Questions about questioning Zetia's effectiveness

Merck-Schering-Plough is the manufacturer of Zetia and Vytorin.
Associated Press photo.

A recent story about the cholesterol-lowering drug, Zetia (“New study raises questions about Merck pill,” by Marilynn Marchione, AP Medical Writer, link to Kansas City Star archive here) illustrates a few problems with the way medical research is conducted and reported.

The purpose of the study (published in the online New England Journal of Medicine; link here, the graphs are easy to read, the text not so much) was to test the efficacy of extended release niacin versus Zetia in reducing carotid artery wall thickness. Niacin therapy reduced artery wall thickness by about 0.01 millimeters and Zetia showed no effect. The study was stopped early because of the “significant” benefit of the niacin in reducing artery wall thickness and of what appeared to be an increased risk of heart attack in the Zetia group (5% versus 1%).

The study had a relatively small sample size (about 180 patients in each group). Small sample size can be problematic in any experiment, particularly if the sampling is not sufficiently randomization. (This may be of particular note here, where both the experimental groups were chosen from a population of people with pre-existing cardiovascular issues.) Second, there does not seem to be a control group included – people who were not given either medication. So statistically speaking, no conclusion can be drawn about whether one treatment caused a significant increase in heart attacks compared to an untreated population.

The lead of the AP article was also a bit misleading: “A new study raises fresh concerns about Zetia and its cousin, Vytorin - drugs still taken by millions of Americans to lower cholesterol, despite questions raised last year about how well they work.” It implies that it is the cholesterol-lowering ability of Zetia and Vytorin that are at issue, but that was not the focus of the study. (In fact, Zetia was found to do a better job of yielding additional incremental reductions of triglycerides, LDLs and total cholesterol levels in the patients than did the niacin treatment).

This is a good example of publicity getting ahead of science. Publication of a study in a peer-reviewed journal is but the first step in the process. The results of any study (and particularly those of small scale) are not scientifically accepted until the same results are confirmed by other independent research. The point is, while it may very well be the case that the niacin therapy is preferable to Zetia in reducing artery wall thickness and heart attack risk, no finality can be given to conclusions drawn from the first published results, nor should it be reported that way.

A more interesting storyline might have been to reveal that Abbott Laboratories (which makes the niacin drug used in the study) supported the research. And to investigate the financial ties (e.g., as consultants and paid speakers) between the study authors and drug companies, most of which are competitors with Merck, the company that makes Zetia and Vytorin. Although this bit of information was mentioned in passing in the middle of the story, it required one paragraph for the editors of the New England Journal of Medicine to list all of these potential conflicts of interest.

Financial connections between researchers and drug companies (or any other industry for that matter) are problematic, because bias – intentional or not – can never be ruled out. We could all feel more confident about the results of these kinds of studies if their funding came through an independent agency rather than companies with vested interests in the results.