More Studies Link Painkillers to Heart Problems

Research builds on earlier findings surrounding anti-inflammatory drugs

THURSDAY, June 9, 2005 (HealthDay News) -- Scientists on both sides of the Atlantic continue to uncover troubling news about commonly used painkillers, including ibuprofen and Celebrex.

The latest data comes from a large British study that found that popular painkillers called NSAIDS -- non-steroidal anti-inflammatory drugs -- do elevate the risk of heart attack. These drugs include ibuprofen and Vioxx, one of a newer generation of anti-inflammatories called cox-2 inhibitors that was pulled from the U.S. market in September after studies linked it to heightened risks for heart attack and stroke.

The authors of the study, which appears in the June 11 issue of the British Medical Journal, cautioned against stopping use of the drugs just yet, however.

"We don't think patients/physicians should change treatments/practice on the basis of this study as it is an observational study, not a randomized, controlled clinical trial," said Dr. Julia Hippisley-Cox, lead author of the study. She is a professor of clinical epidemiology and general practice at the University of Nottingham's Centre for Population Studies.

An observational study is considered less reliable than a randomized trial.

A separate study in the same issue of the journal, this one out of Canada, found that Celebrex seemed safer than Vioxx and other NSAIDs in elderly patients with congestive heart failure.

But that study, too, had some methodological problems, experts said.

"It's hard to take much away from these (studies). The reason is because of the way these studies are set up and because it would have been more valuable if investigators had told us what the event rates (numbers of heart attacks, rather than percentages) were," said Dr. Robert J. Myerburg, professor of medicine and physiology at the University of Miami School of Medicine. "It's hard to know, from an impact point of view on individual patients, what all this means."

On the other hand, Myerburg added, this new data does support previous research on cox-2 drugs.

Cox-2 inhibitors, a subclass of non-steroidal anti-inflammatory drugs, have been under intense scrutiny since September when Vioxx was withdrawn from the market due to concerns about cardiovascular safety. Then similar concerns were raised about Bextra, another cox-2, then Celebrex and then naproxen -- a traditional NSAID. Bextra was later withdrawn from the market.

As the dominoes started falling, patients and doctors worried whether the cardiovascular effects extended to all cox-2s or even to all NSAIDs, including aspirin, which so far has not been associated with heart problems.

That is one question these two studies tried to address. The question is an important one as many people, especially the elderly, have switched from Vioxx and Bextra to other cox-2s or NSAIDs and may still be at risk for heart-related problems.

For the British study, researchers identified over 9,200 patients across the United Kingdom who had had a first heart attack within a four-year period. Then they analyzed what drugs the patients had been prescribed and compared this information with data on more than 86,000 comparable healthy people.

People who had been prescribed NSAIDs in the three months before their heart attack were at a higher risk when compared with people who had not taken NSAIDs in the previous three years, the study found.

People taking ibuprofen were at a 24 percent increased risk while those taking diclofenac (Solaraze, Voltaren) faced a 55 percent increased risk.

Cox-2 inhibitors were also associated with higher rates of first-time heart attacks. People prescribed Celebrex in the three months prior to the heart attack were at a 21 percent higher risk and those prescribed Vioxx were at a 32 percent increased risk versus people who did not use these drugs at all, the researchers found.

That translates into one extra heart attack in a year for every 695 patients aged 65 and over taking Vioxx. For ibuprofen, there would be one additional heart attack for every 1,005 patients in this age group and, for diclofenac, there would be one extra heart attack for every 521 patients, according to the researchers.

"Our results show the increase in risk of myocardial infarction [heart attack] observed in the VIGOR study is genuine but also raise concerns about the toxicity of conventional NSAIDs such as diclofenac and ibuprofen and the newer selective NSAIDs [Cox-2s]," Hippisley-Cox said in an e-mail interview.

The scientists also found no evidence of heart-protective effects for naproxen, which includes such brand-name medications as Aleve and Naprosyn.

Hippisley-Cox said the researchers still need to look at all safety data for the drugs including that from unpublished studies.

The Canadian study looked at prescribing information for 2,256 patients aged 66 or over in Quebec.

The risk of death and recurrent congestive heart failure combined was 26 percent higher in people who had been prescribed NSAIDs or Vioxx than in those prescribed Celebrex.

This indicates that Celebrex may be safer in this group of people and that differences may exist between NSAIDs and cox-2s as well as among cox-2s, the researchers said.

But the implication that a cox-2 is safer than an NSAID is a strong statement with challenging implications and needs to be backed by strong science, Myerburg said. He also believes these two new studies lack the rigorous science found in the highest level of research -- a randomized, double-blind, placebo-controlled trial.

More information

The U.S. Food and Drug Administration has a public health advisory on NSAIDs.

SOURCES: Julia Hippisley-Cox, M.D., Ph.D., professor of clinical epidemiology and general practice, Centre for Population Studies, University of Nottingham, England; Robert J. Myerburg, M.D., professor of medicine and physiology, University of Miami School of Medicine; June 11, 2005, British Medical Journal
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