Counterintuitive outcome of cholesterol drug trial prompts renewed scrutiny of cholesterol’s role in heart disease.

by Craig Weatherby

Last month, we reported on the unexpected outcome of a study that tested the effects of Vytorin: a drug that combines two cholesterol-lowering medications of different types.

Vytorin contains both Zocor (simivistatin)—a statin-type drug that reduces the body’s production of cholesterol—and Zetia: a non-statin drug that reduces absorption of cholesterol from foods.

The clinical trial—whose negative outcome the makers of Vytorin seemed suspiciously slow to reveal—showed that the combination drug did no better than Zocor alone: see “Major Heart and Mood Drugs Take Huge Credibility Hits.”

There is clinical evidence that Zocor—unlike some other statins and unlike Zetia—reduces the risk of heart attacks and other adverse cardiac events.

But a key question remains unanswered: Do statins bring these benefits by lowering cholesterol, or by other means, such as their ability to reduce inflammation markers associated with risk of adverse cardiac events?

As it should have, the surprising outcome of the Vytorin trial led to a series of newspaper stories on the increasingly shaky foundations of the cholesterol theory of cardiovascular disease (CVD).

Rather than make a case for or against the cholesterol theory of CVD, we'd like to direct you to the responses the Vytorin affair elicited from health writers at two major newspapers: The New York Times and The Boston Globe (see links below).

Cholesterol theory's weak underpinnings
The cholesterol hypothesis—whose lack of conclusive evidence argues against it even being called a theory –holds that high levels of cholesterol (especially LDL and VLDL cholesterol)—cause CVD.

In fact, the evidence that elevated cholesterol causes CVD has never enjoyed direct cause-effect evidence.

Instead, the hypothesis has been based on the kinds of correlations (statistical associations) that official bodies dismiss as inconclusive in all other contexts... including the potential roles of nutrients and antioxidants in disease prevention.

Despite this lack of solid cause-effect evidence for the cholesterol hypothesis of CVD, the US FDA automatically allows disease-prevention claims for any drug—such as Zetia—proven to lower cholesterol.

Incredibly, the agency allows therapeutic claims for cholesterol-lowering drugs... even drugs never proven to prevent major symptoms of CVD (e.g., buildup of arterial plaque) or its deadly outcomes, such as stroke, heart attacks, congestive heart failure, and sudden death.

(Sadly, fish oil does enjoy such evidence, but as a non-patentable natural product, it is unlikely to ever get the funding necessary to get it through the nearly $1 billion drug approval process.)

The aforementioned articles—four from The New York Times and one from The Boston Globe—are presented here in order of publication date:

• “What That Cholesterol Trial Didn’t Show” by Tara Parker-Pope. The New York Times, January 22, 2008
• “What’s Cholesterol Got to Do With It?” by Gary Taubes. The New York Times, January 22, 2008
• “Will Cholesterol Pills Save Your Life?” by Tara Parker-Pope. The New York Times, January 28, 2008
• “Great Drug, but Does It Prolong Life?” by Tara Parker-Pope. The New York Times, January 29, 2008
• “No Easy Answers: Even in the age of statins, heart disease threat remains” by Stephen Smith. The Boston Globe, February 11, 2008

We think you will find these writers' analyses informative and thought-provoking.