Vioxx Heart Risk Persists One Year After Stopping Use

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Main Category: Clinical Trials / Drug Trials
Also Included In: Cardiovascular / Cardiology;  Arthritis / Rheumatology;  Colorectal Cancer
Article Date: 14 Oct 2008 - 1:00 PDT

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A new international study found that Merck's pain killer Vioxx (rofecoxib), which the drug company voluntarily withdrew from the market in 2004, found that a near two-fold increased risk of heart, stroke and death persisted for up to one year after stopping use.

The study was the work of Dr Robert Bresalier, a professor of medicine at the MD Anderson Cancer Center in Houston, Texas, and colleagues from other research centres in the US, Canada, Spain and the UK, is published in the 14 October 2008 issue of The Lancet.

In this latest study, Bresalier and colleagues found that the "risk was increased close to twofold, and the risk persisted for approximately a year", according to a statement reported in the Washington Post.

But, "the good news is that, after a year, the risk seemed to go back down toward normal," Bresalier told the press.

Vioxx (rofecoxib) is a type of non-steroidal anti-inflammatory drug (NSAID). Specifically, it is a cox-2 inhibitor that targets an enzyme involved in inflammation, the cyclooxygenase 2 (cox-2) enzyme. It was approved by the US Food and Drug Administration in 1999 for the treatment of osteoarthritis, acute pain conditions, and dysmenorrhoea. But in 2004, Merck withdrew it because of concerns about raised risk of heart attack, stroke and death.

Other less targeted NSAIDs include ibuprofen and naproxen.

Bresalier said that he and other experts believed that all non-aspirin NSAIDs raised the risk of cardiovascular events.

"In fact, it seems to be a class effect for most if not all NSAIDs," said Bresaliers, adding that:

"There is a dose-dependent risk with Celebrex [an NSAID made by Pfizer] as well, whose magnitude was not that much different from Vioxx."

For the study, Bresalier and colleagues followed up participants who took part in the international trial APPROVe that compared Vioxx to placebo for 3 years. APPROVe was a multicentre, randomized, placebo controlled, double blind trial involving nearly 2,600 patients with a history of colorectal adenomas (growths or polyps in the colon) who were recruited at 108 centres worldwide during 2000 and 2001.

APPROVe, which was designed to see if Vioxx could reduce the recurrence of colon growths or polyps, was stopped in 2004 because of increased risk of heart attack and stroke. But Bresalier and colleagues were able to get in touch with 84 per cent of the participants and follow their progress for another year after their treatment stopped.

The analysis looked for the combined incidence of "non-fatal myocardial infarction, non-fatal stroke, and death from cardiovascular, haemorrhagic, and unknown causes", wrote the authors.

The results showed that a year after they stopped using Vioxx, the participants still carried a 79 per cent higher risk of heart attack, stroke or death compared to the participants who had been on placebo during the 3 year trial.

The risk of heart attack or stroke for participants on Vioxx during the trial was double that of the participants on placebo for up to year after the trial, while the risk of death was up by 31 per cent compared to placebo.

Bresalier and colleagues said this was consistent with the increased risk observed in the trial, where the risk of having a cardiovascular event for the participants taking Vioxx was double that of participants taking placebo.

Merck said in a statement reported by Reuters that:

"Using limited data from a prematurely terminated study needs to be interpreted very cautiously and in the context of the rest of the data from the extensive clinical development program for Vioxx."

Bresalier and colleagues did find that Vioxx reduced the incidence of colon polyps.

Speaking to the press about NSAIDs, Bresalier said for people taking them only intermittently, for short term pain relief for example, the risk would most likely be very small. Taking one or two pills is not going likely to give you a heart attack, and for the majority of people taking NSAIDs, they are safe and effective. But you need to be more careful about taking high doses over a long period:

"If you have a history of cardiovascular disease, speak to your doctor to understand the relative risks and benefits. If you're somebody who really needs to take these drugs because of chronic pain or severe arthritis, be aware of the issues. But you shouldn't be afraid to take these drugs if you need them," said Bresalier, according to the Washington Post.

"Cardiovascular events associated with rofecoxib: final analysis of the APPROVe trial."
John A Baron, Robert S Sandler, Robert S Bresalier, Angel Lanas, Dion G Morton, Robert Riddell, Erik R Iverson, and David L DeMets.
The Lancet Early Online Publication, 14 October 2008.
DOI:10.1016/S0140-6736(08)61490-7

Click here for Abstract.

Source: Journal Abstract, Washington Post, Reuters.

Written by: Catharine Paddock, PhD.




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