Vioxx-Like Risks Linked to Another Pain Pill

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Vioxx-Like Risks Linked to Another Pain Pill

A report says diclofenac increases the chance of a heart attack. The

FDA calls for further review.

By Gellene, Times Staff Writer

September 13, 2006

http://www.latimes.com/news/printedition/asection/la-sci-

painpills13sep13,1,7643966.story

The widely used pain reliever diclofenac poses the same

cardiovascular risk as the withdrawn drug Vioxx and should not be

used by people with heart disease or high blood pressure, researchers

reported Tuesday.

Diclofenac, an older drug sold as Cataflam or Voltaren, increased

patients' chance of heart attack by 40%, according to an analysis of

23 clinical studies — the same risk observed in patients who took low

doses of Vioxx.

The report was released early by the Journal of the American Medical

Assn. because of its health implications.

Diclofenac, which has been sold for more than 30 years, is available

only by prescription in the U.S. and is not widely used here. But it

is sold over the counter elsewhere and ranks among the most popular

pain relievers in the world.

But now, " there is no reason to keep it on the market, " said Dr. Curt

D. Furberg of Wake Forest University, who was not involved in the

study. " It clearly increases the risk of heart attack, and patients

have other choices. "

Dr. Henry of the University of Newcastle in Australia, an

author of the study, said that diclofenac posed little risk for

younger people with no signs of heart disease, but that given the

availability of other drugs, " I would say it has no saving graces. "

The FDA said in a statement that it did not consider the findings on

diclofenac conclusive, but that the study warranted further review.

The report contained reassuring findings about some other pain

relievers. Naproxen, sold over the counter as Aleve and by

prescription as Naprosyn, posed no cardiac risk.

Celebrex was safe at recommended doses of 200 milligrams or less a

day. Henry said he could not give Celebrex " a clean bill of health "

because other studies have detected increased cardiovascular risks at

doses of 400 milligrams or greater a day.

" Naproxen looks best from a cardiovascular point of view, " he

said. " It is an old, cheap generic drug, and we would tend to favor

it. "

Because naproxen can cause ulcers and bleeding, patients should take

the drug with medicines used to treat ulcers and control stomach

acid, such as Prilosec, Henry said.

With his colleague, Dr. McGettigan, Henry analyzed the

results of clinical studies of eight pain relievers involving more

than 1.2 million patients. All drugs in the analysis belonged to a

class of medications known as nonsteroidal anti-inflammatory drugs,

or NSAIDs. About 30 million people worldwide take an NSAID daily for

pain and inflammation.

Two drugs included in the analysis, Vioxx and Celebrex, belong to a

subset of NSAIDs known as -2 inhibitors, which were developed as

stomach-friendly alternatives to older NSAIDs, such as ibuprofen and

naproxen.

The -2 drugs were tremendous moneymakers because they were

expensive and widely used. But in September 2004, Merck & Co. removed

Vioxx from the market after it was found to cause heart attacks in

some patients.

The latest study confirmed the cardiovascular risks of Vioxx,

concluding it was not safe at any dose. The chance of heart attack

was 33% higher at the daily 25-milligram dose — in the range of risk

associated with diclofenac — and more than double at doses above 25

milligrams.

Researchers found a hint of elevated cardiovascular risk with

ibuprofen, sold as Advil or Motrin, and piroxicam, sold as Feldene,

but the increases were not significant on a statistical basis.

Added risk was associated with meloxicam, sold as Mobic, and

indomethacin, sold as Indocin, but the findings were based on a

limited number of reports.

Tuesday's study seemed to bring some clarity to the confusion that

has surrounded pain relievers since the withdrawal of Vioxx two years

ago. Assailed for failing to recognize the dangers of Vioxx sooner,

the FDA in April 2005 said all prescription NSAIDs should carry

a " black box " warning — the strongest possible — about cardiovascular

risk.

The latest study showed the FDA's relabeling order was too broad and

based on inadequate evidence, Furberg said. " The FDA has to reassess

the scare it created, " he said. " It said every painkiller is harmful,

and that clearly is not the case. "

The FDA, however, said the warnings remained appropriate because

cardiovascular risk appeared to be common to all NSAIDs and it did

not have enough clinical information to distinguish any differences

in risk among the drugs.

" This is a tough call for the FDA, " said Dr. Nissen of the

Cleveland Clinic, who as a member of an FDA advisory committee

endorsed the strong warnings. Although informative, the study's

analysis does not have the weight of a head-to-head clinical trial,

he said.

Indirectly, the diclofenac findings could be bad news for Merck. The

company has reported that its new drug Arcoxia, a potential successor

to Vioxx, has the same cardiovascular risks as diclofenac.

Dr. Graham, of the FDA's office of surveillance and drug

safety, said Arcoxia, which is now being sold in 62 countries, should

not be approved in the U.S. because it was unsafe.

Graham wrote in an editorial accompanying the study that the FDA's

decision on Arcoxia would be a test of the FDA's commitment to

patient safety.

The FDA said it could not comment on a drug that was under review.

Merck said its results were consistent with FDA's finding of no

differences in the risks posed by NSAID drugs.