Sep 18 2006
Two major studies by experts in the U.S. and Australia have provided new evidence of the cardiovascular and kidney risks attached to both COX-2 inhibitors and NSAID painkillers.
Researchers now say the drug Vioxx can cause kidney problems as well as heart attacks and strokes.
Vioxx was withdrawn from the market in September 2004 after a three-year study showed it doubled the risk of heart attack and strokes in patients taking it for at least 18 months.
Two new studies have confirmed the dangers of taking the drug, one from Boston's Brigham and Women's Hospital and Harvard Medical School conducted an analysis of 114 studies involving more than 116,000 people and found that Vioxx was linked to an increased risk of kidney and heart arrhythmia problems.
Meanwhile Australian researchers at Newcastle University in New South Wales, found evidence that standard doses of the non-steroidal anti-inflammatory Voltaren (diclofenac), increased users' risk of heart attack by 40%.
Dr. Patricia McGettigan the lead author says that diclofenac's licence should be reviewed as it appears to be harmful at commonly used doses and they believe there are grounds for reviewing its regulatory status.
The Australian team examined 23 studies and also confirm the increased risk of heart problems with Vioxx that exists during the first 30 days of treatment rather than only after 18 months.
Drug manufacturer Merck is now facing 14,000 lawsuits from people claiming to have been harmed by Vioxx.
The studies appear in the current issue of the Journal of the American Medical Association (JAMA).
An accompanying editorial from Dr. David Graham, a physician who works for the U.S. Food and Drug Administration (FDA) says the results question the safety of another COX-2 inhibitor, Arcoxia (etoricoxib), for which Merck is currently seeking a U.S. licence.
Dr. Graham says that it has been assumed that Arcoxia poses no cardiovascular risk on the basis that it causes around the same number of cardiovascular events as diclofenac, but this latest evidence of a link between diclofenac and heart attacks, now places Arcoxia's safety in doubt.
The findings have been posted online ahead of schedule by JAMA because of their 'public health implications' and are due to appear in the October 4 issue of the journal.
Dr. Graham says in view of recent history the FDA's concerns should now be focused on patient safety rather than corporate profitability.
COX-2 inhibitors, Vioxx and Valdecoxib (Bextra), have already been withdrawn from the market.
Merck has said it stands by earlier data which says the increased heart risk begins only after the the drug had been taken for 18 months and the JAMA articles and opinions regarding potential increased risks with short-term Vioxx use "are not supported by the current weight of clinical data."
The good news is that the Australian team found that Pfizer's drug Celebrex was not associated with heart problems at a dose no greater than 200 milligrams a day.
Graham says Celebrex increases heart risk at doses higher than 200 milligrams per day along with several other non-steroidal anti-inflammatory drugs (NSAIDs), while the studies agree naproxen is "neutral" for heart attack risk.
Graham says that for most patients with arthritis or other conditions requiring chronic pain relief "naproxen appears to be the safest NSAID choice from a cardiovascular perspective."
Graham also says the controversy over the side-effects of painkillers illustrates the need for better ongoing safety studies and physicians and patients both need complete information about risks and benefits to properly use COX-2 inhibitors and other clinical treatments.