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The first two weeks of treatment with the pain drug Vioxx can be one of the riskiest times to take the drug from a heart health point of view, a new study suggests.

The study, by a team of Canadian researchers, found that a quarter of the people who suffered a heart attack while taking the drug did so within the first two weeks of treatment. Previous studies have suggested the risk of cardiovascular events was associated with use of the drug for 18 months or longer.

In light of these findings, doctors prescribing Celebrex — the only drug of the cox-2 inhibitor class currently on North American markets — ought to follow up patients closely in the period after writing a first prescription, the lead author said Tuesday.

“The results emphasize first that we can't necessarily assume that the risk takes 18 months or more to appear and that there's a need for early monitoring of people who take these medications,” said Linda Levesque, a professor of community health and epidemiology at Queen's University in Kingston, Ont.

The findings could have implications in the myriad lawsuits drug giant Merck faces in relation to Vioxx, once one of biggest sellers in the world.

Merck pulled Vioxx from the market in September 2004 when a study — called the APPROVE trial — showed that people on Vioxx had twice the risk of having a heart attack than people taking a placebo. The trial was actually designed to see if Vioxx could be used to prevent colon cancer.

It suggested the risk of heart problems only arose after 18 months. But Prof. Levesque's study, which was published online Tuesday by the Canadian Medical Association Journal, challenges that finding.

“We've been hearing for over a year and a half now that there is no risk in the first 18 months of use,” she said from Montreal.

“There are multiple lawsuits being argued in the States and there seems to be a line being drawn between those occurring earlier than 18 months as being non-viable and those occurring after.”

Prof. Levesque, who was a doctoral student at McGill when she and colleagues there did the research, mined the records of 125,000 Quebec residents aged 66 and older who were given prescriptions for cox-2 drugs between Jan. 1, 1999 and June 30, 20002. The median age of the people whose records they studied was 75 years.

Patients taking Vioxx for the first time were at a significantly elevated risk of having a heart attack between their sixth and 13th day on the drug. A smaller risk was seen in patients first taking Celebrex, but the finding for that drug wasn't statistically significant.

An expert on the controversy over the cox-2 drugs was unconvinced by the findings, drawn as they were from an observational study, which observes outcomes retrospectively.

Such studies, though useful, aren't considered to provide as robust evidence as randomized controlled trials, where people given a treatment are compared to those who get a placebo or another therapy.

“I think given the evidence we have, including this new study, I would tend to put more weight on the APPROVE placebo controlled randomized trial, which showed an 18-month delay ... as opposed to an observational study which does not take into account differences in underlying illness (of study participants),” said Dr. Mark Fendrick, an internal medicine specialist at the University of Michigan.

Prof. Levesque's findings contain some positive news for people who've taken cox-2 drugs. Based on her data, the heart attack risk the drugs pose appears to diminish rapidly once people stop taking them. By one month after cessation of the drug, the user's heart attack risk appears to return to normal, she said.