Two leading heart experts called for urgent investigations on Wednesday into whether all painkilling drugs known as COX-2 inhibitors may raise the risk of heart attack in some people.

They also called for a Congressional investigation into whether regulators acted too timidly in last month’s recall of Vioxx, Merck’s best-selling COX-2 inhibitor.

Merck recalled the drug, ironically developed to be a safer alternative to aspirin and similar drugs such as ibuprofen, after learning it more than tripled the number of heart attacks in patients taking it in one study.

“I believe that there should be a full Congressional review of this case,” Dr. Eric Topol of the Cleveland Clinic in Ohio wrote in a commentary in this week’s New England Journal of Medicine.

“The senior executives at Merck and the leadership at the Food and Drug Administration share responsibility for not having taken appropriate action and not recognizing that they are accountable for the public health,” Topol added.

“Sadly, it is clear to me that Merck’s commercial interest in rofecoxib (Vioxx) sales exceeded its concern about the drug’s potential cardiovascular toxicity.”

The FDA has approved three drugs in the COX-2 class - Vioxx, which Merck decided on its own to withdraw, Celebrex, made by Pfizer under the generic name celecoxib, and Pfizer’s Bextra or valdecoxib.

The drugs are spectacularly successful, because they are designed to be taken long-term by patients with arthritis and other chronic ills. Makers had hoped they would be less likely to cause stomach bleeding and ulcers than older drugs called non-steroidal anti-inflammatory agents or NSAIDS.

Topol, who reviewed the data given to the advisory committee that recommended approving the drugs, said he and fellow experts had strongly recommended a trial testing whether the drugs may raise heart risks.

“Unfortunately, such a trial was never done,” Topol wrote.

“Meanwhile, Merck was spending more than $100 million per year in direct-to-consumer advertising - another activity regulated by the FDA and a critical mechanism in building the ‘blockbuster’ status of a drug with annual sales of more than $1 billion.”

Dr. Garret FitzGerald of the University of Pennsylvania said it was possible all COX-2 inhibitors could affect heart risk by acting on the epithelium that lines blood vessels.

“We now have clear evidence of an increase in cardiovascular risk that revealed itself in a manner consistent with a mechanistic explanation that extends to all the coxibs,” he wrote in a separate editorial in the Journal.

“It seems to be time for the FDA urgently to adjust its guidance to patients and doctors to reflect this new reality. Only the FDA can provide unbiased and informed guidance; it has a role to play beyond watchful waiting.”

FitzGerald said doctors should be cautious in prescribing COX-2 inhibitors to patients with heart disease.

The European Medicines Agency said earlier on Wednesday it would review the cardiovascular safety of COX-2 inhibitors and would strengthen existing warnings about them.