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Risk from Celebrex in a Colorectal-Adenoma Prevention Trial

Celecoxib recipients had more than triple the risk for nonfatal MI or death from cardiovascular causes, compared with placebo recipients.

When an increased risk for thrombotic events among rofecoxib (Vioxx) recipients surfaced in the randomized, double-blind, multicenter APPROVe trial (Journal Watch Cardiology Apr 1 2005), the data and safety monitoring board of a similar adenoma-prevention trial (APC) involving celecoxib (Celebrex) requested a focused assessment of cardiovascular endpoints by an independent committee. We now have the data from the APC trial, in which 2035 patients (mean age, 59; 69% men) with histories of colorectal adenomas and endoscopic polypectomy had been randomized to receive celecoxib (200 mg or 400 mg twice daily) or placebo. Of the subjects, about 4% had histories of MI and 7% histories of angina. Follow-up lasted about 3 years.

The incidence of nonfatal MI or death from cardiovascular causes was 2.0% among celecoxib recipients (low-dose, 1.8%; high-dose, 2.2%) -- significantly higher than the 0.6% incidence among placebo recipients (hazard ratio, 3.4). Differences on other major cardiovascular endpoints were less pronounced, such that the combined incidence of cardiovascular death, nonfatal MI, stroke, heart failure, angina, or need for a cardiovascular procedure showed a borderline significant difference between celecoxib recipients and placebo recipients (4.2% [3.8% low-dose, 4.6% high-dose] vs. 2.5%; HR, 1.7; 95% CI, 1.0-2.9). A trend toward increased risk for venous thromboembolic events with celecoxib also emerged.

Comment: This trial documents an increased risk for vascular events associated with the use of celecoxib. Although the trial included only patients with previous colorectal adenomas, the design was randomized; therefore, the evidence of cardiovascular harm from celecoxib in this trial should offset some of the seemingly reassuring data on this drug that emerged in a recent observational study of various nonsteroidal anti-inflammatory drugs (Journal Watch Cardiology Apr 1 2005).

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology April 1, 2005

Citation(s):

Solomon SD et al. for the Adenoma Prevention with Celecoxib (APC) Study Investigators. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005 Mar 17; 352:1071-80.

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