Wednesday, January 23, 2008

Beyond Zetia

This Zetia business seems to be rocking the cardiology world just like the Women's Health Initiative blew up conventional wisdom on hormone replacement therapy.

Cholesterol in the body comes from two sources: one pool manufactured in the body, and the other from the diet. Zetia is a drug that lowers LDL-cholesterol levels by partially blocking the absorption of cholesterol from the small intestine. Statins such as Zocor and Lipitor, on the other hand, decrease some of the activity of an enzyme that is important in the body's own cholesterol production. Zetia has been heavily marketed as a good drug for persons with high cholesterol who either can't tolerate statins or who don't reach their goal LDL-cholesterol levels on statins alone.

The ENHANCE trial found that persons taking the Zetia-Zocor combination for 2 years (aka Vytorin) did no better than those on Zocor alone with respect to unwanted thickening of their carotid arteries. As a result, not only are cardiologists taking sides in the Zetia/no-Zetia debate, now they're wondering if lowering LDL-cholesterol is even an important goal in the war against heart disease. Consider these varied opinions from the nation's top heart specialists:

The idea that you're just going to lower LDL and people are going to get better, that's too simplistic, much too simplistic.
Dr. Eric Topol, Scripps Institute

The message for me is not that lowering LDL cholesterol doesn't work to prevent disease progression or to prevent clinical events. The important thing to remember is how the cholesterol levels are lowered...There are many advocates out there who espouse lowering LDL cholesterol by any means possible. But let's be clear: 95% of the studies that form the basis for the cholesterol hypothesis are based on studies of statins
Dr. Steven Nissen, Cleveland Clinic

Anytime you can lower LDL-cholesterol levels safely, you are going to see reductions in the risk of clinical events.
Dr. Patrick McBride, University of Wisconsin

Per Dr. Nissen, the bottom line here is that statins not only lower LDL-cholesterol, but they also can raise HDL-cholesterol (a weensy bit), decrease triglycerides, and lower c-reactive protein or CRP. CRP is a pro-inflammatory molecule in the body; when present in elevated amounts, CRP not only is a marker for risk of coronary artery disease, the substance actually causes trouble in arteries whose walls are streaked with fat.

The Premarin drug rep started sneaking through our door after the 2002 WHI results were released, sheepishly bearing samples and M&M's. The Avandia reps don't even come around anymore. Come to think of it, haven't seen the smiling face of the Vytorin rep in the last week either.

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