Cholesterol Redux--The Great Zetia/Vitorin Bust

Sunday, January 27

Admittedly they were clever: those TV commercials for Vitorin where people were photo-stylized to resemble foods. Not since Carmen Miranda wore those crazy Chiquita Banana headdresses have food stylists had so much fun. "Is it your Aunt Cherie, or Cherries Jubilee?" "Is it your Uncle Fred, or Spaghetti al Fredo"?

The commercials are gone now, amid the backlash to the just-released "ENHANCE" study, which showed no advantages to Zetia given alone, or combined with the Merck statin drug Zocor in Vitorin. No reduction in heart attacks, strokes or death, and no reduction in plaque in the carotid arteries. In fact, mysteriously, Vitorin was slightly worse than Zocor alone in reducing cardiovascular risk.

The results have shaken the pillars of Wall Street and mainstream medicine. Stocks of Schering and Merck are reeling. Patients are calling their cardiologists in droves. Predictably, there's even talk of class-action lawsuits as lawyers roil the waters around the wounded drugs. Meanwhile, the makers of Zetia and Vitorin have placed full-page ads in papers telling consumers to just hang in there and keep taking their meds. Yeah, right!

What happened? Isn't lowering cholesterol the chief way we can reduce cardiovascular risk? Has medicine taken a wrong turn?

Personally, I never liked these drugs and NEVER have prescribed them. Other statin drugs are fine under certain circumstances, but probably not because they lower cholesterol. Rather, it's due to an inadvertent side effect: like expensive designer versions of aspirin, they combat inflammation, a more fundamental risk factor for arterial wall damage.

Gary Taubes, a frequent guest on Health Talk, nailed it in his January 27 Sunday Times op-ed piece entitled "What's Cholesterol Got to Do With It?" In it he notes that we have fallen hook, line and sinker for the "Cholesterol Hypothesis", a mere theory which does not meet the demands of scientific rigor.

(Remember Taubes as the author of the revolutionary Times article entitled "What if it Was All a Big Fat Lie?"-- the cover story for a 2003 edition of the New York Times Magazine that famously featured a picture of a greasy steak on the front.)

Taubes argues convincingly that we're playing cholesterol limbo ("How low can you go?") based on an entirely wrong set of assumptions. Cholesterol levels on their own are not good predictors of heart attacks, but the ratio of cholesterol to HDL is. Half of heart attacks occur in individuals with normal cholesterol. LDL cholesterol is a mixed bag, with new tests that we do at the Hoffman Center revealing that there is both good and bad LDL.

We're conflating the benefits of cholesterol reduction using drugs with the benefits of having low cholesterol and favorable HDL ratios the natural way--which may be the result of good genes and healthy diet and lifestyle. Lowering cholesterol a lot with a drug is the way to go, we speciously reason. That's like saying that the best vacuum cleaner is the one that makes the loudest noise (my analogy): in the case of Vitorin, extra cholesterol reduction leads to no additional therapeutic benefit. Mother Nature always has a way of biting back when you mess with her!

The same thing happened recently with a new Pfizer HDL-raising drug called Torcetrapib. It worked just fine to artificially raise HDL (good concept!), but inexplicably caused so many increased heart attacks and deaths during the test phase that Pfizer had to abandon the project. Apparently HDL in a pill is no substitute for good diet and exercise.

So the onus is now on the drug-makers to demonstrate an advantage to these medications. I'm not holding my breath. Meanwhile, I'll continue to eschew their use until I see compelling evidence for their benefits, which I doubt will be forthcoming.