Zetia and/or Statins: The Good, the Bad and the Ugly

Halle-Wittenberg, GermanyCan a drug designed to curb heart attacks also cause heart attacks in some people? Apparently, it's possible with statins or medication like Zetia when used in combination with a statin. Statins are designed to lower the "bad" cholesterol thought to be a contributing factor for heart attack and stroke, while leaving the so-called "good" cholesterol to do the good work that good cholesterol, ultimately, does.

But trying to separate good cholesterol from bad cholesterol and the impact of statins on heart attack—good and bad—is more like the good, the bad and the ugly. Trying to figure it all out is the ugly.

The JUPITER study possesses bragging rights that it was so successful in showing the positive impact of statins (in this case, rosuvastatin) on the reduction of low-density lipo-protein cholesterol (LDL, the so-called "bad" cholesterol) that it was halted seven months early. The study was funded by AstraZeneca but led by a researcher from Harvard Medical School. The international study recruited 18,000 patients from 26 countries.

Based on past studies, researchers expected something in the neighborhood of a 25 percent reduction in heart attacks and strokes. The reality, however, was better than twice that number: a 54 percent reduction in the risk for heart attack, with strokes down by 48 percent. The combined risk of heart attack, stroke and heart-related death fell by 47 percent thanks to the intervention of the stain used in the study.

Now, compare that with a German study that found statin use could actually cause heart attacks in some patients. How can that be?

Well, researchers at the Martin Luther University in Halle-Wittenberg studied more than 1,000 patients with coronary artery disease (CAD) and discovered a subset with high levels of phospholipid transferprotein (PLTP). The latter is an enzyme that has been shown to influence the metabolism of both HDL (the "good") and LDL (the "bad") cholesterol, and also plays a part in the buildup of plaque (atherosclerosis) on arterial walls and heart disease.

Researchers wanted to know just what that enzyme could do and its effect on future cardiovascular events amongst patients who already had CAD.

After five years, 156 of the 1,085 study participants already afflicted with coronary disease had either suffered fatal or non-fatal heart attacks. That figure included 47 of 395 participants who were taking statin drugs. Ultimately, the researchers discovered that study participants with high PLTP levels were not having more heart attacks unless they were taking statins…

Thus, statins were found in one study to be akin to a knight in shining amour, bringing heart attack risk to its knees by slaying levels of bad LDL cholesterol. In another, they were found to increase heart attack risk in a subset of patients already afflicted with coronary disease.

What's Zetia's relationship in all this?

First off, Zetia isn't even a statin, although it is designed to have the same outcome as a statin—lower cholesterol. Zetia just does it in a different way. Ezetimibe (Zetia) is an anti-hyperlipidemic that blocks the absorption of cholesterol in the small intestine.

Zetia is often prescribed with a statin to provide a one-two punch in patients with problematic and challenging cholesterol levels. Zetia is also combined with Zocor in one product, Vytorin.

However, along with its own list of side effects and adverse reactions, Zetia is alleged to have a hand in adverse heart health when used with statins—which puts us back to the statin as a drug that can help, as well as harm.

To that end, researchers have found that statins alone, together with statins when used in concert with Zetia, can activate the atrogen-1 gene in the heart muscle. The atrogen-1 gene is known to drive muscle degeneration. In the heart, that can lead to cardiomyopathy or the weakening of the heart muscle. A weak heart fosters an inability to pump blood sufficiently—and that can lead to a heart attack.

Further—and this goes back to the controversial ENHANCE study that dealt with the combination of Zetia with Zocor in Vytorin—the involvement of Zetia with a statin was found to foster the growth of arterial plaque twice as fast than study participants who were taking simvastatin (Zocor) alone. Yes, cholesterol levels were reduced. But the increase in plaque buildup rendered the cholesterol reductions moot, and resulted in an increased risk of heart attack through the narrowing of arterial walls.

Conclusion: for most people, statins prevent heart attacks. But for some, statins can increase the risk of heart attacks—as can Zetia, when used in combination with a statin.

The good, the bad and the ugly…