Cardiovascular Risk with Celecoxib (Celebrex), UK Agency Informs

Main Category: Cardiovascular / Cardiology
Article Date: 19 Dec 2004 - 11:00 PST

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We have today been informed of new clinical trial data for celecoxib (Celebrex), showing an increased risk of heart attack, stroke and death (relative to placebo). The data come from a single clinical trial. The increased relative risk was statistically significant and was 3.4 for 800mg and 2.5 for 400mg (which is the maximum licensed dose for arthritis). A second trial has also been stopped on the basis of these results, although this (second) trial did not itself show an increased risk.

We do not yet have access to full details of the trials - the only information we have has been extracted from the website of the manufacturer for celecoxib (Pfizer) and is below. We have urgently requested access to the new study information from the company. Once these data have been carefully assessed by the MHRA and Committee on Safety of Medicines (CSM), definitive advice will be issued.

The CSM is setting up an Expert Working Group to specifically examine the cardiovascular safety of all COX-2 inhibitor anti-inflammatory medicines and will be playing a leading role in the forthcoming European review of this area, in the coming months.

The celecoxib product information for patients already contains warnings that patients who have heart disease should discuss this with their doctor before initiating treatment.

The European Medicines Evaluation Agency has issued a press release which can be accessed at www.emea.org.

From the Pfzier global website (www.pfizer.com)

'In the Adenoma Prevention with Celecoxib (APC) trial, patients taking 400mg and 800mg of Celebrex daily had an approximately 2.5 fold increase in their risk of experiencing a major fatal or non-fatal cardiovascular event compared to those patients taking placebo, according to the National Cancer Institute (NCI). Based on these statistically significant findings, the sponsor of the trial, the NCI, has suspended the dosing of Celebrex in the study.

In a separate long-term study, the Prevention of Spontaneous Adenomatopus Polyps (PreSAP) trial, there has been no increased risk for Celebrex patients taking 400mg daily compared with those taking placebo.

These findings are based on an identical analysis used to assess cardiovascular risk in the APC trial and conducted by the same independent safety review board. The information from this Pfizer sponsored trial was also received by Pfizer last night and, as with the APC information, was immediately shared by the company with the U.S. Food and Drug Administration.

The two studies, which are following patients over a five-year period, have enrolled a total of about 3,600 patients, some of whom have participated for more than four years. Pfizer estimates that about 2,400 patients evaluated in the cardiovascular analysis have completed two years of treatment.

A third long-term study involving Celebrex in patients at high-risk for Alzheimer's disease is also under way with about 2,000 patients enrolled, about 750 of whom are on 400mg per day of Celebrex. As with the cancer studies, this study is monitored by independent safety experts who meet regularly to assess adverse events. A review by this board as recent as December 10 did not result in any recommendations to change the conduct of this study.

In September and October, the Data Safety and Monitoring Boards of the APC and PreSAP cancer trials conducted a preliminary review of all the thenavailable data and determined to proceed with the studies. With the cooperation of Pfizer, the safety review boards convened a panel of cardiovascular experts to conduct additional reviews and analyses of the data from these two trials. Last evening, Pfizer received preliminary information resulting from the reviews. The company has not yet received the full analyses of these studies.'
http://www.mhra.gov.uk/news/2004/celecoxib_171204.pdf

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