Non-Cox-2 Painkillers May Also Carry Heart Risks

British study finds hazards with ibuprofen, diclofenac; other experts disagree

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By Ed Edelson
HealthDay Reporter

FRIDAY, June 2, 2006 (HealthDay News) -- High doses of older painkiller drugs may pose the same cardiac risk as newer medications such as Vioxx and other cox-2 inhibitor drugs, according to a British study that looked at what is regarded as the best evidence from randomized, controlled trials.

Data from 138 such trials with 140,000 participants showed a 42 percent increased risk of serious blood vessel problems such as heart attack and stroke in those taking selective cox-2 inhibitors, the chemical class that includes Vioxx (withdrawn in 2004), Bextra (withdrawn in 2005) and Celebrex, which is still on drugstore shelves.

Cox-2 inhibitors belong to a broader class of pain relievers called nonsteroidal anti-inflammatory drugs (NSAIDs), which also include non-cox-2 medications such as ibuprofen, diclofenac, naproxen and aspirin.

And the study -- which was funded by various U.K. public-sector medical groups -- also found a similar increase in cardiac risk for other NSAIDs, said Dr. Colin Baigent, a reader in clinical epidemiology at the University of Oxford and an author of the report in the June 3 issue of the British Medical Journal.

Specifically, long-term use of high-dose (800 milligrams three times per day) ibuprofen was associated with a 51 percent higher risk for "vascular events" compared to placebo, while long-term use of high-dose (75 milligrams two times a day) diclofenac boosted the risk by 63 percent, the U.K. team reported. No such risk was seen with long-term use of naproxen (sold under the brand name Aleve).

Ibuprofen is marketed under many brand names, including Motrin and Advil, and diclofenac is sold under brand names such as Cataflam and Voltaren. Both are NSAIDs.

"The main thing that has not been shown directly is that ibuprofen and diclofenac at high doses appears to increase the risk by about the same amount," Baigent said. "This is the first demonstration using randomized data showing an increased risk of heart disease."

The new study, Baigent said, provides "the first really reliable evidence to initiate discussions with patients about whether these risks are acceptable."

Dr. Steven Nissen, interim chairman of cardiovascular medicine at the Cleveland Clinic, who is deeply involved in the issue, begged to differ, partly on technical grounds.

The study results are not nearly as definite as they appear, Nissen said. For example, the reported 42 percent increased risk of heart problems with cox-2 inhibitor use was accompanied by a note saying the increase could be as low as 13 percent or as high as 78 percent, he said.

"The problem is that these trials are heterogenous," Nissen said. "There are only so many times you can massage the same data. A meta-analysis is just not the same as doing a careful prospective trial," he added.

It happens that Nissen is leading such a trial, planned to include 20,000 people. It will compare the incidence of cardiovascular events among people taking either ibuprofen or naproxen (Aleve, Naprosyn), to that of people taking Celebrex.

The trial results will be available in two to three years, Nissen said. Meanwhile, he said, potential users of such painkillers should discuss the benefits versus the risks of any painkiller with their physicians, and that doctors "should use these drugs in the lowest doses you can for the least time you can."

The study appeared just after the Vioxx controversy flared again, when Merck & Co., which marketed the drug, acknowledged that it had erred in reporting that a crucial statistical test said the drug caused heart problems only after 18 months of continuous use.

Nissen, who has been a consistent critic of Merck, has said "there is no biologically plausible reason to expect an 18-month delay" in the cardiac risks associated with Vioxx.

More information

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SOURCES: Colin Baigent, M.D., reader in clinical epidemiology, University of Oxford, England; Steven Nissen, M.D., interim chairman, cardiovascular medicine, Cleveland Clinic; June 3, 2006 British Medical Journal

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