Vioxx, the painkiller recalled last September because of safety concerns, may have caused up to 140,000 cases of serious heart disease in the United States, researchers said on Tuesday.

Dr David Graham, the associate director of the U.S. Food and Drug Administration’s (FDA) Office of Drug Safety who warned about the risks months ago, said many of the cases associated with Vioxx, or rofecoxib, which was launched by Merck & Co Inc in 1999, were probably fatal.

“An estimated 88,000-140,000 excess cases of serious coronary heart disease probably occurred in the USA over the market life of rofecoxib,” said Graham, whose study was reported online by the Lancet medical journal.

“The U.S. national estimate of case-fatality rate was 44 percent, which suggests that many of the excess cases attributable to rofecoxib use were fatal,” he added.

The case fatality rate includes fatal acute heart attacks plus sudden cardiac death.

Graham and his colleagues based their estimate on data on 1.4 million people in California over five years.

Merck described the estimates in the study as speculation and said there were several factors such as high blood pressure, smoking and raised cholesterol that increased the risk heart attack and stroke.

Graham, a 20-year veteran of the agency, first gave the estimates of harm from the drug to a Senate hearing last November.

Two months earlier, the drug had been pulled from the market following research that showed it increased the risk of heart attack and stroke in patients taking it for more than 18 months.

PAIN

“There is no reliable way to measure actual use in a population and therefore no reliable way to estimate the actual number of events,” a Merck spokesman in the United States said in response to the findings.

“Determination of whether Vioxx was responsible for many patient’s myocardial infarction (heart attack) or stroke can only be made on a case by case basis,” he added.

Vioxx belongs to a class of drugs known as COX-2 inhibitors which are prescribed to relieve arthritis pain.

The people studied by Graham and his colleagues used painkillers called non-steroidal anti-inflammatory drugs, or NSAIDs, such as ibuprofen and the newer COX-2 inhibitors Vioxx and Pfizer Inc.‘s Celebrex, or celecoxib.

NSAIDs work by suppressing two enzymes called COX-1 and COX-2. But they can cause gastrointestinal bleeding. COX-2 inhibitors were designed to limit the damage.

There were 8,143 people who suffered coronary heart disease in the study, including 1,508 sudden cardiac deaths. The researchers matched each case with four controls of a similar age and sex to compare the risk among people taking Vioxx and the other drugs.

They found Vioxx users had a 34 percent higher chance of coronary heart disease compared to patients taking other NSAIDs. People on the standard dose of Vioxx were 1.6 times more likely to suffer heart disease than those taking Celebrex. If the dose was higher, the risk rose to 3.6 times.

In a commentary on the research, David Webb and Simon Maxwell, of the University of Edinburgh, said the spotlight would now focus on the safety of COX-2 inhibitors.

“It now falls to the manufacturers, under the careful review of the regulatory authorities, to provide all the evidence of that this class of drugs is safe,” they said.