If you thought Vioxx was bad, Bextra could be even worse. Things are unravelling quickly for the COX-2 inhibitor painkillers, which were pushed as a safer and better option than the NSAIDs (non-steroidal, anti-inflammatory drugs). Within days of Vioxx being pulled from the market by its manufacturer because of a link to serious heart problems last September (see Viewpoint, page 5), its successor Bextra is now being accused of the exact same thing.
A pooled analysis of clinical-trial results has shown that patients taking Bextra are twice as likely to have a heart attack or stroke as those taking a placebo. In fact, an analysis of nearly 6000 patients showed that the risk with Bextra was even higher than that of Vioxx.
Bextra quickly became the anti-inflammatory of choice among doctors after Vioxx was discredited. The COX-2s became the preferred painkillers after the NSAIDs were found to cause stomach bleeding and other gastric problems.
The US drugs regulator, the Food and Drug Administration (FDA), is so concerned by the latest findings that it is expected to order a complete review of the anti-inflammatories. In doing this, it joins the European Medicines Evaluation Agency, which has already ordered a safety review of the COX-2 family.
The drugs watchdogs need to redeem themselves as soon as possible, judging by their past performances. WDDTY discovered that the FDA had approved Vioxx for use in children just days before its manufacturer, Merck, finally did the right thing.
Vioxx almost doubles the risk of heart attack and stroke in patients who had taken the drug for at least 18 months. The FDA reckons that Vioxx may have caused more than 27,000 heart attacks in the four years it had been on the market – of which 7000 have been fatal.
Given this information, it’s especially surprising that it was also the FDA that approved the drug for paediatric use, after studying a three-month trial carried out by the manufacturer on a group of children. An FDA spokesman told a newspaper that the decision was the correct one based on the information available at the time. Paradoxically, he added that it was also the correct decision of the manufacturer to withdraw the drug – an odd statement given the enormous amount of data already pointing to the drug’s dangers. It was even taken up by one of the FDA’s own officials, who found further evidence of a link to cardiovascular disorders. But the agency chose to ignore the findings as they did not meet the ‘gold standard’ of research – meaning that they weren’t derived from the double-blind placebo-controlled studies beloved of medical researchers and journals.
Even so, there were plenty of ‘gold-standard’ studies that might have given the FDA pause. As far back as February 2000, WDDTY was telling its readers that the common adverse reactions of COX-2 inhibitors included abdominal pain, dizziness, fluid retention and hypertension; three years later, we were able to confirm that Vioxx patients were twice as likely to suffer a cardiovascular problem as those taking an NSAID.
It also appears these health problems were not a mystery to the drug’s manufacturer either. According to e-mails circulated among Merck senior officials, the company knew that Vioxx was linked to heart problems long before it released the information to the market (USA Today, 10 November 2004; http://www.fda.gov).