New Research Indicates Link Between COX-2 Inhibitors, Increased Risk for Heart Attack, Stroke
New research released Monday on the journal Circulation's Web site indicates new evidence linking all COX-2 inhibitors with increased risk of heart attack and stroke, the Washington Post reports (Kaufman, Washington Post, 1/18). The results raise concerns from some experts that an upcoming Pfizer study on the effects of the COX-2 inhibitor Celebrex in people with cardiovascular disease could be unsafe, the Wall Street Journal reports (Winslow, Wall Street Journal, 1/18).
The safety of COX-2 inhibitors has come into question recently, after Merck in late September 2004 withdrew from the market its COX-2 inhibitor, Vioxx, because of safety concerns, and FDA recently announced that Bextra, a COX-2 inhibitor manufactured by Pfizer, could increase patient risk for heart attack and stroke.
Pfizer officials in October announced plans to begin a global clinical trial with more than 4,000 patients who have had a recent heart attack and a history of osteoarthritis to determine whether Celebrex has the same cardiovascular risks as Vioxx. Although Pfizer has said that Celebrex might improve the cardiovascular conditions of patients with coronary artery disease, the company is designing the new trial to determine whether Celebrex increases the risk of heart-related problems.
The randomized trial will compare the outcomes of participants who take Celebrex with those who take placebos (American Health Line, 10/19/2004). Participants in the study also would receive low doses of aspirin (Wall Street Journal, 1/18). Pfizer officials plan to begin the trial early this year and examine the outcomes of participants over at least a two-year period.
The trial will mark the first long-term study that compares Celebrex with placebos (American Health Line, 10/19/2004).
In a recent study, researchers from the University of Pennsylvania gave mice a COX-2 inhibitor similar to Celebrex in combination with an aspirin substitute -- similar to the drug regimen called for in the Pfizer trial -- and observed "dangerously unstable" deposits of plaque, which makes artery walls more likely to rupture and activate clotting and could lead to a heart attack or stroke in humans, the Post reports.
Lead researcher Garret FitzGerald of the University of Pennsylvania acknowledged that mice often have different reactions to medications than humans; however, he "also noted that the earliest evidence of cardiovascular risks associated with COX-2 drugs also came from animal experiments," the Post reports.
The Circulation Web site includes a meta-analysis of two previous studies involving 2,000 people, showing that participants who previously had undergone heart bypass surgery and took Bextra were three times as likely as those taking a placebo to experience a heart attack or stroke.
FitzGerald said, "The clear emergence of a cardiovascular hazard from COX-2 inhibitors in patients, the weak rationale for a study of their protective properties in the first instance, and now this evidence from mice would indicate to me that a trial in high-risk patients, such as that proposed for Celebrex is, at best, ill advised" (Washington Post, 1/18).
He added that giving Celebrex to patients with a pre-existing heart condition to lower their risk "would be just the wrong thing to do."
Pfizer officials have said that concerns related to heart risks and COX-2 inhibitors should be addressed at a three-day FDA advisory panel meeting scheduled to begin Feb. 16 (Wall Street Journal, 1/18).This is part of the California Healthline Daily Edition, a summary of health policy coverage from major news organizations. Sign up for an email subscription.