implication to the contrary."
01/25/2005 00:01 GMT - AFP