You are hereby cautioned that the anti-retroviral Ziagen (also known as Abacavir), which is included as part of many anti-AIDS regimens worldwide, may almost double your risks of heart problems. That’s what a major study conducted in the United States, Europe and Australia has revealed.

Yes, the study by Jens D. Lundgren of the University of Copenhagen and colleagues analyzed data from more than 33,000 people infected with the AIDS virus in Europe, the U.S. and Australia to study the long-term effects of five AIDS drugs. The patients were followed for up to five years.

The researchers found that in the 517 patients, who had heart attacks, 192 had already taken Ziagen and 124 had recently taken Videx. Those given Ziagen had twice the chances of a heart attack compared to patients on other AIDS drugs, while those on Videx had a 50 percent higher chance. However, the risk disappeared six months after patients stopped taking the drugs. But, the researchers didn’t find increased heart attack risk in patients on the other drugs, such as zidovudine (AZT), stavudine (Zerit) or lamivudine (Epivir). These drugs block an enzyme that the AIDS virus needs to multiply. The findings of the study were published online by the journal Lancet on Tuesday.

Dr. Charlie Gilks, director of AIDS treatment and prevention at the World Health Organization, who was not involved in the study, said, “These anti-retrovirals are wonderful and lifesaving, but they do have toxicity problems. It may be that we can continue to see them, but we need to be aware of their long-term problems.”

According to the researchers, the increased risk of heart attack from Ziagen and Videx could be attributed to a cardiovascular inflammatory response to the drugs, but pointed out more research is needed in this area. They added that patients already susceptible to heart problems, such as smokers and the obese were most at risk.

"This is a head-scratcher, in the sense that we don't really understand the biology here," said Paul Dalton, director of Treatment and Advocacy for Project Inform in San Francisco.

Reacting quickly, the US FDA, which had approved Abacavir in 1998, on Thursday posted a notice that it was reviewing whether to take regulatory action. However, the agency emphasized that it had not concluded that the drug was responsible for the higher heart attack rate, nor was it advising doctors to stop prescribing it.

Dr. Steven Deeks, a UCSF professor who treats HIV-positive patients at San Francisco General Hospital, said the study was thorough and large-scale, but it is not definitive. It shows a near doubling of heart attack risk, but does not show why. "The concerns it raises are legitimate," he said.

John Pottage, a vice president for abacavir maker GlaxoSmithKline, said the company is taking the study results very seriously. However, he cautioned that while the risk of heart attack doubled, it was relatively low to begin with - about three per 1,000 patients annually.

On the contrary, Dr. Didier Lapierre of GlaxoSmithKline claimed the company’s own analysis of 54 studies did not suggest an increased risk of heart attack from Ziagen, but also said, “GSK takes the finding seriously and is committed to understanding these data more fully and to communicating openly with treating physicians and regulatory agencies globally.”

GlaxoSmithKline PLC makes Ziagen, while Bristol-Meyers Squibb makes Videx.