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I’m a bit puzzled by all the excitement about Merck’s new drug, Anacetrapib (MK-0859), that’s said to lower risk for cardiovascular disease by lowering bad cholesterol. Earlier this week at the annual meeting of the American Heart Association, researchers presented promising findings on the drug, including results from the phase III DEFINE (Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib) trial. The list of disclosures for that abstract is long and fairly shocking. On Wednesday, the results were published on-line in the NEJM.*

The new drug interests me, as an oncologist, because it’s an enzyme inhibitor – in some ways like many new and in-the-pipeline cancer treatments. Anacetrapib raises high-density lipoprotein (HDL, a.k.a. “good cholesterol”) and lowers low-density lipoprotein (LDL, a.k.a. “bad cholesterol”) by interfering with a cholesterol enzyme transfer protein (CETP). The experimental medication is a pill that, based on earlier safety studies, is taken at 100 mg by mouth, once daily. So it’s convenient enough.

In some respects, the results of this randomized, placebo-controlled large trial are knock-your-socks-off impressive: patients on the drug had, an average, a more-than doubling of their serum HDL levels, from 41 to 101 mg per deciliter.** At the same time, the HDL shift was just 40 to 46 for patients assigned to the placebo (control). Conversely, LDL levels went down dramatically in patients taking Anacetrapib, from 81 to 45 mg per deciliter on average, and the corresponding drop seen among the control patients was only 82 to 77. These numbers are really terrific, and the results highly significant from a statistical perspective. The study lasted for 76 weeks, i.e. well over a year, and the drug was very-well tolerated according to all published reports.

What’s wrong here? Well, it’s that we don’t know for sure how this new drug affects heart disease and other vascular conditions. In this study, the plasma cholesterol levels were monitored as surrogate markers for risk of atherosclerotic events, but these laboratory parameters are not the same thing as direct measures of disease. It is uncertain if this drug has any impact on mortality, or even on heart attacks, strokes or other clinical endpoints.

In my opinion, we need a lot more information about this new drug before we prescribe it to thousands or millions of people who have hyperlipidemia. Fortunately, as pointed out by Dr. Harlan Krumholz, writing for Forbes, Merck is “doing the right thing” by testing the drug in additional studies now, with clinical endpoints in mind. Still, his enthusiasm for what amount to very favorable blood testing seems extreme in light of the previous experience to which he refers with Pfizer’s torcetrapib, a drug of the same class that turned out to have significant side effects, and Merck’s previous marketing of Zetia.

According to the New York Times, John Boris, an analyst at Citigroup, wrote in a note to investors on Wednesday that the drug could potentially have sales of more than $1 billion a year. Dr. Steven Nissen, a sometimes cautious leader in the field, found the results encouraging, according to widely-cited comments such as those appearing in the Dow Jones Newswires.

In a few years, we’ll see what Merck finds out with the ongoing trials, and if the drug really helps reduce heart attacks and deaths in people with hyperlipidemia.

Meanwhile, since my cholesterol’s crept up, just a bit above 200, I’ve started eating oatmeal and quinoa more often. I take only skim milk in my cereal at breakfast, cut out most cheese and pizza, and enjoy ice cream but occasionally. I don’t wish to ingest any experimental enzyme inhibitors that aren’t essential in the life-saving sense.

The NIH offers tips for therapeutic lifestyle changes that can help reduce hyperlipidemia in many patients.

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**cholesterol units: milligrams per deciliter

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