Merck & Co’s withdrawn COX-2 inhibitor, Vioxx (rofecoxib), could have been linked to as many as 140,000 cases of serious heart disease in the five years it was on the market, according to new figures published in the current edition of The Lancet – significantly more than previous estimates had suggested [[07/10/04a]].
US Food and Drug Administration scientist, Dr David Graham, who has found himself at the centre of the furore surrounding drug safety in the USA [[25/11/04b]], had already warned about the risks, but had been barred from publishing his research in the US by the country’s Food and Drug Administration [[04/01/05a]]. He estimated that “between 80,000 and 140,000 excess cases of serious coronary heart disease probably occurred in the USA over the market-life of [Vioxx].” He went on to say: “The US national estimate of the case-fatality rate (fatal [heart attack] plus sudden cardiac death) was 44%, which suggests that many of the excess cases attributable to [Vioxx] were fatal.”
Dr Graham and his colleagues analyses data from almost 1.4 million patient records in California. The people in question used Vioxx, Pfizer’s Celebrex (celecoxib), and various non-steroidal anti-inflammatory drugs, including the generically-available naproxen. During the follow-up, 8,143 cases of serious coronary heart disease occurred, of which 2,210 (27%) were fatal. Overall, Vioxx was associated with a 34% increased risk of suffering a heart attack compared to other NSAIDs, and a four-fold increased risk of serious thromboembolic event versus placebo.
The withdrawal of the multi-billion dollar drug has hit Merck hard, with billions wiped off its share price and millions lost in sales [[26/01/05b]]. The company has been forced to revise downwards its financial expectations for the coming year [[09/12/04c]], and has also launched a dramatic restructuring plan in a bid to save $2 billion by 2008 [[15/12/04a]]. The firm has already been subject of countless lawsuits claiming that it should have acted as soon as it was aware of the risks associated with Vioxx’s use back in 2001 [[04/10/04b]], [[09/02/01a]]. The move has also had knock-on effects for other COX-2 manufacturers, with Pfizer and Novartis also coming under the cosh, and regulators on both sides of the Atlantic launching investigations in a bid to determine whether it is a class effect [[21/01/05b]], [[20/10/04c]]. Earlier this week, influential US consumer group, Public Citizen, called for the market withdrawal of Pfizer’s Celebrex and Bextra (valdecoxib), saying the risks outweigh their treatment benefits [[25/01/05b]], and urged the FDA to shelve plans to approve the new offerings currently waiting in the wings – namely Novartis’ Prexige (lumiracoxib), and Merck & Co’s Arcoxia (etoricoxib). However, these latest data seem to exonerate Celebrex to some extent, with figures seeming to show that the drug is cleared from any link with cardiac events.