Medical journals raising doubts over four years

Spanish article claimed Merck Sharp committed scientific fraud, writes Dr Muiris Houston.

Spanish article claimed Merck Sharp committed scientific fraud, writes Dr Muiris Houston.

Concerns about the safety of the drug Vioxx (Rofecoxib) and other Cox II inhibitors were raised as far back as 2000, it has emerged.

An article in the Journal of the American Medical Association in December 2001, titled "Risk of cardiovascular events associated with selective Cox II inhibitors", from the Department of Cardiovascular Medicine at the Cleveland Clinic, found that patients taking Rofecoxib were almost 2½ times more likely to have a heart attack or stroke than those taking an older non-steroidal anti-inflammatory drug (NSAID), Naproxen.

The authors based their conclusion on an analysis of a large trial involving 8,000 patients, the Vioxx Gastrointestinal Outcomes Research study.

READ MORE

The trial, published in the New England Journal of Medicine in November 2000, found that Rofecoxib was associated with significantly fewer gastrointestinal side effects than the older NSAID.

However, it reported a higher incidence of heart attack with the new drug.

Although an analysis of a similar trial into another Cox II inhibitor, Celecoxib, found no increase in cardiovascular events associated with it, the authors concluded: "The available data raise a cautionary flag about the risk of cardiovascular events with Cox II inhibitors."

An article in the patient-orientated Evidence that Matters series in the British Medical Journal in March 2003 found that "harms outweigh benefits of Cox II for many patients".

It was based on an article that had appeared in the Canadian Medical Association Journal a year earlier, which highlighted "the double-edged sword of Cox II selective NSAIDS".

"While there still may be a role for these drugs in patients who are at a particular high risk for serious gastrointestinal events, they certainly should not be a drug of choice for the average arthritis patient," the British journal article said.

It concluded that "Cox II inhibitors have serious potential harms that have been minimised in reports of research sponsored by drug companies".

Earlier this year, the British Medical Journal reported on a case taken by Merck Sharp and Dohme, the manufacturers of Vioxx, against the publisher of an independent drug bulletin in Spain.

Butlletí Groc had published an article that claimed Merck Sharp and Dohme had committed scientific fraud in the Vioxx trial.

The drug company wanted the article retracted and replaced with text prepared by the company,

However, Prof Jean-Ramón Laporte, the bulletin's editor, refused to acquiesce. He called the company's move an attack on independent information on drugs.

In a ruling at the end of January Judge Maria Victoria Salcedo rejected the company's demands, saying the company knew of the cardiovascular risks of Rofecoxib.

"The judgment echoes the international debate which took place regarding the irregularities in the Vioxx Gastrointestinal Outcomes Research trial and the omission of cardiovascular adverse events in Merck Sharp and Dohme's promotional material," said Prof Laporte at the case's conclusion.