By the way, doctor: If COX-2 drugs are anti-inflammatory, why are they associated with heart attacks?

Content provided by the Faculty of the Harvard Medical School

By the way, doctor: If COX-2 drugs are anti-inflammatory, why are they associated with heart attacks?

By the way, doctor

If COX-2 drugs are anti-inflammatory, why are they associated with heart attacks?

Q. I'm confused. I've read articles about heart disease being caused by inflammation. If the COX-2 drugs are anti-inflammatory, why do they seem to make heart disease worse, not better?

A. That's a good question and one that's certainly been in the news!

First, some background. For many years, doctors thought that heart attacks could be fully explained by cholesterol buildup. We knew that the atherosclerotic plaques that narrow coronary arteries are filled with LDL ("bad") cholesterol. There was also good evidence from clinical trials that drugs that lower blood levels of total cholesterol and LDL cholesterol reduce the risk of a heart attack.

But researchers have discovered that it isn't cholesterol accumulation that matters most. Heart attacks occur when the top of a cholesterol-rich plaque ruptures, and the contents spill into the artery, causing clots to form and stopping blood flow to heart muscle. Plaques rupture primarily because of the inflammation raging inside.

COX-2 drugs like celecoxib (Celebrex), rofecoxib (Vioxx), and valdecoxib (Bextra) quell inflammation. But they also cause arteries to narrow and encourage blood clots to form. Vioxx and Bextra were more likely to do this, which is why they have been removed from the market.

Aspirin and the other traditional nonsteroidal anti-inflammatory drugs (NSAIDs) — like ibuprofen (Advil, Motrin, other brands) and naproxen (Aleve, other brands) — have the anti-inflammatory benefits but not the vasoconstrictive and pro-clot effects of the COX-2 drugs. In fact, many studies have shown that regular use of low-dose aspirin (325 mg or less), particularly in men over age 50, reduces the risk of heart attacks. And the results of a Harvard study reported in March 2005 found that low dose aspirin may protect women against stroke, although not against heart attacks.

— Anthony L. Komaroff, M.D., Editor in Chief Harvard Health Lette

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Last updated:	June 05, 2007

Medical content reviewed by the Faculty of the Harvard Medical School. Harvard Health Publications, Copyright © 2007 by President and Fellows of Harvard College. All rights reserved. Used with permission of StayWell.

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