Contrary to misleading reports, Vioxx users could still be at risk after withdrawal

[Guest guest]

Contrary to misleading reports, Vioxx users could still be at risk

after withdrawal



May 12, 2006



Gandey

Whitehouse Station, NJ - Media outlets across the US carried mistaken

headlines yesterday assuring doctors and patients that stopping

rofecoxib (Vioxx, Merck) confers no added cardiovascular risk. But

results of the study summary that journalists were reporting on say

the opposite [1]. " Merck, in presenting these data, misrepresented

the results, " Dr Nissen (Cleveland Clinic, OH) told

rheumawire. " Media reports are now saying there is no increased risk

after Vioxx is stopped, when the results show that there is actually

a 74% excess risk of cardiovascular thrombotic events compared with

placebo. "

Nissen continued, " This is a very surprising result, because many

believed that when patients stopped taking Vioxx, the prothrombotic

effect would be eliminated. " He says physicians and patients need to

be aware that there is an ongoing cardiovascular risk for those

previously exposed, and vigilant follow-up is in order.

But during a conference call with reporters yesterday, Merck

executives said the findings should make it difficult to link

rofecoxib to cardiovascular events after patients have stopped taking

the drug. The new data are from the off-drug period from the

Adenomatous Polyp Prevention on Vioxx (APPROVE) trial—the study that

brought rofecoxib down in 2004. The latest findings released by Merck

provide data on confirmed thrombotic cardiovascular events and

mortality from the off-drug extension of the trial.











This is a very surprising result, because many believed that when

patients stopped taking Vioxx, the prothrombotic effect would be

eliminated.













APPROVE was a 2587-patient, multicenter, randomized, placebo-

controlled, double-blind study designed to evaluate the efficacy of

three years of treatment with Vioxx 25 mg in preventing the

recurrence of polyps in patients with a history of colorectal

adenomas. As previously reported in the 156-week base study, there

was an increased relative risk for confirmed thrombotic

cardiovascular events beginning after 18 months of treatment in

patients taking rofecoxib compared with those on placebo [2].

Merck faces thousands of lawsuits and has already lost half of the

six cases that have come to trial so far. " Our strategy has been to

defend the product litigation on a case-by-case basis, "

Frazier, Merck's general counsel, said during the conference call

with the press. " The follow-up data from APPROVE do not change that

strategy. "

Responding to questions from reporters, Dr Kim, president of

Merck Research Laboratories, said, " If you look at the confirmed

cardiovascular thrombotic events in these patients after they stopped

taking Vioxx, there's not a statistically significant difference

between patients who took Vioxx vs patients who took placebo. If,

however, " he continued, " you look at the full four-year data in this

intention-to-treat type of analysis, which includes the time when the

patients were on drug as well as when they were off drug, there's a

statistically significant difference. "



This is what Nissen says is worrying. Merck's study summary shows

that the relative risk of patients having confirmed thrombotic

cardiovascular events in the 156-week on-drug base study was 1.92

(95% CI 1.19-3.11; p=0.008). And this difference remained significant

after data from the off-drug follow-up period were included. In the

intention-to-treat analysis through week 210, the relative risk was

1.74 (95% CI 1.19-2.55; p=0.004). Mortality was found to be similar

between groups.

But the lead investigator of the APPROVE trial, Dr Bresalier

(University of Texas MD Cancer Center in Houston), says it's

still too early to tell whether there is an appreciable ongoing risk

when rofecoxib is withdrawn. His group will be further analyzing the

findings over the next couple of weeks.

" My gut feeling is that I would be very surprised if there were an

ongoing effect, " Bresalier told rheumawire. " This is definitely not

the end of the story. "

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